WO2025257413A1 - Pecticidally active dihydroazole derivatives - Google Patents
Pecticidally active dihydroazole derivativesInfo
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- WO2025257413A1 WO2025257413A1 PCT/EP2025/066632 EP2025066632W WO2025257413A1 WO 2025257413 A1 WO2025257413 A1 WO 2025257413A1 EP 2025066632 W EP2025066632 W EP 2025066632W WO 2025257413 A1 WO2025257413 A1 WO 2025257413A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P7/00—Arthropodicides
- A01P7/04—Insecticides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Definitions
- Pesticidally Active Dihydroazole Derivatives The present invention relates to pesticidally active, in particular insecticidally active dihydroazole derivative compounds, to processes for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Lepidoptera. There have now been found novel pesticidally active dihydroazole derivative compounds.
- the present invention accordingly relates, in a first aspect, to a compound of Formula (I): wherein R1 to R4 are independently H, halogen, C1-6alkyl, or C1-6haloalkoxy; wherein W is C1-6alkyl, phenyl, 5- or 6-membered heteroaryl, wherein the heteroaryl ring, independent of each other, comprises 1 or 2 heteroatoms independently selected from nitrogen and sulphur, and wherein the ring of the phenyl, 5- or 6-membered heteroaryl, independently of each other, are unsubstituted or independently substituted by 1, 2 or 3 halogen substituents; wherein A1, A2 and A3, together with the adjoining carbon atoms, form a 5-membered ring comprising 2 or 3 heteroatoms and an endocyclic double bond and are, independently, selected from NR9, N, C(O), or O, and wherein R9 is H or CH3; wherein R5 is H or C1haloalkyl; wherein T is
- Compounds of formula (I) which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as C1-C4alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as C1-C4alkane- or arylsulfonic acids which are unsubstituted or substituted
- Compounds of formula (I) which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine.
- bases for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts
- salts with ammonia or an organic amine such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, die
- the compounds of formula (I) according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
- N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
- the compounds of formula (I) according to the invention also include hydrates which may be formed during the salt formation.
- halogen refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo).
- hydroxyl or “hydroxy” means an -OH group.
- hydrosulfido or “mercapto” means an -SH group.
- cyano means a -CN group.
- amino means an -NH2 group.
- nitro means an -NO2 group.
- acyl means a -C(O)CH3 group.
- formyl means a -C(O)H group.
- C1-n alkyl refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to n carbon atoms, and which is attached to the rest of the molecule by a single bond.
- C1-6alkyl is to be construed accordingly.
- C1-6alkyl examples include, but are not limited to, methyl, ethyl, n- propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso-propyl, iso-butyl, sec-butyl, tert-butyl or iso-amyl.
- a “C1-4alkylene” group refers to the corresponding definition of C1-4alkyl, except that such radical is attached to the rest of the molecule by two single bonds.
- the term “C1-2alkylene” is to be construed accordingly.
- C1-4alkylene examples include, but are not limited to, -CH2-, - CH2CH2- and -(CH2)3-.
- C2-n alkenyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that may be of either the (E) or (Z)configuration, having from two to n carbon atoms, which is attached to the rest of the molecule by a single bond.
- C2-6alkenyl is to be construed accordingly.
- Examples of C2-C6alkenyl include, but are not limited to, prop-1-enyl, allyl (prop-2-enyl), and but-1-enyl.
- C2-n alkynyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to n carbon atoms, and which is attached to the rest of the molecule by a single bond.
- C2- 6alkynyl is to be construed accordingly. Examples of C2-6alkynyl include, but are not limited to, prop- 1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.
- C1-n haloalkyl refers to a C1-n alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
- C1-4haloalkyl and C1-2haloalkyl are to be construed accordingly.
- Examples of C1-6haloalkyl include, but are not limited to fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, and 2,2,2-trifluoroethyl.
- C2-n haloalkenyl refers to a C2-n alkenyl group as defined above substituted by one or more of the same or different halogen atoms.
- C2-6haloalkenyl examples include, but are not limited to 3,3-dichloroallyl, 2,3,3-trichloroallyl, 2,3-dichloroallyl, 3,3-dibromoallyl, 2,3,3-tribromoallyl, and 2,3-dibromoallyl.
- C2-n haloalkynyl refers to a C2-n alkynyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
- cyanoC1-n alkyl refers to a C1-n alkyl radical as generally defined above substituted by one or more cyano groups.
- CyanoC1-6alkyl is to be construed accordingly.
- Examples of cyanoC1-6alkyl include, but are not limited to, cyanomethyl.
- hydroxyC1-n alkyl refers to a C1-n alkyl radical as generally defined above substituted by one or more hydroxy groups.
- aminoC1-n alkyl refers to a radical of the formula H2NRa- wherein Ra is a C1-n alkylene radical as generally defined above.
- C1-n alkylcarbonylC1-n alkyl refers to a radical of the formula -RbC(O)Ra wherein Ra is a C1-n alkyl as generally defined above and Rb is a C1-n alkylene radical as generally defined above.
- C1-n alkoxycarbonylC1-n alkyl refers to a radical of the formula -RbC(O)ORa, wherein Ra is a C1-n alkyl radical as generally defined above and Rb is a C1-n alkylene radical as generally defined above.
- C1-n alkoxy refers to a radical of the formula -ORa wherein Ra is a C1-n alkyl radical as generally defined above.
- C1-6alkoxy is to be construed accordingly.
- Examples of C1- 6alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, and tert-butoxy.
- C1-n alkenoxy refers to a radical of the formula RaO-, wherein Ra is a C1-n alkenyl radical as generally defined above.
- C1-n haloalkoxy refers to a C1-n alkoxy group as defined above substituted by one or more of the same or different halogen atoms. C1-6haloalkoxy is to be construed accordingly. Examples of C1-6haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.
- C1-n alkylcarbonyloxy refers to a radical of the formula -OC(O)Ra wherein Ra is a C1-n alkyl radical as generally defined above.
- C1-n alkoxyC1-n alkyl refers to a radical of the formula Rb-O-Ra- wherein Rb is a C1-n alkyl radical as generally defined above, and Ra is a C1-n alkylene radical as generally defined above.
- C1-n alkoxyC1-n alkoxy refers to a radical of the formula Ra-O-Rb- wherein Ra is a C1-n alkyl radical as generally defined above, and Rb is a C1-n alkoxy radical as generally defined above.
- C1-n alkylcarbonyl refers to a radical of the formula RaC(O)-, wherein Ra is a C1-n alkyl radical as generally defined above.
- C1-Cn haloalkylcarbonyl refers to a C1-Cn alkylcarbonyl radical as generally defined above, substituted by one or more of the same or different halogen atoms.
- C1-n alkoxycarbonyl refers to a radical of the formula RaOC(O)-, wherein Ra is a C1-n alkyl radical as generally defined above.
- C1-Cn alkylaminocarbonyl refers to a radical of the formula RaNHC(O)- wherein Ra is a C1-Cn alkyl radical as generally defined above.
- C1-n alkylcarbonylamino refers to a radical of the formula RaC(O)N(H)- wherein Ra is a C1-n alkyl radical as generally defined above.
- C3-8cycloalkyl refers to a stable, monocyclic ring radical which is saturated and contains 3 to 8 carbon atoms. C3-6cycloalkyl is to be construed accordingly.
- C3- 8cycloalkyl examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
- C3-10cycloalkenyl refers to a radical which is a monocyclic non-aromatic ring system consisting solely of carbon and hydrogen atoms and which contains 3 to 10 carbon atoms and 1 or 2 endocyclic double bonds. They may include bridged structures (e.g., norbornene and 2,5- norbornadiene).
- C3-C10cycloalkenyl examples include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl.
- C3-6halocycloalkyl refers to a C3-6cycloalkyl ring as defined above substituted by one or more of the same or different halogen atoms.
- C3-8cycloalkylC1-2alkyl refers to a C3-8cycloalkyl ring as defined above attached to the rest of the molecule by a C1-2alkylene radical as defined above.
- C3- 6cycloalkylC1-2alkyl should be construed accordingly.
- Examples of C3-8cycloalkylC1-2alkyl include, but are not limited to cyclopropyl-methyl and cyclobutyl-ethyl.
- phenylC1-2alkyl refers to a phenyl ring attached to the rest of the molecule by a C1-2alkylene radical as defined above. Examples of phenylC1-2alkyl include benzyl.
- aryl refers to an aromatic ring system consisting solely of carbon and hydrogen atoms which may be mono, bi or tricyclic.
- heteroaryl refers to a 5- or 6-membered aromatic monocyclic ring radical which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S.
- heteroaryl examples include, but are not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl.
- heteroarylC1-2alkyl refers to a heteroaryl ring as defined above which is attached to the rest of the molecule by a C1-2alkylene radical as defined above.
- heteroodiaryl refers to a 9- or 10-membered bicyclic aromatic system which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S.
- heterodiaryl include, but are not limited to, quinolinyl and indolinyl.
- heterocyclyl or “heterocyclic” refers to a stable 5- or 6-membered non- aromatic monocyclic ring radical which comprises 1, 2, or 3 heteroatoms individually selected from nitrogen, oxygen and sulfur.
- the heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom.
- heterocyclyl examples include, but are not limited to, pyrrolinyl, pyrrolidyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidyl, piperazinyl, tetrahydropyranyl, dioxolanyl, morpholinyl, oxazinanyl, oxetanyl, or ⁇ -lactamyl.
- heterocyclylC1-2alkyl refers to a heterocyclic ring as defined above which is attached to the rest of the molecule by a C1-2alkylene radical as defined above.
- controlling refers to reducing the number of pests, eliminating pests and/or preventing further pest damage such that damage to a plant or to a plant derived product is reduced.
- pest refers to pests that cause damage and /or inconcenience in agriculture, in horticulture, in ornamentals, in forests, in the storage of products of vegetable origin (such as fruit, grain and timber) including damage of man-made structures, or on organs, such as fruits, flowers, foliage, stalks, tubers, plant propagation material (such as seeds), and roots, of such plants, and in some cases even plant organs which are formed at a later point in time.
- the term pest encompasses all stages in the life cycle of the pest.
- insects examples include arthropod pests, and nematodes; preferably insects, mities and acarina, particularly insects.
- the term "effective amount" refers to the amount of the compound, or a salt thereof, which, upon single or multiple applications provides the desired effect. An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances. Embodiments according to the invention are provided as set out below.
- R1 to R4 are independently H, F, Cl, C1-3alkyl or C1- 3haloalkoxy.
- W is phenyl, pyridine, thiophene, thiazole, or C1- 4alkyl, wherein the ring of the phenyl, pyridine, thiophene, or thiazole is unsubstituted or independently substituted by 1, 2 or 3 fluorine or chlorine substituents.
- A1, A2 and A3 together with the adjoining carbon atoms, form a 5-membered ring comprising 3 heteroatoms and an endocyclic double bond.
- the 3 heteroatoms comprise two nitrogen atoms and an oxygen.
- R5 is trifluoromethyl, difluoromethyl or fluoromethyl.
- R6 to R8 are H or methyl.
- A is monosubstituted.
- A is monosubstituted by F, Cl, C1-3alkyl or C1- 3haloalkoxy, preferably in the para position.
- the present invention makes available a composition comprising a compound of formula (I) as defined in the first aspect, one or more auxiliaries and diluent, and optionally one more other active ingredient.
- the present invention makes available a method of combating and controlling one or more pests which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest a pesticidally effective amount of a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.
- the present invention makes available a method for the protection of plant propagation material from the attack by one or more pests, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.
- the present invention makes available a plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.
- the present invention in a further aspect provides a method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound of formula (I) of the first aspect.
- the present invention further provides a method of controlling ectoparasites on an animal in need thereof comprising administering an effective amount of a compound of formula (I) as defined om the first aspect.
- the present invention further provides a method for preventing and/or treating diseases transmitted by ectoparasites comprising administering an effective amount of a compound of formula (I) as defined in the first aspect, to an animal in need thereof.
- the uses and methods described herein exclude treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
- the use is a non-therapeutic use.
- the method is a non-therapeutic method.
- a compound of Formula (I) can exist in different tautomeric forms and a skilled person would readily understand what they are.
- Compounds of Formula (I) can be prepared by those skilled in the art following known methods.
- Reactions are well known to a person skilled in the art and are usually carried out in the presence of a palladium catalyst, such as tetrakis(triphenylphosphine)-palladium(0) or 1,1’-bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex, and a base, such as sodium or potassium carbonate, in a solvent, such as N,N-dimethylformamide, dioxane or dioxane-water mixtures, at temperatures between room temperature and 160°C, optionally under microwave heating conditions and preferably under inert atmosphere.
- a palladium catalyst such as tetrakis(triphenylphosphine)-palladium(0) or 1,1’-bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex
- a base such as sodium or potassium carbonate
- a solvent such as N,N-dimethyl
- Metalorganic compounds of formula (X) are commercially available. Metalorganic compounds of formula (Xa) may be prepared via trans metalation. This reaction is shown in Scheme 7. Scheme 7 Compounds of formula (IX) can be prepared from compounds of formula (XI) by treatment with a compound of formula (II), for example trifluoroacetic chloride, trifluoroacetic fluoride, or trifluoroacetic anhydride in the presence of a base (eg, pyridine or 4-dimethylaminopyridine) in a suitable solvent, such as tetrahydrofuran or ethanol, at a temperature between 25°C and 75°C. For related examples, see WO 2003/028729 and WO 2010/045251. This reaction is shown in Scheme 8.
- a base eg, pyridine or 4-dimethylaminopyridine
- suitable solvent such as tetrahydrofuran or ethanol
- Compounds of formula (XIII) can be prepared from compounds of formula (XIV), wherein X is Br or I, via metal-promoted reaction with a suitable cyanide reagent, such as Pd(0)/Zn(CN)2 or CuCN, in a suitable solvent (eg, dimethylformamide or N-methylpyrrolidone) at elevated temperature between 100°C and 120°C.
- a suitable cyanide reagent such as Pd(0)/Zn(CN)2 or CuCN
- a suitable solvent eg, dimethylformamide or N-methylpyrrolidone
- Scheme 11 Compounds of formula (XVa), wherein T is T1, can be prepared by reduction of nitro compound of formula (XVIa) using reducing agents such as Iron or SnCI2 in acid medium as described in the experimental section. This reaction is shown in Scheme 12.
- methyliodide or dimethylsulfate The reaction may be carried out in an inert organic solvent such as tetrahydrofuran or dimethylformamide at ambient or elevated temperature, optionally in the presence of a suitable base such as potassium or caesium carbonate or a strong base such as sodium t-butoxide or lithium bis(trimethylsilyl)amide (LiHMDS).
- a suitable base such as potassium or caesium carbonate or a strong base such as sodium t-butoxide or lithium bis(trimethylsilyl)amide (LiHMDS).
- Scheme 16 Compounds of formula (IIb), wherein A1 is N(CO)CH3, A2 is N, and A3 is O can be prepared via cyclisation and acylation reaction of compounds of formula (XXIa) with acetic anhydride as described in the experimental section. This reaction is shown in Scheme 17.
- Scheme 17 Compounds of formula (XXI), wherein A1 and A2 are N, and A3 is O can be prepared via condensation reaction of compounds of formula (XXII) and compounds of formula (XXIII) as described in the experimental section. This reaction is shown in Scheme 18.
- Salts of compounds of Formula (I) can be prepared in a manner known per se.
- acid addition salts of compounds of Formula (I) are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.
- Salts of compounds of Formula (I) can be converted in the customary manner into the free compounds I, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent.
- Salts of compounds of Formula (I) can be converted in a manner known per se into other salts of compounds of formula I, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.
- a salt of inorganic acid such as hydrochloride
- a suitable metal salt such as a sodium, barium or silver salt
- an acid for example with silver acetate
- a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.
- the compounds of formula I, which have salt- forming properties can be obtained in free form or in the form of salts.
- the compounds of Formula (I) and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.
- Diastereomer mixtures or racemate mixtures of compounds of formula I, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diastereomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
- Enantiomer mixtures such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl cellulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the di
- N-oxides can be prepared by reacting a compound of the Formula (I) with a suitable oxidizing agent, for example the H2O2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride.
- a suitable oxidizing agent for example the H2O2/urea adduct
- an acid anhydride e.g. trifluoroacetic anhydride.
- the biologically more effective isomer for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity.
- the compounds of Formula (I) and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
- A-1.001 is I ndex Cx 1 O CF3 N O N N H C H 3 Index Cx 2 3 4 5 6 7 8 9 10 Index Cx 11 12 13 14 15 16
- Table A-2 provides 16 compounds A-2.001 to A-2.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 2 and Cx are as defined in table A.
- Table A-3 provides 16 compounds A-3.001 to A-3.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 3 and Cx are as defined in table A.
- Table A-4 provides 16 compounds A-4.001 to A-4.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 4 and Cx are as defined in table A.
- Table A-5 provides 16 compounds A-5.001 to A-5.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 5 and Cx are as defined in table A.
- Table A-6 provides 16 compounds A-6.001 to A-6.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 6 and Cx are as defined in table A.
- Table A-7 provides 16 compounds A-7.001 to A-7.016 of formula I-A wherein Bx is (3,5-dichlorophenyl), Qx is 1 and Cx are as defined in table A.
- Table A-8 provides 16 compounds A-8.001 to A-8.016 of formula I-A wherein Bx is (3,5-dichlorophenyl), Qx is 2 and Cx are as defined in table A.
- Table A-9 provides 16 compounds A-9.001 to A-9.016 of formula I-A wherein Bx is (3,5-dichlorophenyl), Qx is 3 and Cx are as defined in table A.
- Table A-10 provides 16 compounds A-10.001 to A-10.016 of formula I-A wherein Bx is (3,5- dichlorophenyl), Qx is 4 and Cx are as defined in table A.
- Table A-11 provides 16 compounds A-11.001 to A-11.016 of formula I-A wherein Bx is (3,5- dichlorophenyl), Qx is 5 and Cx are as defined in table A.
- Table A-12 provides 16 compounds A-12.001 to A-12.016 of formula I-A wherein Bx is (3,5- dichlorophenyl), Qx is 6 and Cx are as defined in table A.
- Table A-13 provides 16 compounds A-13.001 to A-13.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 1 and Cx are as defined in table A.
- Table A-14 provides 16 compounds A-14.001 to A-14.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 2 and Cx are as defined in table A.
- Table A-15 provides 16 compounds A-15.001 to A-15.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 3 and Cx are as defined in table A.
- Table A-16 provides 16 compounds A-16.001 to A-16.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 4 and Cx are as defined in table A.
- Table A-17 provides 16 compounds A-17.001 to A-17.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 5 and Cx are as defined in table A.
- Table A-18 provides 16 compounds A-18.001 to A-18.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 6 and Cx are as defined in table A.
- Table A-19 provides 16 compounds A-19.001 to A-19.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 1 and Cx are as defined in table A.
- Table A-20 provides 16 compounds A-20.001 to A-20.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 2 and Cx are as defined in table A.
- Table A-21 provides 16 compounds A-21.001 to A-21.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 3 and Cx are as defined in table A.
- Table A-22 provides 16 compounds A-22.001 to A-22.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 4 and Cx are as defined in table A.
- Table A-23 provides 16 compounds A-23.001 to A-23.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 5 and Cx are as defined in table A.
- Table A-24 provides 16 compounds A-24.001 to A-24.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 6 and Cx are as defined in table A.
- Table A-25 provides 16 compounds A-25.001 to A-25.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 1 and Cx are as defined in table A.
- Table A-26 provides 16 compounds A-26.001 to A-26.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 2 and Cx are as defined in table A.
- Table A-27 provides 16 compounds A-27.001 to A-27.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 3 and Cx are as defined in table A.
- Table A-28 provides 16 compounds A-28.001 to A-28.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 4 and Cx are as defined in table A.
- Table A-29 provides 16 compounds A-29.001 to A-29.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 5 and Cx are as defined in table A.
- Table A-30 provides 16 compounds A-30.001 to A-30.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 6 and Cx are as defined in table A.
- Table A-31 provides 16 compounds A-31.001 to A-31.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 1 and Cx are as defined in table A.
- Table A-32 provides 16 compounds A-32.001 to A-32.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 2 and Cx are as defined in table A.
- Table A-33 provides 16 compounds A-33.001 to A-33.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 3 and Cx are as defined in table A.
- Table A-34 provides 16 compounds A-34.001 to A-34.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 4 and Cx are as defined in table A.
- Table A-35 provides 16 compounds A-35.001 to A-35.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 5 and Cx are as defined in table A.
- Table A-36 provides 16 compounds A-36.001 to A-36.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 6 and Cx are as defined in table A.
- Table A-37 provides 16 compounds A-37.001 to A-37.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 1 and Cx are as defined in table A.
- Table A-38 provides 16 compounds A-38.001 to A-38.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 2 and Cx are as defined in table A.
- Table A-39 provides 16 compounds A-39.001 to A-39.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 3 and Cx are as defined in table A.
- Table A-40 provides 16 compounds A-40.001 to A-40.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 4 and Cx are as defined in table A.
- Table A-41 provides 16 compounds A-41.001 to A-41.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 5 and Cx are as defined in table A.
- Table A-42 provides 16 compounds A-42.001 to A-42.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 6 and Cx are as defined in table A.
- Table A-43 provides 16 compounds A-43.001 to A-43.016 of formula I-A wherein Bx is isopropyl, Qx is 1 and Cx are as defined in table A.
- Table A-44 provides 16 compounds A-44.001 to A-44.016 of formula I-A wherein Bx is isopropyl, Qx is 2 and Cx are as defined in table A.
- Table A-45 provides 16 compounds A-45.001 to A-45.016 of formula I-A wherein Bx is isopropyl, Qx is 3 and Cx are as defined in table A.
- Table A-46 provides 16 compounds A-46.001 to A-46.016 of formula I-A wherein Bx is isopropyl, Qx is 4 and Cx are as defined in table A.
- Table A-47 provides 16 compounds A-47.001 to A-47.016 of formula I-A wherein Bx is isopropyl, Qx is 5 and Cx are as defined in table A.
- Table A-48 provides 16 compounds A-48.001 to A-48.016 of formula I-A wherein Bx is isopropyl, Qx is 6 and Cx are as defined in table A.
- Table A-49 provides 16 compounds A-49.001 to A-49.016 of formula I-A wherein Bx is butyl, Qx is 1 and Cx are as defined in table A.
- Table A-50 provides 16 compounds A-50.001 to A-50.016 of formula I-A wherein Bx is butyl, Qx is 2 and Cx are as defined in table A.
- Table A-51 provides 16 compounds A-51.001 to A-51.016 of formula I-A wherein Bx is butyl, Qx is 3 and Cx are as defined in table A.
- Table A-52 provides 16 compounds A-52.001 to A-52.016 of formula I-A wherein Bx is butyl, Qx is 4 and Cx are as defined in table A.
- Table A-53 provides 16 compounds A-53.001 to A-53.016 of formula I-A wherein Bx is butyl, Qx is 5 and Cx are as defined in table A.
- Table A-54 provides 16 compounds A-54.001 to A-54.016 of formula I-A wherein Bx is butyl, Qx is 6 and Cx are as defined in table A.
- the compounds of formula (I) according to the invention are preventively and/or curatively valuable active ingredients in the field of pest control, even at low rates of application, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants.
- the active ingredients according to the invention act against all or individual developmental stages of normally sensitive, but also resistant, animal pests, such as insects or representatives of the order Acarina.
- the insecticidal or acaricidal activity of the active ingredients according to the invention can manifest itself directly, i. e. in destruction of the pests, which takes place either immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example in a reduced oviposition and/or hatching rate.
- animal pests are: from the order Acarina, for example, Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemus spp, Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsone latus
- Tetranychus spp. from the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example, Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus s
- Trogoderma spp. from the order Diptera, for example, Aedes spp., Anopheles spp, Antherigona soccata,Bactrocea oleae, Bibio hortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella fri
- Hemiptera for example, Acanthocoris scabrator, Acrosternum spp, Adelphocoris lineolatus, Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp, Cimex spp., Clavigralla tomentosicollis, Creontiades spp, Distantiella theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp, Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes spp, Murgantia histrionic, Neomegalotomus spp, Nesidiocoris tenuis, Nezara s
- Thyanta spp Triatoma spp., Vatiga illudens; Acyrthosium pisum, Adalges spp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus aoni
- Vespa spp. from the order Isoptera, for example, Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate from the order Lepidoptera, for example, Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Cly
- Trichodectes spp. from the order Orthoptera, for example, Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp.; from the order Psocoptera, for example, Liposcelis spp.; from the order Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp.
- Orthoptera for example, Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schisto
- Thysanoptera for example, Calliothrips phaseoli, Frankliniella spp., Heliothrips spp, Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp; from the order Thysanura, for example, Lepisma saccharina.
- the invention may also relate to a method of controlling damage to plant and parts thereof by plant parasitic nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic nematodes), especially plant parasitic nematodes such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolai
- the compounds of the invention may also have activity against the molluscs.
- Examples of which include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H.
- the active ingredients according to the invention can be used for controlling, i. e.
- pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests.
- Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodder beet; fruit, for example pomaceous fruit, stone fruit or soft fruit, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soya; oil crops, such as oilseed rape, mustard, poppies, olives, sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts,
- a compound of the formula (I) controls mites, rust mites and spider mites in crops, tress, and plants selected from vegetables (especially tomatoes and cucurbits), citrus, pome fruits, stone fruit, tree nuts, cotton, tropical crops, avocados, ornamentals, beans, soybean, strawberry, and grapes.
- vegetables especially tomatoes and cucurbits
- the compositions and/or methods of the present invention may be also used on any ornamental and/or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreens.
- the invention may be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubéreux), Bougainvillea spp., Brachycome spp., Brassica spp.
- Ageratum spp. Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubéreux), Bougainvillea spp., Brachycome s
- Coreopsis spp. Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I.
- Iresines spp. Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp., Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp.
- the invention may be used on any of the following vegetable species: Allium spp. (A. sativum, A.. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A.
- Daucus carota Foeniculum vulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L. esculentum, L. lycopersicum), Mentha spp., Ocimum basilicum, Petroselinum crispum, Phaseolus spp. (P. vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica, Solanum melongena, Spinacea oleracea, Valerianella spp. (V. locusta, V.
- Preferred ornamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber.
- the active ingredients according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, maize, rice and soya crops.
- the active ingredients according to the invention are further especially suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice).
- the compounds of formula (I) are particularly suitable for control of mites, spider mites and rust mites, for example, Acarapis spp; Acarapis woodi; Acarus siro; Acarus spp; Aceria sheldoni; Aculops pelekassi; Aculops spp; Aculus pointedendali; Aculus spp; Amblyseius fallacis; Brevipalpus spp; Brevipalpus phoenicis; Bryobia praetiosa; Bryobia rubrioculus; Caloglyphus spp; Cheyletiella blakei; Cheyletiella spp; Cheyletiella yasguri; Chorioptes bovis; Chorioptes spp; Cytodites spp; Demodex bovis; Demodex caballi; Demodex canis; Demodex caprae; Demodex equi; Demodex ovis; Demo
- a compound of formula (I) are especially suitable for controlling one or more of: Aceria sheldoni ; Aculus lycopersici; Aculus pelekassi; Aculus pointedendali; Brevipalpus phoenicis; Brevipalpus spp.; Bryobia rubrioculus; Eotetranychus carpini; Eotetranychus spp.; Epitrimerus pyri; Eriophyes piri; Eriophyes spp.; Eriophyes vitis; Eutetranychus africanus; Eutetranychus orientalis; Oligonychus pratensis; Panonychus citri; Panonychus ulmi; Phyllocoptes vitis; Phyllocoptruta oleivora; Polyphagotarsonemus latus; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp.; and Tetranychus
- a compound of formula (I) are more especially suitable for controlling one or more of: Aceria sheldoni ; Aculus pelekassi; Brevipalpus phoenicis; Brevipalpus spp.; Eriophyes piri; Eriophyes vitis; Eutetranychus africanus; Eutetranychus orientalis; Oligonychus pratensis; Panonychus ulmi; Phyllocoptes vitis; Phyllocoptruta oleivora; Polyphagotarsonemus latus; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp.; and Tetranychus urticae.
- crops is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
- Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as ⁇ -endotoxins, e.g.
- Vip vegetative insecticidal proteins
- Vip e.g. Vip1, Vip2, Vip3 or Vip3A
- insecticidal proteins of bacteria colonising nematodes for example Photorhabdus spp.
- Xenorhabdus spp. such as Photorhabdus luminescens, Xenorhabdus nematophilus
- toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins
- toxins produced by fungi such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins
- agglutinins proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors
- steroid metabolism enzymes such as 3-hydroxysteroidoxidase, ecdysteroid- UDP-glycosyl-transferase, cholesterol oxidases, ecd
- ⁇ -endotoxins for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A
- Vip vegetative insecticidal proteins
- Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701).
- Truncated toxins for example a truncated Cry1Ab, are known.
- modified toxins one or more amino acids of the naturally occurring toxin are replaced.
- preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G- recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
- Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0374753, WO 93/07278, WO 95/34656, EP-A-0427529, EP-A-451878 and WO 03/052073.
- transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
- CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0367 474, EP-A-0401979 and WO 90/13651.
- the toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects.
- Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera).
- Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard ⁇ (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm ⁇ (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink ⁇ (maize variety that expresses a Cry9C toxin); Herculex I ⁇ (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B ⁇ (cotton variety that expresses a Cry1Ac toxin); Bollgard I ⁇ (cotton variety that express
- transgenic crops are: 1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St.
- This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence.
- the preparation of such transgenic maize plants is described in WO 03/018810.
- MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9.
- MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5.
- NK603 ⁇ MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer. Transgenic crops of insect-resistant plants are also described in BATS (Zentrum für Bioschreib und Nachhalttechnik, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch).
- crops is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225).
- PRPs pathogenesis-related proteins
- Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0392225, WO 95/33818 and EP-A-0353191.
- the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
- Crops may also be modified for enhanced resistance to fungal (for example Fusarium, Anthracnose, or Phytophthora), bacterial (for example Pseudomonas) or viral (for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens.
- Crops also include those that have enhanced resistance to nematodes, such as the soybean cyst nematode.
- Crops that are tolerance to abiotic stress include those that have enhanced tolerance to drought, high salt, high temperature, chill, frost, or light radiation, for example through expression of NF-YB or other proteins known in the art.
- Antipathogenic substances which can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called "pathogenesis-related proteins" (PRPs; see e.g. EP-A-0392225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g. WO 95/33818) or protein or polypeptide factors involved in plant pathogen defence (so-called "plant disease resistance genes", as described in WO 03/000906).
- ion channel blockers such as blockers for sodium and calcium channels
- the viral KP1, KP4 or KP6 toxins stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called "pathogenesis-related
- compositions according to the invention are the protection of stored goods and store rooms and the protection of raw materials, such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, especially the protection of humans, domestic animals and productive livestock against pests of the mentioned type.
- the present invention provides a compound of the first aspect for use in therapy.
- the present invention provides a compound of the first aspect, for use in controlling parasites in or on an animal.
- the present invention further provides a compound of the first aspect, for use in controlling ectoparasites on an animal.
- present invention further provides a compound of the first aspect, for use in preventing and/or treating diseases transmitted by ectoparasites.
- the present invention provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling parasites in or on an animal.
- the present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling ectoparasites on an animal.
- the present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for preventing and/or treating diseases transmitted by ectoparasites.
- the present invention provides the use of a compound of the first aspect, in controlling parasites in or on an animal.
- the present invention further provides the use of a compound of the first aspect , in controlling ectoparasites on an animal.
- controlling when used in context of parasites in or on an animal refers to reducing the number of pests or parasites, eliminating pests or parasites and/or preventing further pest or parasite infestation.
- treating when used in context of parasites in or on an animal refers to restraining, slowing, stopping or reversing the progression or severity of an existing symptom or disease.
- preventing when used used in context of parasites in or on an animal refers to the avoidance of a symptom or disease developing in the animal.
- animal when used used used in context of parasites in or on an animal may refer to a mammal and a non-mammal, such as a bird or fish.
- Non-human mammals include, but are not limited to, livestock animals and companion animals.
- Livestock animals include, but are not limited to, cattle, camellids, pigs, sheep, goats and horses.
- Companion animals include, but are not limited to, dogs, cats and rabbits.
- a "parasite” is a pest which lives in or on the host animal and benefits by deriving nutrients at the host animal's expense.
- An "endoparasite” is a parasite which lives in the host animal.
- An “ectoparasite” is a parasite which lives on the host animal.
- Ectoparasites include, but are not limited to, acari, insects and crustaceans (e.g. sea lice).
- the Acari (or Acarina) sub-class comprises ticks and mites.
- Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (Boophilus) microplus and Rhipicephalus sanguineus; Amblyomrna; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros.
- Mites include, but are not limited to, members of the following genera: Chorioptes, for example Chorioptes bovis; Psoroptes, for example Psoroptes ovis; Cheyletiella; Dermanyssus; for example Dermanyssus gallinae; Ortnithonyssus; Demodex, for example Demodex canis; Sarcoptes, for example Sarcoptes scabiei; and Psorergates.
- Insects include, but are not limited to, members of the orders: Siphonaptera, Diptera, Phthiraptera, Lepidoptera, Coleoptera and Homoptera.
- Members of the Siphonaptera order include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis.
- Members of the Diptera order include, but are not limited to, Musca spp.; bot fly, for example Gasterophilus intestinalis and Oestrus ovis; biting flies; horse flies, for example Haematopota spp. and Tabunus spp.; haematobia, for example haematobia irritans; Stomoxys; Lucilia; midges; and mosquitoes.
- Members of the Phthiraptera class include, but are not limited to, blood sucking lice and chewing lice, for example Bovicola Ovis and Bovicola Bovis.
- effective amount when used in context of parasites in or on an animal refers to the amount or dose of the compound of the invention, or a salt thereof, which, upon single or multiple dose administration to the animal, provides the desired effect in or on the animal.
- the effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances.
- a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the parasite to be controlled and the degree of infestation; the specific disease or disorder involved; the degree of or involvement or the severity of the disease or disorder; the response of the individual; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances.
- the compounds of the invention may be administered to the animal by any route which has the desired effect including, but not limited to topically, orally, parenterally ' and subcutaneously. Topical administration is preferred.
- Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions and may take the form of a pour-on, spot-on, spray-on, spray race or dip.
- the compounds of the invention may be administered by means of an ear tag or collar.
- Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinary acceptable salts, which can be different to agrochemically acceptable salts.
- Pharmaceutically and veterinary acceptable salts and common methodology for preparing them are well known in the art. See, for example, Gould, P.L., "Salt selection for basic drugs", International Journal of Pharmaceutics, 33: 201 -217 (1986); Bastin, R.J., et al.
- the present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/).
- the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping.
- an IRS indoor residual spraying
- a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention.
- the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate.
- a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate.
- Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention.
- an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface.
- a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
- Substrates including non-woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like.
- the polyesters are particularly suitable.
- compositions according to the invention are known, e.g. WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, WO2006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.
- Further areas of use of the compositions according to the invention are the field of tree injection/trunk treatment for all ornamental trees as well all sort of fruit and nut trees.
- the compounds according to the present invention are especially suitable against wood-boring insects from the order Lepidoptera as mentioned above and from the order Coleoptera, especially against woodborers listed in the following tables A and B: Table A. Examples of exotic woodborers of economic importance.
- the present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults.
- the present invention may be used to control insect pests that feed on the roots of turfgrass including white grubs (such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica), Phyllophaga spp. (e.g.
- Ataenius spp. e.g. Black turfgrass ataenius, A. spretulus
- Maladera spp. e.g. Asiatic garden beetle, M. castanea
- Tomarus spp. ground pearls
- Margarodes spp. mole crickets (tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana) and leatherjackets (European crane fly, Tipula spp.).
- the present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta), cutworms, billbugs (Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis).
- armyworms such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta
- cutworms such as S. venatus verstitus and S. parvulus
- sod webworms such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis.
- the present invention may also be used to control insect pests of turfgrass that live above the ground and feed on the turfgrass leaves, including chinch bugs (such as southern chinch bugs, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug (Propsapia bicincta), leafhoppers, cutworms (Noctuidae family), and greenbugs.
- the present invention may also be used to control other pests of turfgrass such as red imported fire ants (Solenopsis invicta) that create ant mounds in turf.
- compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.
- ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.
- parasites are: Of the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp..
- Nematocerina and Brachycerina for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Glossina spp., Calliphora spp., Glossina spp., Call
- Siphonapta for example Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp..
- Heteropterida for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp..
- Blattarida for example Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp..
- Actinedida Prostigmata
- Acaridida Acaridida
- Acarapis spp. Cheyletiella spp., Ornitrocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp.
- compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and buildings.
- compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec.,Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec.
- the compounds of formula I, or salts thereof, are especially suitable for controlling one or more pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae,
- a compound TX controls one or more of pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae.
- the compounds of formula I, or salts thereof, are especially suitable for controlling one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. .
- a compound TX controls one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.
- pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.
- the compounds of formula I, or salts thereof, are especially suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis incIudens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi, and Chilo suppressalis.
- a compound TX controls one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis incIudens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis, such as Spodoptera littoralis + TX, Plutella xylostella + TX; Frankliniella occidentalis + TX, Thrips tabaci + TX, Euschistus heros + TX, Cydia pomonella + TX, Nilaparvata lugens + TX, Myzus
- one compound from Tables A-1 to A-42 and Table P is suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis incIudens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice and soya crops.
- one compound from from Tables A-1 to A-42 and Table P is suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice).
- the compounds of Formula (I) or salts thereof are especially suitable for controlling one or more pests selected from order Lepidoptera, especially one or more of the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn), which insect demonstrates resistance against IRAC MoA Group 28 insecticides.
- a compound TX controls one or more of pests selected from the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn), which insect demonstrates resistance against IRAC MoA Group 28 insecticides.
- the compounds of formula I, or salts thereof, are especially suitable for controlling one or more of the insects having diamide resistance selected from: Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta.
- a compound TX controls one or more of the insects having diamide resistance selected from: Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta.
- Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).
- advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).
- certain compounds of formula (I) may show an advantageous safety profile with respect to non-target arthropods, in particular pollinators such as honey bees, solitary bees, and bumble bees.
- Apis mellifera is particularly, for example, Apis mellif
- the compounds according to the invention can be used as pesticidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances.
- formulation adjuvants such as carriers, solvents and surface-active substances.
- the formulations can be in various physical forms, e.g.
- Such formulations can either be used directly or diluted prior to use.
- the dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
- the formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions.
- the active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
- the active ingredients can also be contained in very fine microcapsules.
- Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release).
- Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight.
- the active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution.
- the encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art.
- very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
- the formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known per se.
- liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p- diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4- dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxi
- Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.
- a large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use.
- Surface- active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes.
- Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of
- pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
- compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives.
- the amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the mixture to be applied.
- the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared.
- Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow.
- Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively).
- Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10 th Edition, Southern Illinois University, 2010.
- the inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
- the end user will normally employ dilute formulations.
- the rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
- a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
- Preferred formulations can have the following compositions (weight %): Emulsifiable concentrates: active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 % Dusts: active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 % Suspension concentrates: active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 % Wettable powders: active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 % Granules: active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid
- W ettable powders a) b) c) active ingredients 25 % 50 % 75 % sodium lignosulfonate 5 % 5 % - sodium lauryl sulfate 3 % - 5 % sodium diisobutylnaphthalenesulfonate - 6 % 10 % phenol polyethylene glycol ether (7-8 mol of ethylene - 2 % - oxide) highly dispersed silicic acid 5 % 10 % 10 % K aolin 62 % 27 % - The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
- P owders for dry seed treatment a) b) c) active ingredients 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % - Kaolin 65 % 40 % - Talcum - 20 % The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
- Emulsifiable concentrate a ctive ingredients 10 % octylphenol polyethylene glycol ether (4-5 mol of ethylene oxide) 3 % calcium dodecylbenzenesulfonate 3 % castor oil polyglycol ether (35 mol of ethylene oxide) 4 % Cyclohexanone 30 % xylene mixture 50 % Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
- D usts a) b) c) Active ingredients 5 % 6 % 4 % Talcum 95 % - - Kaolin - 94 % - mineral filler - - 96 % Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed. Extruder granules A ctive ingredients 15 % sodium lignosulfonate 2 % carboxymethylcellulose 1 % Kaolin 82 % The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
- Coated granules Active ingredients 8 % polyethylene glycol (mol. wt.200) 3 % K aolin 89 % The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
- Suspension concentrate a ctive ingredients 40 % propylene glycol 10 % nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 % Sodium lignosulfonate 10 % carboxymethylcellulose 1 % silicone oil (in the form of a 75 % emulsion in water) 1 % Water 32 %
- the finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
- Flowable concentrate for seed treatment a ctive ingredients 40 % propylene glycol 5 % copolymer butanol PO/EO 2 % Tristyrenephenole with 10-20 moles EO 2 % 1,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 % monoazo-pigment calcium salt 5 % Silicone oil (in the form of a 75 % emulsion in water) 0.2 % Water 45.3 % The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
- the mixture is agitated until the polymerization reaction is completed.
- the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
- the capsule suspension formulation contains 28% of the active ingredients.
- the medium capsule diameter is 8-15 microns.
- the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
- Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo- emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP), a soluble granule (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
- EC emulsion concentrate
- SC suspension concentrate
- SE suspo- emulsion
- CS capsule suspension
- WG water dispersible granule
- Examples which follow serve to illustrate the invention.
- the compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates, if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.
- Compounds of Formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
- advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
- temperatures are given in degrees Celsius (°C) and “mp.” means melting point.
- LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus, and the method (Method A) is as follows: Analytical methods Method 1: Spectra were recorded on a Mass Spectrometer from Waters (Acquity QDa Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8 kV, Cone range: 25 V, Extractor: V (No extractor voltage for QDa detector) Source Temperature: 120°C, Desolvation Temperature: 600°C, Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment , diode-array detector.
- Method 1 Spectra were recorded on a Mass Spectrometer from Waters (Acquity QDa Mass Spectrometer) equipped with an electrosp
- Method 2 Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 l/h, Desolvation Gas Flow: 650-1000 l/h, Mass range: 100 to 900 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment , diode-array detector and ELSD.
- SQD SQDII or QDA Single quadrupole mass spectrometer
- Capillary 0.8-3.00 kV
- Cone 5-30 V
- Source Temperature 120-150°C
- Desolvation Temperature 350-600°C
- Cone Gas Flow 50-150 l/h
- Method 3 Spectra were recorded on a ACQUITY Mass Spectrometer from Waters Corporations (SQD or SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150°C, Desolvation Temperature: 400°C, Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/hr, Mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters Corporations with solvent degasser, binary pump, heated column compartment and diode-array detector.
- an electrospray source Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150°C, Desolvation Temperature: 400°C, Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/h
- Example 1 This example illustrates the preparation of N-[1-[4-[4-acetyl-5-(3-chlorophenyl)-5- (trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 1 of Table P).
- Step 1 Preparation of 4-bromobenzohydrazide To a stirred solution of methyl 4-bromobenzoate (4.00 g, 18.6 mmol) in ethanol (50 mL) was added hydrazine hydrate (2.71 mL, 55.8 mmol) at RT. The reaction mixture was heated at 85 °C for 16 hours.
- Step 2 Preparation of 4-bromo-N-[[1-(3-chlorophenyl)-2,2,2-trifluoro-ethylidene]amino]benzamide
- 1-propanol 20 mL
- 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone 0.70 g, 4.65 mmol
- acetic acid 2 mL
- the reaction mixture was heated at 100 °C for 18 hours. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was diluted with water and extracted with ethyl acetate.
- Step 3 Preparation of 1-[5-(4-bromophenyl)-2-(3-chlorophenyl)-2-(trifluoromethyl)-1,3,4-oxadiazol-3- yl]ethanone
- Step 4 Preparation of 1-[2-(3-chlorophenyl)-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]- 2-(trifluoromethyl)-1,3,4-oxadiazol-3-yl]ethanone
- 1-[5-(4-bromophenyl)-2-(3-chlorophenyl)-2-(trifluoromethyl)- 1,3,4-oxadiazol-3-yl]ethanone 100 mg, 0.223 mmol
- potassium acetate 67.8 mg, 0.670 mmol
- bis(pinacolato)diboron 119 mg, 0.447 mmol
- 1,4-dioxane 2 mL
- Step 5 Preparation of N-[1-[4-[4-acetyl-5-(3-chlorophenyl)-5-(trifluoromethyl)-1,3,4-oxadiazol-2- yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- Example 2 This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-2-methyl-5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 3 of Table P).
- Step 1 Preparation of 1-4-bromobenzaldehyde oxime To a stirred solution of hydroxylamine hydrochloride (452 mg, 6.38 mmol) and 4- bromobenzaldehyde (1.00 g, 5.40 mmol) in ethanol (20 mL) was added pyridine (1 mL) at RT.
- Step 2 Preparation of 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanimine
- methanol 10 mL
- lithium bis(trimethylsilyl)amide 1.88 g, 10.5 mmol
- the reaction mixture was heated at 80 °C for 48 hours. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was concentrated under reduced pressure, basified with sodium bicarbonate sat. aq. and extracted with ethyl acetate.
- Step 3 Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-4H-1,2,4-oxadiazole To a stirred solution of 1-4-bromobenzaldehyde oxime (1.00 g, 5.00 mmol) in DMF (5 mL) was added N-chlorosuccinimide (871 mg, 6.00 mmol) at RT.
- the reaction mixture was heated at 50 °C for 2 hours, then cooled at RT, quenched with water and extracted with dichloromethane (35 mL). The organic layer was dried over sodium sulphate and used directly with a solution of 1-(3-chlorophenyl)- 2,2,2-trifluoro-ethanimine (3.11 g, 15.0 mmol) in diethyl ether (35 mL). The reaction mixture was cooled to 0 °C and then triethylamine (3.50 mL, 25.0 mmol) was added dropwise. The reaction mixture was stirred at RT for 12 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with DCM.
- Step 4 Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-2-methyl-5-(trifluoromethyl)-1,2,4- oxadiazole
- 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-4H-1,2,4- oxadiazole 700 mg, 1.73 mmol
- DMAc 3 mL
- cesium carbonate (1.12 g, 3.45 mmol
- iodomethane (1.64 mL, 25.9 mmol
- Step 5 Preparation of N-[1-[4-[5-(3-chlorophenyl)-2-methyl-5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- 3-(4-bromophenyl)-5-(3-chlorophenyl)-2-methyl-5-(trifluoromethyl)- 1,2,4-oxadiazole 250 mg, 0.596 mmol
- 1,4-dioxane 20 mL
- N-(3-methyl-1H-pyrazol-4- yl)-4-(trifluoromethoxy)benzamide 170 mg, 0.596 mmol
- cesium carbonate (582 mg, 1.79 mmol)
- 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene 7.1.1 mg, 0.119 mmol
- Example 3 This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(difluoromethyl)- 4H-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 4 of Table P).
- Step 1 Preparation of 4-(3-methyl-4-nitro-pyrazol-1-yl)benzonitrile To a stirred solution of 3-methyl-4-nitro-1H-pyrazole (5.00 g, 39.3 mmol) in DMSO (28 mL) was added potassium tert-butoxide (4.82 g, 42.1 mmol) at RT.
- the reaction mixture was heated at 70 °C for 4 hours. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was filtered over Celite pad and washed with ethyl acetate. The filtrate was carefully neutralized with sodium bicarbonate sat. aq. It was then extracted with ethyl acetate and washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (3.80 g).
- Step 3 Preparation of N-[1-(4-cyanophenyl)-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- 4-(4-amino-3-methyl-pyrazol-1-yl)benzonitrile (3.80 g, 19.2 mmol) in ethyl acetate (115 mL)
- 4-(trifluoromethoxy)benzoic acid (4.35 g, 21.1 mmol)
- N,N- diisopropylethylamine (10.0 mL, 57.5 mmol)
- 1-propanephosphonic anhydride 50% solution in ethyl acetate, 34.9 mL, 57.5 mmol
- Step 4 Preparation of N-[1-[4-[N'-hydroxycarbamimidoyl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide
- N-[1-(4-cyanophenyl)-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide (4.20 g, 10.9 mmol) in ethanol (44 mL) were added triethylamine (3.05 mL, 21.7 mmol) and hydroxylamine hydrochloride (1.51 g, 21.7 mmol) at RT.
- the reaction mixture was heated at 80 °C for 2 hours.
- Step 5 Preparation of N-[1-[4-[5-(difluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide
- N-[1-[4-[N'-hydroxycarbamimidoyl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide 200 mg, 0.477 mmol
- 2-methyltetrahydrofuran 2.4 mL
- Step 6 Preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(difluoromethyl)-4H-1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- 1-bromo-3-chlorobenzene 0.044 mL, 0.376 mmol
- 2- methyltetrahydrofuran (1 mL) was added dropwise n-butyllithium (1.6M in hexane, 0.230 mL, 0.376 mmol) at -78 °C.
- the reaction mixture was stirred at -78 °C for 30 minutes.
- Example 4 This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)- 1,4,2-dioxazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 9 of Table P).
- Step 1 Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-1,4,2-dioxazole
- 1-4-bromobenzaldehyde oxime 300 mg, 1.50 mmol
- DMF 5 mL
- N-chlorosuccinimide 218 mg, 1.50 mmol
- the reaction mixture was heated at 55 °C for 1 hour.
- 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone (313 mg, 1.50 mmol) and sodium bicarbonate (140 mg, 1.50 mmol) were added to the reaction mixture.
- Step 2 Preparation of 5-(3-chlorophenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5- (trifluoromethyl)-1,4,2-dioxazole
- 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)- 1,4,2-dioxazole 200 mg, 0.492 mmol
- potassium acetate 96.6 mg, 0.984 mmol
- bis(pinacolato)diboron 151 mg, 0.590 mmol
- 1,4-dioxane 4 mL.
- Step 3 Preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)-1,4,2-dioxazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- a mixture of crude 5-(3-chlorophenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1,4,2-dioxazole 190 mg, 0.420 mmol
- N-(3-methyl-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide 80.0 mg, 0.280 mmol
- copper(II) acetate 7.8.0 mg, 0.420 mmol
- boric acid 37.0 mg, 0.560 mmol
- pyridine 0.046 mL, 0.560 mmol
- Example 5 This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-4-oxo-5- (trifluoromethyl)-1H-imidazol-2-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 10 of Table P).
- Step 1 Preparation of 3-(3-chlorophenyl)-1,1,1-trifluoro-propan-2-one
- N-isopropylpropan-2-amine 9.14 mL, 64.2 mmol
- n-butyllithium 2M in cyclohexane, 32.0 mL, 64.2 mmol
- 2-(3-chlorophenyl)acetic acid 5.00 g, 29.3 mmol
- the reaction mixture was allowed to reach RT and stirred for 2 hours.
- Step 2 Preparation of 2-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-1H-imidazol-4-one
- 3-(3-chlorophenyl)-1,1,1-trifluoro-propan-2-one (661 mg, 2.97 mmol) in dry DMF (18 mL) were added 4-bromobenzamidine hydrochloride (350 mg, 1.49 mmol) and potassium carbonate (430 mg, 3.72 mmol) at RT.
- the reaction mixture was heated at 70 °C for 12 hours. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was quenched with sodium bicarbonate sat. aq.
- Step 4 Preparation of N-[1-[4-[5-(3-chlorophenyl)-4-oxo-5-(trifluoromethyl)-1H-imidazol-2-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- N-(3-methyl-1H-pyrazol-4-yl)- 4-(trifluoromethoxy)benzamide 110 mg, 0.368 mmol
- copper(II) acetate 85.3 mg, 0.460 mmol
- boric acid 39.9 mg, 0.613 mmol
- pyridine 0.050 mL, 0.613
- Example 6 This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-4-cyclopropyl-5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 11 of Table P).
- Step 1 Preparation of 1-4-bromo-N-hydroxy-benzimidoyl chloride
- 4-bromobenzaldehyde oxime (2.00 g, 9.49 mmol) in acetonitrile (19 mL)
- N-chlorosuccinimide (1.68 g, 12.3 mmol)
- the reaction mixture was stirred at RT for 2 hours.
- the progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was quenched with water and extracted with ethyl acetate.
- the organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (2.11 g).
- Step 2 Preparation of 1-(3-chlorophenyl)-N-cyclopropyl-2,2,2-trifluoro-ethanimine
- 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone (1.50 g, 7.20 mmol) in toluene (22 mL)
- cyclopropanamine (2.00 mL, 29.0 mmol)
- p-toluenesulfonic acid (0.760 g, 4.30 mmol
- Step 3 Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-4-cyclopropyl-5-(trifluoromethyl)-1,2,4- oxadiazole
- 1-(3-chlorophenyl)-N-cyclopropyl-2,2,2-trifluoro-ethanimine 500 mg, 2.02 mmol
- 2-methyltetrahydrofuran 8 mL
- 1-4-bromo-N-hydroxy-benzimidoyl chloride 260 mg, 1.11 mmol
- the reaction mixture was heated at 50 °C and then a solution of N,N- diisopropylethylamine (0.350 mL, 2.02 mmol) in 2-methyltetrahydrofuran (8 mL) was added dropwise. The reaction mixture was heated at 80 °C for 2 hours. Then it was cooled back to 50 °C and 1-4-bromo- N-hydroxy-benzimidoyl chloride (260 mg, 1.11 mmol) and N,N-diisopropylethylamine (0.350 mL, 2.02 mmol) were added again. The reaction mixture was heated at 80 °C overnight. The progress of the reaction was monitored by LCMS analysis.
- Step 4 Preparation of 5-(3-chlorophenyl)-4-cyclopropyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole
- 3-(4-bromophenyl)-5-(3-chlorophenyl)-4-cyclopropyl-5-(trifluoromethyl)- 1,2,4-oxadiazole (30 mg, 0.067 mmol) in DMSO (0.4 mL) were added under argon bis(pinacolato)diboron (51 mg, 0.20 mmol), potassium acetate (20 mg, 0.20 mmol) and bis(triphenylphosphine)palladium chloride (4.7 mg, 0.0067 mmol) at RT.
- Step 5 Preparation of N-[1-[4-[5-(3-chlorophenyl)-4-cyclopropyl-5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- a mixture of 5-(3-chlorophenyl)-4-cyclopropyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (16 mg, 0.032 mmol), N-(3-methyl-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide (10 mg, 0.036 mmol), copper(II) acetate (8.8 mg, 0.049 mmol), pyridine (0.011 mL, 0.13 mmol) and DMSO (0
- Example 7 This example illustrates the preparation of 4-[5-butyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol- 3-yl]-2-fluoro-N-[4-(trifluoromethyl)phenyl]benzamide (Compound 14 of Table P).
- Step 1 Preparation of 2-fluoro-4-(N'-hydroxycarbamimidoyl)benzoic acid
- 4-cyano-2-fluoro-benzoic acid (25.0 g, 151 mmol) in ethanol (251 mL)
- a solution of hydroxylamine hydrochloride (21.3 g, 303 mmol) in water (150 mL) at RT
- a solution of potassium carbonate (33.5 g, 242 mmol) in water (365 mL) at RT.
- 8-hydroxyquinoline (289 mg, 1.97 mmol) was added to the reaction mixture at RT and it was heated at 80 °C for 3.5 hours.
- Step 2 Preparation of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid
- 2-fluoro-4-(N'-hydroxycarbamimidoyl)benzoic acid 22.3 g, 112 mmol
- THF 420 mL
- trifluoroacetic anhydride 23.8 mL, 169 mmol
- Step 3 Preparation of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzamide
- 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid (334 mg, 1.21 mmol) in ethyl acetate (8 mL) were added 4-(trifluoromethyl)aniline (0.182 mL, 1.45 mmol), pyridine (0.294 mL, 3.63 mmol) and 1-propanephosphonic anhydride (50% solution in ethyl acetate, 2.17 mL, 3.63 mmol) at RT.
- Step 4 Preparation of 4-[5-butyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]-2-fluoro-N-[4- (trifluoromethyl)phenyl]benzamide
- n-butyllithium 1.5M in hexane, 0.21 mL, 0.33 mmol
- THF 1.2 mL
- 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzamide 55 mg, 0.13 mmol
- THF 1.2 mL
- Example 8 This example illustrates the preparation of 5-butyl-3-[4-[1-[4-(trifluoromethoxy)phenyl]- 1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)-4H-1,2,4-oxadiazole (Compound 15 of Table P).
- Step 2 Preparation of 4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzonitrile
- 3-bromo-1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazole 400 mg, 1.30 mmol
- acetonitrile 3.9 mL
- water 0.39 mL
- potassium phosphate tribasic 562 mg, 2.60 mmol
- 4-cyanophenylboronic acid (191 mg, 1.30 mmol
- reaction mixture was degassed with argon for 10 minutes and then XPhos Pd G4 (58.8 mg, 0.0649 mmol) was added.
- the reaction mixture was heated at 80 °C for 3 hours.
- the progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (280 mg).
- LC-MS (Method 1) Rt 1.08 min., MS: m/z 331 (M+H) + .
- Step 3 Preparation of N'-hydroxy-4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzamidine
- 4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzonitrile 280 mg, 0.848 mmol
- ethanol 2.9 mL
- water 0.98 mL
- hydroxylamine hydrochloride 119 mg, 1.70 mmol
- triethylamine 0.237 mL, 1.70 mmol
- Step 4 Preparation of 3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)- 1,2,4-oxadiazole
- N'-hydroxy-4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3- yl]benzamidine 220 mg, 0.606 mmol
- tetrahydrofuran 2.4 mL
- trifluoroacetic anhydride 0.128 mL, 0.908 mmol
- Step 5 Preparation of 5-butyl-3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5- (trifluoromethyl)-4H-1,2,4-oxadiazole
- Example 9 This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)- 4H-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 18 of Table P).
- Step 2 Preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
- 1-bromo-3-chlorobenzene 0.170 mL, 1.45 mmol
- tetrahydrofuran 4 mL
- n-butyllithium 1.5M in hexane, 0.900 mL, 1.45 mmol
- reaction mixture was stirred at -78 °C for 30 minutes, then a solution of N-[3-methyl-1-[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]phenyl]pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (400 mg, 0.804 mmol) in tetrahydrofuran (4 mL) was added dropwise.
- the reaction mixture was stirred at -78 °C for 30 minutes, then allowed to reach RT and stirred for 1 hour. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate.
- Example 10 This example illustrates the preparation of 5-(3-chlorophenyl)-3-[4-[1-[4- (trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)-4H-1,2,4-oxadiazole (Compound 19 of Table P).
- reaction mixture was stirred at -78 °C for 30 minutes, then a solution of 3-[4-[1-[4- (trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (50.0 mg, 0.113 mmol) in tetrahydrofuran (0.4 mL) was added dropwise.
- the reaction mixture was stirred at -78 °C for 30 minutes, then allowed to reach RT and stirred for 1 hour. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate.
- Example 11 This example illustrates the preparation of 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H- 1,2,4-oxadiazol-3-yl]-N-[4-(trifluoromethyl)phenyl]benzamide (Compound 24 of Table P).
- Step 1 Preparation of tert-butyl 2-fluoro-4-[N'-hydroxycarbamimidoyl]benzoate
- hydroxylamine hydrochloride (1.19 g, 17.2 mmol)
- triethylamine (2.39 mL, 17.2 mmol)
- the reaction mixture was heated at 80 °C for 1 hour. The progress of the reaction was monitored by LCMS analysis.
- the reaction mixture was concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (2.18 g).
- Step 2 Preparation of tert-butyl 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoate To a stirred solution of tert-butyl 2-fluoro-4-[N'-hydroxycarbamimidoyl]benzoate (2.18 g, 8.57 mmol) in tetrahydrofuran (28 mL) was added dropwise trifluoroacetic anhydride (1.82 mL, 12.9 mmol) at RT. The reaction mixture was stirred at RT overnight.
- Step 3 Preparation of tert-butyl 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3- yl]benzoate
- tert-butyl 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoate (1.00 g, 3.01 mmol) in tetrahydrofuran (20 mL) was added dropwise isopropylmagnesium chloride lithium chloride (1.3M in THF, 4.6 mL, 6.02 mmol) at RT.
- Step 4 Preparation of 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]benzoic acid
- a mixture of tert-butyl 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3- yl]benzoate (700 mg, 1.86 mmol) and hydrochloric acid (4M in 1,4-dioxane, 4.70 mL, 18.6 mmol) was heated at 60 °C for 3 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate.
- mixtures of the compounds of formula (I) with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use.
- Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridinylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.
- TX means “one compound selected from the compounds defined in the Tables A-1 to A-42 and Table P”
- TX means “one compound selected from the compounds defined in the Tables A-1 to A-42 and Table P”
- Israelensis + TX Bacillus thuringiensis subsp. Japonensis + TX, Bacillus thuringiensis subsp. Kurstaki + TX, Bacillus thurin ⁇ giensis subsp. Tenebrionis + TX, Bacillus thuringiensis subspec.
- lecontei NPV + TX nickel bis(dimethyldithiocarbamate) + TX, niclosamide + TX, niclosamide-olamine + TX, nicofluprole + TX, nitenpyram + TX, nithiazine + TX, nitrapyrin + TX, octadeca-2,13-dien-1-yl acetate + TX, octadeca-3,13-dien-1-yl acetate + TX, octhilinone + TX, omethoate + TX, orfralure + TX, Orius spp.
- TX trifenmorph + TX, trifluenfuronate + TX, triflumezopyrim + TX, trimedlure + TX, trimedlure A + TX, trimedlure B1 + TX, trimedlure B2 + TX, trimedlure C + TX, trimethacarb + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, trunc-call + TX, tyclopyrazoflor + TX, Typhlodromus occidentalis + TX, uredepa + TX, Verticillium lecanii + TX, Verticillium spp.
- acridum + TX Metarhizium anisopliae var. anisopliae + TX, metarylpicoxamid + TX, metconazole + TX, metepa + TX, methacrifos + TX, methanesulfonyl fluoride + TX, methasulfo ⁇ carb + TX, methiotepa + TX, methocrotophos + TX, methoprene + TX, methoquin-butyl + TX, methothrin + TX, methoxychlor + TX, methyl (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate + TX, methyl (Z)-2-(5- cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate (these compounds may be prepared from the methods described in WO2020/193387) + TX,
- Bacillus subtilis strain AQ178 + TX Bacillus subtilis strain AQ153 + TX, Bacillus subtilis strain AQ743 + TX, Bacillus subtilis strain QST 713 (CEASE®, Serenade®, Rhapsody®) + TX, Bacillus subtilis strain QST 714 (JAZZ®) + TX, Bacillus subtilis strain QST3002 + TX, Bacillus subtilis strain QST3004 + TX, Bacillus subtilis var.
- amyloliquefaciens strain FZB24 (Taegro®, Rhizopro®) + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1Ab + TX, Bacillus thuringiensis israelensis (BMP123®, Aquabac®, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin®, Deliver®, CryMax®, Bonide®, Scutella WP®, Turilav WP ®, Astuto®, Dipel WP®, Biobit®, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF / 3P®) + TX
- TX Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Burkholderia cepacia (Deny®, Intercept®, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp.
- TX Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida reuêtii + TX, Candida saitoana (Bio-Coat®, Biocure®) + TX, Candida sake + TX, Candida spp.
- TX Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp.
- TX Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean®, Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop®, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp.
- TX Lagenidium giganteum (Laginex®) + TX, Lecanicillium lecanii (formerly known as Verticillium lecanii (Mycotal®) conidia of strain KV01 (e.g. Vertalec® by Koppert/Arysta) + TX, Lecanicillium longisporum (Vertiblast®) + TX, Lecanicillium muscarium (Vertikil®) + TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus®) + TX, Marinococcus halophilus + TX, Meira geulakonigii + TX, Metarhizium anisopliae (Destruxin WP®) + TX, Metarhizium anisopliae (Met52®) + TX, Metschnikowia fruticola (Shemer®) + TX, Metschnikowia pulcherrima + TX, Microdochium dimerum (Antibot®) + TX
- NRRL 305408 + TX, Mycorrhizae spp. (AMykor®, Root Maximizer®) + TX, Myrothecium verrucaria strain AARC-0255 (DiTera®, BROS PLUS®) + TX, Ophiostoma piliferum strain D97 (Sylvanex®) + TX, Paecilomyces farinosus + TX, Paecilomyces lilacinus strain 251 (MeloCon WG®) + TX, Paecilomyces linacinus (Biostat WP®) + TX, Paenibacillus polymyxa + TX, Pantoea agglomerans (BlightBan C9-1®) + TX, Pantoea spp.
- TX Pasteuria nishizawae in particular strain Pn1 (CLARIVA from Syngenta/ChemChina); + TX, Pasteuria spp. (Econem®) + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart®, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp.
- TX Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, phosphate solubilizing bacteria (Phosphomeal®) + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilliermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa + TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, P
- TX Pseudomonas syringae (Bio-Save®) + TX, Pseudomonas viridiflava + TX, Pseudozyma flocculosa strain PF-A22 UL (Sporodex L®) + TX, Puccinia canaliculata + TX, Puccinia thlaspeos (Wood Warrior®) + TX, Pythium paroecandrum + TX, Pythium oligandrum (Polygandron®, Polyversum®) + TX, Pythium periplocum + TX, Rhanella aquatilis + TX, Rhanella spp.
- Rhizobia Distal®, Vault®
- Rhizoctonia + TX Rhodococcus globerulus strain AQ719 + TX, Rhodosporidium diobovatum + TX, Rhodosporidium toruloides + TX, Rhodotorula glutinis + TX, Rhodotorula graminis + TX, Rhodotorula mucilagnosa + TX, Rhodotorula rubra + TX, Rhodotorula spp.
- Trichoderma asperellum T34 Biocontrol®
- TX Trichoderma atroviride
- Trichoderma gamsii TX
- Trichoderma hamatum TH 382 + TX Trichoderma harzianum rifai (Mycostar®) + TX
- Trichoderma harzianum T-22 Trianum- P®, PlantShield HC®, RootShield®, Trianum-G® + TX, Trichoderma harzianum T-39 (Trichodex®) + TX, Trichoderma inhamatum + TX, Trichoderma koningii + TX, Trichoderma lignorum + TX, Trichoderma longibrachiatum + TX, Trichoderma polysporum (Binab T®) + TX, Trichoderma spp.
- LC 52 (Sentinel®) + TX, Trichoderma taxi + TX, Trichoderma virens (formerly Gliocladium virens GL-21) (SoilGuard®) + TX, Trichoderma virens + TX, Trichoderma viride + TX, Trichoderma viride strain ICC 080 (Remedier®) + TX, Trichosporon pullulans + TX, Trichosporon spp. + TX, Trichothecium roseum + TX, Trichothecium spp.
- TX maydis + TX, various bacteria and supplementary micronutrients (Natural II®) + TX, various fungi (Millennium Microbes®) + TX, Verticillium chlamydosporium + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv.
- TX Bombus terrestris (Beeline®, Tripol®) + TX, Bombus terrestris (Natupol Beehive®) + TX, Cephalonomia stephanoderis + TX, Chilocorus nigritus + TX, Chrysoperla carnea (Chrysoline®, Chrysopa®) + TX, Chrysoperla rufilabris + TX, Cirrospilus ingenuus + TX, Cirrospilus quadristriatus + TX, Citrostichus phyllocnistoides + TX, Closterocerus chamaeleon + TX, Closterocerus spp.
- TX Coccidoxenoides perminutus (Planopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia flavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug®, Cryptoline®) + TX, Cybocephalus nipponicus + TX, Dacnusa sibirica (Minusa®, DacDigline®, Minex®) + TX, Delphastus catalinae (Delphastus®) + TX, Delphastus pusillus + TX, Diachasmimorpha krausii + TX, Diachasmimorpha longicaudata + TX, Diaparsis jucunda + TX, Diaphorencyrtus aligarhensis + TX, Diglyphus isaea (Diminex®, Miglyphus,
- TX Steinernematid spp. (Guardian Nematodes®) + TX, Stethorus punctillum (Stethorus®) + TX, Tamarixia radiate + TX, Tetrastichus setifer + TX, Thripobius semiluteus + TX, Torymus sinensis + TX, Trichogramma brassicae (Tricholine b®) + TX, Trichogramma brassicae (Tricho-Strip®) + TX, Trichogramma evanescens + TX, Trichogramma minutum + TX, Trichogramma ostriniae + TX, Trichogramma platneri + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator + TX; abscisic acid + TX, Aminomite® + TX, BioGain® + TX, bioSea® + TX, CAS Number: 2643947-26-4 + TX, Chondroster
- NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX
- Bacillus pumilus in particular strain BU F-33, having NRRL Accession No. 50185 (CARTISSA® from BASF, EPA Reg. No. 71840-19) + TX
- Bacillus subtilis CX-9060 from Certis USA LLC
- Bacillus sp. in particular strain D747 (available as DOUBLE NICKEL® from Kumiai Chemical Industry Co., Ltd.), having Accession No. FERM BP-8234, U.S.
- Patent No.7,094,592 + TX Bacillus subtilis strain BU1814, (VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No.70127-5)) + TX, Bacillus subtilis, in particular strain QST713/AQ713 (having NRRL Accession No. B-21661 and described in U.S.
- Patent No.6,060,051 available as SERENADE® OPTI or SERENADE® ASO from Bayer CropScience LP, US
- TX Paenibacillus polymyxa
- strain AC-1 e.g. TOPSEED® from Green Biotech Company Ltd.
- TX Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX, Pantoea agglomerans, in particular strain E325 (Accession No.
- NRRL B-21856 (available as BLOOMTIME BIOLOGICALTM FD BIOPESTICIDE from Northwest Agri Products) + TX, Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or mixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR® and BLOSSOM PROTECT® from bio-ferm, CH) + TX, Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem) + TX, Saccharomyces cerevisiae, in particular strains CNCM No.1-3936, CNCM No.1-3937, CNCM No.1-3938 or CNCM No.1-3939 (WO 2010/086790) from
- DSM 23117 (available as RHIZOVITAL® from ABiTEP, DE) + TX
- Bacillus amyloliquefaciens in particular strain D747 (available as Double NickelTM from Kumiai Chemical Industry Co., Ltd., having accession number FERM BP-8234, US Patent No.7,094,592) + TX
- Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (QUARTZO® (WG) and PRESENCE® (WP) from FMC Corporation) + TX
- Bacillus licheniformis in particular strain SB3086, having Accession No.
- ATCC 55406, WO 2003/000051 (available as ECOGUARD® Biofungicide and GREEN RELEAFTM from Novozymes) + TX, Bacillus methylotrophicus strain BAC-9912 (from Chinese Academy of Sciences’ Institute of Applied Ecology) + TX, Bacillus mycoides, isolate, having Accession No. B-30890 (available as BMJ TGAI® or WG and LifeGardTM from Certis USA LLC) + TX, Bacillus pumilus, in particular strain GB34 (available as Yield Shield® from Bayer AG, DE) + TX, Bacillus pumilus, in particular strain QST2808 (available as SONATA® from Bayer CropScience LP, US, having Accession No.
- Patent No.5,061,495 + TX Bacillus subtilis strain Y1336 (available as BIOBAC® WP from Bion- Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277) + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No.70127-5)) + TX, Bacillus subtilis Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.
- NRRL B-50897, WO 2017/019448 e.g., HOWLERTM and ZIO® from AgBiome Innovations, US
- TX Pseudomonas chlororaphis
- strain MA342 e.g. CEDOMON®, CERALL®, and CEDRESS® by Bioagri and Koppert
- TX Pseudomonas fluorescens strain A506 (e.g. BLIGHTBAN® A506 by NuFarm) + TX
- Pseudomonas proradix e.g.
- PRORADIX® from Sourcon Padena + TX
- Streptomyces griseoviridis strain K61 also known as Streptomyces galbus strain K61
- DSM 7206 Streptomyces galbus strain K61
- MYCOSTOP® from Verdera, PREFENCE® from BioWorks, cf.
- BIOKUPRUMTM by AgriLife + TX
- Chaetomium globosum available as RIVADIOM® by Rivale
- TX Cladosporium cladosporioides
- strain H39 having Accession No. CBS122244, US 2010/0291039 (by Stichting Moowgrass Onderzoek) + TX
- Coniothyrium minitans in particular strain CON/M/91-8 (Accession No. DSM9660, e.g.
- strain ICC 080 having Accession No. IMI 392151 (e.g., BIO-TAMTM from Isagro USA, Inc. or BIODERMA® by Agrobiosol de Mexico, S.A. de C.V.) + TX, Penicillium vermiculatum + TX, Phlebiopsis gigantea strain VRA 1992 (ROTSTOP® C from danstar Ferment) + TX, Pseudozyma flocculosa, strain PF-A22 UL (available as SPORODEX® L by Plant Products Co., CA) + TX, Saccharomyces cerevisiae strain LAS117 cell walls (CEREVISANE® from Lesaffre, ROMEO® from BASF SE) + TX, Saccharomyces cerevisiae strains CNCM No.1-3936, CNCM No.1-3937, CNCM No.1-3938, CNCM No.1-3939 (WO 2010/086790) from Lesaffre et Compag
- T-Gro from Andermatt Biocontrol + TX
- Trichoderma atroviride strain 77B T77 from Andermatt Biocontrol
- Trichoderma atroviride strain ATCC 20476 IMI 206040
- Trichoderma atroviride strain LC52 e.g. Tenet by Agrimm Technologies Limited
- Trichoderma atroviride strain LU132 e.g. Sentinel from Agrimm Technologies Limited
- TX Trichoderma atroviride strain NMI no. V08/002388 + TX
- Trichoderma atroviride strain NMI no. V08/002389 + TX Trichoderma atroviride strain NMI no.
- Trichoderma atroviride Trichoderma atroviride,strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR) + TX, Trichoderma fertile (e.g. product TrichoPlus from BASF) + TX, Trichoderma gamsii (formerly T. viride) + TX, Trichoderma gamsii (formerly T. viride) strain ICC 080 (IMI CC 392151 CABI) (available as BIODERMA® by AGROBIOSOL DE MEXICO, S.A. DE C.V.), + TX, Trichoderma gamsii strain ICC080 (IMI CC 392151 CABI, e.g.
- Trianum-P from Koppert TX
- Trichoderma harzianum strain T-22 e.g. Trianum-P from Andermatt Biocontrol or Koppert
- Trichoderma harzianum strain TH35 e.g. Root-Pro by Mycontrol
- Trichoderma polysporum strain IMI 206039 e.g. Binab TF WP by BINAB Bio-Innovation AB, Sweden
- Trichoderma stromaticum having Accession No. Ts3550 (e.g. Tricovab by CEPLAC, Brazil) + TX
- Trichoderma virens also known as Gliocladium virens
- strain GL-21 e.g.
- Trichoderma virens strain G-41 formerly known as Gliocladium virens (Accession No. ATCC 20906) (e.g., ROOTSHIELD® PLUS WP and TURFSHIELD® PLUS WP from BioWorks, US) + TX, Trichoderma viride in particular strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125-137) + TX, Trichoderma viride strain TV1(e.g. Trianum-P by Koppert) + TX, Ulocladium oudemansii strain U3, having Accession No.
- NM 99/06216 e.g., BOTRY-ZEN® by Botry-Zen Ltd, New Zealand and BOTRYSTOP® from BioWorks, Inc.
- TX Verticillium albo-atrum (formerly V. dahliae) strain WCS850 having Accession No.
- WCS850 deposited at the Central Bureau for Fungi Cultures (e.g., DUTCH TRIG® by Tree Care Innovations) + TX, Verticillium chlamydosporium + TX; a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE® from Agrinos) + TX, a mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (available as QUARTZO® (WG), PRESENCE® (WP) from FMC Corporation) + TX, Azorhizobium caulinodans, in particular strain ZB-SK-5 + TX, Azospirillum brasilense (e.g., VIGOR® from KALO, Inc.) + TX, Azospirillum lipoferum (e.g., VERTEX-IFTM from TerraMax, Inc.) + TX, Azotobacter chroococcum, in particular strain H
- NRRL B-5015 + TX
- Bacillus amyloliquefaciens in particular strain FZB42 e.g. RHIZOVITAL® from ABiTEP, DE
- Bacillus amyloliquefaciens in particular strain IN937a + TX Bacillus amyloliquefaciens pm414 (LOLI-PEPTA® from Biofilm Crop Protection) + TX
- Bacillus amyloliquefaciens SB3281 ATCC # PTA-7542, WO 2017/205258
- Bacillus amyloliquefaciens TJ1000 available as QUIKROOTS® from Novozymes
- Bacillus cereus family member EE128 NRRL No.
- YIELD SHIELD® from Bayer Crop Science, DE
- + TX Bacillus pumilus in particular strain QST2808 (Accession No. NRRL No. B-30087) + TX
- Bacillus siamensis in particular strain KCTC 13613T + TX Bacillus subtilis in particular strain AQ30002 (Accession No. NRRL No. B-50421 and described in U.S. Patent Application No. 13/330,576) + TX
- Bacillus subtilis in particular strain AQ30004 (NRRL No. B-50455 and described in U.S. Patent Application No.13/330,576) + TX, Bacillus subtilis in particular strain MBI 600 (e.g.
- BIOBOOST® from Brett Young Seeds + TX, Lactobacillus sp. (e.g. LACTOPLANT® from LactoPAFI) + TX, Mesorhizobium cicer (e.g., NODULATOR from BASF SE) + TX, Paenibacillus polymyxa in particular strain AC-1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX, Pseudomonas aeruginosa in particular strain PN1 + TX, Pseudomonas proradix (e.g.
- PRORADIX® from Sourcon Padena + TX, Rhizobium leguminosarium biovar viciae (e.g., NODULATOR from BASF SE) + TX, Rhizobium leguminosarum in particular bv. viceae strain Z25 (Accession No. CECT 4585) + TX, Serratia marcescens in particular strain SRM (Accession No. MTCC 8708), + TX, Sinorhizobium meliloti strain NRG-185-1 (NITRAGIN® GOLD from Bayer CropScience) + TX, Thiobacillus sp. (e.g.
- Trichoderma atroviride strain SC1 (described in WO2009/116106) + TX, Trichoderma harzianum strain 1295-22 + TX, Trichoderma harzianum strain ITEM 908 + TX, Trichoderma harzianum strain T- 22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) + TX, Trichoderma harzianum strain TSTh20, + TX, Trichoderma virens strain GI-3 + TX, Trichoderma virens strain GL-21 (e.g.
- aizawai in particular serotype H-7 (e.g. FLORBAC® WG from Valent BioSciences, US) + TX, Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372, e.g. XENTARI® from Valent BioSciences) + TX, Bacillus thuringiensis subsp. israelensis (serotype H-14) strain AM65-52 (Accession No. ATCC 1276) (e.g. VECTOBAC® by Valent BioSciences, US) + TX, Bacillus thuringiensis subsp.
- serotype H-7 e.g. FLORBAC® WG from Valent BioSciences, US
- TX Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372, e.g. XENTARI® from Valent BioSciences) + TX
- israeltaki strain ABTS 351 + TX Bacillus thuringiensis subsp. kurstaki strain BMP 123 (from Becker Microbial Products, IL, BARITONE from Bayer CropScience) + TX, Bacillus thuringiensis subsp. kurstaki strain EG 2348 (LEPINOX from Certis, US) + TX, Bacillus thuringiensis subsp. kurstaki strain EG 7841 (CRYMAX from Certis, US) + TX, Bacillus thuringiensis subsp. kurstaki strain HD-1 (e.g. DIPEL® ES from Valent BioSciences, US) + TX, Bacillus thuringiensis subsp.
- BMP 123 from Becker Microbial Products, IL, BARITONE from Bayer CropScience
- TX Bacillus thuringiensis subsp. kurstaki strain EG 2348 (LEPINOX from Certis, US) + TX
- israeltaki strain PB 54 + TX Bacillus thuringiensis subsp. kurstaki strain SA 11 (JAVELIN from Certis, US) + TX, Bacillus thuringiensis subsp. kurstaki strain SA 12 (THURICIDE from Certis, US) + TX, Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428, e.g. NOVODOR® FC from BioFa DE) + TX, Bacillus thuringiensis var. Colmeri (e.g. TIANBAOBTC by Changzhou Jianghai Chemical Factory) + TX, Bacillus thuringiensis var.
- SD-5428 e.g. NOVODOR® FC from BioFa DE
- Bacillus thuringiensis var. Colmeri e.g. TIANBAOBTC by Changzhou Jianghai Chemical Factory
- MBI206 TGAI and ZELTO® from Marrone Bio Innovations + TX
- Chromobacterium subtsugae in particular strain PRAA4-1T e.g. MBI-203, e.g. GRANDEVO® from Marrone Bio Innovations
- TX Chromobacterium subtsugae in particular strain PRAA4-1T
- MBI-203 e.g. GRANDEVO® from Marrone Bio Innovations
- TX Lecanicillium muscarium Ve6 (MYCOTAL from Koppert) + TX
- Paenibacillus popilliae (formerly Bacillus popilliae, e.g. MILKY SPORE POWDERTM or MILKY SPORE GRANULARTM from St. Gabriel Laboratories) + TX
- Serratia entomophila e.g.
- ATCC74250 e.g. BOTANIGUARD® ES and MYCONTROL-O® from Laverlam International Corporation
- TX Metarhizium anisopliae 3213-1 (deposited under NRRL accession number 67074 disclosed in WO 2017/066094, Pioneer Hi-Bred International) + TX, Metarhizium robertsii 15013-1 (deposited under NRRL accession number 67073) + TX, Metarhizium robertsii 23013-3 (deposited under NRRL accession number 67075) + TX, Paecilomyces lilacinus strain 251 (MELOCON from Certis, US) + TX; Cydia pomonella (codling moth) granulosis virus (GV) + TX, Helicoverpa armigera (cotton bollworm) nuclear polyhedrosis virus (NPV) + TX, of Adoxophyes orana (summer fruit tortrix) granul
- Burkholderia cepacia (formerly known as Pseudomonas cepacia) + TX, Gigaspora spp. + TX, Glomus spp. + TX, Laccaria spp. + TX, LactoBacillus buchneri + TX, Paraglomus spp. + TX, Pisolithus tinctorus + TX, Pseudomonas spp. + TX, Rhizobium spp. in particular Rhizobium trifolii + TX, Rhizopogon spp. + TX, Scleroderma spp. + TX, Streptomyces spp. + TX, Suillus spp.
- the designation is not a "common name”, the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the IUPAC/Chemical Abstracts name, a "chemical name”, a “traditional name”, a “compound name” or a “develoment code” is used or, if neither one of those designations nor a "common name” is used, an "alternative name” is employed.
- “CAS Reg. No” means the Chemical Abstracts Registry Number.
- the active ingredient mixture of the compounds of formula (I) with active ingredients described above comprises a compound selected from one compound defined in the Tables A-1 to A-42 and Table P and an active ingredient as described above, preferably in a mixing ratio of from 100:1 to 1:6000, especially from 50:1 to 1:50, more especially in a ratio of from 20:1 to 1:20, even more especially from 10:1 to 1:10, very especially from 5:1 and 1:5, special preference being given to a ratio of from 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or
- the mixing ratios are by weight.
- the compounds and compositions pesas described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
- the mixtures comprising a compound of formula (I) selected from the compounds defined in the Tables A-1 to A-42 and Table P and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture com ⁇ posed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequen ⁇ tial manner, i.e. one after the other with a reasonably short period, such as a few hours or days.
- the order of applying the compounds of formula (I) and the active ingredients as described above is not essential for working the present invention.
- compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
- auxiliaries such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides
- compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries).
- auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries).
- compositions that is the methods of controlling pests of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring - which are to be selected to suit the intended aims of the prevailing circumstances - and the use of the compositions for controlling pests of the abovementioned type are other subjects of the invention.
- Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient.
- the rate of application per hectare is generally 1 to 2000 g of active ingredient per hectare, in particular 10 to 1000 g/ha, preferably 10 to 600 g/ha.
- a preferred method of application in the field of crop protection is application to the foliage of the plants (foliar application), it being possible to select frequency and rate of application to match the danger of infestation with the pest in question.
- the active ingredient can reach the plants via the root system (systemic action), by drenching the locus of the plants with a liquid composition or by incorporating the active ingredient in solid form into the locus of the plants, for example into the soil, for example in the form of granules (soil application). In the case of paddy rice crops, such granules can be metered into the flooded paddy-field.
- the compounds of formula (I) of the invention and compositions thereof are also be suitable for the protection of plant propagation material, for example seeds, such as fruit, tubers or kernels, or nursery plants, against pests of the abovementioned type.
- the propagation material can be treated with the compound prior to planting, for example seed can be treated prior to sowing.
- the compound can be applied to seed kernels (coating), either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted to the site of application, for example into the seed furrow during drilling.
- Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 to 200 grams per 100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds, such as between 10 to 100 grams per 100 kg of seeds.
- seed embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds.
- the present invention also comprises seeds coated or treated with or containing a compound of formula I.
- coated or treated with and/or containing generally signifies that the active ingredient is for the most part on the surface of the seed at the time of application, although a greater or lesser part of the ingredient may penetrate into the seed material, depending on the method of application.
- the seed product When the said seed product is (re)planted, it may absorb the active ingredient.
- the present invention makes available a plant propagation material adhered thereto with a compound of formula I. Further, it is hereby made available, a composition comprising a plant propagation material treated with a compound of formula I.
- Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting.
- the seed treatment application of the compound formula (I) can be carried out by any known methods, such as spraying or by dusting the seeds before sowing or during the sowing/planting of the seeds.
- the compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates and/or different pest control, which can be verified by the person skilled in the art using the experimental procedures, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of AI per m2.
- Chilo suppressalis (Striped rice stemborer) 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions by pipetting. After drying, the plates were infested with L2 larvae (6-8 per well). The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 6 days after infestation. Control of Chilo suppressalis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.
- the following compounds resulted in at least 80% control at an application rate of 200 ppm: P2, P4, P5, P6, P7, P8, P10, P11, P12, P13, P14, P17, P18, P19, P20, P22, P23, P24, P28 Diabrotica balteata (Corn root worm)
- Maize sprouts placed onto an agar layer in 24-well microtiter plates were treated with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions by spraying. After drying, the plates were infested with L2 larvae (6 to 10 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 4 days after infestation.
- Intrinsic activity Test compounds prepared from 10'000 ppm DMSO stock solutions were applied by pipette into 24-well microtiter plates and mixed with sucrose solution. The plates were closed with a stretched Parafilm. A plastic stencil with 24 holes was placed onto the plate and infested pea seedlings were placed directly on the Parafilm. The infested plate was closed with a gel blotting paper and another plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation.
- the following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm: P2, P4, P5, P6, P7, P10, P12, P13, P15, P17, P18, P19, P21, P22, P24, P27, P28, P34 Spodoptera littoralis (Egyptian cotton leaf worm)
- Cotton leaf discs were placed onto agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions. After drying the leaf discs were infested with five L1 larvae.
- the samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 3 days after infestation.
- Control of Spodoptera littoralis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.
- the following compounds resulted in at least 80% control at an application rate of 200 ppm: P3, P5, P7, P13, P18, P19, P27
- the invention is defined by the claims.
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Abstract
Compounds of Formula (I) where the substituents are as defined in claim 1, and the agronomically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides and acaricides.
Description
Pesticidally Active Dihydroazole Derivatives The present invention relates to pesticidally active, in particular insecticidally active dihydroazole derivative compounds, to processes for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Lepidoptera. There have now been found novel pesticidally active dihydroazole derivative compounds. The present invention accordingly relates, in a first aspect, to a compound of Formula (I):
wherein R1 to R4 are independently H, halogen, C1-6alkyl, or C1-6haloalkoxy; wherein W is C1-6alkyl, phenyl, 5- or 6-membered heteroaryl, wherein the heteroaryl ring, independent of each other, comprises 1 or 2 heteroatoms independently selected from nitrogen and sulphur, and wherein the ring of the phenyl, 5- or 6-membered heteroaryl, independently of each other, are unsubstituted or independently substituted by 1, 2 or 3 halogen substituents; wherein A1, A2 and A3, together with the adjoining carbon atoms, form a 5-membered ring comprising 2 or 3 heteroatoms and an endocyclic double bond and are, independently, selected from NR9, N, C(O), or O, and wherein R9 is H or CH3; wherein R5 is H or C1haloalkyl; wherein T is selected from:
, or is a direct bond, R6 to R8 are independently selected from H, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, 2- (acetamid)ethyl,2-ethoxyethyl, oxolan-3-yl, thietan-3-yl, oxetan-3-yl, propen-2-yl, 2-methoxyethyl, 2,2- diethoxyethyl, oxan-4-yl, 3-methoxypropyl, 2-hydroxyethyl, 3,3-imethoxypropyl, 2-cyanoethyl or 2- methylsulfonylethyl, or R6 and R7 together with the nitrogen atom to which they are attached form an imidazole or morpholine group; Q is selected from
or is a direct bond; with the proviso that T and Q cannot both be a direct bond; A is a phenyl group, a C6cycloalkyl, or piperidine ring, wherein A is optionally substituted by one or more of halogen, C1-6alkyl, C1-6cycloalkyl, C1-6alkoxy, C1-6haloalkyl, C1-6halocycloalkyl, C1-6haloalkoxy, or an agronomically acceptable salt, isomer, enantiomer, tautomer and/or N-oxide of the compound of Formula (I). Compounds of formula (I) which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as C1-C4alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as C1-C4alkane- or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example methane- or p-toluenesulfonic acid. Compounds of formula (I) which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine. In each case, the compounds of formula (I) according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form. N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991. The compounds of formula (I) according to the invention also include hydrates which may be formed during the salt formation. As used herein, the term "halogen" refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo). As used herein, the term “hydroxyl” or “hydroxy” means an -OH group.
As used herein, the term “hydrosulfido” or “mercapto” means an -SH group. As used herein, the term “cyano” means a -CN group. As used herein, amino means an -NH2 group. As used herein, nitro means an -NO2 group. As used herein, acyl means a -C(O)CH3 group. As used herein, formyl means a -C(O)H group. As used herein, oxo means an =O group (eg, as in a carbonyl (C=O) group). As used herein, the term "C1-n alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to n carbon atoms, and which is attached to the rest of the molecule by a single bond. The term "C1-6alkyl" is to be construed accordingly. Examples of C1-6alkyl include, but are not limited to, methyl, ethyl, n- propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso-propyl, iso-butyl, sec-butyl, tert-butyl or iso-amyl. A “C1-4alkylene” group refers to the corresponding definition of C1-4alkyl, except that such radical is attached to the rest of the molecule by two single bonds. The term “C1-2alkylene” is to be construed accordingly. Examples of C1-4alkylene, include, but are not limited to, -CH2-, - CH2CH2- and -(CH2)3-. As used herein, the term "C2-n alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that may be of either the (E) or (Z)configuration, having from two to n carbon atoms, which is attached to the rest of the molecule by a single bond. C2-6alkenyl is to be construed accordingly. Examples of C2-C6alkenyl include, but are not limited to, prop-1-enyl, allyl (prop-2-enyl), and but-1-enyl. As used herein, the term "C2-n alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to n carbon atoms, and which is attached to the rest of the molecule by a single bond. The term "C2- 6alkynyl" is to be construed accordingly. Examples of C2-6alkynyl include, but are not limited to, prop- 1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl. As used herein, the term "C1-n haloalkyl" refers to a C1-n alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. C1-4haloalkyl and C1-2haloalkyl are to be construed accordingly. Examples of C1-6haloalkyl include, but are not limited to fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, and 2,2,2-trifluoroethyl. As used herein, the term "C2-n haloalkenyl" refers to a C2-n alkenyl group as defined above substituted by one or more of the same or different halogen atoms. Examples of C2-6haloalkenyl include, but are not limited to 3,3-dichloroallyl, 2,3,3-trichloroallyl, 2,3-dichloroallyl, 3,3-dibromoallyl, 2,3,3-tribromoallyl, and 2,3-dibromoallyl.
As used herein, the term "C2-n haloalkynyl" refers to a C2-n alkynyl radical as generally defined above substituted by one or more of the same or different halogen atoms. As used herein, the term “cyanoC1-n alkyl” refers to a C1-n alkyl radical as generally defined above substituted by one or more cyano groups. CyanoC1-6alkyl is to be construed accordingly. Examples of cyanoC1-6alkyl include, but are not limited to, cyanomethyl. As used herein, the term “hydroxyC1-n alkyl” refers to a C1-n alkyl radical as generally defined above substituted by one or more hydroxy groups. As used herein, the term “aminoC1-n alkyl” refers to a radical of the formula H2NRa- wherein Ra is a C1-n alkylene radical as generally defined above. As used herein, the term “C1-n alkylcarbonylC1-n alkyl” refers to a radical of the formula -RbC(O)Ra wherein Ra is a C1-n alkyl as generally defined above and Rb is a C1-n alkylene radical as generally defined above. As used herein, the term “C1-n alkoxycarbonylC1-n alkyl” refers to a radical of the formula -RbC(O)ORa, wherein Ra is a C1-n alkyl radical as generally defined above and Rb is a C1-n alkylene radical as generally defined above. As used herein, the term "C1-n alkoxy" refers to a radical of the formula -ORa wherein Ra is a C1-n alkyl radical as generally defined above. C1-6alkoxy is to be construed accordingly. Examples of C1- 6alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, and tert-butoxy. As used herein, the term "C1-n alkenoxy" refers to a radical of the formula RaO-, wherein Ra is a C1-n alkenyl radical as generally defined above. As used herein, the term "C1-n haloalkoxy" refers to a C1-n alkoxy group as defined above substituted by one or more of the same or different halogen atoms. C1-6haloalkoxy is to be construed accordingly. Examples of C1-6haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy. As used herein, the term "C1-n alkylcarbonyloxy" refers to a radical of the formula -OC(O)Ra wherein Ra is a C1-n alkyl radical as generally defined above. The term "C1-6alkylcarbonyloxy" is to be construed accordingly. As used herein, the term "C1-n alkoxyC1-n alkyl" refers to a radical of the formula Rb-O-Ra- wherein Rb is a C1-n alkyl radical as generally defined above, and Ra is a C1-n alkylene radical as generally defined above.
As used herein, the term “C1-n alkoxyC1-n alkoxy” refers to a radical of the formula Ra-O-Rb- wherein Ra is a C1-n alkyl radical as generally defined above, and Rb is a C1-n alkoxy radical as generally defined above. As used herein, the term "C1-n alkylcarbonyl" refers to a radical of the formula RaC(O)-, wherein Ra is a C1-n alkyl radical as generally defined above. As used herein, the term "C1-Cn haloalkylcarbonyl" refers to a C1-Cn alkylcarbonyl radical as generally defined above, substituted by one or more of the same or different halogen atoms. As used herein, the term “C1-n alkoxycarbonyl” refers to a radical of the formula RaOC(O)-, wherein Ra is a C1-n alkyl radical as generally defined above. As used herein, the term “C1-Cn alkylaminocarbonyl” refers to a radical of the formula RaNHC(O)- wherein Ra is a C1-Cn alkyl radical as generally defined above. As used herein, the term "C1-n alkylcarbonylamino" refers to a radical of the formula RaC(O)N(H)- wherein Ra is a C1-n alkyl radical as generally defined above. As used herein, the term "C3-8cycloalkyl" refers to a stable, monocyclic ring radical which is saturated and contains 3 to 8 carbon atoms. C3-6cycloalkyl is to be construed accordingly. Examples of C3- 8cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. As used herein, the term "C3-10cycloalkenyl" refers to a radical which is a monocyclic non-aromatic ring system consisting solely of carbon and hydrogen atoms and which contains 3 to 10 carbon atoms and 1 or 2 endocyclic double bonds. They may include bridged structures (e.g., norbornene and 2,5- norbornadiene). Examples of C3-C10cycloalkenyl include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. As used herein, the term "C3-6halocycloalkyl" refers to a C3-6cycloalkyl ring as defined above substituted by one or more of the same or different halogen atoms. As used herein, the term "C3-8cycloalkylC1-2alkyl" refers to a C3-8cycloalkyl ring as defined above attached to the rest of the molecule by a C1-2alkylene radical as defined above. The term "C3- 6cycloalkylC1-2alkyl" should be construed accordingly. Examples of C3-8cycloalkylC1-2alkyl include, but are not limited to cyclopropyl-methyl and cyclobutyl-ethyl. As used herein, the term "phenylC1-2alkyl" refers to a phenyl ring attached to the rest of the molecule by a C1-2alkylene radical as defined above. Examples of phenylC1-2alkyl include benzyl.
As used herein, the term "aryl" refers to an aromatic ring system consisting solely of carbon and hydrogen atoms which may be mono, bi or tricyclic. Examples of such ring systems include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic ring radical which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S. Examples of heteroaryl include, but are not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl. As used herein, the term "heteroarylC1-2alkyl" refers to a heteroaryl ring as defined above which is attached to the rest of the molecule by a C1-2alkylene radical as defined above. As used herein, the term "heterodiaryl" refers to a 9- or 10-membered bicyclic aromatic system which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S. Examples of heterodiaryl include, but are not limited to, quinolinyl and indolinyl. As used herein, the term "heterocyclyl" or "heterocyclic" refers to a stable 5- or 6-membered non- aromatic monocyclic ring radical which comprises 1, 2, or 3 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heterocyclyl include, but are not limited to, pyrrolinyl, pyrrolidyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidyl, piperazinyl, tetrahydropyranyl, dioxolanyl, morpholinyl, oxazinanyl, oxetanyl, or δ-lactamyl. As used herein, the term "heterocyclylC1-2alkyl" refers to a heterocyclic ring as defined above which is attached to the rest of the molecule by a C1-2alkylene radical as defined above. As used herein, the term "controlling" refers to reducing the number of pests, eliminating pests and/or preventing further pest damage such that damage to a plant or to a plant derived product is reduced. As used herein, the term "pest" refers to pests that cause damage and /or inconcenience in agriculture, in horticulture, in ornamentals, in forests, in the storage of products of vegetable origin (such as fruit, grain and timber) including damage of man-made structures, or on organs, such as fruits, flowers, foliage, stalks, tubers, plant propagation material (such as seeds), and roots, of such plants, and in some cases even plant organs which are formed at a later point in time. The term pest encompasses all stages in the life cycle of the pest. Examples of pests include arthropod pests, and nematodes; preferably insects, mities and acarina, particularly insects. As used herein, the term "effective amount" refers to the amount of the compound, or a salt thereof, which, upon single or multiple applications provides the desired effect.
An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances. Embodiments according to the invention are provided as set out below. In an embodiment of each aspect of the invention R1 to R4 are independently H, F, Cl, C1-3alkyl or C1- 3haloalkoxy. In an embodiment of each aspect of the invention W is phenyl, pyridine, thiophene, thiazole, or C1- 4alkyl, wherein the ring of the phenyl, pyridine, thiophene, or thiazole is unsubstituted or independently substituted by 1, 2 or 3 fluorine or chlorine substituents. In an embodiment of each aspect of the invention A1, A2 and A3, together with the adjoining carbon atoms, form a 5-membered ring comprising 3 heteroatoms and an endocyclic double bond. In an embodiment of each aspect of the invention the 3 heteroatoms comprise two nitrogen atoms and an oxygen. In an embodiment of each aspect of the invention R5 is trifluoromethyl, difluoromethyl or fluoromethyl. In an embodiment of each aspect of the invention R6 to R8 are H or methyl. In an embodiment of each aspect of the invention A is monosubstituted. In an embodiment of each aspect of the invention A is monosubstituted by F, Cl, C1-3alkyl or C1- 3haloalkoxy, preferably in the para position. In a second aspect, the present invention makes available a composition comprising a compound of formula (I) as defined in the first aspect, one or more auxiliaries and diluent, and optionally one more other active ingredient. In a third aspect, the present invention makes available a method of combating and controlling one or more pests which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest a pesticidally effective amount of a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.
In a fourth aspect, the present invention makes available a method for the protection of plant propagation material from the attack by one or more pests, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect. In a fifth aspect, the present invention makes available a plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect. The present invention in a further aspect provides a method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound of formula (I) of the first aspect. The present invention further provides a method of controlling ectoparasites on an animal in need thereof comprising administering an effective amount of a compound of formula (I) as defined om the first aspect. The present invention further provides a method for preventing and/or treating diseases transmitted by ectoparasites comprising administering an effective amount of a compound of formula (I) as defined in the first aspect, to an animal in need thereof. In an embodiment, the uses and methods described herein exclude treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body. In an embodiment, the use is a non-therapeutic use. In an embodiment, the method is a non-therapeutic method. A compound of Formula (I) can exist in different tautomeric forms and a skilled person would readily understand what they are. Compounds of Formula (I) can be prepared by those skilled in the art following known methods. More specifically compounds of formulae I, and intermediates therefore can be prepared as described below in the schemes and examples. The process according to the invention for preparing compounds of formula (I) is carried out by methods known to those skilled in the art.
General synthesis Compounds of formula (I) where Q is -C(=O)-NH-, can be obtained by an amide coupling transformation starting from acid compounds of formula (V), and amino compound of formula (VI), preferably in a suitable solvent (eg, dimethylformamide, dimethylacetamide, dichloromethane or tetrahydrofuran), preferably at a temperature of between 25°C and 100°C, and optionally in the presence of a base such as triethylamine or N,N-diisopropylethylamine, or under conditions described in the literature for an amide coupling. For examples, see WO 2003/028729 or as described in March's Advanced Organic Chemistry 6th edition, Michael B. Smith and Jerry March. Compounds of formula (VI) are commercially available or prepared using known methods. This reaction is shown in Scheme 1.
Scheme 1 Compounds of formula (I) where Q is NH-C(=O)-, can be obtained by an amide coupling transformation starting from acid compounds of formula (VIII), and amino compound of formula (VII), preferably in a suitable solvent (eg, dimethylformamide, dimethylacetamide, dichloromethane or tetrahydrofuran), preferably at a temperature of between 25°C and 100°C, and optionally in the presence of a base such as triethylamine or N,N-diisopropylethylamine, or under conditions described in the literature for an amide coupling. For examples, see WO 2003/028729 or as described in March's Advanced Organic Chemistry 6th edition, Michael B. Smith and Jerry March. Compounds of formula (VIII) are commercially available or prepared using known methods. This reaction is shown in Scheme 2.
Scheme 2
Compounds of formula (I) wherein T is T1 can be prepared from Chan-Lam coupling reaction between pyrazole compounds of formula (IVa), wherein T is T1 and aryl boronic acid compounds of formula (II) in analogy as described in WO2009110520. This reaction is shown in Scheme 3.
Scheme 3 Alternatively compounds of formula (I) wherein T is T1 can be prepared via coupling reaction starting from compounds of formula (III), wherein X is a halogen, preferably Cl, Br or I, and compounds of compounds of formula (IVa), wherein T is T1. The reaction may be carried out in an inert organic solvent such as tetrahydrofuran or dimethylformamide at ambient or elevated temperature, optionally in the presence of a suitable base such as potassium or caesium carbonate or a strong base such as sodium t-butoxide or lithium bis(trimethylsilyl)amide (LiHMDS). This reaction is shown in Scheme 4.
Scheme 4 Compounds of formula (I) wherein T is T2, T3, T4 or a direct bond can be prepared via Suzuki coupling reaction starting from boronic acid compounds of formula (II), and compounds of formula (IVb), wherein T is T2, T3, T4 or a direct bond. The reaction may be carried out in the presence of a palladium (II) catalyst (e.g. palladium acetate) together with phosphine ligand (e.g. triphenylphosphine). This reaction is shown in Scheme 5.
Scheme 5 Alternatively ccompounds of formula (I), wherein T is T2, T3, T4 or a direct bond may be prepared via Suzuki-Miyaura cross-coupling reactions between boronic acid compounds of formula (IVc), and compounds of formula (III), wherein T is T2, T3, T4 or a direct bond. Reactions are well known to a person skilled in the art and are usually carried out in the presence of a palladium catalyst, such as
tetrakis(triphenylphosphine)-palladium(0) or 1,1’-bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex, and a base, such as sodium or potassium carbonate, in a solvent, such as N,N-dimethylformamide, dioxane or dioxane-water mixtures, at temperatures between room temperature and 160°C, optionally under microwave heating conditions and preferably under inert atmosphere. Such reactions have been reviewed for example in J. Organomet. Chem.1999, 576,147- 168.This reaction is shown in Scheme 6.
Scheme 6 Compounds of formula (I) wherein R5 is C1fluoroalkyl, A1 is O, A2 and A3 are N can be prepared via addition reaction of metalorganic compounds of formula (X) or (Xa), to oxadiazole compounds of formula (IX), wherein A1 is O, A2 and A3 are N as described in the experimental section. The suitable organometallic such as (WLi or WMgX), optionally in the presence of a suitable catalyst and in a suitable solvent. Suitable catalysts may include lanthanum (III) chloride bis(lithium chloride) complex. Suitable solvents may include THF. Some metalorganic compounds of formula (X) are commercially available. Metalorganic compounds of formula (Xa) may be prepared via trans metalation. This reaction is shown in Scheme 7.
Scheme 7 Compounds of formula (IX) can be prepared from compounds of formula (XI) by treatment with a compound of formula (II), for example trifluoroacetic chloride, trifluoroacetic fluoride, or trifluoroacetic anhydride in the presence of a base (eg, pyridine or 4-dimethylaminopyridine) in a suitable solvent, such as tetrahydrofuran or ethanol, at a temperature between 25°C and 75°C. For related examples, see WO 2003/028729 and WO 2010/045251. This reaction is shown in Scheme 8.
Scheme 8 Compounds of formula (XI) can be prepared from compounds of formula (XIII) by treatment with a hydroxylamine hydrochloride salt in the presence of a base, such as triethylamine, in a suitable solvent, such as methanol, at a temperature between 0°C and 100°C. For related examples, see Kitamura, S. et al Chem. Pharm. Bull. (2001), 49, 268 and WO 2013/066838. This reaction is shown in Scheme 9.
Compounds of formula (XIII) can be prepared from compounds of formula (XIV), wherein X is Br or I, via metal-promoted reaction with a suitable cyanide reagent, such as Pd(0)/Zn(CN)2 or CuCN, in a suitable solvent (eg, dimethylformamide or N-methylpyrrolidone) at elevated temperature between 100°C and 120°C. For related examples, see US 2007/0155739 and WO 2009/022746. This reaction is shown in Scheme 10.
Scheme 10 Compounds of formula (XIIIa), wherein T is T1, Q is NH-C(=O)-, can be obtained by an amide coupling transformation starting from acid compounds of formula (VIII), and amino compound of formula (XVa) as described in the experimental section. This reaction is shown in Scheme 11.
Scheme 11 Compounds of formula (XVa), wherein T is T1, can be prepared by reduction of nitro compound of formula (XVIa) using reducing agents such as Iron or SnCI2 in acid medium as described in the experimental section. This reaction is shown in Scheme 12.
Scheme 12 Compounds of formula (XVa), wherein T is T1, can be prepared by SNAr reaction between commercially available pyrazole compounds of formula (XVIIa) and commercially available p-fluoro benzonitrile compound of formula (XVIII) as described in the experimental section. This reaction is shown in Scheme 13.
(XVIII) (XVIIa) (XVIa) Scheme 13 Compounds of formula (IIIa) wherein T is T1, A1 is O, A3 is N, A2 is N-methyl and X is bromo can be prepared by alkylation of compounds of formula (IIIaa), wherein T is T1, A1 is O, A2 and A3 are N, and X is bromo with an alkylation reagent e.g. methyliodide or dimethylsulfate. The reaction may be carried out in an inert organic solvent such as tetrahydrofuran or dimethylformamide at ambient or elevated temperature, optionally in the presence of a suitable base such as potassium or caesium carbonate or a strong base such as sodium t-butoxide or lithium bis(trimethylsilyl)amide (LiHMDS). This reaction is described in the experimental section and shown in Scheme 14.
Scheme 14 Compounds of formula (IIIaa), wherein A1 is O, A2 and A3 are N, and X is bromo can be prepared by 1-3-dipolar cycloaddition reaction of in situ generated nitrile oxides from hydroxymoylchloride via aldoxime compound of formula (IXX), wherein A1 is O, A2 and A3 are N, and X is bromo and compounds of formula (XX) as described for example in Tetrahedron Letters 61 (2020) 152213 or in the experimental section. Intermediates of formula (IXX) and (XX) are commercially available or can be prepared performing reactions well known to a person skilled in the art. This reaction is shown in Scheme 15.
Scheme 15 Compounds of formula (IIa), wherein A1 is N(CO)CH3, A2 is N, and A3 is O can be prepared via palladium-catalyzed borylation reaction of aryl halide compounds of formula (IIIb) wherein X is a halogen, preferably Br or I, with bis(pinacolato)diboron or pinacolborane as described for example in J. Org. Chem. 2008, 73, 14, 5589–5591. This reaction is described in the experimental section and shown in Scheme 16.
Scheme 16 Compounds of formula (IIb), wherein A1 is N(CO)CH3, A2 is N, and A3 is O can be prepared via cyclisation and acylation reaction of compounds of formula (XXIa) with acetic anhydride as described in the experimental section. This reaction is shown in Scheme 17.
Scheme 17 Compounds of formula (XXI), wherein A1 and A2 are N, and A3 is O can be prepared via condensation reaction of compounds of formula (XXII) and compounds of formula (XXIII) as described in the experimental section. This reaction is shown in Scheme 18.
Scheme 18 Compounds of formula (IIb), wherein A1 and A3 are O and A2 is N can be prepared via palladium- catalysed borylation reaction of aryl halide compounds of formula (IIIc) wherein X is a halogen, preferably Br or I, with bis(pinacolato)diboron or pinacolborane as described for example in J. Org. Chem. 2008, 73, 14, 5589–5591. This reaction is described in the experimental section and shown in Scheme 19.
Scheme 19 Compounds of formula (IIc), wherein A1 is (CO), A2 and A3 are N can be prepared via palladium- catalyzed borylation reaction of aryl halide compounds of formula (IIIc) wherein X is a halogen, preferably Br or I, with bis(pinacolato)diboron or pinacolborane as described for example in J. Org. Chem. 2008, 73, 14, 5589–5591. This reaction is described in the experimental section and shown in Scheme 20.
Scheme 20 Compounds of formula (IIId), wherein A1 is (CO), A2 and A3 are N can be prepared cyclocondensation reaction of amidine compounds of formula (XXV) with ketone compounds of formula (XXIV). This reaction is described in the experimental section and shown in Scheme 21.
Scheme 21 Compounds of formula (IId), wherein A1 is O, A2 is N and A3 is N(cyclopropyl) can be prepared via palladium-catalyzed borylation reaction of aryl halide compounds of formula (IIIc) wherein X is a halogen, preferably Br or I, with bis(pinacolato)diboron or pinacolborane as described for example in J. Org. Chem. 2008, 73, 14, 5589–5591. This reaction is described in the experimental section and shown in Scheme 22.
Scheme 22 Compounds of formula (IIIe), wherein A1 is O, A2 is N and A3 is N(cyclopropyl) can be prepared via 1- 3-dipolar cycloaddition reaction of in situ generated nitrile oxides from hydroxymoylchloride compound of formula (XXVI), wherein A1 is O, A2 is N, and X is bromo and compounds of formula (XXa) where A3 is N(cyclopropyl) as described in the experimental section. Intermediates of formula (IXX) and (XX) are commercially available or can be prepared performing reactions well known to a person skilled in the art. This reaction is shown in Scheme 23.
Scheme 23 Compounds of formula (XIII), where T is T2, Q is a direct bond may be prepared via Suzuki-Miyaura cross-coupling reactions between boronic acid compounds of formula (XXVII), and compounds of formula (IVa), wherein T is T2, Q is a direct bond X is Br or I. This reaction is shown in Scheme 24.
Scheme 24 Compounds of formula (XIII), where T is T3, Q is a direct bond may be prepared via Suzuki-Miyaura cross-coupling reactions between boronic acid compounds of formula (XXVII), and compounds of formula (IVa), wherein T is T2, Q is a direct bond X is Br or I. This reaction is shown in Scheme 24.
Scheme 24 Intermediates of formula (IVb), where W is a direct bond and A is p-trifluoromethoxybenzene may be prepared in two steps from 3,5-Dibromo-1H-1,2,4-triazole (XXIX) under conditions described WO 2022033991. Compounds of formula (XXX) were obtained via Chan-Lam reaction,followed by amine substitution reaction with compounds of formula (XXXI) as described in WO 2022033991.This reaction is shown in Scheme 25.
Scheme 25
Compounds of formula (XIII), where T is T4, Q is a direct bond may be prepared via Suzuki-Miyaura cross-coupling reactions between boronic acid compounds of formula (XXVII), and a halo-azole compounds of formula (IVc), wherein T is T4, Q is a direct bond X is Br or I as described in WO 2016040449 or WO 2018233633. Suitable azoles of general formula (IVc) (where X can be chlorine, bromine, iodine and triflate) and phenylboronic acids of formula (XXVIII) are commercially available or could be synthesized following known literatures. This reaction is shown in Scheme 26.
Scheme 26 Intermediates of formula (IVd), where T is T4, Q is -C(=O)-NH- can be prepared from methyl 3-halo-1H- 1,2,4-triazole-5-carboxylate via N-alkylation to build compounds of formula (XVIIb) by using amide formation reactions with compounds of formula (X) as described in WO2022053453 using Me3Al in toluene or THF to form compound (IVd). This reaction is shown in Scheme 27.
(XVIIb) (IVd) Scheme 27
Salts of compounds of Formula (I) can be prepared in a manner known per se. Thus, for example, acid addition salts of compounds of Formula (I) are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent. Salts of compounds of Formula (I) can be converted in the customary manner into the free compounds I, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent. Salts of compounds of Formula (I) can be converted in a manner known per se into other salts of compounds of formula I, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture. Depending on the procedure or the reaction conditions, the compounds of formula I, which have salt- forming properties can be obtained in free form or in the form of salts. The compounds of Formula (I) and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case. Diastereomer mixtures or racemate mixtures of compounds of formula I, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diastereomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography. Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl cellulose, with the aid of suitable microorganisms, by cleavage with specific,
immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents. Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry. N-oxides can be prepared by reacting a compound of the Formula (I) with a suitable oxidizing agent, for example the H2O2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride. Such oxidations are known from the literature, for example from J. Med. Chem., 32 (12), 2561-73, 1989 or WO 2000/15615. It is advantageous to isolate or synthesize in each case the biologically more effective isomer, for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity. The compounds of Formula (I) and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
The compounds of formula I-A according to the following Tables A-1 to A-54 can be prepared according to the methods described above. The examples which follow are intended to illustrate the invention and show preferred compounds of formula I, in the form of a compound of formula I-A.
I-A Table A-1 provides 16 compounds A-1.001 to A-1.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 1 and Cx are as defined in table A. For example, A-1.001 is
Index Cx 1 O CF3 N O N N H CH 3
Index Cx 2 3 4 5 6 7 8 9 10
Index Cx 11 12 13 14 15 16 Table A-2 provides 16 compounds A-2.001 to A-2.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 2 and Cx are as defined in table A. Table A-3 provides 16 compounds A-3.001 to A-3.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 3 and Cx are as defined in table A. Table A-4 provides 16 compounds A-4.001 to A-4.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 4 and Cx are as defined in table A. Table A-5 provides 16 compounds A-5.001 to A-5.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 5 and Cx are as defined in table A. Table A-6 provides 16 compounds A-6.001 to A-6.016 of formula I-A wherein Bx is (3-chlorophenyl), Qx is 6 and Cx are as defined in table A.
Table A-7 provides 16 compounds A-7.001 to A-7.016 of formula I-A wherein Bx is (3,5-dichlorophenyl), Qx is 1 and Cx are as defined in table A. Table A-8 provides 16 compounds A-8.001 to A-8.016 of formula I-A wherein Bx is (3,5-dichlorophenyl), Qx is 2 and Cx are as defined in table A. Table A-9 provides 16 compounds A-9.001 to A-9.016 of formula I-A wherein Bx is (3,5-dichlorophenyl), Qx is 3 and Cx are as defined in table A. Table A-10 provides 16 compounds A-10.001 to A-10.016 of formula I-A wherein Bx is (3,5- dichlorophenyl), Qx is 4 and Cx are as defined in table A. Table A-11 provides 16 compounds A-11.001 to A-11.016 of formula I-A wherein Bx is (3,5- dichlorophenyl), Qx is 5 and Cx are as defined in table A. Table A-12 provides 16 compounds A-12.001 to A-12.016 of formula I-A wherein Bx is (3,5- dichlorophenyl), Qx is 6 and Cx are as defined in table A. Table A-13 provides 16 compounds A-13.001 to A-13.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 1 and Cx are as defined in table A. Table A-14 provides 16 compounds A-14.001 to A-14.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 2 and Cx are as defined in table A. Table A-15 provides 16 compounds A-15.001 to A-15.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 3 and Cx are as defined in table A. Table A-16 provides 16 compounds A-16.001 to A-16.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 4 and Cx are as defined in table A. Table A-17 provides 16 compounds A-17.001 to A-17.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 5 and Cx are as defined in table A. Table A-18 provides 16 compounds A-18.001 to A-18.016 of formula I-A wherein Bx is (3,5-dichloro-4- fluoro-phenyl), Qx is 6 and Cx are as defined in table A. Table A-19 provides 16 compounds A-19.001 to A-19.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 1 and Cx are as defined in table A. Table A-20 provides 16 compounds A-20.001 to A-20.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 2 and Cx are as defined in table A. Table A-21 provides 16 compounds A-21.001 to A-21.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 3 and Cx are as defined in table A. Table A-22 provides 16 compounds A-22.001 to A-22.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 4 and Cx are as defined in table A. Table A-23 provides 16 compounds A-23.001 to A-23.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 5 and Cx are as defined in table A. Table A-24 provides 16 compounds A-24.001 to A-24.016 of formula I-A wherein Bx is (2,4- difluorophenyl), Qx is 6 and Cx are as defined in table A. Table A-25 provides 16 compounds A-25.001 to A-25.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 1 and Cx are as defined in table A. Table A-26 provides 16 compounds A-26.001 to A-26.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 2 and Cx are as defined in table A.
Table A-27 provides 16 compounds A-27.001 to A-27.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 3 and Cx are as defined in table A. Table A-28 provides 16 compounds A-28.001 to A-28.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 4 and Cx are as defined in table A. Table A-29 provides 16 compounds A-29.001 to A-29.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 5 and Cx are as defined in table A. Table A-30 provides 16 compounds A-30.001 to A-30.016 of formula I-A wherein Bx is 2-pyridyl, Qx is 6 and Cx are as defined in table A. Table A-31 provides 16 compounds A-31.001 to A-31.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 1 and Cx are as defined in table A. Table A-32 provides 16 compounds A-32.001 to A-32.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 2 and Cx are as defined in table A. Table A-33 provides 16 compounds A-33.001 to A-33.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 3 and Cx are as defined in table A. Table A-34 provides 16 compounds A-34.001 to A-34.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 4 and Cx are as defined in table A. Table A-35 provides 16 compounds A-35.001 to A-35.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 5 and Cx are as defined in table A. Table A-36 provides 16 compounds A-36.001 to A-36.016 of formula I-A wherein Bx is thiazol-2-yl, Qx is 6 and Cx are as defined in table A. Table A-37 provides 16 compounds A-37.001 to A-37.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 1 and Cx are as defined in table A. Table A-38 provides 16 compounds A-38.001 to A-38.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 2 and Cx are as defined in table A. Table A-39 provides 16 compounds A-39.001 to A-39.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 3 and Cx are as defined in table A. Table A-40 provides 16 compounds A-40.001 to A-40.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 4 and Cx are as defined in table A. Table A-41 provides 16 compounds A-41.001 to A-41.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 5 and Cx are as defined in table A. Table A-42 provides 16 compounds A-42.001 to A-42.016 of formula I-A wherein Bx is (5-chloro-2- thienyl), Qx is 6 and Cx are as defined in table A. Table A-43 provides 16 compounds A-43.001 to A-43.016 of formula I-A wherein Bx is isopropyl, Qx is 1 and Cx are as defined in table A. Table A-44 provides 16 compounds A-44.001 to A-44.016 of formula I-A wherein Bx is isopropyl, Qx is 2 and Cx are as defined in table A. Table A-45 provides 16 compounds A-45.001 to A-45.016 of formula I-A wherein Bx is isopropyl, Qx is 3 and Cx are as defined in table A. Table A-46 provides 16 compounds A-46.001 to A-46.016 of formula I-A wherein Bx is isopropyl, Qx is 4 and Cx are as defined in table A.
Table A-47 provides 16 compounds A-47.001 to A-47.016 of formula I-A wherein Bx is isopropyl, Qx is 5 and Cx are as defined in table A. Table A-48 provides 16 compounds A-48.001 to A-48.016 of formula I-A wherein Bx is isopropyl, Qx is 6 and Cx are as defined in table A. Table A-49 provides 16 compounds A-49.001 to A-49.016 of formula I-A wherein Bx is butyl, Qx is 1 and Cx are as defined in table A. Table A-50 provides 16 compounds A-50.001 to A-50.016 of formula I-A wherein Bx is butyl, Qx is 2 and Cx are as defined in table A. Table A-51 provides 16 compounds A-51.001 to A-51.016 of formula I-A wherein Bx is butyl, Qx is 3 and Cx are as defined in table A. Table A-52 provides 16 compounds A-52.001 to A-52.016 of formula I-A wherein Bx is butyl, Qx is 4 and Cx are as defined in table A. Table A-53 provides 16 compounds A-53.001 to A-53.016 of formula I-A wherein Bx is butyl, Qx is 5 and Cx are as defined in table A. Table A-54 provides 16 compounds A-54.001 to A-54.016 of formula I-A wherein Bx is butyl, Qx is 6 and Cx are as defined in table A.
The compounds of formula (I) according to the invention are preventively and/or curatively valuable active ingredients in the field of pest control, even at low rates of application, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants. The active ingredients according to the invention act against all or individual developmental stages of normally sensitive, but also resistant, animal pests, such as insects or representatives of the order Acarina. The insecticidal or acaricidal activity of the active ingredients according to the invention can manifest itself directly, i. e. in destruction of the pests, which takes place either immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example in a reduced oviposition and/or hatching rate. Examples of the above mentioned animal pests are: from the order Acarina, for example, Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemus spp, Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus spp.; from the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example, Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa decemlineata, Lissorhoptrus spp., Liogenys spp, Maecolaspis spp, Maladera castanea, Megascelis spp, Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp, Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp., Somaticus spp, Sphenophorus spp, Sternechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp.; from the order Diptera, for example, Aedes spp., Anopheles spp, Antherigona soccata,Bactrocea oleae, Bibio hortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Rhagoletis spp, Rivelia quadrifasciata, Scatella spp, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.; from the order Hemiptera, for example,
Acanthocoris scabrator, Acrosternum spp, Adelphocoris lineolatus, Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp, Cimex spp., Clavigralla tomentosicollis, Creontiades spp, Distantiella theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp, Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes spp, Murgantia histrionic, Neomegalotomus spp, Nesidiocoris tenuis, Nezara spp., Nysius simulans, Oebalus insularis, Piesma spp., Piezodorus spp, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp. , Thyanta spp , Triatoma spp., Vatiga illudens; Acyrthosium pisum, Adalges spp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana spectra, Cryptomyzus spp, Cicadulina spp, Coccus hesperidum, Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia, Dysaphis spp, Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp, Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp, Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp., Neotoxoptera sp, Nephotettix spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae, Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis, Perkinsiella spp, Phorodon humuli, Phylloxera spp, Planococcus spp., Pseudaulacaspis spp., Pseudococcus spp., Pseudatomoscelis seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp., Scaphoideus spp., Schizaphis spp., Sitobion spp., Sogatella furcifera, Spissistilus festinus, Tarophagus Proserpina, Toxoptera spp, Trialeurodes spp, Tridiscus sporoboli, Trionymus spp, Trioza erytreae , Unaspis citri, Zygina flammigera, Zyginidia scutellaris, ; from the order Hymenoptera, for example, Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplo- campa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Pogonomyrmex spp, Slenopsis invicta, Solenopsis spp. and Vespa spp.; from the order Isoptera, for example, Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate from the order Lepidoptera, for example, Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp, Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis, Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis
castanea, Earias spp., Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., Epinotia spp, Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp., Hellula undalis, Herpetogramma spp, Hyphantria cunea, Keiferia lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp., Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Mythimna spp, Noctua spp, Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis flammea, Papaipema nebris, Pectinophora gossypiela, Perileucoptera coffeella, Pseudaletia unipuncta, Phthorimaea operculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp., Pseudoplusia spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia spp., Sparganothis spp., Spodoptera spp., Sylepta derogate, Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tuta absoluta, and Yponomeuta spp.; from the order Mallophaga, for example, Damalinea spp. and Trichodectes spp.; from the order Orthoptera, for example, Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp.; from the order Psocoptera, for example, Liposcelis spp.; from the order Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis; from the order Thysanoptera, for example, Calliothrips phaseoli, Frankliniella spp., Heliothrips spp, Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp; from the order Thysanura, for example, Lepisma saccharina. In a further aspect, the invention may also relate to a method of controlling damage to plant and parts thereof by plant parasitic nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic nematodes), especially plant parasitic nematodes such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolaimus longicaudatus and other Belonolaimus species; Pine nematodes, Bursaphelenchus xylophilus and other Bursaphelenchus species; Ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; Awl nematodes, Dolichodorus species; Spiral nematodes, Heliocotylenchus multicinctus and other Helicotylenchus species; Sheath and sheathoid nematodes, Hemicycliophora species and Hemicriconemoides species; Hirshmanniella species; Lance nematodes, Hoploaimus species; false rootknot nematodes, Nacobbus species; Needle
nematodes, Longidorus elongatus and other Longidorus species; Pin nematodes, Pratylenchus species; Lesion nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; Burrowing nematodes, Radopholus similis and other Radopholus species; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus species; Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other plant parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp.. The compounds of the invention may also have activity against the molluscs. Examples of which include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae Helicigona arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides. The active ingredients according to the invention can be used for controlling, i. e. containing or destroying, pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests. Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodder beet; fruit, for example pomaceous fruit, stone fruit or soft fruit, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soya; oil crops, such as oilseed rape, mustard, poppies, olives, sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts, coffee, eggplants, sugarcane, tea, pepper, grapevines, hops, the plantain family and latex plants. In a particular embodiment, a compound of the formula (I) controls mites, rust mites and spider mites in crops, tress, and plants selected from vegetables (especially tomatoes and cucurbits), citrus, pome fruits, stone fruit, tree nuts, cotton, tropical crops, avocados, ornamentals, beans, soybean, strawberry, and grapes.
The compositions and/or methods of the present invention may be also used on any ornamental and/or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreens. For example the invention may be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubéreux), Bougainvillea spp., Brachycome spp., Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I. Walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp., Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp. (pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (rose), Rudbeckia spp., Saintpaulia spp., Salvia spp., Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other bedding plants. For example the invention may be used on any of the following vegetable species: Allium spp. (A. sativum, A.. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Cichorium endivia, Cichorum spp. (C. intybus, C. endivia), Citrillus lanatus, Cucumis spp. (C. sativus, C. melo), Cucurbita spp. (C. pepo, C. maxima), Cyanara spp. (C. scolymus, C. cardunculus), Daucus carota, Foeniculum vulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L. esculentum, L. lycopersicum), Mentha spp., Ocimum basilicum, Petroselinum crispum, Phaseolus spp. (P. vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica, Solanum melongena, Spinacea oleracea, Valerianella spp. (V. locusta, V. eriocarpa) and Vicia faba. Preferred ornamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber. The active ingredients according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, maize, rice and soya crops. The active ingredients according to the invention are
further especially suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice). The compounds of formula (I) are particularly suitable for control of mites, spider mites and rust mites, for example, Acarapis spp; Acarapis woodi; Acarus siro; Acarus spp; Aceria sheldoni; Aculops pelekassi; Aculops spp; Aculus schlechtendali; Aculus spp; Amblyseius fallacis; Brevipalpus spp; Brevipalpus phoenicis; Bryobia praetiosa; Bryobia rubrioculus; Caloglyphus spp; Cheyletiella blakei; Cheyletiella spp; Cheyletiella yasguri; Chorioptes bovis; Chorioptes spp; Cytodites spp; Demodex bovis; Demodex caballi; Demodex canis; Demodex caprae; Demodex equi; Demodex ovis; Demodex spp; Demodex suis; Dermanyssus gallinae; Dermanyssus spp; Eotetranychus spp; Eotetranychus willamettei; Epitrimerus pyri; Eriophyes ribis; Eriophyes spp; Eriophyes vitis; Eutetranychus spp; Halotydeus destructor; Hemitarsonemus spp; Knemidocoptes spp; Laminosioptes spp; Listrophorus spp; Myobia spp; Neoschongastia xerothermobia; Neotrombicula autumnalis; Neotrombicula desaleri; Notoedres cati; Notoedres spp; Oligonychus coffeae; Oligonychus ilicis; Oligonychus spp; Ornithocheyletia spp; Ornithonyssus bursa; Ornithonyssus spp; Ornithonyssus sylviarum; Otodectes cynotis; Otodectes spp; Panonychus citri; Panonychus spp; Panonychus ulmi; Phyllocoptruta oleivora; Phyllocoptruta spp.; Phytoseiulus spp.; Pneumonyssoides caninum; Polyphagotarsonemus latus; Polyphagotarsonemus spp; Psorergates ovis; Psorergates spp; Psoroptes cuniculi; Psoroptes equi; Psoroptes ovis; Psoroptes spp; Pterolichus spp; Raillietia spp; Rhizoglyphus spp; Sarcoptes bovis; Sarcoptes canis; Sarcoptes caprae; Sarcoptes equi; Sarcoptes ovis; Sarcoptes rupicaprae; Sarcoptes spp; Sarcoptes suis; Steneotarsonemus spinki; Steneotarsonemus spp; Sternostoma spp; Tarsonemus spp; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp; Tetranychus urticae; Trombicula akamushi; Trombicula spp; Typhlodromus occidentalis; Tyrophagus spp; Varroa jacobsoni; Varroa spp; Vasates lycopersici; and Zetzellia mali. In an embodiment, a compound of formula (I) are especially suitable for controlling one or more of: Aceria sheldoni ; Aculus lycopersici; Aculus pelekassi; Aculus schlechtendali; Brevipalpus phoenicis; Brevipalpus spp.; Bryobia rubrioculus; Eotetranychus carpini; Eotetranychus spp.; Epitrimerus pyri; Eriophyes piri; Eriophyes spp.; Eriophyes vitis; Eutetranychus africanus; Eutetranychus orientalis; Oligonychus pratensis; Panonychus citri; Panonychus ulmi; Phyllocoptes vitis; Phyllocoptruta oleivora; Polyphagotarsonemus latus; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp.; and Tetranychus urticae. In a further embodiment, a compound of formula (I) are more especially suitable for controlling one or more of: Aceria sheldoni ; Aculus pelekassi; Brevipalpus phoenicis; Brevipalpus spp.; Eriophyes piri; Eriophyes vitis; Eutetranychus africanus; Eutetranychus orientalis; Oligonychus pratensis; Panonychus ulmi; Phyllocoptes vitis; Phyllocoptruta oleivora; Polyphagotarsonemus latus; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp.; and Tetranychus urticae.
The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus. Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as ^-endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid- UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases. In the context of the present invention there are to be understood by ^-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G- recognition sequence is inserted into a Cry3A toxin (see WO 03/018810). Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0374753, WO 93/07278, WO 95/34656, EP-A-0427529, EP-A-451878 and WO 03/052073. The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0367 474, EP-A-0401979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera). Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard^ (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm^ (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink^ (maize variety that expresses a Cry9C toxin); Herculex I^ (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B^ (cotton variety that expresses a Cry1Ac toxin); Bollgard I^ (cotton variety that expresses a Cry1Ac toxin); Bollgard II® (cotton variety that expresses a Cry1Ac and a Cry2Ab toxin); VipCot^ (cotton variety that expresses a Vip3A and a Cry1Ab toxin); NewLeaf^ (potato variety that expresses a Cry3A toxin); NatureGard^, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta^. Further examples of such transgenic crops are: 1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a Cry1Ab toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium. 7. NK603 × MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 × MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer. Transgenic crops of insect-resistant plants are also described in BATS (Zentrum für Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch). The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0392225, WO 95/33818 and EP-A-0353191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Crops may also be modified for enhanced resistance to fungal (for example Fusarium, Anthracnose, or Phytophthora), bacterial (for example Pseudomonas) or viral (for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens. Crops also include those that have enhanced resistance to nematodes, such as the soybean cyst nematode. Crops that are tolerance to abiotic stress include those that have enhanced tolerance to drought, high salt, high temperature, chill, frost, or light radiation, for example through expression of NF-YB or other proteins known in the art. Antipathogenic substances which can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called "pathogenesis-related proteins" (PRPs; see e.g. EP-A-0392225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g. WO 95/33818)
or protein or polypeptide factors involved in plant pathogen defence (so-called "plant disease resistance genes", as described in WO 03/000906). Further areas of use of the compositions according to the invention are the protection of stored goods and store rooms and the protection of raw materials, such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, especially the protection of humans, domestic animals and productive livestock against pests of the mentioned type. The present invention provides a compound of the first aspect for use in therapy. The present invention provides a compound of the first aspect, for use in controlling parasites in or on an animal. The present invention further provides a compound of the first aspect, for use in controlling ectoparasites on an animal. The present invention further provides a compound of the first aspect, for use in preventing and/or treating diseases transmitted by ectoparasites. The present invention provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling ectoparasites on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for preventing and/or treating diseases transmitted by ectoparasites. The present invention provides the use of a compound of the first aspect, in controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect , in controlling ectoparasites on an animal. The term "controlling" when used in context of parasites in or on an animal refers to reducing the number of pests or parasites, eliminating pests or parasites and/or preventing further pest or parasite infestation. The term "treating" when used used in context of parasites in or on an animal refers to restraining, slowing, stopping or reversing the progression or severity of an existing symptom or disease. The term "preventing" when used used in context of parasites in or on an animal refers to the avoidance of a symptom or disease developing in the animal. The term "animal" when used used in context of parasites in or on an animal may refer to a mammal and a non-mammal, such as a bird or fish. In the case of a mammal, it may be a human or non-human mammal. Non-human mammals include, but are not limited to, livestock animals and companion animals. Livestock animals include, but are not limited to, cattle, camellids, pigs, sheep, goats and horses. Companion animals include, but are not limited to, dogs, cats and rabbits. A "parasite" is a pest which lives in or on the host animal and benefits by deriving nutrients at the host animal's expense. An "endoparasite" is a parasite which lives in the host animal. An "ectoparasite" is a
parasite which lives on the host animal. Ectoparasites include, but are not limited to, acari, insects and crustaceans (e.g. sea lice). The Acari (or Acarina) sub-class comprises ticks and mites. Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (Boophilus) microplus and Rhipicephalus sanguineus; Amblyomrna; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, for example Chorioptes bovis; Psoroptes, for example Psoroptes ovis; Cheyletiella; Dermanyssus; for example Dermanyssus gallinae; Ortnithonyssus; Demodex, for example Demodex canis; Sarcoptes, for example Sarcoptes scabiei; and Psorergates. Insects include, but are not limited to, members of the orders: Siphonaptera, Diptera, Phthiraptera, Lepidoptera, Coleoptera and Homoptera. Members of the Siphonaptera order include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis. Members of the Diptera order include, but are not limited to, Musca spp.; bot fly, for example Gasterophilus intestinalis and Oestrus ovis; biting flies; horse flies, for example Haematopota spp. and Tabunus spp.; haematobia, for example haematobia irritans; Stomoxys; Lucilia; midges; and mosquitoes. Members of the Phthiraptera class include, but are not limited to, blood sucking lice and chewing lice, for example Bovicola Ovis and Bovicola Bovis. The term "effective amount" when used used in context of parasites in or on an animal refers to the amount or dose of the compound of the invention, or a salt thereof, which, upon single or multiple dose administration to the animal, provides the desired effect in or on the animal. The effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the parasite to be controlled and the degree of infestation; the specific disease or disorder involved; the degree of or involvement or the severity of the disease or disorder; the response of the individual; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances. The compounds of the invention may be administered to the animal by any route which has the desired effect including, but not limited to topically, orally, parenterally' and subcutaneously. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions and may take the form of a pour-on, spot-on, spray-on, spray race or dip. In the alternative, the compounds of the invention may be administered by means of an ear tag or collar. Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinary acceptable salts, which can be different to agrochemically acceptable salts. Pharmaceutically and veterinary acceptable salts and common methodology for preparing them are well known in the art.
See, for example, Gould, P.L., "Salt selection for basic drugs", International Journal of Pharmaceutics, 33: 201 -217 (1986); Bastin, R.J., et al. "Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities", Organic Process Research and Development, 4: 427-435 (2000); and Berge, S.M., et al., "Pharmaceutical Salts", Journal of Pharmaceutical Sciences, 66: 1-19, (1977). One skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as a salt, such as a hydrochloride salt, using techniques and conditions well known to one of ordinary skill in the art. In addition, one skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as the corresponding free base from the corresponding salt. The present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, an IRS (indoor residual spraying) application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention. In another embodiment, it is contemplated to apply such compositions to a substrate such as non-woven or a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents. In one embodiment, the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate. Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention. By way of example, an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface. In another embodiment, it is contemplated to apply such compositions for residual control of pests on a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents. Substrates including non-woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like. The polyesters are particularly suitable. The methods of textile treatment are known, e.g. WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, WO2006/128870, EP 1724392, WO 2005113886 or WO 2007/090739. Further areas of use of the compositions according to the invention are the field of tree injection/trunk treatment for all ornamental trees as well all sort of fruit and nut trees.
In the field of tree injection/trunk treatment, the compounds according to the present invention are especially suitable against wood-boring insects from the order Lepidoptera as mentioned above and from the order Coleoptera, especially against woodborers listed in the following tables A and B: Table A. Examples of exotic woodborers of economic importance. Family Species Host or Crop Infested Buprestidae Agrilus planipennis Ash Cerambycidae Anoplura glabripennis Hardwoods Xylosandrus crassiusculus Hardwoods Scolytidae X. mutilatus Hardwoods Tomicus piniperda Conifers Table B. Examples of native woodborers of economic importance. Family Species Host or Crop Infested Agrilus anxius Birch Agrilus politus Willow, Maple Agrilus sayi Bayberry, Sweetfern Agrilus vittaticolllis Apple, Pear, Cranberry, Serviceberry, Hawthorn Chrysobothris femorata Apple, Apricot, Beech, Boxelder, Cherry, Chestnut, Currant, Elm, Buprestidae Hawthorn, Hackberry, Hickory, Horsechestnut, Linden, Maple, Mountain-ash, Oak, Pecan, Pear, Peach, Persimmon, Plum, Poplar, Quince, Redbud, Serviceberry, Sycamore, Walnut, Willow Texania campestris Basswood, Beech, Maple, Oak, Sycamore, Willow, Yellow-poplar Goes pulverulentus Beech, Elm, Nuttall, Willow, Black oak, Cherrybark oak, Water oak, Sycamore Goes tigrinus Oak Neoclytus acuminatus Ash, Hickory, Oak, Walnut, Birch, Cerambycidae Beech, Maple, Eastern hophornbeam, Dogwood, Persimmon, Redbud, Holly, Hackberry, Black locust, Honeylocust, Yellow-poplar, Chestnut, Osage-
Family Species Host or Crop Infested orange, Sassafras, Lilac, Mountain- mahogany, Pear, Cherry, Plum, Peach, Apple, Elm, Basswood, Sweetgum Neoptychodes trilineatus Fig, Alder, Mulberry, Willow, Netleaf hackberry Oberea ocellata Sumac, Apple, Peach, Plum, Pear, Currant, Blackberry Oberea tripunctata Dogwood, Viburnum, Elm, Sourwood, Blueberry, Rhododendron, Azalea, Laurel, Poplar, Willow, Mulberry Oncideres cingulata Hickory, Pecan, Persimmon, Elm, Sourwood, Basswood, Honeylocust, Dogwood, Eucalyptus, Oak, Hackberry, Maple, Fruit trees Saperda calcarata Poplar Strophiona nitens Chestnut, Oak, Hickory, Walnut, Beech, Maple Corthylus columbianus Maple, Oak, Yellow-poplar, Beech, Boxelder, Sycamore, Birch, Basswood, Chestnut, Elm Dendroctonus frontalis Pine Dryocoetes betulae Birch, Sweetgum, Wild cherry, Beech, Pear Monarthrum fasciatum Oak, Maple, Birch, Chestnut, Scolytidae Sweetgum, Blackgum, Poplar, Hickory, Mimosa, Apple, Peach, Pine Phloeotribus liminaris Peach, Cherry, Plum, Black cherry, Elm, Mulberry, Mountain-ash Pseudopityophthorus pruinosus Oak, American beech, Black cherry, Chickasaw plum, Chestnut, Maple, Hickory, Hornbeam, Hophornbeam Paranthrene simulans Oak, American chestnut Sannina uroceriformis Persimmon Synanthedon exitiosa Peach, Plum, Nectarine, Cherry, Sesiidae Apricot, Almond, Black cherry Synanthedon pictipes Peach, Plum, Cherry, Beach, Black Cherry
Family Species Host or Crop Infested Synanthedon rubrofascia Tupelo Synanthedon scitula Dogwood, Pecan, Hickory, Oak, Chestnut, Beech, Birch, Black cherry, Elm, Mountain-ash, Viburnum, Willow, Apple, Loquat, Ninebark, Bayberry Vitacea polistiformis Grape The present invention may be also used to control any insect pests that may be present in turfgrass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites, mole crickets, scales, mealybugs, ticks, spittlebugs, southern chinch bugs and white grubs. The present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults. In particular, the present invention may be used to control insect pests that feed on the roots of turfgrass including white grubs (such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica), Phyllophaga spp. (e.g. May/June beetle), Ataenius spp. (e.g. Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g. Asiatic garden beetle, M. castanea) and Tomarus spp.), ground pearls (Margarodes spp.), mole crickets (tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana) and leatherjackets (European crane fly, Tipula spp.). The present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta), cutworms, billbugs (Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis). The present invention may also be used to control insect pests of turfgrass that live above the ground and feed on the turfgrass leaves, including chinch bugs (such as southern chinch bugs, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug (Propsapia bicincta), leafhoppers, cutworms (Noctuidae family), and greenbugs. The present invention may also be used to control other pests of turfgrass such as red imported fire ants (Solenopsis invicta) that create ant mounds in turf. In the hygiene sector, the compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.
Examples of such parasites are: Of the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp.. Of the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp. and Felicola spp.. Of the order Diptera and the suborders Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp. and Melophagus spp.. Of the order Siphonapterida, for example Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp.. Of the order Heteropterida, for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.. Of the order Blattarida, for example Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp.. Of the subclass Acaria (Acarida) and the orders Meta- and Meso-stigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp. and Varroa spp.. Of the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.. The compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and buildings.
The compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec.,Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec. and Dinoderus minutus, and also hymenopterans such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus augur, and termites such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus, and bristletails such as Lepisma saccharina.The compounds of formula I, or salts thereof, are especially suitable for controlling one or more pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-42 and Table P”) controls one or more of pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. The compounds of formula I, or salts thereof, are especially suitable for controlling one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. . In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-42 and Tables P”) controls one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. The compounds of formula I, or salts thereof, are especially suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis incIudens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi, and Chilo suppressalis. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-42 and Table P”) controls one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis incIudens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis, such as Spodoptera littoralis + TX, Plutella xylostella + TX; Frankliniella occidentalis + TX, Thrips tabaci + TX, Euschistus heros + TX, Cydia pomonella + TX, Nilaparvata lugens + TX, Myzus persicae + TX, Chrysodeixis
incIudens + TX, Aphis craccivora + TX, Diabrotica balteata + TX, Rhopalosiphum Padi + TX, and Chilo suppressalis + TX. In an embodiment, of each aspect, one compound from Tables A-1 to A-42 and Table P is suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis incIudens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice and soya crops. In an embodiment, one compound from from Tables A-1 to A-42 and Table P is suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice). The compounds of Formula (I) or salts thereof, are especially suitable for controlling one or more pests selected from order Lepidoptera, especially one or more of the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn), which insect demonstrates resistance against IRAC MoA Group 28 insecticides. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds in Tables A-1 to A-42 and P”) controls one or more of pests selected from the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn), which insect demonstrates resistance against IRAC MoA Group 28 insecticides. The compounds of formula I, or salts thereof, are especially suitable for controlling one or more of the insects having diamide resistance selected from: Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds in Tables A-1 to A-42 and P”) controls one or more of the insects having diamide resistance selected from: Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta. Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).
In particular, it has been surprisingly found that certain compounds of formula (I) may show an advantageous safety profile with respect to non-target arthropods, in particular pollinators such as honey bees, solitary bees, and bumble bees. Most particularly, Apis mellifera. The compounds according to the invention can be used as pesticidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water- dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil- in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water- miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can either be used directly or diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents. The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof. The active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated. The formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane,
cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p- diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4- dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone and the like. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances. A large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface- active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di- alkylphosphate esters; and also further substances described e.g. in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981). Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion
inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers. The compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the mixture to be applied. For example, the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010. The inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance. Whereas commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations. The rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. As a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha. Preferred formulations can have the following compositions (weight %): Emulsifiable concentrates: active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 % Dusts: active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 % Suspension concentrates: active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 %
surface-active agent: 1 to 40 %, preferably 2 to 30 % Wettable powders: active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 % Granules: active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 % The following Examples further illustrate, but do not limit, the invention. Wettable powders a) b) c) active ingredients 25 % 50 % 75 % sodium lignosulfonate 5 % 5 % - sodium lauryl sulfate 3 % - 5 % sodium diisobutylnaphthalenesulfonate - 6 % 10 % phenol polyethylene glycol ether (7-8 mol of ethylene - 2 % - oxide) highly dispersed silicic acid 5 % 10 % 10 % Kaolin 62 % 27 % - The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration. Powders for dry seed treatment a) b) c) active ingredients 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % - Kaolin 65 % 40 % - Talcum - 20 % The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment. Emulsifiable concentrate active ingredients 10 % octylphenol polyethylene glycol ether (4-5 mol of ethylene oxide) 3 % calcium dodecylbenzenesulfonate 3 %
castor oil polyglycol ether (35 mol of ethylene oxide) 4 % Cyclohexanone 30 % xylene mixture 50 % Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water. Dusts a) b) c) Active ingredients 5 % 6 % 4 % Talcum 95 % - - Kaolin - 94 % - mineral filler - - 96 % Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed. Extruder granules Active ingredients 15 % sodium lignosulfonate 2 % carboxymethylcellulose 1 % Kaolin 82 % The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air. Coated granules Active ingredients 8 % polyethylene glycol (mol. wt.200) 3 % Kaolin 89 % The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner. Suspension concentrate active ingredients 40 % propylene glycol 10 % nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 % Sodium lignosulfonate 10 % carboxymethylcellulose 1 % silicone oil (in the form of a 75 % emulsion in water) 1 % Water 32 % The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such
dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Flowable concentrate for seed treatment active ingredients 40 % propylene glycol 5 % copolymer butanol PO/EO 2 % Tristyrenephenole with 10-20 moles EO 2 % 1,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 % monoazo-pigment calcium salt 5 % Silicone oil (in the form of a 75 % emulsion in water) 0.2 % Water 45.3 % The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Slow Release Capsule Suspension 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose. Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo- emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP), a soluble granule (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants. The Examples which follow serve to illustrate the invention.
Examples The compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates, if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm. Compounds of Formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability). Throughout this description, temperatures are given in degrees Celsius (°C) and “mp.” means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus, and the method (Method A) is as follows: Analytical methods Method 1: Spectra were recorded on a Mass Spectrometer from Waters (Acquity QDa Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8 kV, Cone range: 25 V, Extractor: V (No extractor voltage for QDa detector) Source Temperature: 120°C, Desolvation Temperature: 600°C, Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment , diode-array detector. Column: Acquity UPLC HSS T3 C18, 1.8 µm, 30 x 2.1 mm, Temp: 40 °C, DAD Wavelength range (nm): 200 to 400, Solvent Gradient: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.05 % HCOOH: gradient: 0 min 10% B; 0.-0.2 min 10- 50% B; 0.2-0.6 min 50-100% B; 0.6-1.3 min 100% B; 1.3-1.4 min 100-10% B; 1.4-1.6 min 10% B; Flow (mL/min) 0.6. Method 2: Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 l/h, Desolvation Gas Flow: 650-1000 l/h, Mass range: 100 to 900 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment , diode-array detector and ELSD. Column: Waters UPLC HSS T3, 1.8 µm, 30 x 2.1 mm,
Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Runtime: 1.5 min; Solvents: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH; Flow (ml/min) 0.85, Gradient: 10% B isocratic for 0.2 min, then 10-100% B in 1.0 min, 100% B isocratic for 0.2min, 100-10% B in 0.05min, 10% B isocratic for 0.05 min. Method 3: Spectra were recorded on a ACQUITY Mass Spectrometer from Waters Corporations (SQD or SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150°C, Desolvation Temperature: 400°C, Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/hr, Mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters Corporations with solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 µm, 30 x 2.1 mm, Temp: 60°C, DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A = Water/Methanol 9:1 + 0.1% formic acid, B= Acetonitrile + 0.1% formic acid, gradient: 0-100% B in 2.5 min; Flow (ml/min) 0.75. Example 1: This example illustrates the preparation of N-[1-[4-[4-acetyl-5-(3-chlorophenyl)-5- (trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 1 of Table P).
Step 1: Preparation of 4-bromobenzohydrazide
To a stirred solution of methyl 4-bromobenzoate (4.00 g, 18.6 mmol) in ethanol (50 mL) was added hydrazine hydrate (2.71 mL, 55.8 mmol) at RT. The reaction mixture was heated at 85 °C for 16 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with brine. The organic layers were dried over magnesium sulphate and concentrated under reduced pressure to obtain the desired product as a white solid (4.00 g). Mp.245-249 °C. LC-MS (Method 1) Rt = 0.60 min., MS: m/z 215 (M+H)+. Step 2: Preparation of 4-bromo-N-[[1-(3-chlorophenyl)-2,2,2-trifluoro-ethylidene]amino]benzamide
To a stirred solution of crude 4-bromobenzohydrazide (1.00 g, 4.65 mmol) in 1-propanol (20 mL) was added 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone (0.970 g, 4.65 mmol), followed by slow addition of acetic acid (2 mL) at RT. The reaction mixture was heated at 100 °C for 18 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (1.10 g). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.80 – 9.05 (m, 1H), 7.68 – 7.91 (m, 2H), 7.56 – 7.69 (m, 4H), 7.38 – 7.43 (m, 1H), 7.28 – 7.33 (m, 1H). Step 3: Preparation of 1-[5-(4-bromophenyl)-2-(3-chlorophenyl)-2-(trifluoromethyl)-1,3,4-oxadiazol-3- yl]ethanone
A mixture of 4-bromo-N-[[1-(3-chlorophenyl)-2,2,2-trifluoro-ethylidene]amino]benzamide (390 mg, 0.865 mmol) and acetic anhydride (0.829 mL, 8.65 mmol) was heated at 140 °C for 24 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with sodium bicarbonate sat. aq. and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (190 mg). LC-MS (Method 2) Rt = 1.33 min., MS: m/z 406 (M-Ac)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.69 (d, 2H) 7.49 – 7.59 (m, 4H) 7.29 – 7.41 (m, 2H) 2.33 (s, 3H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -75.14 (s, 3F). Step 4: Preparation of 1-[2-(3-chlorophenyl)-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]- 2-(trifluoromethyl)-1,3,4-oxadiazol-3-yl]ethanone
In a microwave vial were added 1-[5-(4-bromophenyl)-2-(3-chlorophenyl)-2-(trifluoromethyl)- 1,3,4-oxadiazol-3-yl]ethanone (100 mg, 0.223 mmol), potassium acetate (67.8 mg, 0.670 mmol), bis(pinacolato)diboron (119 mg, 0.447 mmol) and 1,4-dioxane (2 mL). The reaction mixture was degased with argon for 15 minutes. Then 1,1'-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (18.6 mg, 0.0223 mmol) was added and the reaction mixture was heated in the microwave at 100 °C for 2 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was filtered, washed with ethyl acetate and concentrated under reduced pressure to obtain the desired product (190 mg). LC-MS (Method 2) Rt = 2.57 min., MS: m/z 495 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.78 – 7.85 (m, 4H) 7.46 – 7.64 (m, 2H) 7.24 – 7.45 (m, 2H) 2.34 (s, 3H) 1.16 – 1.23 (m, 12H). Step 5: Preparation of N-[1-[4-[4-acetyl-5-(3-chlorophenyl)-5-(trifluoromethyl)-1,3,4-oxadiazol-2- yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
A mixture of crude 1-[2-(3-chlorophenyl)-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-2-(trifluoromethyl)-1,3,4-oxadiazol-3-yl]ethanone (156 mg, 0.316 mmol), N-(3-methyl-1H- pyrazol-4-yl)-4-(trifluoromethoxy)benzamide (60.0 mg, 0.210 mmol), copper(II) acetate (58.5 mg, 0.316 mmol), boric acid (13.1 mg, 0.210 mmol), pyridine (0.034 mL, 0.421 mmol), molecular sieves 4Ǻ and acetonitrile (0.6 mL) was purged with oxygen for 10 minutes, then stirred under air at 80 °C for 2 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by reverse phase column chromatography to obtain the desired product as a solid (35 mg). Mp. 100-102 °C. LC-MS (Method 2) Rt = 1.25 min., MS: m/z 650 (M-H)-. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 8.66 (s, 1H), 8.49 (s, 1H), 8.04 (d, 2H), 7.95 (d, 2H), 7.77 (d, 2H), 7.71 (s, 1H), 7.67 (d, 1H), 7.47 – 7.57 (m, 2H), 7.43 (d, 2H), 2.33 – 2.39 (m, 6H).
Example 2: This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-2-methyl-5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 3 of Table P).
Step 1: Preparation of 1-4-bromobenzaldehyde oxime To a stirred solution of hydroxylamine hydrochloride (452 mg, 6.38 mmol) and 4- bromobenzaldehyde (1.00 g, 5.40 mmol) in ethanol (20 mL) was added pyridine (1 mL) at RT. The reaction mixture was stirred at RT for 8 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure, diluted in water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by column chromatography to obtain the desired product as a white solid (800 mg). LC-MS (Method 2) Rt = 1.03 min., MS: m/z 200 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.10 (s, 1H) 7.49 – 7.56 (m, 2H) 7.44 – 7.48 (m, 2H). Step 2: Preparation of 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanimine
To a stirred solution of 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone (2.00 g, 9.59 mmol) in methanol (10 mL) was added lithium bis(trimethylsilyl)amide (1.88 g, 10.5 mmol) at RT. The reaction mixture was heated at 80 °C for 48 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure, basified with sodium bicarbonate sat. aq. and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the desired product as a colourless oil (2.50 g). LC-MS (Method 2) Rt = 1.11 min., MS: m/z 208 (M+H)+.
Step 3: Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-4H-1,2,4-oxadiazole
To a stirred solution of 1-4-bromobenzaldehyde oxime (1.00 g, 5.00 mmol) in DMF (5 mL) was added N-chlorosuccinimide (871 mg, 6.00 mmol) at RT. The reaction mixture was heated at 50 °C for 2 hours, then cooled at RT, quenched with water and extracted with dichloromethane (35 mL). The organic layer was dried over sodium sulphate and used directly with a solution of 1-(3-chlorophenyl)- 2,2,2-trifluoro-ethanimine (3.11 g, 15.0 mmol) in diethyl ether (35 mL). The reaction mixture was cooled to 0 °C and then triethylamine (3.50 mL, 25.0 mmol) was added dropwise. The reaction mixture was stirred at RT for 12 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with DCM. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified first by normal phase column chromatography, then by reverse phase column chromatography to obtain the desired product as an off-white solid (2.50 g). LC-MS (Method 2) Rt = 1.22 min., MS: m/z 405 (M+H)+. Step 4: Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-2-methyl-5-(trifluoromethyl)-1,2,4- oxadiazole
To a stirred solution of 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-4H-1,2,4- oxadiazole (700 mg, 1.73 mmol) in DMAc (3 mL) were added cesium carbonate (1.12 g, 3.45 mmol) and iodomethane (1.64 mL, 25.9 mmol) at 0 °C. The reaction mixture was stirred at RT for 3 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by reverse phase column chromatography to obtain the desired product as a white solid (290 mg). LC-MS (Method 2) Rt = 1.96 min., MS: m/z 418 (M-H)-. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.73 – 7.82 (m, 4H) 7.55 – 7.66 (m, 4H) 3.16 (s, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm -80.99 (s, 3F). Step 5: Preparation of N-[1-[4-[5-(3-chlorophenyl)-2-methyl-5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
To a stirred solution of 3-(4-bromophenyl)-5-(3-chlorophenyl)-2-methyl-5-(trifluoromethyl)- 1,2,4-oxadiazole (250 mg, 0.596 mmol) in 1,4-dioxane (20 mL) were added N-(3-methyl-1H-pyrazol-4- yl)-4-(trifluoromethoxy)benzamide (170 mg, 0.596 mmol), cesium carbonate (582 mg, 1.79 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (71.1 mg, 0.119 mmol) at RT. The reaction mixture was degased with argon for 15 minutes. Then tris(dibenzylideneacetone)dipalladium(0) (56.2 mg, 0.059 mmol) was added and the reaction mixture was heated at 100 °C for 8 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with ethyl acetate and filtered over Celite pad. The filtrate was dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product as a white solid (165 mg). LC-MS (Method 2) Rt = 1.33 min., MS: m/z 622 (M-H)-. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.15 (s, 1H) 8.84 (s, 1H) 8.10 (d, J=7.91 Hz, 2H) 8.01 (m, J=8.88 Hz, 2H) 7.92 (m, J=8.88 Hz, 2H) 7.64 – 7.68 (m, 2H) 7.53 – 7.64 (m, 4H) 3.21 (s, 3H) 2.34 (s, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm -56.67 (s, 3F) -80.61 (s, 3F). Example 3: This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(difluoromethyl)- 4H-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 4 of Table P).
Step 1: Preparation of 4-(3-methyl-4-nitro-pyrazol-1-yl)benzonitrile
To a stirred solution of 3-methyl-4-nitro-1H-pyrazole (5.00 g, 39.3 mmol) in DMSO (28 mL) was added potassium tert-butoxide (4.82 g, 42.1 mmol) at RT. The reaction mixture was stirred at RT for 15 minutes. Then 4-fluorobenzonitrile (5.00 g, 41.3 mmol) was added and it was heated at 120 °C for 30
minutes. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (5.70 g). LC-MS (Method 1) Rt = 0.92 min., MS: m/z 229 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.71 (s, 1 H) 7.85 - 7.90 (m, 2 H) 7.81 - 7.85 (m, 2 H) 2.66 (s, 3 H). Step 2: Preparation of 4-(4-amino-3-methyl-pyrazol-1-yl)benzonitrile
To a stirred solution of 4-(3-methyl-4-nitro-pyrazol-1-yl)benzonitrile (5.30 g, 23.2 mmol) in ethanol (230 mL) was added carefully concentrated hydrochloric acid (42.3 mL, 511 mmol), followed by portionwise addition of iron (7.63 g, 116 mmol) at RT. The reaction mixture was heated at 70 °C for 4 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was filtered over Celite pad and washed with ethyl acetate. The filtrate was carefully neutralized with sodium bicarbonate sat. aq. It was then extracted with ethyl acetate and washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (3.80 g). LC-MS (Method 1) Rt = 0.50 min., MS: m/z 199 (M+H)+. Step 3: Preparation of N-[1-(4-cyanophenyl)-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
To a stirred solution of 4-(4-amino-3-methyl-pyrazol-1-yl)benzonitrile (3.80 g, 19.2 mmol) in ethyl acetate (115 mL) were added 4-(trifluoromethoxy)benzoic acid (4.35 g, 21.1 mmol), N,N- diisopropylethylamine (10.0 mL, 57.5 mmol) and 1-propanephosphonic anhydride (50% solution in ethyl acetate, 34.9 mL, 57.5 mmol) at RT. The reaction mixture was stirred at RT for 1 hour. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with sodium bicarbonate sat. aq. and extracted with ethyl acetate. The organic layers were washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (4.20 g). LC-MS (Method 1) Rt = 1.05 min., MS: m/z 387 (M+H)+.
1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.70 (s, 1 H) 7.89 - 8.01 (m, 2 H) 7.78 - 7.85 (m, 2 H) 7.68 - 7.78 (m, 2 H) 7.55 (s, 1 H) 7.32 - 7.42 (m, 2 H) 2.42 (s, 3 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -57.70 (s, 3 F). Step 4: Preparation of N-[1-[4-[N'-hydroxycarbamimidoyl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide
To a stirred solution of N-[1-(4-cyanophenyl)-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide (4.20 g, 10.9 mmol) in ethanol (44 mL) were added triethylamine (3.05 mL, 21.7 mmol) and hydroxylamine hydrochloride (1.51 g, 21.7 mmol) at RT. The reaction mixture was heated at 80 °C for 2 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (3.90 g). LC-MS (Method 1) Rt = 0.76 min., MS: m/z 420 (M+H)+. 1H NMR (400 MHz, MeOD) δ ppm 8.53 (s, 1 H) 8.02 - 8.12 (m, 2 H) 7.76 (s, 4 H) 7.43 (d, J=8.36 Hz, 2 H) 2.37 (s, 3 H). 19F NMR (377 MHz, MeOD) δ ppm -59.35 (s, 3 F). Step 5: Preparation of N-[1-[4-[5-(difluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide
To a stirred solution of N-[1-[4-[N'-hydroxycarbamimidoyl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide (200 mg, 0.477 mmol) in 2-methyltetrahydrofuran (2.4 mL) was added dropwise difluoroacetic anhydride (0.092 mL, 0.715 mmol) at RT. The reaction mixture was stirred at RT overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was extracted with ethyl acetate and washed with sodium bicarbonate sat. aq. and brine. The organic layers
were dried over sodium sulphate and concentrated under reduced pressure to obtain the desired product as a white solid (230 mg). LC-MS (Method 1) Rt = 1.13 min., MS: m/z 480 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.05 - 10.18 (m, 1 H) 8.73 - 8.88 (m, 1 H) 8.01 - 8.27 (m, 6 H) 7.50 - 7.64 (m, 1 H) 7.38 - 7.72 (m, 2 H) 2.28 - 2.41 (m, 3 H). 19F NMR (377 MHz, DMSO-d6) δ ppm -56.64 (s, 1 F) -121.68 (s, 1 F). Step 6: Preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(difluoromethyl)-4H-1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
To a stirred solution of 1-bromo-3-chlorobenzene (0.044 mL, 0.376 mmol) in 2- methyltetrahydrofuran (1 mL) was added dropwise n-butyllithium (1.6M in hexane, 0.230 mL, 0.376 mmol) at -78 °C. The reaction mixture was stirred at -78 °C for 30 minutes. Then a solution of N-[1-[4- [5-(difluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (100 mg, 0.209 mmol) in 2-methyltetrahydrofuran (1 mL) was added dropwise at -78 °C. The reaction mixture was stirred at -78 °C for 30 minutes, then allowed to reach RT and stirred for additional 2 hours. Another additional solution of 1-bromo-3-chlorobenzene (0.088 mL, 0.752 mmol) in 2- methyltetrahydrofuran (2 mL) was prepared and additional n-butyllithium (1.6M in hexane, 0.460 mL, 0.752 mmol) was added at -78 °C. This solution was then added dropwise to the initial reaction mixture at -78 °C. The reaction mixture was stirred at RT for 5 minutes. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (72 mg). LC-MS (Method 1) Rt = 1.17 min., MS: m/z 592 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.98 - 10.19 (m, 1 H) 8.85 - 8.99 (m, 1 H) 8.73 - 8.83 (m, 1 H) 8.06 - 8.19 (m, 2 H) 7.93 - 8.02 (m, 2 H) 7.83 - 7.91 (m, 2 H) 7.65 - 7.73 (m, 1 H) 7.58 - 7.63 (m, 1 H) 7.52 - 7.58 (m, 4 H) 6.30 - 6.75 (m, 1 H) 2.30 - 2.39 (m, 3 H). 19F NMR (377 MHz, DMSO-d6) δ ppm -56.65 (s, 3 F) -132.22 (br d, J=162.67 Hz, 2 F). Example 4: This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)- 1,4,2-dioxazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 9 of Table P).
Step 1: Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-1,4,2-dioxazole
To a stirred solution of 1-4-bromobenzaldehyde oxime (300 mg, 1.50 mmol) in DMF (5 mL) was added N-chlorosuccinimide (218 mg, 1.50 mmol) at RT. The reaction mixture was heated at 55 °C for 1 hour. Then 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone (313 mg, 1.50 mmol) and sodium bicarbonate (140 mg, 1.50 mmol) were added to the reaction mixture. It was stirred at 55 °C for additional 3 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified first by normal phase column chromatography, then by reverse phase column chromatography to obtain the desired product as a colorless oil (400 mg). LC-MS (Method 2) Rt = 1.42 min., no mass. Step 2: Preparation of 5-(3-chlorophenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5- (trifluoromethyl)-1,4,2-dioxazole
In a microwave vial were added 3-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)- 1,4,2-dioxazole (200 mg, 0.492 mmol), potassium acetate (96.6 mg, 0.984 mmol), bis(pinacolato)diboron (151 mg, 0.590 mmol) and 1,4-dioxane (4 mL). The reaction mixture was degased with nitrogen for 10 minutes. Then 1,1'-bis(diphenylphosphino)ferrocene- palladium(ii)dichloride dichloromethane complex (41.0 mg, 0.0492 mmol) was added and the reaction mixture was heated in the microwave at 100 °C for 1.5 hours. The progress of the reaction was
monitored by LCMS analysis. The reaction mixture was filtered on Celite pad, washed with ethyl acetate and concentrated under reduced pressure to obtain the desired product (200 mg). LC-MS (Method 2) Rt = 1.56 min., no mass. Step 3: Preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)-1,4,2-dioxazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
A mixture of crude 5-(3-chlorophenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1,4,2-dioxazole (190 mg, 0.420 mmol), N-(3-methyl-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide (80.0 mg, 0.280 mmol), copper(II) acetate (78.0 mg, 0.420 mmol), boric acid (37.0 mg, 0.560 mmol), pyridine (0.046 mL, 0.560 mmol), molecular sieves 4Ǻ and acetonitrile (15 mL) was purged with oxygen for 10 minutes, then stirred under air at 90 °C for 8 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was filtered over Celite pad and concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by reverse phase column chromatography to obtain the desired product as a sticky solid (15 mg). LC-MS (Method 2) Rt = 1.39 min., MS: m/z 611 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.15 (s, 1 H) 8.86 (s, 1 H) 8.10 (d, J=8.80 Hz, 2 H) 7.99 - 8.07 (m, 4 H) 7.84 (s, 1 H) 7.72 - 7.78 (m, 2 H) 7.62 - 7.70 (m, 1 H) 7.56 (br d, J=8.07 Hz, 2 H) 2.34 (s, 3 H). 19F NMR (377 MHz, DMSO-d6) δ ppm -56.90 (s, 3F) -82.91 (s, 3F). Example 5: This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-4-oxo-5- (trifluoromethyl)-1H-imidazol-2-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 10 of Table P).
Step 1: Preparation of 3-(3-chlorophenyl)-1,1,1-trifluoro-propan-2-one
To a stirred solution of N-isopropylpropan-2-amine (9.14 mL, 64.2 mmol) in dry THF (73 mL) was added n-butyllithium (2M in cyclohexane, 32.0 mL, 64.2 mmol) at -65 °C. To this solution was added a solution of 2-(3-chlorophenyl)acetic acid (5.00 g, 29.3 mmol) in dry THF (16 mL) at -65 °C. The reaction mixture was allowed to reach RT and stirred for 2 hours. It was then cooled again to -65 °C and ethyl 2,2,2,-trifluoroacetate (8.02 mL, 67.4 mmol) was added dropwise over 15 minutes. The reaction mixture was stirred at -65 °C for 15 minutes, then at RT for 30 minutes. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with 2N HCl at -65 °C and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product as a light brown liquid (1.99 g). LC-MS (Method 2) Rt = 1.05 min., MS: m/z 221 (M-H)-. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.32 – 7.37 (m, 2H) 7.28 (m, 1H) 7.10 – 7.15 (m, 1H) 4.02 (s, 2H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -78.20 (s, 3F). Step 2: Preparation of 2-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-1H-imidazol-4-one
To a stirred solution of 3-(3-chlorophenyl)-1,1,1-trifluoro-propan-2-one (661 mg, 2.97 mmol) in dry DMF (18 mL) were added 4-bromobenzamidine hydrochloride (350 mg, 1.49 mmol) and potassium carbonate (430 mg, 3.72 mmol) at RT. The reaction mixture was heated at 70 °C for 12 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with sodium bicarbonate sat. aq. and cold water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product as a white solid (280 mg). LC-MS (Method 2) Rt = 1.22 min., MS: m/z 417 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.63 (br s, 1H) 8.07 (d, J=8.63 Hz, 2H) 7.82 – 7.90 (m, 4H) 7.53 – 7.63 (m, 2H). 19F NMR (377 MHz, DMSO-d6) δ ppm -73.68 (s, 3F). Step 3: Preparation of 5-(3-chlorophenyl)-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5- (trifluoromethyl)-1H-imidazol-4-one
In a microwave vial were added 2-(4-bromophenyl)-5-(3-chlorophenyl)-5-(trifluoromethyl)-1H- imidazol-4-one (100 mg, 0.239 mmol), potassium acetate (47.0 mg, 0.479 mmol), bis(pinacolato)diboron (123 mg, 0.479 mmol) and toluene (2 mL). The reaction mixture was degased with nitrogen for 10 minutes. Then 1,1'-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (10.0 mg, 0.0120 mmol) was added and the reaction mixture was heated in the microwave at 100 °C for 1.5 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was filtered on Celite pad, washed with ethyl acetate and concentrated under reduced pressure to obtain the desired product (50 mg). LC-MS (Method 2) Rt = 1.33 min., MS: m/z 465 (M+H)+. Step 4: Preparation of N-[1-[4-[5-(3-chlorophenyl)-4-oxo-5-(trifluoromethyl)-1H-imidazol-2-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
A mixture of crude 5-(3-chlorophenyl)-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1H-imidazol-4-one (150 mg, 0.307 mmol), N-(3-methyl-1H-pyrazol-4-yl)- 4-(trifluoromethoxy)benzamide (110 mg, 0.368 mmol), copper(II) acetate (85.3 mg, 0.460 mmol), boric acid (39.9 mg, 0.613 mmol), pyridine (0.050 mL, 0.613 mmol), molecular sieves 4Ǻ and acetonitrile (27 mL) was purged with oxygen for 10 minutes, then stirred under air at 90 °C for 8 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was filtered over Celite pad. The filtrate was diluted with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product as a light yellow solid (5 mg). LC-MS (Method 2) Rt = 1.22 min., MS: m/z 622 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.14 – 8.20 (m, 2H) 8.06 (br d, 2H) 8.01 (s, 2H) 7.96 (br s, 2H) 7.55 – 7.68 (m, 3H) 7.34 – 7.47 (m, 4H) 2.41 (s, 3H).
Example 6: This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-4-cyclopropyl-5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 11 of Table P).
Step 1: Preparation of 1-4-bromo-N-hydroxy-benzimidoyl chloride
To a stirred solution of 4-bromobenzaldehyde oxime (2.00 g, 9.49 mmol) in acetonitrile (19 mL) was added N-chlorosuccinimide (1.68 g, 12.3 mmol) at RT. The reaction mixture was stirred at RT for 2 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (2.11 g). LC-MS (Method 1) Rt = 0.93-0.97 min., MS: m/z 234 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.67 - 7.79 (m, 3 H) 7.52 - 7.59 (m, 2 H). Step 2: Preparation of 1-(3-chlorophenyl)-N-cyclopropyl-2,2,2-trifluoro-ethanimine
To a stirred solution of 1-(3-chlorophenyl)-2,2,2-trifluoro-ethanone (1.50 g, 7.20 mmol) in toluene (22 mL) were added cyclopropanamine (2.00 mL, 29.0 mmol) and p-toluenesulfonic acid (0.760 g, 4.30 mmol) at RT. The reaction mixture was heated at 80 °C overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (1.25 g). LC-MS (Method 1) Rt = 1.17 min., MS: m/z 248 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.42 - 7.51 (m, 2 H) 7.39 (s, 1 H) 7.25 - 7.29 (m, 1 H) 2.91 (tt, J=6.63, 3.18 Hz, 1 H) 1.12 - 1.17 (m, 2 H) 0.98 - 1.04 (m, 2 H).
Step 3: Preparation of 3-(4-bromophenyl)-5-(3-chlorophenyl)-4-cyclopropyl-5-(trifluoromethyl)-1,2,4- oxadiazole
To a stirred solution of 1-(3-chlorophenyl)-N-cyclopropyl-2,2,2-trifluoro-ethanimine (500 mg, 2.02 mmol) in 2-methyltetrahydrofuran (8 mL) was added 1-4-bromo-N-hydroxy-benzimidoyl chloride (260 mg, 1.11 mmol) at RT. The reaction mixture was heated at 50 °C and then a solution of N,N- diisopropylethylamine (0.350 mL, 2.02 mmol) in 2-methyltetrahydrofuran (8 mL) was added dropwise. The reaction mixture was heated at 80 °C for 2 hours. Then it was cooled back to 50 °C and 1-4-bromo- N-hydroxy-benzimidoyl chloride (260 mg, 1.11 mmol) and N,N-diisopropylethylamine (0.350 mL, 2.02 mmol) were added again. The reaction mixture was heated at 80 °C overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified first by normal phase column chromatography, then by reverse phase column chromatography to obtain the desired product as a white solid (130 mg). LC-MS (Method 1) Rt = 1.29 min., MS: m/z 445 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.78 (s, 1 H) 7.58 - 7.69 (m, 3 H) 7.40 - 7.52 (m, 4 H) 2.23 - 2.30 (m, 1 H) 0.36 - 0.48 (m, 3 H) 0.08 - 0.21 (m, 1 H). Step 4: Preparation of 5-(3-chlorophenyl)-4-cyclopropyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole
To a stirred solution of 3-(4-bromophenyl)-5-(3-chlorophenyl)-4-cyclopropyl-5-(trifluoromethyl)- 1,2,4-oxadiazole (30 mg, 0.067 mmol) in DMSO (0.4 mL) were added under argon bis(pinacolato)diboron (51 mg, 0.20 mmol), potassium acetate (20 mg, 0.20 mmol) and bis(triphenylphosphine)palladium chloride (4.7 mg, 0.0067 mmol) at RT. The reaction mixture was heated at 80 °C for 2 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (16 mg). LC-MS (Method 1) Rt = 1.37 min., MS: m/z 493 (M+H)+.
Step 5: Preparation of N-[1-[4-[5-(3-chlorophenyl)-4-cyclopropyl-5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
A mixture of 5-(3-chlorophenyl)-4-cyclopropyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (16 mg, 0.032 mmol), N-(3-methyl-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide (10 mg, 0.036 mmol), copper(II) acetate (8.8 mg, 0.049 mmol), pyridine (0.011 mL, 0.13 mmol) and DMSO (0.20 mL) was stirred under air at 80 °C overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were washed with water, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified first by normal phase column chromatography, then by reverse phase column chromatography to obtain the desired product as a light yellow solid (5 mg). LC-MS (Method 1) Rt = 1.30 min., MS: m/z 650 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.69 (s, 1 H) 7.95 (d, J=8.72 Hz, 2 H) 7.77 - 7.83 (m, 3 H) 7.66 - 7.72 (m, 3 H) 7.36 - 7.55 (m, 5 H) 2.43 (s, 3 H) 2.30 (br d, J=9.45 Hz, 1 H) 0.34 - 0.50 (m, 3 H) 0.11 - 0.20 (m, 1 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -57.70 (s, 3 F) -78.02 (s, 3 F). Example 7: This example illustrates the preparation of 4-[5-butyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol- 3-yl]-2-fluoro-N-[4-(trifluoromethyl)phenyl]benzamide (Compound 14 of Table P).
Step 1: Preparation of 2-fluoro-4-(N'-hydroxycarbamimidoyl)benzoic acid
To a stirred solution of 4-cyano-2-fluoro-benzoic acid (25.0 g, 151 mmol) in ethanol (251 mL) was added a solution of hydroxylamine hydrochloride (21.3 g, 303 mmol) in water (150 mL) at RT,
followed by dropwise addition of a solution of potassium carbonate (33.5 g, 242 mmol) in water (365 mL) at RT. Then 8-hydroxyquinoline (289 mg, 1.97 mmol) was added to the reaction mixture at RT and it was heated at 80 °C for 3.5 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure to remove ethanol. The remaining mixture was acidified with 2N HCl until pH reached 3. The resulting suspension was filtered, washed with water and dried in vacuum oven to obtain the desired product as a yellow-green solid (22.3 g). Mp. > 250 °C. LC-MS (Method 1) Rt = 0.19 min., MS: m/z 199 (M+H)+. Step 2: Preparation of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid
To a stirred suspension of 2-fluoro-4-(N'-hydroxycarbamimidoyl)benzoic acid (22.3 g, 112 mmol) in THF (420 mL) was added dropwise trifluoroacetic anhydride (23.8 mL, 169 mmol) at 5 °C. The reaction mixture was stirred at RT overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure. The crude material was stirred in heptane with a small amount of diethyl ether and the resulting residue was filtered and washed with more heptane to obtain the desired product as a beige solid (21.8 g). Mp.158-160 °C. LC-MS (Method 1) Rt = 0.92 min., MS: m/z 277 (M+H)+. Step 3: Preparation of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzamide
To a stirred suspension of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid (334 mg, 1.21 mmol) in ethyl acetate (8 mL) were added 4-(trifluoromethyl)aniline (0.182 mL, 1.45 mmol), pyridine (0.294 mL, 3.63 mmol) and 1-propanephosphonic anhydride (50% solution in ethyl acetate, 2.17 mL, 3.63 mmol) at RT. The reaction mixture was stirred at RT overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (128 mg). LC-MS (Method 1) Rt = 1.18 min., MS: m/z 420 (M+H)+.
1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.59 (br d, J=15.62 Hz, 1 H) 8.37 (t, J=7.99 Hz, 1 H) 8.13 (dd, J=8.17, 1.63 Hz, 1 H) 8.01 (dd, J=12.35, 1.45 Hz, 1 H) 7.83 (d, J=8.36 Hz, 2 H) 7.65 - 7.75 (m, 2 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -62.23 (s, 3 F) -65.27 (s, 3 F) -111.38 (s, 1 F). Step 4: Preparation of 4-[5-butyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]-2-fluoro-N-[4- (trifluoromethyl)phenyl]benzamide
To a stirred solution of n-butyllithium (1.6M in hexane, 0.21 mL, 0.33 mmol) in THF (1.2 mL) was added a solution of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzamide (55 mg, 0.13 mmol) in THF (1.2 mL) at -78 °C. The reaction mixture was stirred at -78 °C for 15 minutes. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (15 mg). LC-MS (Method 1) Rt = 1.18 min., MS: m/z 478 (M+H)+. 1H NMR (400 MHz, MeOD) δ ppm 7.93 (br d, J=8.72 Hz, 2H) 7.83 - 7.90 (m, 1H) 7.65 - 7.70 (m, 3H) 7.61 (dd, J=10.90, 1.45 Hz, 1H) 2.01 (br t, J=7.45 Hz, 2H) 1.38 - 1.52 (m, 4H) 0.96 - 1.01 (m, 3H). Example 8: This example illustrates the preparation of 5-butyl-3-[4-[1-[4-(trifluoromethoxy)phenyl]- 1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)-4H-1,2,4-oxadiazole (Compound 15 of Table P).
To a stirred solution of 1-iodo-4-(trifluoromethoxy)benzene (1.643 mL, 10.4 mmol) and 3- bromo-1H-1,2,4-triazole (3.08 g, 20.8 mmol) in DMSO (5 mL) were added caesium carbonate (6.79 g, 20.8 mmol) and copper(I) iodide (397 mg, 2.08 mmol) at RT. The reaction mixture was heated at 110 °C for 20 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with ammonium chloride sat. aq., diluted with ethyl acetate and filtered over Celite pad. The filtrate was washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (1.40 g). LC-MS (Method 1) Rt = 1.02 min., MS: m/z 308 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.43 (s, 1 H) 7.67 - 7.74 (m, 2 H) 7.38 (d, J=7.99 Hz, 2 H). Step 2: Preparation of 4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzonitrile
To a stirred solution of 3-bromo-1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazole (400 mg, 1.30 mmol) in acetonitrile (3.9 mL) and water (0.39 mL) were added potassium phosphate tribasic (562 mg, 2.60 mmol and 4-cyanophenylboronic acid (191 mg, 1.30 mmol) at RT. The reaction mixture was degassed with argon for 10 minutes and then XPhos Pd G4 (58.8 mg, 0.0649 mmol) was added. The reaction mixture was heated at 80 °C for 3 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (280 mg). LC-MS (Method 1) Rt = 1.08 min., MS: m/z 331 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.61 (s, 1 H) 8.30 - 8.35 (m, 2 H) 7.76 - 7.84 (m, 4 H) 7.42 (d, J=8.36 Hz, 2 H). Step 3: Preparation of N'-hydroxy-4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzamidine
To a stirred solution of 4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzonitrile (280 mg, 0.848 mmol) in ethanol (2.9 mL) and water (0.98 mL) were added hydroxylamine hydrochloride (119 mg, 1.70 mmol) and triethylamine (0.237 mL, 1.70 mmol) at RT. The reaction mixture was heated at 80 °C for 3 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (270 mg). LC-MS (Method 1) Rt = 0.73 min., MS: m/z 364 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.75 (s, 1 H) 9.40 - 9.44 (m, 1 H) 8.06 - 8.12 (m, 4 H) 7.80 - 7.85 (m, 2 H) 7.63 (d, J=8.36 Hz, 2 H) 5.87 (s, 2 H). Step 4: Preparation of 3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)- 1,2,4-oxadiazole
To a stirred solution of N'-hydroxy-4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3- yl]benzamidine (220 mg, 0.606 mmol) in tetrahydrofuran (2.4 mL) was added trifluoroacetic anhydride (0.128 mL, 0.908 mmol) at RT. The reaction mixture was stirred at RT for 20 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with ethyl acetate and neutralized with sodium bicarbonate sat. aq. The organic layers were washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (245 mg). LC-MS (Method 1) Rt = 1.27 min., MS: m/z 442 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.48 (s, 1 H) 8.29 - 8.40 (m, 2 H) 8.19 - 8.28 (m, 2 H) 8.05 - 8.15 (m, 2 H) 7.64 (d, J=8.36 Hz, 2 H). 19F NMR (377 MHz, DMSO-d6) δ ppm -56.95 (s, 3 F) -64.71 (s, 3 F). Step 5: Preparation of 5-butyl-3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5- (trifluoromethyl)-4H-1,2,4-oxadiazole
To a stirred solution of 3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5- (trifluoromethyl)-1,2,4-oxadiazole (50.0 mg, 0.113 mmol) in tetrahydrofuran (1 mL) was added dropwise n-butyllithium (1.6M in hexane, 0.250 mL, 0.397 mmol) at -78 °C. The reaction mixture was stirred at - 78 °C for 30 minutes, then allowed to reach RT and stirred for 1 hour. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate. The organic layers were washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (6.5 mg). LC-MS (Method 1) Rt = 1.22 min., MS: m/z 500 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.56 - 8.64 (m, 1 H) 8.22 - 8.36 (m, 2 H) 7.73 - 7.91 (m, 4 H) 7.41 (d, J=8.36 Hz, 2 H) 4.81 (s, 1 H) 2.05 - 2.16 (m, 1 H) 1.91 - 2.05 (m, 1 H) 1.50 - 1.74 (m, 2 H) 1.38 - 1.50 (m, 2 H) 0.90 - 1.01 (m, 3 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -57.82 (s, 3 F) -85.40 (s, 3 F). Example 9: This example illustrates the preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)- 4H-1,2,4-oxadiazol-3-yl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (Compound 18 of Table P). CSDN385115
Step 1: Preparation of N-[3-methyl-1-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]pyrazol-4-yl]-4- (trifluoromethoxy)benzamide
To a stirred suspension of N-[1-[4-[N'-hydroxycarbamimidoyl]phenyl]-3-methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide (306 mg, 0.730 mmol) in 2-methyltetrahydrofuran (4 mL) was added trifluoroacetic anhydride (0.154 mL, 1.09 mmol) at RT. The reaction mixture was stirred at RT overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was extracted with ethyl acetate and washed with sodium bicarbonate sat. aq. and water. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (330 mg). LC-MS (Method 1) Rt = 1.24 min., MS: m/z 498 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.74 (s, 1 H) 8.18 - 8.24 (m, 2 H) 7.93 - 7.98 (m, 2 H) 7.86 - 7.91 (m, 2 H) 7.47 - 7.52 (m, 1 H) 7.38 (d, J=7.99 Hz, 2 H) 2.44 (s, 3 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -57.70 (s, 3 F) -65.36 (s, 3 F). Step 2: Preparation of N-[1-[4-[5-(3-chlorophenyl)-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide
To a stirred solution of 1-bromo-3-chlorobenzene (0.170 mL, 1.45 mmol) in tetrahydrofuran (4 mL) was added dropwise n-butyllithium (1.6M in hexane, 0.900 mL, 1.45 mmol) at -78 °C. The reaction mixture was stirred at -78 °C for 30 minutes, then a solution of N-[3-methyl-1-[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]phenyl]pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (400 mg, 0.804 mmol) in tetrahydrofuran (4 mL) was added dropwise.The reaction mixture was stirred at -78 °C for 30 minutes, then allowed to reach RT and stirred for 1 hour. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (258 mg). LC-MS (Method 1) Rt = 1.21 min., MS: m/z 610 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.06 - 10.13 (m, 1 H) 9.36 (s, 1 H) 8.80 (s, 1 H) 8.09 (s, 2 H) 7.98 (s, 2 H) 7.88 (d, J=9.08 Hz, 2 H) 7.70 - 7.76 (m, 1 H) 7.51 - 7.68 (m, 5 H) 2.28 - 2.40 (m, 3 H). 19F NMR (377 MHz, DMSO-d6) δ ppm -56.65 (s, 3 F) -82.07 (s, 3 F). Example 10: This example illustrates the preparation of 5-(3-chlorophenyl)-3-[4-[1-[4- (trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)-4H-1,2,4-oxadiazole (Compound 19 of Table P).
To a stirred solution of 1-bromo-3-chlorobenzene (0.020 mL, 0.170 mmol) in tetrahydrofuran (0.4 mL) was added dropwise n-butyllithium (1.6M in hexane, 0.110 mL, 0.170 mmol) at -78 °C. The reaction mixture was stirred at -78 °C for 30 minutes, then a solution of 3-[4-[1-[4- (trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole (50.0 mg, 0.113 mmol) in tetrahydrofuran (0.4 mL) was added dropwise.The reaction mixture was stirred at -78 °C for 30 minutes, then allowed to reach RT and stirred for 1 hour. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with ammonium chloride sat. aq. and extracted with ethyl acetate. The organic layers were washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (8 mg). LC-MS (Method 1) Rt = 1.26 min., MS: m/z 554 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.59 (s, 1 H) 8.21 - 8.36 (m, 2 H) 7.79 - 7.88 (m, 4 H) 7.69 (s, 1 H) 7.58 (d, J=7.27 Hz, 1 H) 7.39 - 7.49 (m, 4 H) 5.25 (s, 1 H). 19F NMR (377 MHz, DMSO-d6) δ ppm -57.83 (s, 3 F) -82.72 (s, 3 F). Example 11: This example illustrates the preparation of 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H- 1,2,4-oxadiazol-3-yl]-N-[4-(trifluoromethyl)phenyl]benzamide (Compound 24 of Table P).
Step 1: Preparation of tert-butyl 2-fluoro-4-[N'-hydroxycarbamimidoyl]benzoate
To a stirred solution of tert-butyl 4-cyano-2-fluorobenzoate (2.00 g, 8.59 mmol) in ethanol (30 mL) were added hydroxylamine hydrochloride (1.19 g, 17.2 mmol) and triethylamine (2.39 mL, 17.2 mmol) at RT. The reaction mixture was heated at 80 °C for 1 hour. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (2.18 g).
LC-MS (Method 1) Rt = 0.82 min., MS: m/z 255 (M+H)+. Step 2: Preparation of tert-butyl 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoate
To a stirred solution of tert-butyl 2-fluoro-4-[N'-hydroxycarbamimidoyl]benzoate (2.18 g, 8.57 mmol) in tetrahydrofuran (28 mL) was added dropwise trifluoroacetic anhydride (1.82 mL, 12.9 mmol) at RT. The reaction mixture was stirred at RT overnight. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with ethyl acetate and neutralized with sodium bicarbonate sat. aq. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (2.71 g). LC-MS (Method 1) Rt = 1.27 min., no mass. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.97 - 8.05 (m, 1 H) 7.95 (dd, J=8.07, 1.47 Hz, 1 H) 7.89 (dd, J=10.64, 1.47 Hz, 1 H) 1.63 (s, 9 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm -65.30 (s, 3 F) -108.03 (s, 1 F) Step 3: Preparation of tert-butyl 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3- yl]benzoate
To a stirred solution of tert-butyl 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoate (1.00 g, 3.01 mmol) in tetrahydrofuran (20 mL) was added dropwise isopropylmagnesium chloride lithium chloride (1.3M in THF, 4.6 mL, 6.02 mmol) at RT. The reaction mixture was stirred at RT for 6 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and diluted with ethyl acetate and ammonium chloride (5M aq.). It was then extracted with more ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (700 mg). LC-MS (Method 1) Rt = 1.19 min., MS: m/z 377 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.90 - 7.95 (m, 1 H) 7.47 - 7.54 (m, 1 H) 7.45 (dd, J=10.82, 1.65 Hz, 1 H) 4.79 (s, 1 H) 2.42 (d, J=6.97 Hz, 1 H) 1.61 (s, 9 H) 1.08 - 1.17 (m, 6 H). Step 4: Preparation of 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]benzoic acid
A mixture of tert-butyl 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3- yl]benzoate (700 mg, 1.86 mmol) and hydrochloric acid (4M in 1,4-dioxane, 4.70 mL, 18.6 mmol) was heated at 60 °C for 3 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (410 mg). LC-MS (Method 1) Rt = 0.91 min., MS: m/z 321 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.51 (br s, 1H), 8.58 (s, 1H), 7.98 (t, J=7.9 Hz, 1H), 7.60-7.69 (m, 2H), 2.24-2.35 (m, 1H), 1.06 (d, J=6.6 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm -79.95 (s, 3F), -109.47 (s, 1F). Step 5: Preparation of 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzamide
To a stirred suspension of 4-(trifluoromethyl)aniline (0.024 mL, 0.187 mmol) in ethyl acetate (1 mL) were added 2-fluoro-4-[5-isopropyl-5-(trifluoromethyl)-4H-1,2,4-oxadiazol-3-yl]benzoic acid (50 mg, 0.156 mmol), 1-propanephosphonic anhydride (50% solution in ethyl acetate, 0.279 mL, 0.469 mmol) and pyridine (0.038 mL, 0.469 mmol) at RT. The reaction mixture was stirred at RT for 18 hours. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by normal phase column chromatography to obtain the desired product (60 mg). LC-MS (Method 1) Rt = 1.16 min., MS: m/z 464 (M+H)+. 1H NMR (400 MHz, MeOD) δ ppm 7.91 (d, J=8.4 Hz, 2H), 7.80-7.87 (m, 1H), 7.65-7.70 (m, 3H), 7.62 (dd, J=11.0, 1.5 Hz, 1H), 2.36 (quin, J=6.8 Hz, 1H), 1.07-1.14 (m, 6H). 19F NMR (377 MHz, MeOD) δ ppm -63.68 (s, 3F), -82.44 (s, 3F), -114.68 (s, 1F).
Table P of prepared compounds: Entr IUPAC name Molecule RT [M+H] Metho y (min (measured d ) ) P1 N-[1-[4-[4-acetyl-5-(3- 1.25 650.1 (M-H) 1 chlorophenyl)-5- (trifluoromethyl)-1,3,4-oxadiazol- 2-yl]phenyl]-3-methyl-pyrazol-4- yl]-4- (trifluoromethoxy)benzamide P2 N-[1-[4-[5-(3-chloro-4-fluoro- 1.20 628.2 1 phenyl)-5-(trifluoromethyl)-4H- 1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P3 N-[1-[4-[5-(3-chlorophenyl)-2- 1.33 622 (M-H) 1 methyl-5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P4 N-[1-[4-[5-(3-chlorophenyl)-5- 1.17 592 2 (difluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P5 N-[3-methyl-1-[4-[5-(2-pyridyl)-5- 1.18 577.2 1 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]pyrazol-4- yl]-4- (trifluoromethoxy)benzamide P6 N-[3-methyl-1-[4-[5-thiazol-2-yl- 1.16 583.1 1 5-(trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]pyrazol-4- yl]-4- (trifluoromethoxy)benzamide
Entr IUPAC name Molecule RT [M+H] Metho y (min (measured d ) ) P7 N-[1-[4-[5-(5-chloro-2-thienyl)-5- 1.23 616.1 1 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P8 N-[1-[4-[5-(3,5-dichloro-4-fluoro- 1.24 662.1 1 phenyl)-5-(trifluoromethyl)-4H- 1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P9 N-[1-[4-[5-(3-chlorophenyl)-5- 1.39 611.1 1 (trifluoromethyl)-1,4,2-dioxazol- 3-yl]phenyl]-3-methyl-pyrazol-4- yl]-4- (trifluoromethoxy)benzamide P10 N-[1-[4-[4-(3-chlorophenyl)-5- 1.22 622.2 1 oxo-4-(trifluoromethyl)-1H- imidazol-2-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P11 N-[1-[4-[5-(3-chlorophenyl)-4- 1.30 650 2 cyclopropyl-5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]phenyl]-3- methyl-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P12 N-[1-[4-[(5S)-5-(3-chlorophenyl)- 1.21 610 2 5-(trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P13 N-[1-[4-[(5R)-5-(3-chlorophenyl)- 1.21 610 2 5-(trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide
Entr IUPAC name Molecule RT [M+H] Metho y (min (measured d ) ) P14 4-[5-butyl-5-(trifluoromethyl)-4H- 1.18 478 2 1,2,4-oxadiazol-3-yl]-2-fluoro-N- [4- (trifluoromethyl)phenyl]benzami de P15 5-butyl-3-[4-[1-[4- 1.22 500 2 (trifluoromethoxy)phenyl]-1,2,4- triazol-3-yl]phenyl]-5- (trifluoromethyl)-4H-1,2,4- oxadiazole P16 N-[1-[4-[5-butyl-5- 1.18 556 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P17 N-[1-[4-[5-(3,5-dichlorophenyl)- 1.29 644 2 5-(trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P18 N-[1-[4-[5-(3-chlorophenyl)-5- 1.21 610 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P19 5-(3-chlorophenyl)-3-[4-[1-[4- 1.26 554 2 (trifluoromethoxy)phenyl]-1,2,4- triazol-3-yl]phenyl]-5- (trifluoromethyl)-4H-1,2,4- oxadiazole P20 5-isopropyl-3-[4-[1-[4- 1.16 486 2 (trifluoromethoxy)phenyl]-1,2,4- triazol-3-yl]phenyl]-5- (trifluoromethyl)-4H-1,2,4- oxadiazole
Entr IUPAC name Molecule RT [M+H] Metho y (min (measured d ) ) P21 N-[1-[4-[5-isopropyl-5- 1.12 542 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]phenyl]-3-methyl- pyrazol-4-yl]-4- (trifluoromethoxy)benzamide P22 2-fluoro-4-[(5S)-5-isopropyl-5- 1.14 464 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzami de P23 2-fluoro-4-[(5R)-5-isopropyl-5- 1.14 464 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzami de P24 2-fluoro-4-[5-isopropyl-5- 1.16 464 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-[4- (trifluoromethyl)phenyl]benzami de P25 2-fluoro-4-[5-isopropyl-5- 1.14 464 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-[2- (trifluoromethyl)phenyl]benzami de P26 2-fluoro-4-[5-isopropyl-5- 1.23 479 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-(2-thiazol-2- ylphenyl)benzamide P27 N-[2-(4-chlorophenyl)phenyl]-2- 1.23 506 2 fluoro-4-[5-isopropyl-5- (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]benzamide
Entr IUPAC name Molecule RT [M+H] Metho y (min (measured d ) ) P28 2-fluoro-4-[5-isopropyl-5- 1.16 464 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-[3- (trifluoromethyl)phenyl]benzami de P29 2-fluoro-4-[5-isopropyl-5- 1.14 426 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-(2- methoxyphenyl)benzamide P30 2-fluoro-4-[5-isopropyl-5- 1.07 426 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-(3- methoxyphenyl)benzamide P31 2-fluoro-4-[5-isopropyl-5- 1.06 426 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-(4- methoxyphenyl)benzamide P32 N-cyclopentyl-3-[5-isopropyl-5- 1.03 370 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]benzamide P33 3-[5-isopropyl-5- 1.05 378 2 (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]-N-phenyl- benzamide P34 N-[2-(2- 2.09 476 3 cyclopropylcyclopropyl)phenyl]- 2-fluoro-4-[5-isopropyl-5- (trifluoromethyl)-4H-1,2,4- oxadiazol-3-yl]benzamide The activity of the compositions according to the invention can be broadened considerably, and adapted to prevailing circumstances, by adding other insecticidally, acaricidally and/or fungicidally active ingredients. The mixtures of the compounds of formula (I) with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be
described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use. Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridinylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations. The following combinations of a compound of Formula (I) with another active substance in a weight ratio of 1:1 are preferred (where the abbreviation “TX” means “one compound selected from the compounds defined in the Tables A-1 to A-42 and Table P”): (7E,9Z)-dodeca-7,9-dien-1-yl acetate + TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate + TX, (9Z,12E)- tetradeca-9,12-dien-1-yl acetate + TX, (E)-6-methylhept-2-en-4-ol + TX, (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol + TX, (E)-tridec-4-en-1-yl acetate + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate + TX, (Z)-dodec-7-en-1-yl acetate + TX, (Z)-hexadec-11-en-1-yl acetate + TX, (Z)-hexadec-11-enal + TX, (Z)- hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-icos-13-en-10-one + TX, (Z)-tetradec-7-en-1-al + TX, (Z)- tetradec-9-en-1-ol + TX, (Z)-tetradec-9-en-1-yl acetate + TX, 1,2-dibromo-3-chloropropane + TX, 1,2- dichloropropane + TX, 1,2-dichloropropane with 1,3-dichloropropene + TX, 1,3-dichloropropene + TX, 14-methyloctadec-1-ene + TX, 1-hydroxy-1H-pyridine-2-thione + TX, 2-(octylthio)¬ethanol + TX, 2- chlorophenyl N-methylcarbamate (CPMC) + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 3,4- dichlorotetrahydrothio¬phene 1,1-dioxide + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide + TX, 4- methylnonan-5-ol with 4-methylnonan-5-one + TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid + TX, 6-isopentenylaminopurine + TX, 8-hydroxyquinoline sulfate + TX, abamectin + TX, acequinocyl + TX, acetamiprid + TX, acetoprole + TX, acrinathrin + TX, acynonapyr + TX, Adoxophyes orana GV + TX, afidopyropen + TX, afoxolaner + TX, Agrobacterium radiobacter + TX, AKD-3088 + TX, alanycarb + TX, aldicarb + TX, aldoxycarb + TX, allethrin + TX, alpha-cypermethrin + TX, alphamethrin + TX, alpha-multistriatin + TX, Amblyseius spp. + TX, amidoflumet + TX, amino acids + TX, aminocarb + TX, Anagrapha falcifera NPV + TX, Anagrus atomus + TX, Aphelinus abdominalis + TX, Aphidius colemani + TX, Aphidoletes aphidimyza + TX, apholate + TX, Autographa californica NPV + TX, AZ 60541 + TX, azadirachtin + TX, azocyclotin + TX, Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL Accession No B-21618) + TX, Bacillus firmus + TX, Bacillus kurstaki + TX, Bacillus mycoides AQ726 (NRRL Accession No. B-21664) + TX, Bacillus pumilus (NRRL Accession No B-30087) + TX, Bacillus pumilus AQ717 (NRRL Accession No. B-21662) + TX, Bacillus sp. AQ175 (ATCC Accession No.55608) + TX, Bacillus sp. AQ177 (ATCC Accession No.55609) + TX, Bacillus sp. AQ178 (ATCC Accession No.53522) + TX, Bacillus sphaericus Neide + TX, Bacillus subtilis AQ153 (ATCC Accession No.55614) + TX, Bacillus subtilis AQ30002 (NRRL Accession No. B-50421) + TX, Bacillus subtilis AQ30004 (NRRL Accession No. B- 50455) + TX, Bacillus subtilis AQ713 (NRRL Accession No. B-21661) + TX, Bacillus
subtilis AQ743 (NRRL Accession No. B-21665) + TX, Bacillus subtilis unspecified + TX, Bacillus thuringiensis AQ52 (NRRL Accession No. B-21619) + TX, Bacillus thuringiensis BD#32 (NRRL Accession No B-21530) + TX, Bacillus thuringiensis Berliner + TX, Bacillus thuringiensis subsp. Aizawai + TX, Bacillus thuringiensis subsp. Israelensis + TX, Bacillus thuringiensis subsp. Japonensis + TX, Bacillus thuringiensis subsp. Kurstaki + TX, Bacillus thurin¬giensis subsp. Tenebrionis + TX, Bacillus thuringiensis subspec. kurstaki BMP 123 + TX, Beauveria bassiana + TX, Beauveria brongniartii + TX, benclothiaz + TX, benomyl + TX, bensultap + TX, benzoximate + TX, benzpyrimoxan + TX, betacyfluthrin + TX, beta-cypermethrin + TX, bethoxazin + TX, bifenazate + TX, bifenthrin + TX, binapacryl + TX, bioallethrin + TX, bioresmethrin + TX, bis(tributyltin) oxide + TX, bisazir + TX, bistrifluron + TX, bisulflufen + TX, brevicomin + TX, broflanilide + TX, brofluthrinate + TX, bromoacetamide + TX, bromophos-ethyl + TX, bronopol + TX, busulfan + TX, butocarboxim + TX, butopyronoxyl + TX, butoxy(polypropylene glycol) + TX, butylpyridaben + TX, cadusafos + TX, calcium arsenate + TX, carbaryl + TX, carbofuran + TX, carbon disulfide + TX, carbosulfan + TX, cartap + TX, CAS number: 1594624-87-9 + TX, CAS number: 1922957-47-8 + TX, CAS number: 1255091-74-7 + TX, CAS number: 1365070-72-9 + TX, CAS number: 1445683-71-5 + TX, CAS number: 1445684-82-1 + TX, CAS Number: 158062-71-6 + TX, CAS number: 1594626-19-3 + TX, CAS number: 1594637-65- 6 + TX, CAS number: 1632218-00-8 + TX, CAS number: 1808115-49-2 + TX, CAS number: 1922957- 46-7 + TX, CAS number: 1922957-48-9 + TX, CAS number: 1956329-03-5 + TX, CAS number: 1990457-52-7 + TX, CAS number: 1990457-55-0 + TX, CAS number: 1990457-57-2 + TX, CAS number: 1990457-66-3 + TX, CAS number: 1990457-77-6 + TX, CAS number: 1990457-85-6 + TX, CAS number: 2032403-97-5 + TX, CAS number: 2044701-44-0 + TX, CAS number: 2095470-94-1 + TX, CAS Number: 2128706-04-5 + TX, CAS number: 2128706-05-6 + TX, CAS number: 2133042-31- 4 + TX, CAS number: 2133042-44-9 + TX, CAS number: 2171099-09-3 + TX, CAS number: 2220132- 55-6 + TX, CAS number: 2396747-83-2 + TX, CAS number: 2408220-91-5 + TX, CAS number: 2408220-94-8 + TX, CAS number: 2415706-16-8 + TX, CAS Number: 2566451-67-8 + TX, CAS Number: 2644770-30-7 + TX, CAS number: 2719848-60-7 + TX, CAS number: RNA (Leptinotarsa decemlineata-specific recombinant double-stranded interfering GS2) + TX, chlorantraniliprole + TX, chlordane + TX, chlorfenapyr + TX, chloropicrin + TX, chloroprallethrin + TX, chlorpyrifos + TX, chromafenozide + TX, Chrysoperla carnea + TX, clenpirin + TX, cloethocarb + TX, clothianidin + TX, codlelure + TX, codlemone + TX, copper acetoarsenite + TX, copper dioctanoate + TX, copper hydroxide + TX, copper sulfate + TX, cresol + TX, crufomate + TX, Cryptolaemus montrouzieri + TX, cuelure + TX, cyanofenphos + TX, cyantraniliprole + TX, cybutryne + TX, cyclaniliprole + TX, cyclobutrifluram + TX, cycloprothrin + TX, cycloxaprid + TX, Cydia pomonella GV + TX, cyenopyrafen + TX, cyetpyrafen + TX, cyflumetofen + TX, cyfluthrin + TX, cyhalodiamide + TX, cylohalothrin + TX, cypermethrin + TX, cyphenothrin + TX, cyproflanilide + TX, cyromazine + TX, cytokinins + TX, Dacnusa sibirica + TX, dazomet + TX, DBCP + TX, DCIP + TX, deltamethrin + TX, diafenthiuron + TX, dialifos + TX, diamidafos + TX, dibrom + TX, dibutyl adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, dichlofenthion + TX, dichlone + TX, dichlorophen + TX, dicliphos + TX, dicloromezotiaz + TX, diethyltoluamide + TX, diflubenzuron + TX, Diglyphus isaea + TX, dimatif + TX, dimethoate + TX, dimethyl carbate + TX, dimethyl phthalate + TX, dimpropyridaz + TX, dinactin + TX, dinocap + TX,
dinotefuran + TX, dioxabenzofos + TX, dipyrithione + TX, disparlure + TX, D-limonene + TX, dodec-8- en-1-yl acetate + TX, dodec-9-en-1-yl acetate + TX, dodeca-8,10-dien-1-yl acetate + TX, dodicin + TX, dominicalure + TX, doramectin + TX, emamectin + TX, emamectin benzoate + TX, empenthrin + TX, Encarsia formosa + TX, endothal + TX, endrin + TX, eprinomectin + TX, epsilon - momfluorothrin + TX, epsilon-metofluthrin + TX, Eretmocerus eremicus + TX, esfenvalerate + TX, ethion + TX, ethiprole + TX, ethoprophos + TX, ethyl 4-methyloctanoate + TX, ethyl hexanediol + TX, ethylene dibromide + TX, etofenprox + TX, etoxazole + TX, etpyrafen + TX, eugenol + TX, Extract of seaweed and fermentation product derived from melasse + TX, Extract of seaweed and fermentation product derived from melasse comprising urea + TX, Extract of seaweed and fermented plant products + TX, Extract of seaweed and fermented plant products comprising phytohormones, vitamins, EDTA-chelated copper, zinc, and iron + TX, famphur + TX, fenaminosulf + TX, fenamiphos + TX, fenazaquin + TX, fenfluthrin + TX, fenitrothion + TX, fenmezoditiaz + TX, fenobucarb + TX, fenothiocarb + TX, fenoxycarb + TX, fenpropathrin + TX, fenpyrad + TX, fenpyroximate + TX, fensulfothion + TX, fenthion + TX, fentin + TX, fentinacetate + TX, fenvalerate + TX, ferric phosphate + TX, fipronil + TX, flometoquin + TX, flonicamid + TX, fluacrypyrim + TX, fluazaindolizine + TX, fluazuron + TX, flubendiamide + TX, flubenzimine + TX, fluchlordiniliprole + TX, flucitrinate + TX, flucycloxuron + TX, flucythrinate + TX, fluensulfone [318290-98-1] + TX, fluensulfone + TX, flufenerim + TX, flufenprox + TX, flufiprole + TX, fluhexafon + TX, flumethrin + TX, fluopyram + TX, flupyradifurone + TX, flupyrimin + TX, flupyroxystrobin + TX, fluralaner + TX, fluvalinate + TX, fluxametamide + TX, formaldehyde + TX, fosthiazate + TX, fosthietan + TX, frontalin + TX, furfural + TX, gamma-cyhalothrin + TX, Gossyplure® (1:1 mixture of the (Z,E) and (Z,Z) isomers of hexadeca- 7,11-dien-1-yl-acetate) + TX, grandlure + TX, grandlure I + TX, grandlure II + TX, grandlure III + TX, grandlure IV + TX, Granulovirus + TX, guadipyr + TX, GY-81 + TX, halfenprox + TX, halofenozide + TX, Harpin + TX, Helicoverpa armigera Nucleopolyhedrovirus + TX, Helicoverpa zea NPV + TX, Helicoverpa zea Nucleopolyhedrovirus + TX, Heliothis punctigera Nucleopolyhedrovirus + TX, Heliothis virescens Nucleopolyhedrovirus + TX, hemel + TX, hempa + TX, heptafluthrin + TX, heterophos + TX, Heterorhabditis bacteriophora and H. megidis + TX, hexalure + TX, hexamide + TX, hexythiazox + TX, Hippodamia convergens + TX, hydramethylnon + TX, hydrargaphen + TX, hydrated lime + TX, imicyafos + TX, imidacloprid + TX, imiprothrin + TX, Indazapyroxamet + TX, indoxacarb + TX, iodomethane + TX, iprodione + TX, ipsdienol + TX, ipsenol + TX, isamidofos + TX, isazofos + TX, isocycloseram + TX, Isoflualanam (CAS number: 2892524-05-7) + TX, isothioate + TX, ivermectin + TX, japonilure + TX, kappa-bifenthrin + TX, kappa-tefluthrin + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, kinetin + TX, lambda-cyhalothrin + TX, ledprona + TX, lepimectin + TX, Leptomastix dactylopii + TX, lineatin + TX, litlure + TX, looplure + TX, lotilaner + TX, lufenuron + TX, Macrolophus caliginosus + TX, Mamestra brassicae NPV + TX, mecarphon + TX, medlure + TX, megatomoic acid + TX, metaflumizone + TX, metaldehyde + TX, metam + TX, metam-potassium + TX, metam-sodium + TX, Metaphycus helvolus + TX, Metarhizium anisopliae var. acridum + TX, Metarhizium anisopliae var. anisopliae + TX, Metarhizium spp. + TX, metepa + TX, methiocarb + TX, methiotepa + TX, methomyl + TX, methoquin-butyl + TX, methoxyfenozide + TX, methyl apholate + TX, methyl bromide + TX, methyl eugenol + TX, methyl isothiocyanate + TX, methylneodecanamide + TX, metofluthrin + TX, metolcarb + TX, mexacarbate + TX, milbemectin + TX, milbemycin oxime + TX,
momfluorothrin + TX, morzid + TX, moxidectin + TX, muscalure + TX, Muscodor albus 620 (NRRL Accession No.30547) + TX, Muscodor roseus A3-5 (NRRL Accession No.30548) + TX, Myrothecium verrucaria composition + TX, nabam + TX, NC-184 + TX, Neem tree based products + TX, Neodiprion sertifer NPV and N. lecontei NPV + TX, nickel bis(dimethyldithiocarbamate) + TX, niclosamide + TX, niclosamide-olamine + TX, nicofluprole + TX, nitenpyram + TX, nithiazine + TX, nitrapyrin + TX, octadeca-2,13-dien-1-yl acetate + TX, octadeca-3,13-dien-1-yl acetate + TX, octhilinone + TX, omethoate + TX, orfralure + TX, Orius spp. + TX, oryctalure + TX, ostramone + TX, oxamate + TX, oxamyl + TX, oxazosulfyl + TX, oxolinic acid + TX, oxytetracycline + TX, Paecilomyces fumosoroseus + TX, Paecilomyces lilacinus + TX, parathion-ethyl + TX, Pasteuria nishizawae + TX, Pasteuria penetrans + TX, Pasteuria ramosa + TX, Pasteuria thornei + TX, Pasteuria usgae + TX, P-cymene + TX, penfluron + TX, pentachlorophenol + TX, permethrin + TX, phenothrin + TX, phorate + TX, phosphamidon + TX, phosphocarb + TX, Phytoseiulus persimilis + TX, picaridin + TX, pioxaniliprole + TX, piperazine + TX, piperflanilide (CAS number: 2615135-05-0) + TX, piperonylbutoxide + TX, pirimicarb + TX, pirimiphos-ethyl + TX, pirimiphos-methyl + TX, Plutella xylostella Granulosis virus + TX, Plutella xylostella Nucleopolyhedrovirus + TX, Polyhedrosis virus + TX, potassium and molybdenum and EDTA-chelated manganese + TX, potassium ethylxanthate + TX, potassium hydroxyquinoline sulfate + TX, prallethrin + TX, probenazole + TX, profenofos + TX, profluthrin + TX, propargite + TX, propetamphos + TX, propoxur + TX, prothiophos + TX, protrifenbute + TX, pyflubumide + TX, pymetrozine + TX, pyraclofos + TX, pyrafluprole + TX, pyrethrum + TX, pyridaben + TX, pyridalyl + TX, pyridin-4-amine + TX, pyrifluquinazon + TX, pyrimidifen + TX, pyriminostrobin + TX, pyriprole [394730-71-3] + TX, pyriprole + TX, pyriproxyfen + TX, QRD 420 (a terpenoid blend) + TX, QRD 452 (a terpenoid blend) + TX, QRD 460 (a terpenoid blend) + TX, Quillaja saponaria + TX, quinoclamine + TX, quinonamid + TX, resmethrin + TX, Rhodococcus globerulus AQ719 (NRRL Accession No B- 21663) + TX, sarolaner + TX, S-bioallethrin + TX, sebufos + TX, selamectin + TX, siglure + TX, silafluofen + TX, simazine + TX, sodium pentachlorophenoxide + TX, sordidin + TX, spidoxamat + TX, spinetoram + TX, spinosad + TX, spirobudifen + TX, spirodiclofen + TX, spiromesifen + TX, spiropidion + TX, spirotetramat + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus + TX, Spodoptera frugiperda Nucleopolyhedrovirus + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Streptomyces galbus (NRRL Accession No. 30232) + TX, Streptomyces sp. (NRRL Accession No. B-30145) + TX, streptomycin + TX, streptomycin sesquisulfate + TX, strychnine + TX, sulcatol + TX, sulfiflumin (CAS number: 2377084- 09-6) + TX, sulfoxaflor + TX, tazimcarb + TX, tebufenozide + TX, tebufenpyrad + TX, tebupirimiphos + TX, tecloftalam + TX, tefluthrin + TX, temephos + TX, tepa + TX, terbam + TX, terbufos + TX, terpenoid blend + TX, tetrachlorantraniliprole + TX, tetrachlorothiophene + TX, tetradec-11-en-1-yl acetate + TX, tetradiphon + TX, tetramethrin + TX, tetramethylfluthrin + TX, tetranactin + TX, tetraniliprole + TX, theta- cypermethrin + TX, thiacloprid + TX, thiafenox + TX, thiamethoxam + TX, thiocyclam + TX, thiodicarb + TX, thiofanox + TX, thiohempa + TX, thiomersal + TX, thiometon + TX, thionazin + TX, thiophanate + TX, thiosultap + TX, thiotepa + TX, tigolaner + TX, tiorantraniliprole + TX, tioxazafen + TX, tolfenpyrad + TX, toxaphene + TX, tralomethrin + TX, transfluthrin + TX, tretamine + TX, triazamate + TX, triazophos
+ TX, triazuron + TX, tributyltin oxide + TX, trichlorfon + TX, trichloronate + TX, trichlorphon + TX, Trichogramma spp. + TX, trifenmorph + TX, trifluenfuronate + TX, triflumezopyrim + TX, trimedlure + TX, trimedlure A + TX, trimedlure B1 + TX, trimedlure B2 + TX, trimedlure C + TX, trimethacarb + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, trunc-call + TX, tyclopyrazoflor + TX, Typhlodromus occidentalis + TX, uredepa + TX, Verticillium lecanii + TX, Verticillium spp. + TX, xylenols + TX, YI-5302 + TX, zeatin + TX, zeta-Cypermethrin + TX; N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1- benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-ethyl-N’-[5-methoxy-2- methyl-4-[(2-trifuoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine (these compounds may be prepared from the methods described in WO2019/110427) + TX, (3',4',5'-trifluoro-biphenyl-2-yl)- amide + TX, (3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone (these compounds may be prepared from the methods described in WO 2017/220485) + TX, (4- phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-3-carboxylate (this compound may be prepared from the methods described in WO 2014/006945) + TX, (5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]methanone + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate + TX, (9Z,11E)- tetradeca-9,11-dien-1-yl acetate + TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate + TX, (E)-6- methylhept-2-en-4-ol + TX, (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol + TX, (E)-tridec-4-en-1-yl acetate + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate, + TX, (R)-3-(difluoromethyl)-1-methyl-N-[1,1,3- trimethylindan-4-yl]pyrazole-4-carboxamide + TX, (Z)-dodec-7-en-1-yl acetate + TX, (Z)-hexadec-11- en-1-yl acetate + TX, (Z)-hexadec-11-enal + TX, (Z)-hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-icos- 13-en-10-one + TX, (Z)-tetradec-7-en-1-al + TX, (Z)-tetradec-9-en-1-ol + TX, (Z)-tetradec-9-en-1-yl acetate + TX, (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3- enamide (this compound may be prepared from the methods described in WO 2018/153707) + TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide + TX, , [2- [3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]- 3-chloro-phenyl] methanesulfonate + TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3- dimethyl-isoquinoline + TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline + TX, 1-(6,7- dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline + TX, 1-(6-chloro-7- methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline (these compounds may be prepared from the methods described in WO2017/025510) + TX, 1,1-bis(4-chloro¬phenyl)-2- ethoxyethanol + TX, 1,1-dichloro-2,2-bis(4-ethylphenyl)¬ethane + TX, 1,2-dibromo-3-chloropropane + TX, 1,2-dichloropropane with 1,3-dichloropropene + TX, 1,3-dichloropropene + TX, 1,3-dimethoxy-1- [[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea + TX, 1-[2-[[1-(4-chlorophenyl)pyrazol- 3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one + TX, 10-dien-1-yl acetate + TX, 14- methyloctadec-1-ene + TX, 1-bromo-2-chloroethane + TX, 1-dichloro-1-nitroethane + TX, 1-hydroxy- 1H-pyridine-2-thione + TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]urea + TX, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1- yl)phenoxy]methyl]phenyl]tetrazol-5-one + TX, 2- (difluoromethyl) - N- ((3R) - 1, 1, 3- trimethylindan- 4-
yl) pyridine- 3- carboxamide + TX, 2- (difluoromethyl) - N- ((3R) - 1, 1, 3- trimethylindan- 4-yl) pyridine- 3- carboxamide + TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate + TX, 2-(2-butoxyethoxy)¬ethyl piperonylate + TX, 2-(2-butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-(difluoromethyl)-N-(3-ethyl-1,1- dimethyl-indan-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl- indan-4-yl]pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4- yl]pyridine-3-carboxamide (this compound may be prepared from the methods described in WO 2014/095675) + TX, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, 2-(octylthio)¬ethanol + TX, 2,2,2-trichloro-1-(3,4-dichloro¬phenyl)ethyl acetate + TX, 2,2- dichlorovinyl 2-ethylsulfinylethyl methyl phosphate + TX, 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX, 2,4-dichlorophenyl benzenesulfonate + TX, 2,6-Dimethyl- 1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone (this compound may be prepared from the methods described in WO 2011/138281) + TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3- quinolyl)oxy]phenyl]propan-2-ol + TX, 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4- triazol-1-yl)propan-2-ol (this compound may be prepared from the methods described in WO 2017/029179) + TX, 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2- ol (this compound may be prepared from the methods described in WO 2017/029179) + TX, 2- chlorovinyl diethyl phosphate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 2-imidazolidone + TX, 2-isovalerylindan-1,3-dione + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate + TX, 2- oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide (this compound may be prepared from the methods described in WO 2018/065414) + TX, 2-thiocyanatoethyl laurate + TX, 3- (4,4-difluoro-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole (these compounds may be prepared from the methods described in WO2016/156085) + TX, 3-(4,4-difluoro- 3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 3,4- dichlorotetrahydrothio¬phene 1,1-dioxide + TX, 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2- hydroxy-propyl]imidazole-4-carbonitrile (this compound may be prepared from the methods described in WO 2016/156290) + TX, 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy- propyl]imidazole-4-carbonitrile (this compound may be prepared from the methods described in WO 2016/156290) + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6- trifluorophenyl)pyridazine + TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid + TX, 3-ethyl- 1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea + TX, 3-methyl-1- phenylpyrazol-5-yl dimethyl¬carbamate + TX, 4- (2- bromo- 4- fluorophenyl) - N- (2- chloro- 6- fluorophenyl) - 1, 3- dimethyl- 1H- pyrazol- 5- amine + TX, 4-(2,6-difluorophenyl)-6-methyl-5-phenyl- pyridazine-3-carbonitrile + TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl- pyrazol-3-amine + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide + TX, 4,4-difluoro-1-(5-fluoro-4- methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline + TX, 4,4-difluoro-3,3-dimethyl-1-(6- methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5- a]pyridin-3-yl)isoquinoline + TX, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]isoxazolidin-3-one + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-
triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy- 3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1- difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-chloro-2- (2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one + TX, 4-chlorophenyl phenyl sulfone + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate + TX, 4-methylnonan-5-ol with 4- methylnonan-5-one + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone + TX, 5,5-dimethyl-2-[[4- [5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, 5,5-dimethyl-3- oxocyclohex-1-enyl dimethylcarbamate + TX, 5-amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1) + TX, 5- methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid + TX, 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-N- [2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (may be prepared from the methods described in WO 2020/109391) + TX, 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-N-[2- (3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (may be prepared from the methods described in WO 2020/109391) + TX, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4- methylbenzimidazol-1-yl)isoquinoline + TX, 6-chloro-N-[2-(2-chloro-4-methyl-phenyl)-2,2-difluoro- ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide (may be prepared from the methods described in WO 2020/109391) + TX, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2- c]isothiazole-3-carbonitrile + TX, 6-isopentenylaminopurine + TX, 8-fluoro-N-[(1R)-1-[(3- fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide + TX, 8-fluoro-N-[(1S)-1-[(3- fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide + TX, 8-hydroxyquinoline sulfate + TX, acethion + TX, acetoprole + TX, acibenzolar + TX, acibenzolar-S-methyl + TX, acrylonitrile + TX, Adoxophyes orana GV + TX, Agrobacterium radiobacter + TX, aldoxycarb + TX, aldrin + TX, allosamidin + TX, allyxycarb + TX, alpha-chlorohydrin + TX, alpha-ecdysone + TX, alpha-multistriatin + TX, aluminium phosphide + TX, Amblyseius spp. + TX, amectotractin + TX, ametoctradin + TX, amidithion + TX, amidothioate + TX, aminocarb + TX, aminopyrifen + TX, amisulbrom + TX, amiton + TX, amiton hydrogen oxalate + TX, amitraz + TX, anabasine + TX, Anagrapha falcifera NPV + TX, Anagrus atomus + TX, ancymidol + TX, anilazine + TX, anisiflupurin + TX, anthraquinone + TX, antu + TX, Aphelinus abdominalis + TX, Aphidius colemani + TX, Aphidoletes aphidimyza + TX, apholate + TX, aramite + TX, arsenous oxide + TX, athidathion + TX, Autographa californica NPV + TX, azaconazole + TX, azamethiphos + TX, azobenzene + TX, azothoate + TX, azoxystrobin + TX, Bacillus sphaericus Neide + TX, Bacillus thuringiensis delta endotoxins + TX, barium carbonate + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, barthrin + TX, Bayer 22/190 + TX, Bayer 22408 + TX, Beauveria brongniartii + TX, benalaxyl + TX, benclothiaz + TX, benomyl + TX, benoxa¬fos + TX, benthiavalicarb + TX, benzothiostrobin + TX, benzovindiflupyr + TX, benzyl benzoate + TX, beta-cyfluthrin + TX, beta- cypermethrin + TX, bethoxazin + TX, bioethanomethrin + TX, biopermethrin + TX, bis(2-chloroethyl) ether + TX, bis(tributyltin) oxide + TX, bisazir + TX, bisthiosemi + TX, bitertanol + TX, bixafen + TX, blasticidin-S + TX, borax + TX, bordeaux mixture + TX, boscalid + TX, brevicomin + TX, brodifacoum + TX, brofenvalerate + TX, bromadiolone + TX, bromethalin + TX, bromfenvinfos + TX, bromoacetamide + TX, bromo¬cyclen + TX, bromo-DDT + TX, bromophos + TX, bromopropylate + TX, bromuconazole + TX, bronopol + TX, bufencarb + TX, bupirimate + TX, buprofezin + TX, busulfan + TX, but-3-ynyl N- [6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX,
butacarb + TX, butathiofos + TX, butocarboxim + TX, butonate + TX, butopyronoxyl + TX, butoxy(polypropylene glycol) + TX, butoxycarboxim + TX, butylpyridaben + TX, calcium arsenate + TX, calcium cyanide + TX, calcium polysulfide + TX, camphechlor + TX, captafol + TX, captan + TX, carbanolate + TX, carbendazim + TX, carbon disulfide + TX, carbon tetrachloride + TX, carbophenothion + TX, carboxin + TX, cartap hydrochloride + TX, CAS Number: 2132414-04-9 + TX, CAS Number: 2344721-61-3 + TX, CAS Number: 2454319-63-0 + TX, cevadine + TX, chino¬methionat + TX, chloralose + TX, chlorbenside + TX, chlorbicyclen + TX, chlordane + TX, chlordecone + TX, chlordimeform + TX, chlordimeform hydrochloride + TX, chlorfenethol + TX, chlorfenson + TX, chlorfensulfide + TX, chlorobenzilate + TX, chloroform + TX, chloroinconazide + TX, chloromebuform + TX, chloromethiuron + TX, chloroneb + TX, chlorophacinone + TX, chloropicrin + TX, chloropropylate + TX, chloro¬tha¬lo¬nil + TX, chlorphoxim + TX, chlorprazophos + TX, chlorthiophos + TX, chlozolinate + TX, cholecalciferol + TX, Chrysoperla carnea + TX, cinerin I + TX, cinerin II + TX, cinerins + TX, cismethrin + TX, cis-resmethrin + TX, clocythrin + TX, closantel + TX, codlelure + TX, codlemone + TX, copper acetoarsenite + TX, copper arsenate + TX, copper dioctanoate + TX, copper hydroxide + TX, copper naphthenate + TX, copper oleate + TX, copper oxide + TX, copper oxychloride + TX, copper sulfate + TX, coumachlor + TX, coumafuryl + TX, coumaphos + TX, coumatetralyl + TX, coumethoxystrobin (jiaxiangjunzhi) + TX, coumithoate + TX, coumoxystrobin + TX, cresol + TX, crimidine + TX, crotamiton + TX, crotoxyphos + TX, crufomate + TX, cryolite + TX, Cryptolaemus montrouzieri + TX, CS 708 + TX, cuelure + TX, cufraneb + TX, cyanofenphos + TX, cyanophos + TX, cyanthoate + TX, cyazofamid + TX, cybutryne + TX, cyclethrin + TX, cyclobutrifluram + TX, Cydia pomonella GV + TX, cyflufenamid + TX, cymiazole + TX, cymoxanil + TX, cyproconazole + TX, cyprodinil + TX, cythioate + TX, cytokinins + TX, Dacnusa sibirica + TX, DAEP + TX, dazomet + TX, DCIP + TX, DCPM + TX, DDT + TX, debacarb + TX, decarbofuran + TX, demephion + TX, demephion- O + TX, demephion-S + TX, demeton-methyl + TX, demeton-O + TX, demeton-O-methyl + TX, demeton-S + TX, demeton-S-methyl + TX, demeton-S-methylsulfon + TX, diamidafos + TX, dibutyl adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, dicapthon + TX, dichlobentiazox + TX, dichlofenthion + TX, dichlofluanid + TX, dichlone + TX, dichlorophen + TX, dichlorvos + TX, dichlozoline + TX, dicliphos + TX, diclocymet + TX, diclomezine + TX, dicloran + TX, dicresyl + TX, dicyclanil + TX, dicyclopentadiene + TX, dieldrin + TX, dienochlor + TX, diethofencarb + TX, diethyl 5-methylpyrazol-3- yl phosphate + TX, diethyltoluamide + TX, difenacoum + TX, difenoconazole + TX, difethialone + TX, diflovidazin + TX, Diglyphus isaea + TX, dilor + TX, dimatif + TX, dimefluthrin + TX, dimefox + TX, dimetan + TX, dimethirimol + TX, dimetho¬morph + TX, dimethrin + TX, dimethyl carbate + TX, dimethyl phthalate + TX, dimethylvinphos + TX, dimetilan + TX, dimoxystrobin + TX, dinex + TX, dinex-diclexine + TX, diniconazole + TX, dinocap-4 + TX, dinocap-6 + TX, dinocton + TX, dino¬penton + TX, dinoprop + TX, dinosam + TX, dinoseb + TX, dinosulfon + TX, dinoterbon + TX, diofenolan + TX, dioxabenzofos + TX, dioxathion + TX, diphacinone + TX, diphenyl sulfone + TX, dipymetitrone + TX, dipyrithione + TX, disparlure + TX, disulfiram + TX, dithianon + TX, dithicrofos + TX, DNOC + TX, dodec-8-en-1-yl acetate + TX, dodec-9-en-1-yl acetate + TX, dodeca-8 + TX, dodemorph + TX, dodicin + TX, dodine + TX, dofenapyn + TX, dominicalure + TX, doramectin + TX, DSP + TX, d-tetramethrin + TX, ecdysterone + TX, edifenphos + TX, EI 1642 + TX, EMPC + TX, Encarsia formosa + TX, endothal + TX, endothion +
TX, enestroburin + TX, enoxastrobin + TX, EPBP + TX, epoxicon¬azole + TX, eprinomectin + TX, Eretmocerus eremicus + TX, ergocalciferol + TX, etaphos + TX, ethaboxam + TX, ethiofencarb + TX, ethirimol + TX, ethoate-methyl + TX, ethyl 1-[[4-[(Z)-2-ethoxy-3,3,3-trifluoro-prop-1- enoxy]phenyl]methyl]pyrazole-3-carboxylate (may be prepared from the methods described in WO 2020/056090) + TX, ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]pyrazole- 3-carboxylate (may be prepared from the methods described in WO 2020/056090) + TX, ethyl 1-[[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate + TX, ethyl 1-[[5-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylate (this compound may be prepared from the methods described in WO 2018/158365) + TX, ethyl 4-methyloctanoate + TX, ethyl formate + TX, ethyl hexanediol + TX, ethylene dibromide + TX, ethylene dichloride + TX, ethylene oxide + TX, etridiazole + TX, etrimfos + TX, eugenol + TX, EXD + TX, famoxa¬done + TX, farnesol + TX, farnesol with nerolidol + TX, fenamidone + TX, fenaminosulf + TX, fenaminstrobin + TX, fenarimol + TX, fenazaflor + TX, fenbuconazole + TX, fenbutatin oxide + TX, fenchlorphos + TX, fenethacarb + TX, fenfuram + TX, fenhexamid + TX, fenitrothion + TX, fenothiocarb + TX, fenoxacrim + TX, fenoxanil + TX, fenpiclonil + TX, fenpicoxamid + TX, fenpirithrin + TX, fenpropidin + TX, fenpropimorph + TX, fenpyrad + TX, fenpyrazamine + TX, fen¬pyroximate + TX, fenson + TX, fensulfothion + TX, fenthion + TX, fenthion-ethyl + TX, fentin + TX, fentrifanil + TX, ferbam + TX, ferimzone + TX, ferric phosphate + TX, flocoumafen + TX, florylpicoxamid + TX, fluazinam + TX, flubeneteram + TX, flubenzimine + TX, flucofuron + TX, flucycloxuron + TX, fludioxonil + TX, fluenetil + TX, flufenoxadiazam + TX, flufenoxystrobin + TX, fluindapyr + TX, flumetylsulforim + TX, flumorph + TX, fluopicolide + TX, fluopimomide + TX, fluopyram + TX, fluorbenside + TX, fluoroacetamide + TX, fluoroimide + TX, fluoxapiprolin + TX, fluoxastrobin + TX, fluoxytioconazole + TX, flupropadine + TX, flupropadine hydrochloride + TX, fluquinconazole + TX, flusilazole + TX, flusulfamide + TX, flutianil + TX, flutolanil + TX, flutriafol + TX, fluxapyroxad + TX, FMC 1137 + TX, folpet + TX, formaldehyde + TX, formetanate + TX, formetanate hydrochloride + TX, formparanate + TX, fosetyl-aluminium + TX, fosmethilan + TX, fospirate + TX, fosthietan + TX, frontalin + TX, fuberidazole + TX, furalaxyl + TX, furametpyr + TX, furathiocarb + TX, furethrin + TX, furfural + TX, gamma-HCH + TX, glyodin + TX, grandlure + TX, grandlure I + TX, grandlure II + TX, grandlure III + TX, grandlure IV + TX, guazatine + TX, guazatine acetates + TX, halfenprox + TX, HCH + TX, hemel + TX, hempa + TX, HEOD + TX, heptachlor + TX, heterophos + TX, Heterorhabditis bacteriophora and H. megidis + TX, hexaconazole + TX, hexadecyl cyclopropanecarboxylate + TX, hexalure + TX, hexamide + TX, HHDN + TX, Hippodamia convergens + TX, hydrargaphen + TX, hydrated lime + TX, hydrogen cyanide + TX, hymexazol + TX, hyquincarb + TX, imanin + TX, imazalil + TX, imiben¬con¬azole + TX, iminoctadine + TX, inpyrfluxam + TX, ipconazole + TX, ipfentrifluconazole + TX, ipflufenoquin + TX, iprobenphos + TX, iprodione + TX, iprovalicarb + TX, ipsdienol + TX, ipsenol + TX, IPSP + TX, isamidofos + TX, isazofos + TX, isobenzan + TX, isocarbophos + TX, isodrin + TX, isofenphos + TX, isofetamid + TX, isoflucypram + TX, isolane + TX, isoprothiolane + TX, isopyrazam + TX, isotianil + TX, isoxathion + TX, japonilure + TX, jasmolin I + TX, jasmolin II + TX, jodfenphos + TX, juvenile hormone I + TX, juvenile hormone II + TX, juvenile hormone III + TX, kadethrin + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, kelevan + TX, kinetin + TX, kinoprene + TX, kresoxim-methyl + TX, lead arsenate + TX, Leptomastix dactylopii
+ TX, leptophos + TX, lindane + TX, lineatin + TX, lirimfos + TX, litlure + TX, looplure + TX, lvbenmixianan + TX, lythidathion + TX, Macrolophus caliginosus + TX, magnesium phosphide + TX, malonoben + TX, Mamestra brassicae NPV + TX, mancopper + TX, mancozeb + TX, mandestrobin + TX, mandipropamid + TX, maneb + TX, mazidox + TX, m-cumenyl methylcarbamate + TX, mecarbam + TX, mecarphon + TX, medlure + TX, mefentrifluconazole + TX, megatomoic acid + TX, menazon + TX, mepanipyrim + TX, meperfluthrin + TX, mephosfolan + TX, mepronil + TX, mercuric oxide + TX, mercurous chloride + TX, mesulfen + TX, mesulfenfos + TX, meta¬laxyl + TX, metam + TX, metam- potassium + TX, metam-sodium + TX, Metaphycus helvolus + TX, Metarhizium anisopliae var. acridum + TX, Metarhizium anisopliae var. anisopliae + TX, metarylpicoxamid + TX, metconazole + TX, metepa + TX, methacrifos + TX, methanesulfonyl fluoride + TX, methasulfo¬carb + TX, methiotepa + TX, methocrotophos + TX, methoprene + TX, methoquin-butyl + TX, methothrin + TX, methoxychlor + TX, methyl (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate + TX, methyl (Z)-2-(5- cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate (these compounds may be prepared from the methods described in WO2020/193387) + TX, methyl (Z)-2-[5-(3-isopropylpyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy-prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-(3-propylpyrazol-1- yl)phenoxy]prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-(4-propyltriazol-2- yl)phenoxy]prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)pyrazol-1- yl]phenoxy]prop-2-enoate (these compounds may be prepared from the methods described in WO2020/079111) + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-[4-(trifluoromethyl)triazol-2- yl]phenoxy]prop-2-enoate + TX, methyl apholate + TX, methyl bromide + TX, methyl eugenol + TX, methyl isothiocyanate + TX, methyl N-[[4-[1-(2,6-difluoro-4-isopropyl-phenyl)pyrazol-4-yl]-2-methyl- phenyl]methyl]carbamate (may be prepared from the methods described in WO 2020/097012) + TX, methyl N-[[4-[1-(4-cyclopropyl-2,6-difluoro-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate (may be prepared from the methods described in WO 2020/097012) + TX, methyl N-[[5-[4-(2,4- dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate + TX, methylchloroform + TX, methylene chloride + TX, methylneodecanamide + TX, metiram + TX, metolcarb + TX, metomi¬nostrobin + TX, metoxadiazone + TX, metrafenone + TX, metyltetraprole + TX, MGK 264 + TX, milbemycin oxime + TX, mipafox + TX, mirex + TX, monocrotophos + TX, morphothion + TX, morzid + TX, moxidectin + TX, muscalure + TX, myclobutanil + TX, myclozoline + TX, Myrothecium verrucaria composition + TX, N-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide (these compounds may be prepared from the methods described in WO2017/153380) + TX, N-((1S)- 1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide (these compounds may be prepared from the methods described in WO2017/153380) + TX, N'-(2,5-dimethyl-4-phenoxy-phenyl)- N-ethyl-N-methyl-formamidine + TX, N'-(2-chloro-5-methyl-4-phenoxy-phenyl)-N-ethyl-N-methyl- formamidine + TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]propanamide + TX, N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]-1,2,4-triazol-3-amine (THESE COMPOUNDS may be prepared from the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689) + TX, N- [(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-1,3- dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-
propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro- quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(E)- methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[(Z)- methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, N-[2-[2,4-dichloro- phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, N-[2-[2-chloro-4- (trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, N'-[2- chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N-ethyl-N-methyl-formamidine (this compound may be prepared from the methods described in WO 2016/202742) + TX, N'-[4-(4,5-dichlorothiazol-2-yl)oxy- 2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2- propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2- propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidine (these compounds may be prepared from the methods described in WO2015/155075) + TX, N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3- pyridyl]-N-ethyl-N-methyl-formamidine (this compound may be prepared from the methods described in IPCOM000249876D) + TX, N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N- ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]- N-ethyl-N-methyl-formamidine + TX, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N- ethyl-N-methyl-formamidine + TX, N-[N-methoxy-C-methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]benzamide (these compounds may be prepared from the methods described in WO 2018/202428) + TX, N’-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]- N-isopropyl-N-methyl-formamidine (these compounds may be prepared from the methods described in WO2018/228896) + TX, nabam + TX, naftalofos + TX, naled + TX, naphthalene + TX, NC-170 + TX, Neodiprion sertifer NPV and N. lecontei NPV + TX, nerolidol + TX, N-ethyl-2-methyl-N-[[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, N-ethyl-N’-[5-methoxy-2- methyl-4-[(2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine + TX, nickel bis(dimethyldithiocarbamate) + TX, niclosamide-olamine + TX, nicotine + TX, nicotine sulfate + TX, nifluridide + TX, nikkomycins + TX, N-isopropyl-N’-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1- phenyl-ethyl)phenyl]-N-methyl-formamidine + TX, nithiazine + TX, nitrapyrin + TX, nitrilacarb + TX, nitrilacarb 1:1 zinc chloride complex + TX, nitrothal-isopropyl + TX, N-methoxy-N-[[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide + TX, N-methyl-4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]benzamide + TX, N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]benzenecarbothioamide + TX, norbormide + TX, nuarimol + TX, O,O,O',O'-tetrapropyl dithiopyrophosphate + TX, octadeca-2,13-dien-1-yl acetate + TX, octadeca-3,13-dien-1-yl acetate + TX, octhilinone + TX, ofurace + TX, oleic acid + TX, omethoate + TX, orfralure + TX, Orius spp. + TX, oryctalure + TX, orysastrobin + TX, ostramone + TX, oxadixyl + TX, oxamate + TX, oxathiapiprolin + TX, oxine-copper + TX, oxolinic acid + TX, oxycarboxin + TX, oxydeprofos + TX, oxydisulfoton + TX, oxytetracycline + TX, paclobutrazole + TX, Paecilomyces fumosoroseus + TX, para-dichlorobenzene + TX, parathion + TX, parathion-methyl + TX, pefurazoate + TX, penconazole + TX, pencycuron + TX, penflufen + TX, penfluron + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, penthiopyrad
+ TX, permethrin + TX, PH 60-38 + TX, phenamacril + TX, phenkapton + TX, phosacetim + TX, phosalone + TX, phosdiphen + TX, phosfolan + TX, phosglycin + TX, phosnichlor + TX, phosphamidon + TX, phosphine + TX, phosphorus + TX, phoxim-methyl + TX, phthalide + TX, Phytoseiulus persimilis + TX, picarbutrazox + TX, picaridin + TX, picoxystrobin + TX, pindone + TX, piperazine + TX, piperonyl butoxide + TX, piprotal + TX, pirimetaphos + TX, polychlorodicyclopentadiene isomers + TX, polychloroterpenes + TX, polynactins + TX, polyoxins + TX, potassium arsenite + TX, potassium ethylxanthate + TX, potassium hydroxyquinoline sulfate + TX, potassium thiocyanate + TX, pp'-DDT + TX, precocene I + TX, precocene II + TX, precocene III + TX, primidophos + TX, probenazole + TX, prochloraz + TX, proclonol + TX, procymi¬done + TX, profluthrin + TX, promacyl + TX, promecarb + TX, propamocarb + TX, propiconazole + TX, propineb + TX, propoxur + TX, propyl isomer + TX, proquinazid + TX, prothidathion + TX, prothioconazole + TX, prothiofos + TX, prothoate + TX, pydiflumetofen + TX, pyraclostrobin + TX, pyrametostrobin + TX, pyraoxystrobin + TX, pyrapropoyne + TX, pyraziflumid + TX, pyrazophos + TX, pyresmethrin + TX, pyrethrin I + TX, pyrethrin II + TX, pyrethrins + TX, pyribencarb + TX, pyridachlometyl + TX, pyridaphenthion + TX, pyridin-4-amine + TX, pyrifenox + TX, pyrimethanil + TX, pyrimitate + TX, pyrimorph + TX, pyrinuron + TX, pyriofenone + TX, pyrisoxazole + TX, pyroquilon + TX, quassia + TX, quinalphos + TX, quinalphos-methyl + TX, quinoclamine + TX, quinofumelin + TX, quinonamid + TX, quinothion + TX, quinoxyfen + TX, quintiofos + TX, quintozene + TX, R-1492 + TX, rafoxanide + TX, resmethrin + TX, Reynoutria sachalinensis extract + TX, ribavirin + TX, R metalaxyl + TX, rotenone + TX, ryania + TX, ryanodine + TX, S421 + TX, sabadilla + TX, schradan + TX, scilliroside + TX, seboctylamine + TX, sebufos + TX, sedaxane + TX, selamectin + TX, sesamex + TX, sesasmolin + TX, SI-0009 + TX, siglure + TX, simazine + TX, simeconazole + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium fluoro¬acetate + TX, sodium hexafluorosilicate + TX, sodium pentachlorophenoxide + TX, sodium selenate + TX, sodium tetrathiocarbonate + TX, sodium thiocyanate + TX, sophamide + TX, sordidin + TX, spiroxamine + TX, SSI-121 + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, streptomycin + TX, streptomycin sesquisulfate + TX, strychnine + TX, sulcatol + TX, sulcofuron + TX, sulcofuron-sodium + TX, sulfiram + TX, sulfluramid + TX, sulfotep + TX, sulfoxide + TX, sulfur + TX, sulfuryl fluoride + TX, sulprofos + TX, tar oils + TX, tau-fluvalinate + TX, tazimcarb + TX, TDE + TX, tebucon¬azole + TX, tebufloquin + TX, tebupirimfos + TX, tecloftalam + TX, temephos + TX, tepa + TX, TEPP + TX, terallethrin + TX, terbam + TX, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2- pyridyl]carbamate + TX, tetrachloroethane + TX, tetrachlorothiophene + TX, tetraconazole + TX, tetradec-11-en-1-yl acetate + TX, tetradifon + TX, tetramethylfluthrin + TX, tetrasul + TX, thallium sulfate + TX, thiaben¬dazole + TX, thiafenox + TX, thiapronil + TX, thicrofos + TX, thifluzamide + TX, thiocarboxime + TX, thiocyclam + TX, thiocyclam hydrogen oxalate + TX, thiodiazole copper + TX, thiofanox + TX, thiohempa + TX, thiomersal + TX, thiometon + TX, thionazin + TX, thiophanate + TX, thiophanate-methyl + TX, thioquinox + TX, thiosultap + TX, thiosultap-sodium + TX, thiotepa + TX, thiram + TX, thuringiensin + TX, tiadinil + TX, tolclofos-methyl + TX, tolprocarb + TX, tolylfluanid + TX, tralomethrin + TX, transpermethrin + TX, tretamine + TX, triadimefon + TX, triadime¬nol + TX,
triamiphos + TX, triarathene + TX, triazamate + TX, triazophos + TX, triazoxide + TX, triazuron + TX, tributyltin oxide + TX, trichlormetaphos-3 + TX, trichloronat + TX, Trichogramma spp. + TX, triclopyricarb + TX, tricyclazole + TX, tridemorph + TX, trifenmorph + TX, trifenofos + TX, trifloxystrobin + TX, triflumizole + TX, triforine + TX, trimedlure + TX, trimedlure A + TX, trimedlure B1 + TX, trimedlure B2 + TX, trimedlure C + TX, trimethacarb + TX, trinactin + TX, trinexapac + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, triprene + TX, triticonazole + TX, trunc-call + TX, Typhlodromus occidentalis + TX, uredepa + TX, validamycin + TX, valifenalate + TX, vamidothion + TX, vaniliprole + TX, veratridine + TX, veratrine + TX, verbutin + TX, Verticillium lecanii + TX, vinclozoline + TX, warfarin + TX, XMC + TX, xylenols + TX, zeatin + TX, zetamethrin + TX, zhongshengmycin + TX, zinc naphthenate + TX, zinc phosphide + TX, zinc thiazole + TX, zineb + TX, ziram + TX; Acinetobacter lwoffii + TX, Acremonium alternatum + TX, Acremonium cephalosporium + TX, Acremonium diospyri + TX, Acremonium obclavatum + TX, Adoxophyes orana granulovirus (AdoxGV) (Capex®) + TX, Agrobacterium radiobacter strain K84 (Galltrol-A®) + TX, Alternaria alternate + TX, Alternaria cassia + TX, Alternaria destruens (Smolder®) + TX, Ampelomyces quisqualis (AQ10®) + TX, Aspergillus flavus AF36 (AF36®) + TX, Aspergillus flavus NRRL 21882 (Aflaguard®) + TX, Aspergillus spp. + TX, Aureobasidium pullulans + TX, Azospirillum (MicroAZ®, TAZO B®) + TX, Azotobacter + TX, Azotobacter chroocuccum (Azotomeal®) + TX, Azotobacter cysts (Bionatural Blooming Blossoms®) + TX, Bacillus amyloliquefaciens + TX, Bacillus cereus + TX, Bacillus chitinosporus strain AQ746 + TX, Bacillus chitinosporus strain CM-1 + TX, Bacillus circulans + TX, Bacillus firmus (BioSafe®, BioNem- WP®) in particular strain CNMC 1-1582 (e.g. VOTIVO® from BASF SE) + TX, Bacillus licheniformis strain 3086 (EcoGuard®, Green Releaf®) + TX, Bacillus licheniformis strain HB-2 (Biostart™ formerly Rhizoboost®) + TX, Bacillus macerans + TX, Bacillus marismortui + TX, Bacillus megaterium + TX, Bacillus mycoides strain AQ726 + TX, Bacillus papillae (Milky Spore Powder®) + TX, Bacillus pumilus spp. + TX, Bacillus pumilus strain AQ717 + TX, Bacillus pumilus strain GB34 (Yield Shield®) + TX, Bacillus pumilus strain QST 2808 (Sonata®, Ballad Plus®) + TX, Bacillus sphaericus (VectoLex®) + TX, Bacillus spp. + TX, Bacillus spp. strain AQ175 + TX, Bacillus spp. strain AQ177 + TX, Bacillus spp. strain AQ178 + TX, Bacillus subtilis strain AQ153 + TX, Bacillus subtilis strain AQ743 + TX, Bacillus subtilis strain QST 713 (CEASE®, Serenade®, Rhapsody®) + TX, Bacillus subtilis strain QST 714 (JAZZ®) + TX, Bacillus subtilis strain QST3002 + TX, Bacillus subtilis strain QST3004 + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 (Taegro®, Rhizopro®) + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1Ab + TX, Bacillus thuringiensis israelensis (BMP123®, Aquabac®, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin®, Deliver®, CryMax®, Bonide®, Scutella WP®, Turilav WP ®, Astuto®, Dipel WP®, Biobit®, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF / 3P®) + TX, Bacillus thuringiensis strain AQ52 + TX, Bacillus thuringiensis strain BD#32 + TX, Bacillus thuringiensis tenebrionis (Novodor®, BtBooster) + TX, Bacillus thuringiensis var. aizawai (XenTari®, DiPel®) + TX, bacteria spp. (GROWMEND®, GROWSWEET®, Shootup®) + TX, bacteriophage of Clavipacter michiganensis (AgriPhage®, Bakflor®) + TX, Beauveria bassiana (Beaugenic®, Brocaril WP®) + TX, Beauveria bassiana GHA (Mycotrol ES®, Mycotrol O®,
BotaniGuard®) + TX, Beauveria brongniartii (Engerlingspilz®, Schweizer Beauveria®, Melocont®) + TX, Beauveria spp. + TX, Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Burkholderia cepacia (Deny®, Intercept®, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp. + TX, Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida reukaufii + TX, Candida saitoana (Bio-Coat®, Biocure®) + TX, Candida sake + TX, Candida spp. + TX, Candida tenius + TX, Cedecea davisae + TX, Cellulomonas flavigena + TX, Chaetomium cochliodes (Nova- Cide®) + TX, Chaetomium globosum (Nova-Cide®) + TX, Chromobacterium subtsugae strain PRAA4- 1T (Grandevo®) + TX, Cladosporium chlorocephalum + TX, Cladosporium cladosporioides + TX, Cladosporium oxysporum + TX, Cladosporium spp. + TX, Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp. + TX, Cryptococcus albidus (YIELDPLUS®) + TX, Cryptococcus humicola + TX, Cryptococcus infirmo-miniatus + TX, Cryptococcus laurentii + TX, Cryptophlebia leucotreta granulovirus (Cryptex®) + TX, Cupriavidus campinensis + TX, Cydia pomonella granulovirus (CYD-X®, Madex®, Madex® Plus, Madex Max, Carpovirusine® + TX, Cylindrobasidium laeve (Stumpout®) + TX, Cylindrocladium + TX, Debaryomyces hansenii + TX, Drechslera hawaiinensis + TX, Enterobacter cloacae + TX, Enterobacteriaceae + TX, Entomophtora virulenta (Vektor®) + TX, Epicoccum nigrum + TX, Epicoccum purpurascens + TX, Epicoccum spp. + TX, Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean®, Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop®, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp. (SoilGard®) + TX, Gliocladium virens (Soilgard®) + TX, Granulovirus (Granupom®) + TX, Halobacillus halophilus + TX, Halobacillus litoralis + TX, Halobacillus trueperi + TX, Halomonas spp. + TX, Halomonas subglaciescola + TX, Halovibrio variabilis + TX, Hanseniaspora uvarum + TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex®) + TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®) + TX, Isaria fumosorosea (previously known as Paecilomyces fumosoroseus strain, PFR-97®, PreFeRal®) + TX, Isoflavone formononetin (Myconate®) + TX, Kloeckera apiculata + TX, Kloeckera spp. + TX, Lagenidium giganteum (Laginex®) + TX, Lecanicillium lecanii (formerly known as Verticillium lecanii (Mycotal®) conidia of strain KV01 (e.g. Vertalec® by Koppert/Arysta) + TX, Lecanicillium longisporum (Vertiblast®) + TX, Lecanicillium muscarium (Vertikil®) + TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus®) + TX, Marinococcus halophilus + TX, Meira geulakonigii + TX, Metarhizium anisopliae (Destruxin WP®) + TX, Metarhizium anisopliae (Met52®) + TX, Metschnikowia fruticola (Shemer®) + TX, Metschnikowia pulcherrima + TX, Microdochium dimerum (Antibot®) + TX, Micromonospora coerulea + TX, Microsphaeropsis ochracea + TX, Muscodor albus 620 (Muscudor®) + TX, Muscodor roseus in particular strain A3-5 (Accession No. NRRL 30548) + TX, Mycorrhizae spp. (AMykor®, Root Maximizer®) + TX, Myrothecium verrucaria strain AARC-0255 (DiTera®, BROS PLUS®) + TX, Ophiostoma piliferum strain D97 (Sylvanex®) + TX, Paecilomyces farinosus + TX, Paecilomyces lilacinus strain 251 (MeloCon WG®) + TX, Paecilomyces linacinus
(Biostat WP®) + TX, Paenibacillus polymyxa + TX, Pantoea agglomerans (BlightBan C9-1®) + TX, Pantoea spp. + TX, Pasteuria nishizawae in particular strain Pn1 (CLARIVA from Syngenta/ChemChina); + TX, Pasteuria spp. (Econem®) + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart®, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp. + TX, Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, phosphate solubilizing bacteria (Phosphomeal®) + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilliermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa + TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, Pseudomonas fluorescens (Zequanox®) + TX, Pseudomonas fluorescens strain A506 (BlightBan A506®) + TX, Pseudomonas putida + TX, Pseudomonas reactans + TX, Pseudomonas spp. + TX, Pseudomonas syringae (Bio-Save®) + TX, Pseudomonas viridiflava + TX, Pseudozyma flocculosa strain PF-A22 UL (Sporodex L®) + TX, Puccinia canaliculata + TX, Puccinia thlaspeos (Wood Warrior®) + TX, Pythium paroecandrum + TX, Pythium oligandrum (Polygandron®, Polyversum®) + TX, Pythium periplocum + TX, Rhanella aquatilis + TX, Rhanella spp. + TX, Rhizobia (Dormal®, Vault®) + TX, Rhizoctonia + TX, Rhodococcus globerulus strain AQ719 + TX, Rhodosporidium diobovatum + TX, Rhodosporidium toruloides + TX, Rhodotorula glutinis + TX, Rhodotorula graminis + TX, Rhodotorula mucilagnosa + TX, Rhodotorula rubra + TX, Rhodotorula spp. + TX, Saccharomyces cerevisiae + TX, Salinococcus roseus + TX, Sclerotinia minor (SARRITOR®) + TX, Sclerotinia minor + TX, Scytalidium spp. + TX, Scytalidium uredinicola + TX, Serratia marcescens + TX, Serratia plymuthica + TX, Serratia spp. + TX, Sordaria fimicola + TX, Spodoptera exigua nuclear polyhedrosis virus (Spod-X®, Spexit®) + TX, Spodoptera littoralis nucleopolyhedrovirus (Littovir®) + TX, Sporobolomyces roseus + TX, Stenotrophomonas maltophilia + TX, Streptomyces albaduncus + TX, Streptomyces exfoliates + TX, Streptomyces galbus + TX, Streptomyces griseoplanus + TX, Streptomyces griseoviridis (Mycostop®) + TX, Streptomyces hygroscopicus + TX, Streptomyces lydicus (Actinovate®) + TX, Streptomyces lydicus WYEC-108 (ActinoGrow®) + TX, Streptomyces violaceus + TX, Tilletiopsis minor + TX, Tilletiopsis spp. + TX, Trichoderma asperellum (T34 Biocontrol®) + TX, Trichoderma atroviride (Plantmate®) + TX, Trichoderma gamsii (Tenet®) + TX, Trichoderma hamatum TH 382 + TX, Trichoderma harzianum rifai (Mycostar®) + TX, Trichoderma harzianum T-22 (Trianum- P®, PlantShield HC®, RootShield®, Trianum-G® + TX, Trichoderma harzianum T-39 (Trichodex®) + TX, Trichoderma inhamatum + TX, Trichoderma koningii + TX, Trichoderma lignorum + TX, Trichoderma longibrachiatum + TX, Trichoderma polysporum (Binab T®) + TX, Trichoderma spp. LC 52 (Sentinel®) + TX, Trichoderma taxi + TX, Trichoderma virens (formerly Gliocladium virens GL-21) (SoilGuard®) + TX, Trichoderma virens + TX, Trichoderma viride + TX, Trichoderma viride strain ICC 080 (Remedier®) + TX, Trichosporon pullulans + TX, Trichosporon spp. + TX, Trichothecium roseum + TX, Trichothecium spp. + TX, Typhula phacorrhiza strain 94670 + TX, Typhula phacorrhiza strain 94671 + TX, Ulocladium atrum + TX, Ulocladium oudemansii (Botry-Zen®) + TX, Ustilago maydis + TX, various bacteria and supplementary micronutrients (Natural II®) + TX, various fungi (Millennium Microbes®) + TX, Verticillium chlamydosporium + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX,
Xanthomonas campestris pv. Poae (Camperico®) + TX, Xenorhabdus bovienii + TX, Xenorhabdus nematophilus + TX; AGNIQUE® MMF + TX, azadirachtin (Plasma Neem Oil®, AzaGuard®, MeemAzal®, Molt-X® e.g. AZATIN XL from Certis, US) + TX, Botanical IGR (Neemazad®, Neemix®) + TX, BugOil® + TX, canola oil (Lilly Miller Vegol®) + TX, Chenopodium ambrosioides near ambrosioides (Requiem®) + TX, Chrysanthemum extract (Crisant®) + TX, essentials oils of Labiatae (Botania®) + TX, extract of neem oil (Trilogy®) + TX, extracts of clove rosemary peppermint and thyme oil (Garden insect killer®) + TX, garlic + TX, Glycinebetaine (Greenstim®) + TX, kaolin (Screen®) + TX, lemongrass oil (GreenMatch®) + TX, Melaleuca alternifolia extract (also called tea tree oil) (Timorex Gold®) + TX, mixture of clove pepermint garlic oil and mint (Soil Shot®) + TX, mixture of clove rosemary and peppermint extract (EF 400®) + TX, mixture of rosemary sesame pepermint thyme and cinnamon extracts (EF 300®) + TX, neem oil + TX, Nepeta cataria (Catnip oil) + TX, Nepeta catarina + TX, nicotine + TX, oregano oil (MossBuster®) + TX, Pedaliaceae oil (Nematon®) + TX, pine oil (Retenol®) + TX, pyrethrum + TX, Quillaja saponaria (NemaQ®) + TX, Reynoutria sachalinensis (Regalia®, Sakalia®) + TX, rotenone (Eco Roten®) + TX, Rutaceae plant extract (Soleo®) + TX, soybean oil (Ortho ecosense®) + TX, storage glucam of brown algae (Laminarin®) + TX, thyme oil + TX; (E,Z)-7,9-Dodecadien-1-yl acetate + TX, (E,Z,Z)-3,8,11 Tetradecatrienyl acetate + TX, (Z,Z,E)-7,11,13- Hexadecatrienal + TX, 2-Methyl-1-butanol + TX, Biolure® + TX, blackheaded fireworm pheromone (3M Sprayable Blackheaded Fireworm Pheromone®) + TX, Calcium acetate + TX, Check-Mate® + TX, Codling Moth Pheromone (Paramount dispenser-(CM)/ Isomate C-Plus®) + TX, Entostat powder (extract from palm tree) (Exosex CM®) + TX, Grape Berry Moth Pheromone (3M MEC-GBM Sprayable Pheromone®) + TX, Lavandulyl senecioate + TX, Leafroller pheromone (3M MEC – LR Sprayable Pheromone®) + TX, Muscamone (Snip7 Fly Bait® + TX, Oriental Fruit Moth Pheromone (3M oriental fruit moth sprayable pheromone®) + TX, Peachtree Borer Pheromone (Isomate-P®) + TX, Scenturion® + TX, Starbar Premium Fly Bait®) + TX, Tomato Pinworm Pheromone (3M Sprayable pheromone®) + TX; Acerophagus papaya + TX, Adalia bipunctata (Adalia-System®) + TX, Adalia bipunctata (Adaline®) + TX, Adalia bipunctata (Aphidalia®) + TX, Ageniaspis citricola + TX, Ageniaspis fuscicollis + TX, Amblyseius andersoni (Anderline®, Andersoni-System®) + TX, Amblyseius californicus (Amblyline®, Spical®) + TX, Amblyseius cucumeris (Thripex®, Bugline cucumeris®) + TX, Amblyseius fallacis (Fallacis®) + TX, Amblyseius swirskii (Bugline swirskii®, Swirskii-Mite®) + TX, Amblyseius womersleyi (WomerMite®) + TX, Amitus hesperidum + TX, Anagrus atomus + TX, Anagyrus fusciventris + TX, Anagyrus kamali + TX, Anagyrus loecki + TX, Anagyrus pseudococci (Citripar®) + TX, Anicetus benefices + TX, Anisopteromalus calandrae + TX, Anthocoris nemoralis (Anthocoris-System®) + TX, Aphelinus abdominalis (Apheline®, Aphiline®), + TX, Aphelinus asychis + TX, Aphidius colemani (Aphipar®) + TX, Aphidius ervi (Aphelinus-System®) + TX, Aphidius ervi (Ervipar®) + TX, Aphidius gifuensis + TX, Aphidius matricariae (Aphipar-M®) + TX, Aphidoletes aphidimyza (Aphidend®, Aphidoline®) + TX, Aphytis lingnanensis + TX, Aphytis melinus + TX, Aprostocetus hagenowii + TX, Atheta coriaria (Staphyline®) + TX, Bombus spp. + TX, Bombus terrestris (Beeline®, Tripol®) + TX, Bombus terrestris (Natupol Beehive®) + TX, Cephalonomia stephanoderis + TX, Chilocorus nigritus +
TX, Chrysoperla carnea (Chrysoline®, Chrysopa®) + TX, Chrysoperla rufilabris + TX, Cirrospilus ingenuus + TX, Cirrospilus quadristriatus + TX, Citrostichus phyllocnistoides + TX, Closterocerus chamaeleon + TX, Closterocerus spp. + TX, Coccidoxenoides perminutus (Planopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia flavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug®, Cryptoline®) + TX, Cybocephalus nipponicus + TX, Dacnusa sibirica (Minusa®, DacDigline®, Minex®) + TX, Delphastus catalinae (Delphastus®) + TX, Delphastus pusillus + TX, Diachasmimorpha krausii + TX, Diachasmimorpha longicaudata + TX, Diaparsis jucunda + TX, Diaphorencyrtus aligarhensis + TX, Diglyphus isaea (Diminex®, Miglyphus®, Digline®) + TX, Diversinervus spp. + TX, Encarsia citrina + TX, Encarsia formosa (Encarsia max®, Encarline®, En-Strip®) + TX, Encarsia guadeloupae + TX, Encarsia haitiensis + TX, Episyrphus balteatus (Syrphidend®) + TX, Eretmoceris siphonini + TX, Eretmocerus californicus + TX, Eretmocerus eremicus (Enermix®, Ercal®, Eretline e®, Bemimix®) + TX, Eretmocerus hayati + TX, Eretmocerus mundus (Bemipar®, Eretline m®) + TX, Eretmocerus siphonini + TX, Exochomus quadripustulatus + TX, Feltiella acarisuga (Feltiline®) + TX, Feltiella acarisuga (Spidend®) + TX, Fopius arisanus + TX, Fopius ceratitivorus + TX, Formononetin (Wirless Beehome®) + TX, Franklinothrips vespiformis (Vespop®) + TX, Galendromus occidentalis + TX, Goniozus legneri + TX, Habrobracon hebetor + TX, Harmonia axyridis (HarmoBeetle®) + TX, Heterorhabditis bacteriophora (NemaShield HB®, Nemaseek®, Terranem-Nam®, Terranem®, Larvanem®, B-Green®, NemAttack ®, Nematop®) + TX, Heterorhabditis megidis (Nemasys H®, BioNem H®, Exhibitline hm®, Larvanem-M®) + TX, Heterorhabditis spp. (Lawn Patrol®) + TX, Hippodamia convergens + TX, Hypoaspis aculeifer (Aculeifer-System®, Entomite-A®) + TX, Hypoaspis miles (Hypoline m®, Entomite-M®) + TX, Lbalia leucospoides + TX, Lecanoideus floccissimus + TX, Lemophagus errabundus + TX, Leptomastidea abnormis + TX, Leptomastix dactylopii (Leptopar®) + TX, Leptomastix epona + TX, Lindorus lophanthae + TX, Lipolexis oregmae + TX, Lucilia caesar (Natufly®) + TX, Lysiphlebus testaceipes + TX, Macrolophus caliginosus (Mirical-N®, Macroline c®, Mirical®) + TX, Mesoseiulus longipes + TX, Metaphycus flavus + TX, Metaphycus lounsburyi + TX, Micromus angulatus (Milacewing®) + TX, Microterys flavus + TX, Muscidifurax raptorellus and Spalangia cameroni (Biopar®) + TX, Neodryinus typhlocybae + TX, Neoseiulus californicus + TX, Neoseiulus cucumeris (THRYPEX®) + TX, Neoseiulus fallacis + TX, Nesideocoris tenuis (NesidioBug®, Nesibug®) + TX, Ophyra aenescens (Biofly®) + TX, Orius insidiosus (Thripor-I®, Oriline i®) + TX, Orius laevigatus (Thripor-L®, Oriline l®) + TX, Orius majusculus (Oriline m®) + TX, Orius strigicollis (Thripor-S®) + TX, Pauesia juniperorum + TX, Pediobius foveolatus + TX, Phasmarhabditis hermaphrodita (Nemaslug®) + TX, Phymastichus coffea + TX, Phytoseiulus macropilus + TX, Phytoseiulus persimilis (Spidex®, Phytoline p®) + TX, Podisus maculiventris (Podisus®) + TX, Pseudacteon curvatus + TX, Pseudacteon obtusus + TX, Pseudacteon tricuspis + TX, Pseudaphycus maculipennis + TX, Pseudleptomastix mexicana + TX, Psyllaephagus pilosus + TX, Psyttalia concolor (complex) + TX, Quadrastichus spp. + TX, Rhyzobius lophanthae + TX, Rodolia cardinalis + TX, Rumina decollate + TX, Semielacher petiolatus + TX, Sitobion avenae (Ervibank®) + TX, Steinernema carpocapsae (Nematac C®, Millenium®, BioNem C®, NemAttack®, Nemastar®, Capsanem®) + TX, Steinernema feltiae (NemaShield®, Nemasys F®, BioNem F®, Steinernema-System®, NemAttack®, Nemaplus®, Exhibitline sf®, Scia-rid®, Entonem®) + TX,
Steinernema kraussei (Nemasys L®, BioNem L®, Exhibitline srb®) + TX, Steinernema riobrave (BioVector®, BioVektor®) + TX, Steinernema scapterisci (Nematac S®) + TX, Steinernema spp. + TX, Steinernematid spp. (Guardian Nematodes®) + TX, Stethorus punctillum (Stethorus®) + TX, Tamarixia radiate + TX, Tetrastichus setifer + TX, Thripobius semiluteus + TX, Torymus sinensis + TX, Trichogramma brassicae (Tricholine b®) + TX, Trichogramma brassicae (Tricho-Strip®) + TX, Trichogramma evanescens + TX, Trichogramma minutum + TX, Trichogramma ostriniae + TX, Trichogramma platneri + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator + TX; abscisic acid + TX, Aminomite® + TX, BioGain® + TX, bioSea® + TX, CAS Number: 2643947-26-4 + TX, Chondrostereum purpureum (Chontrol Paste®) + TX, Colletotrichum gloeosporioides (Collego®) + TX, Copper Octanoate (Cueva®) + TX, Delta traps (Trapline d®) + TX, Erwinia amylovora (Harpin) (ProAct®, Ni-HIBIT Gold CST®) + TX, fatty acids derived from a natural by-product of extra virgin olive oil (FLIPPER®) + TX, Ferri-phosphate (Ferramol®) + TX, Funnel traps (Trapline y®) + TX, Gallex® + TX, Grower's Secret® + TX, Homo-brassonolide + TX, Iron Phosphate (Lilly Miller Worry Free Ferramol Slug & Snail Bait®) + TX, MCP hail trap (Trapline f®) + TX, Microctonus hyperodae + TX, Mycoleptodiscus terrestris (Des-X®) + TX, Nosema locustae (Semaspore Organic Grasshopper Control®) + TX, Pheromone trap (Thripline ams®) + TX, potassium bicarbonate (MilStop®) + TX, potassium iodide + potassiumthiocyanate (Enzicur®) + TX, potassium salts of fatty acids (Sanova®) + TX, potassium silicate solution (Sil-Matrix®) + TX, Spider venom + TX, Sticky traps (Trapline YF®, Rebell Amarillo®) + TX, SuffOil-X® + TX, Traps (Takitrapline y + b®) + TX; Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX, Bacillus pumilus, in particular strain BU F-33, having NRRL Accession No. 50185 (CARTISSA® from BASF, EPA Reg. No. 71840-19) + TX, Bacillus subtilis CX-9060 from Certis USA LLC, Bacillus sp., in particular strain D747 (available as DOUBLE NICKEL® from Kumiai Chemical Industry Co., Ltd.), having Accession No. FERM BP-8234, U.S. Patent No.7,094,592 + TX, Bacillus subtilis strain BU1814, (VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No.70127-5)) + TX, Bacillus subtilis, in particular strain QST713/AQ713 (having NRRL Accession No. B-21661 and described in U.S. Patent No.6,060,051, available as SERENADE® OPTI or SERENADE® ASO from Bayer CropScience LP, US) + TX, Paenibacillus polymyxa, in particular strain AC-1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX, Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX, Pantoea agglomerans, in particular strain E325 (Accession No. NRRL B-21856) (available as BLOOMTIME BIOLOGICAL™ FD BIOPESTICIDE from Northwest Agri Products) + TX, Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or mixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR® and BLOSSOM PROTECT® from bio-ferm, CH) + TX, Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem)
+ TX, Saccharomyces cerevisiae, in particular strains CNCM No.1-3936, CNCM No.1-3937, CNCM No.1-3938 or CNCM No.1-3939 (WO 2010/086790) from Lesaffre et Compagnie, FR + TX; Agrobacterium radiobacter strain K84 (e.g. GALLTROL-A® from AgBioChem, CA) + TX, Bacillus amyloliquefaciens isolate B246 (e.g. AVOGREEN™ from University of Pretoria) + TX, Bacillus amyloliquefaciens strain F727 (also known as strain MBI110) (NRRL Accession No. B-50768, WO 2014/028521) (STARGUS® from Marrone Bio Innovations) + TX, Bacillus amyloliquefaciens strain FZB42, Accession No. DSM 23117 (available as RHIZOVITAL® from ABiTEP, DE) + TX, Bacillus amyloliquefaciens, in particular strain D747 (available as Double Nickel™ from Kumiai Chemical Industry Co., Ltd., having accession number FERM BP-8234, US Patent No.7,094,592) + TX, Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (QUARTZO® (WG) and PRESENCE® (WP) from FMC Corporation) + TX, Bacillus licheniformis, in particular strain SB3086, having Accession No. ATCC 55406, WO 2003/000051 (available as ECOGUARD® Biofungicide and GREEN RELEAF™ from Novozymes) + TX, Bacillus methylotrophicus strain BAC-9912 (from Chinese Academy of Sciences’ Institute of Applied Ecology) + TX, Bacillus mycoides, isolate, having Accession No. B-30890 (available as BMJ TGAI® or WG and LifeGard™ from Certis USA LLC) + TX, Bacillus pumilus, in particular strain GB34 (available as Yield Shield® from Bayer AG, DE) + TX, Bacillus pumilus, in particular strain QST2808 (available as SONATA® from Bayer CropScience LP, US, having Accession No. NRRL B- 30087 and described in U.S. Patent No.6,245,551) + TX, Bacillus subtilis CX-9060 from Certis USA LLC + TX, Bacillus subtilis IAB/BS03 (AVIV™ from STK Bio-Ag Technologies, PORTENTO® from Idai Nature) + TX, Bacillus subtilis KTSB strain (FOLIACTIVE® from Donaghys) + TX, Bacillus subtilis strain BU1814, (available as VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX, Bacillus subtilis strain GB03 (available as Kodiak® from Bayer AG, DE) + TX, Bacillus subtilis strain MBI 600 (available as SUBTILEX from BASF SE), having Accession Number NRRL B-50595, U.S. Patent No.5,061,495 + TX, Bacillus subtilis strain Y1336 (available as BIOBAC® WP from Bion- Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277) + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No.70127-5)) + TX, Bacillus subtilis Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos. 4764, 5454, 5096 and 5277) + TX, Paenibacillus epiphyticus (WO 2016/020371) from BASF SE + TX, Paenibacillus polymyxa ssp. plantarum (WO 2016/020371) from BASF SE + TX, Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX, Pseudomonas chlororaphis strain AFS009, having Accession No. NRRL B-50897, WO 2017/019448 (e.g., HOWLER™ and ZIO® from AgBiome Innovations, US) + TX, Pseudomonas chlororaphis, in particular strain MA342 (e.g. CEDOMON®, CERALL®, and CEDRESS® by Bioagri and Koppert) + TX, Pseudomonas fluorescens strain A506 (e.g. BLIGHTBAN® A506 by NuFarm) + TX, Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX, Streptomyces griseoviridis strain K61 (also known as Streptomyces galbus strain K61) (Accession No. DSM 7206) (MYCOSTOP® from Verdera, PREFENCE® from BioWorks, cf. Crop Protection 2006, 25, 468-475) + TX, Streptomyces lydicus strain WYEC108 (also known as
Streptomyces lydicus strain WYCD108US) (ACTINO-IRON® and ACTINOVATE® from Novozymes) + TX; Trichoderma atroviride strain T11 (IMI352941/ CECT20498) + TX, Ampelomyces quisqualis strain AQ10, having Accession No. CNCM 1-807 (e.g., AQ 10® by IntrachemBio Italia) + TX, Ampelomyces quisqualis, in particular strain AQ 10 (e.g. AQ 10® by IntrachemBio Italia) + TX, Aspergillus flavus strain NRRL 21882 (products known as AFLA-GUARD® from Syngenta/ChemChina) + TX, Aureobasidium pullulans, in particular blastospores of strain DSM 14941 + TX, Aureobasidium pullulans, in particular blastospores of strain DSM14940 + TX, Aureobasidium pullulans, in particular mixtures of blastospores of strains DSM14940 and DSM 14941 (e.g. Botector® by bio-ferm, CH) + TX, Chaetomium cupreum (Accession No. CABI 353812) (e.g. BIOKUPRUM™ by AgriLife) + TX, Chaetomium globosum (available as RIVADIOM® by Rivale) + TX, Cladosporium cladosporioides, strain H39, having Accession No. CBS122244, US 2010/0291039 (by Stichting Dienst Landbouwkundig Onderzoek) + TX, Coniothyrium minitans, in particular strain CON/M/91-8 (Accession No. DSM9660, e.g. Contans ® from Bayer CropScience Biologics GmbH) + TX, Cryptococcus flavescens, strain 3C (NRRL Y-50378), + TX, Dactylaria candida, Dilophosphora alopecuri (available as TWIST FUNGUS®), Fusarium oxysporum, strain Fo47 (available as FUSACLEAN® by Natural Plant Protection) + TX, Gliocladium catenulatum (Synonym: Clonostachys rosea f. catenulate) strain J1446 (e.g. Prestop ® by Lallemand) + TX, Gliocladium roseum (also known as Clonostachys rosea f rosea) strain IK726 (Jensen DF, et al. Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain ’IK726’, Australasian Plant Pathol. 2007,36(2):95-101) + TX, Gliocladium roseum (also known as Clonostachys rosea f rosea), in particular strain 321U from Adjuvants Plus, strain ACM941 as disclosed in Xue A.G. (Efficacy of Clonostachys rosea strain ACM941 and fungicide seed treatments for controlling the root tot complex of field pea, Can Jour Plant Sci 2003, 83(3): 519-524) + TX, Metschnikowia fructicola, in particular strain NRRL Y- 30752 + TX, Microsphaeropsis ochracea, Penicillium steckii (DSM 27859, WO 2015/067800) from BASF SE + TX, mixtures of Trichoderma asperellum strain ICC 012 (also known as Trichoderma harzianum ICC012), having Accession No. CABI CC IMI 392716 and Trichoderma gamsii (formerly T. viride) strain ICC 080, having Accession No. IMI 392151 (e.g., BIO-TAM™ from Isagro USA, Inc. or BIODERMA® by Agrobiosol de Mexico, S.A. de C.V.) + TX, Penicillium vermiculatum + TX, Phlebiopsis gigantea strain VRA 1992 (ROTSTOP® C from Danstar Ferment) + TX, Pseudozyma flocculosa, strain PF-A22 UL (available as SPORODEX® L by Plant Products Co., CA) + TX, Saccharomyces cerevisiae strain LAS117 cell walls (CEREVISANE® from Lesaffre, ROMEO® from BASF SE) + TX, Saccharomyces cerevisiae strains CNCM No.1-3936, CNCM No.1-3937, CNCM No.1-3938, CNCM No.1-3939 (WO 2010/086790) from Lesaffre et Compagnie, FR + TX, Saccharomyces cerevisiae, in particular strain LASO2 (from Agro-Levures et Dérivés) + TX, Simplicillium lanosoniveum + TX, strain T34 (e.g. T34 Biocontrol by Biocontrol Technologies S.L., ES) or strain ICC 012 from Isagro + TX, strain WRL-076 (NRRL Y-30842), U.S. Patent No. 7,579,183 + TX, Talaromyces flavus, strain V117b + TX, Trichoderma asperelloides JM41R (Accession No. NRRL B-50759) (TRICHO PLUS® from BASF SE) + TX, Trichoderma asperellum, in particular strain SKT-1, having Accession No. FERM P-16510 (e.g. ECO-HOPE® from Kumiai Chemical Industry) + TX, Trichoderma asperellum, in particular, strain kd
(e.g. T-Gro from Andermatt Biocontrol) + TX, Trichoderma atroviride strain 77B (T77 from Andermatt Biocontrol) + TX, Trichoderma atroviride strain ATCC 20476 (IMI 206040) + TX, Trichoderma atroviride strain LC52 (e.g. Tenet by Agrimm Technologies Limited) + TX, Trichoderma atroviride strain LU132 (e.g. Sentinel from Agrimm Technologies Limited) + TX, Trichoderma atroviride strain NMI no. V08/002388 + TX, Trichoderma atroviride strain NMI no. V08/002389 + TX, Trichoderma atroviride strain NMI no. V08/002390 + TX, Trichoderma atroviride strain no. V08/002387 + TX, Trichoderma atroviride strain SKT-1 (FERM P-16510), JP Patent Publication (Kokai) 11-253151 A + TX, Trichoderma atroviride strain SKT-2 (FERM P-16511), JP Patent Publication (Kokai) 11-253151 A + TX, Trichoderma atroviride strain SKT-3 (FERM P-17021), JP Patent Publication (Kokai) 11-253151 A + TX, Trichoderma atroviride, in particular strain SC1 (Accession No. CBS 122089, WO 2009/116106 and U.S. Patent No. 8,431,120 (from Bi-PA)) + TX, Trichoderma atroviride,strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR) + TX, Trichoderma fertile (e.g. product TrichoPlus from BASF) + TX, Trichoderma gamsii (formerly T. viride) + TX, Trichoderma gamsii (formerly T. viride) strain ICC 080 (IMI CC 392151 CABI) (available as BIODERMA® by AGROBIOSOL DE MEXICO, S.A. DE C.V.), + TX, Trichoderma gamsii strain ICC080 (IMI CC 392151 CABI, e.g. BioDerma by AGROBIOSOL DE MEXICO, S.A. DE C.V.), + TX, Trichoderma harmatum + TX, Trichoderma harmatum, having Accession No. ATCC 28012 + TX, Trichoderma harzianum + TX, Trichoderma harzianum rifai T39 (e.g. Trichodex® from Makhteshim, US) + TX, Trichoderma harzianum strain Cepa SimbT5 (from Simbiose Agro), + TX, Trichoderma harzianum strain DB 103 (available as T-GRO® 7456 by Dagutat Biolab) + TX, Trichoderma harzianum strain ITEM 908 (e.g. Trianum-P from Koppert) + TX, Trichoderma harzianum strain T-22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) + TX, Trichoderma harzianum strain TH35 (e.g. Root-Pro by Mycontrol) + TX, Trichoderma polysporum strain IMI 206039 (e.g. Binab TF WP by BINAB Bio-Innovation AB, Sweden) + TX, Trichoderma stromaticum having Accession No. Ts3550 (e.g. Tricovab by CEPLAC, Brazil) + TX, Trichoderma virens (also known as Gliocladium virens) in particular strain GL-21 (e.g. SoilGard by Certis, US) + TX, Trichoderma virens strain G-41, formerly known as Gliocladium virens (Accession No. ATCC 20906) (e.g., ROOTSHIELD® PLUS WP and TURFSHIELD® PLUS WP from BioWorks, US) + TX, Trichoderma viride in particular strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125-137) + TX, Trichoderma viride strain TV1(e.g. Trianum-P by Koppert) + TX, Ulocladium oudemansii strain U3, having Accession No. NM 99/06216 (e.g., BOTRY-ZEN® by Botry-Zen Ltd, New Zealand and BOTRYSTOP® from BioWorks, Inc.) + TX, Verticillium albo-atrum (formerly V. dahliae) strain WCS850 having Accession No. WCS850, deposited at the Central Bureau for Fungi Cultures (e.g., DUTCH TRIG® by Tree Care Innovations) + TX, Verticillium chlamydosporium + TX; a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE® from Agrinos) + TX, a mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (available as QUARTZO® (WG), PRESENCE® (WP) from FMC Corporation) + TX, Azorhizobium caulinodans, in particular strain ZB-SK-5 + TX, Azospirillum brasilense (e.g., VIGOR® from KALO, Inc.) + TX, Azospirillum lipoferum (e.g., VERTEX-IF™ from TerraMax, Inc.) + TX, Azotobacter chroococcum, in particular strain H23 + TX, Azotobacter vinelandii, in particular strain ATCC 12837 + TX, Bacillus amyloliquefaciens BS27 (Accession No. NRRL B-5015) + TX, Bacillus amyloliquefaciens in particular
strain FZB42 (e.g. RHIZOVITAL® from ABiTEP, DE) + TX, Bacillus amyloliquefaciens in particular strain IN937a + TX, Bacillus amyloliquefaciens pm414 (LOLI-PEPTA® from Biofilm Crop Protection) + TX, Bacillus amyloliquefaciens SB3281 (ATCC # PTA-7542, WO 2017/205258) + TX, Bacillus amyloliquefaciens TJ1000 (available as QUIKROOTS® from Novozymes) + TX, Bacillus cereus family member EE128 (NRRL No. B-50917) + TX, Bacillus cereus family member EE349 (NRRL No. B-50928) + TX, Bacillus cereus in particular strain BP01 (ATCC 55675, e.g. MEPICHLOR® from Arysta Lifescience, US) + TX, Bacillus mycoides BT155 (NRRL No. B-50921) + TX, Bacillus mycoides BT46- 3 (NRRL No. B-50922) + TX, Bacillus mycoides EE118 (NRRL No. B-50918) + TX, Bacillus mycoides EE141 (NRRL No. B-50916) + TX, Bacillus pumilus in particular strain GB34 (e.g. YIELD SHIELD® from Bayer Crop Science, DE), + TX, Bacillus pumilus in particular strain QST2808 (Accession No. NRRL No. B-30087) + TX, Bacillus siamensis in particular strain KCTC 13613T + TX, Bacillus subtilis in particular strain AQ30002 (Accession No. NRRL No. B-50421 and described in U.S. Patent Application No. 13/330,576) + TX, Bacillus subtilis in particular strain AQ30004 (NRRL No. B-50455 and described in U.S. Patent Application No.13/330,576) + TX, Bacillus subtilis in particular strain MBI 600 (e.g. SUBTILEX® from BASF SE) + TX, Bacillus subtilis rm303 (RHIZOMAX® from Biofilm Crop Protection) + TX, Bacillus subtilis strain BU1814 (available as TEQUALIS® from BASF SE) + TX, Bacillus tequilensis in particular strain NII-0943 + TX, Bacillus thuringiensis BT013A (NRRL No. B- 50924) also known as Bacillus thuringiensis 4Q7 + TX, Bradyrhizobium japonicum (e.g. OPTIMIZE® from Novozymes) + TX, Delftia acidovorans in particular strain RAY209 (e.g. BIOBOOST® from Brett Young Seeds) + TX, Lactobacillus sp. (e.g. LACTOPLANT® from LactoPAFI) + TX, Mesorhizobium cicer (e.g., NODULATOR from BASF SE) + TX, Paenibacillus polymyxa in particular strain AC-1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX, Pseudomonas aeruginosa in particular strain PN1 + TX, Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX, Rhizobium leguminosarium biovar viciae (e.g., NODULATOR from BASF SE) + TX, Rhizobium leguminosarum in particular bv. viceae strain Z25 (Accession No. CECT 4585) + TX, Serratia marcescens in particular strain SRM (Accession No. MTCC 8708), + TX, Sinorhizobium meliloti strain NRG-185-1 (NITRAGIN® GOLD from Bayer CropScience) + TX, Thiobacillus sp. (e.g. CROPAID® from Cropaid Ltd UK) + TX; Myrothecium verrucaria strain AARC-0255 (e.g. DiTera™ from Valent Biosciences) + TX, Penicillium bilaii strain ATCC 22348 (e.g. JumpStart® from Acceleron BioAg) + TX, Penicillium bilaii strain ATCC ATCC20851 + TX, Purpureocillium lilacinum (previously known as Paecilomyces lilacinus) strain 251 (AGAL 89/030550, e.g. BioAct from Bayer CropScience Biologics GmbH) + TX, Pythium oligandrum strain DV74 + TX, Pythium oligandrum strain M1 (ATCC 38472 e.g. Polyversum from Bioprepraty, CZ) + TX, Rhizopogon amylopogon (Myco-Sol from Agri-Enterprise, LLC, formerly Helena Chemical Company) + TX, Rhizopogon fulvigleba (e.g. Myco-Sol from Agri-Enterprise, LLC, formerly Helena Chemical Company) + TX, Talaromyces flavus strain V117b + TX, Trichoderma asperellum strain (Eco- T from Plant Health Products, ZA) + TX, Trichoderma asperellum strain kd (e.g. T-Gro from Andermatt Biocontrol) + TX, Trichoderma atroviride in particular strain no. V08/002387 + TX, Trichoderma atroviride strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR) + TX, Trichoderma atroviride strain LC52 (also known as Trichoderma atroviride strain LU132, e.g. Sentinel from Agrimm Technologies Limited) + TX, Trichoderma atroviride strain no. NMI No. V08/002388 + TX, Trichoderma
atroviride strain no. NMI No. V08/002389 + TX, Trichoderma atroviride strain no. NMI No. V08/002390 + TX, Trichoderma atroviride strain SC1 (described in WO2009/116106) + TX, Trichoderma harzianum strain 1295-22 + TX, Trichoderma harzianum strain ITEM 908 + TX, Trichoderma harzianum strain T- 22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) + TX, Trichoderma harzianum strain TSTh20, + TX, Trichoderma virens strain GI-3 + TX, Trichoderma virens strain GL-21 (e.g. SoilGard® from Certis, USA) + TX, Trichoderma viride strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125- 137) + TX, Verticillium albo-atrum (formerly V. dahliae) strain WCS850 (CBS 276.92, e.g. Dutch Trig from Tree Care Innovations) + TX; Agrobacterium radiobacter strain K84 (Galltrol from AgBiochem Inc.), + TX, Bacillus amyloliquefaciens in particular strain PTS-4838 (e.g. AVEO from Valent Biosciences, US), + TX, Bacillus mycoides, isolate J. (e.g. BmJ from Certis USA LLC), + TX, Bacillus sphaericus in particular Serotype H5a5b strain 2362 (strain ABTS-1743) (e.g. VECTOLEX® from Valent BioSciences, US), + TX, Bacillus thuringiensis israelensis strain BMP 144 (e.g. AQUABAC® by Becker Microbial Products IL) + TX, Bacillus thuringiensis subsp. aizawai strain GC-91 + TX, Bacillus thuringiensis subsp. aizawai, in particular serotype H-7 (e.g. FLORBAC® WG from Valent BioSciences, US) + TX, Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372, e.g. XENTARI® from Valent BioSciences) + TX, Bacillus thuringiensis subsp. israelensis (serotype H-14) strain AM65-52 (Accession No. ATCC 1276) (e.g. VECTOBAC® by Valent BioSciences, US) + TX, Bacillus thuringiensis subsp. kurstaki strain ABTS 351 + TX, Bacillus thuringiensis subsp. kurstaki strain BMP 123 (from Becker Microbial Products, IL, BARITONE from Bayer CropScience) + TX, Bacillus thuringiensis subsp. kurstaki strain EG 2348 (LEPINOX from Certis, US) + TX, Bacillus thuringiensis subsp. kurstaki strain EG 7841 (CRYMAX from Certis, US) + TX, Bacillus thuringiensis subsp. kurstaki strain HD-1 (e.g. DIPEL® ES from Valent BioSciences, US) + TX, Bacillus thuringiensis subsp. kurstaki strain PB 54 + TX, Bacillus thuringiensis subsp. kurstaki strain SA 11 (JAVELIN from Certis, US) + TX, Bacillus thuringiensis subsp. kurstaki strain SA 12 (THURICIDE from Certis, US) + TX, Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428, e.g. NOVODOR® FC from BioFa DE) + TX, Bacillus thuringiensis var. Colmeri (e.g. TIANBAOBTC by Changzhou Jianghai Chemical Factory) + TX, Bacillus thuringiensis var. japonensis strain Buibui + TX, Bacillus thuringiensis var. kurstaki strain EVB-113-19 (e.g., BIOPROTEC® from AEF Global) + TX, Brevibacillus laterosporus + TX, Burkholderia spp. in particular Burkholderia rinojensis strain A396 (also known as Burkholderia rinojensis strain MBI 305) (Accession No. NRRL B-50319, WO 2011/106491 and WO 2013/032693, e.g. MBI206 TGAI and ZELTO® from Marrone Bio Innovations), + TX, Chromobacterium subtsugae in particular strain PRAA4-1T (e.g. MBI-203, e.g. GRANDEVO® from Marrone Bio Innovations) + TX, Lecanicillium muscarium Ve6 (MYCOTAL from Koppert) + TX, Paenibacillus popilliae (formerly Bacillus popilliae, e.g. MILKY SPORE POWDER™ or MILKY SPORE GRANULAR™ from St. Gabriel Laboratories) + TX, Serratia entomophila (e.g. INVADE® by Wrightson Seeds) + TX, Serratia marcescens in particular strain SRM (Accession No. MTCC 8708) + TX, Trichoderma asperellum (TRICHODERMAX from Novozymes) + TX, Wolbachia pipientis ZAP strain (e.g., ZAP MALES® from MosquitoMate) + TX; Beauveria bassiana strain ATCC 74040 (e.g. NATURALIS® from Intrachem Bio Italia) + TX, Beauveria bassiana strain ATP02 (Accession No. DSM 24665), Apopka 97 (PREFERAL from SePRO) + TX,
Beauveria bassiana strain GHA (Accession No. ATCC74250, e.g. BOTANIGUARD® ES and MYCONTROL-O® from Laverlam International Corporation) + TX, Metarhizium anisopliae 3213-1 (deposited under NRRL accession number 67074 disclosed in WO 2017/066094, Pioneer Hi-Bred International) + TX, Metarhizium robertsii 15013-1 (deposited under NRRL accession number 67073) + TX, Metarhizium robertsii 23013-3 (deposited under NRRL accession number 67075) + TX, Paecilomyces lilacinus strain 251 (MELOCON from Certis, US) + TX; Cydia pomonella (codling moth) granulosis virus (GV) + TX, Helicoverpa armigera (cotton bollworm) nuclear polyhedrosis virus (NPV) + TX, of Adoxophyes orana (summer fruit tortrix) granulosis virus (GV) + TX, Spodoptera exigua (beet armyworm) mNPV + TX, Spodoptera frugiperda (fall armyworm) mNPV + TX; Burkholderia spp. in particular Burkholderia cepacia (formerly known as Pseudomonas cepacia) + TX, Gigaspora spp. + TX, Glomus spp. + TX, Laccaria spp. + TX, LactoBacillus buchneri + TX, Paraglomus spp. + TX, Pisolithus tinctorus + TX, Pseudomonas spp. + TX, Rhizobium spp. in particular Rhizobium trifolii + TX, Rhizopogon spp. + TX, Scleroderma spp. + TX, Streptomyces spp. + TX, Suillus spp. + TX, Agrobacterium spp. + TX, Azorhizobium caulinodans + TX, Azospirillum spp. + TX, Azotobacter spp. + TX, Bradyrhizobium spp. + TX, Gigaspora monosporum + TX; Allium sativum (NEMGUARD from Eco-Spray, BRALIC from ADAMA) + TX, Armour-Zen + TX, Artemisia absinthium + TX, Biokeeper WP + TX, Brassicaceae extract in particular oilseed rape powder or mustard powder + TX, Cassia nigricans + TX, Celastrus angulatus + TX, Chenopodium anthelminticum + TX, Chenopodium quinoa saponin extract from quinoa seeds (e.g. Heads Up® (Saponins of Quinoa) from Heads Up plant Protectants, CA) + TX, Chitin + TX, Dryopteris filix-mas + TX, Equisetum arvense + TX, Fortune Aza + TX, Fungastop + TX, Melaleuca alternifolia extract (TIMOREX GOLD from STK) + TX, naturally occurring Blad polypeptide extracted from Lupin seeds (FRACTURE® from FMC) + TX, naturally occurring Blad polypeptide extracted from Lupin seeds (PROBLAD® from Certis EU) + TX, Pyrethrins + TX, Quassia amara + TX, Quercus + TX, Quillaja extract (QL AGRI 35 from BASF) + TX, REGALIA MAXX from Marrone Bio) + TX, Requiem™ Insecticide + TX, Reynoutria sachalinensis extract (REGALLIA + TX, ryania/ryanodine + TX, Symphytum officinale + TX, Tanacetum vulgare + TX, Thymol + TX, Thymol mixed with Geraniol (CEDROZ from Eden Research) + TX, Thymol mixed with Geraniol and Eugenol (MEVALONE from Eden Research) + TX, Triact 70 + TX, TriCon + TX, Tropaeulum majus + TX, Urtica dioica + TX, Veratrin + TX, Viscum album + TX; mercuric oxide + TX, octhilinone + TX, thiophanate-methyl + TX; MGK 264 + TX, 2-(2-butoxyethoxy)¬ethyl piperonylate + TX, 2-isovalerylindan-1,3-dione + TX, 4- (quinoxalin-2-ylamino)benzenesulfonamide + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone + TX, acibenzolar + TX, acibenzolar-S-methyl + TX, alpha-bromadiolone + TX, alpha-chlorohydrin + TX, aluminium phosphide + TX, anthraquinone + TX, antu + TX, arsenous oxide + TX, barium carbonate + TX, benoxacor + TX, bisthiosemi + TX, brodifacoum + TX, bromadiolone + TX, bromethalin + TX, calcium cyanide + TX, chloralose + TX, chlorophacinone + TX, cholecalciferol + TX, cloquintocet
(including cloquintocet-mexyl) + TX, copper naphthenate + TX, copper oxychloride + TX, coumachlor + TX, coumafuryl + TX, coumatetralyl + TX, crimidine + TX, cyprosulfamide + TX, diazinon + TX, dichlormid + TX, dicyclopentadiene + TX, difenacoum + TX, difethialone + TX, diphacinone + TX, ergocalciferol + TX, farnesol + TX, farnesol with nerolidol + TX, fenchlorazole (including fenchlorazole- ethyl) + TX, fenclorim + TX, flocoumafen + TX, fluoroacetamide + TX, flupropadine + TX, flupropadine hydrochloride + TX, fluxofenim + TX, furilazole + TX, gamma-HCH + TX, guazatine + TX, guazatine acetates + TX, HCH + TX, hydrogen cyanide + TX, imanin + TX, iodomethane + TX, isoxadifen (including isoxadifen-ethyl) + TX, lindane + TX, magnesium phosphide + TX, MB-599 + TX, mefenpyr (including mefenpyr-diethyl) + TX, metcamifen + TX, methiocarb + TX, methyl bromide + TX, nerolidol + TX, norbormide + TX, petroleum oils + TX, phosacetim + TX, phosphine + TX, phosphorus + TX, pindone + TX, piperonyl butoxide + TX, piprotal + TX, potassium arsenite + TX, probenazole + TX, propyl isomer + TX, pyridin-4-amine + TX, pyrinuron + TX, Reynoutria sachalinensis extract + TX, ribavirin + TX, S421 + TX, scilliroside + TX, sesamex + TX, sesasmolin + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoro¬acetate + TX, strychnine + TX, sulfoxide + TX, thallium sulfate + TX, thiram + TX, trimethacarb + TX, warfarin + TX, zinc naphthenate + TX, zinc phosphide + TX, ziram + TX. The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound "abamectin" is described under entry number (1). Where "[CCN]" is added hereinabove to the particular compound, the compound in question is included in the "Compendium of Pesticide Common Names", which is accessible on the internet via BCPC; http://www.bcpcpesticidecompendium.org/index.html; for example, the compound "abamectin" is described under the internet address http://www.bcpcpesticidecompendium.org/index_cn_frame.html. Most of the active ingredients described above are referred to hereinabove by a so-called "common name", the relevant "ISO common name" or another "common name" being used in individual cases. If the designation is not a "common name", the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the IUPAC/Chemical Abstracts name, a "chemical name", a "traditional name", a "compound name" or a "develoment code" is used or, if neither one of those designations nor a "common name" is used, an "alternative name" is employed. “CAS Reg. No” means the Chemical Abstracts Registry Number. The active ingredient mixture of the compounds of formula (I) with active ingredients described above comprises a compound selected from one compound defined in the Tables A-1 to A-42 and Table P and an active ingredient as described above, preferably in a mixing ratio of from 100:1 to 1:6000, especially from 50:1 to 1:50, more especially in a ratio of from 20:1 to 1:20, even more especially from
10:1 to 1:10, very especially from 5:1 and 1:5, special preference being given to a ratio of from 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750. The mixing ratios are by weight. The compounds and compositions pesas described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body. The mixtures comprising a compound of formula (I) selected from the compounds defined in the Tables A-1 to A-42 and Table P and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture com¬posed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequen¬tial manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula (I) and the active ingredients as described above is not essential for working the present invention. The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides. The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries). These processes for the preparation of the compositions and the use of the compounds I for the preparation of these compositions are also a subject of the invention. The application methods for the compositions, that is the methods of controlling pests of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring - which are to be selected to suit the intended aims of the prevailing circumstances - and the use of the compositions for controlling pests of the abovementioned type are other subjects of the invention. Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient. The rate of application per hectare is generally 1 to 2000 g of active ingredient per hectare, in particular 10 to 1000 g/ha, preferably 10 to 600 g/ha.
A preferred method of application in the field of crop protection is application to the foliage of the plants (foliar application), it being possible to select frequency and rate of application to match the danger of infestation with the pest in question. Alternatively, the active ingredient can reach the plants via the root system (systemic action), by drenching the locus of the plants with a liquid composition or by incorporating the active ingredient in solid form into the locus of the plants, for example into the soil, for example in the form of granules (soil application). In the case of paddy rice crops, such granules can be metered into the flooded paddy-field. The compounds of formula (I) of the invention and compositions thereof are also be suitable for the protection of plant propagation material, for example seeds, such as fruit, tubers or kernels, or nursery plants, against pests of the abovementioned type. The propagation material can be treated with the compound prior to planting, for example seed can be treated prior to sowing. Alternatively, the compound can be applied to seed kernels (coating), either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted to the site of application, for example into the seed furrow during drilling. These treatment methods for plant propagation material and the plant propagation material thus treated are further subjects of the invention. Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 to 200 grams per 100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds, such as between 10 to 100 grams per 100 kg of seeds. The term seed embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds. The present invention also comprises seeds coated or treated with or containing a compound of formula I. The term "coated or treated with and/or containing" generally signifies that the active ingredient is for the most part on the surface of the seed at the time of application, although a greater or lesser part of the ingredient may penetrate into the seed material, depending on the method of application. When the said seed product is (re)planted, it may absorb the active ingredient. In an embodiment, the present invention makes available a plant propagation material adhered thereto with a compound of formula I. Further, it is hereby made available, a composition comprising a plant propagation material treated with a compound of formula I. Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting. The seed treatment application of the compound formula (I) can be carried out by any known methods, such as spraying or by dusting the seeds before sowing or during the sowing/planting of the seeds. The compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates and/or different pest control, which can be verified by the person skilled
in the art using the experimental procedures, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of AI per m2. The greater efficacy can be observed by an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability). In each aspect and embodiment of the invention, "consisting essentially" and inflections thereof are a preferred embodiment of "comprising" and its inflections, and "consisting of" and inflections thereof are a preferred embodiment of "consisting essentially of” and its inflections. The disclosure in the present application makes available each and every combination of embodiments disclosed herein.
Biological Examples Chilo suppressalis (Striped rice stemborer) 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions by pipetting. After drying, the plates were infested with L2 larvae (6-8 per well). The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 6 days after infestation. Control of Chilo suppressalis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample. The following compounds resulted in at least 80% control at an application rate of 200 ppm: P2, P4, P5, P6, P7, P8, P10, P11, P12, P13, P14, P17, P18, P19, P20, P22, P23, P24, P28 Diabrotica balteata (Corn root worm) Maize sprouts placed onto an agar layer in 24-well microtiter plates were treated with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions by spraying. After drying, the plates were infested with L2 larvae (6 to 10 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 4 days after infestation. The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm: P6, P7, P10, P18 Myzus persicae (Green peach aphid). Intrinsic activity Test compounds prepared from 10'000 ppm DMSO stock solutions were applied by pipette into 24-well microtiter plates and mixed with sucrose solution. The plates were closed with a stretched Parafilm. A plastic stencil with 24 holes was placed onto the plate and infested pea seedlings were placed directly on the Parafilm. The infested plate was closed with a gel blotting paper and another plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation. The following compounds gave an effect of at least 80% control at an application rate of 12.5 ppm: P7 Plutella xylostella (Diamond back moth) 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions by pipetting. After drying, Plutella eggs were pipetted through a plastic stencil onto a gel blotting paper and the plate was closed with it. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 8 days after infestation. The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:
P2, P4, P5, P6, P7, P10, P12, P13, P15, P17, P18, P19, P21, P22, P24, P27, P28, P34 Spodoptera littoralis (Egyptian cotton leaf worm) Cotton leaf discs were placed onto agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions. After drying the leaf discs were infested with five L1 larvae. The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 3 days after infestation. Control of Spodoptera littoralis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample. The following compounds resulted in at least 80% control at an application rate of 200 ppm: P3, P5, P7, P13, P18, P19, P27 The invention is defined by the claims.
Claims
Claims 1. A compound of Formula (I):
wherein R1 to R4 are independently H, halogen, C1-6alkyl, or C1-6haloalkoxy; wherein W is C1-6alkyl, phenyl, 5- or 6-membered heteroaryl, wherein the heteroaryl ring, independent of each other, comprises 1 or 2 heteroatoms independently selected from nitrogen and sulphur, and wherein the ring of the phenyl, 5- or 6-membered heteroaryl, independently of each other, are unsubstituted or independently substituted by 1, 2 or 3 halogen substituents; wherein A1, A2 and A3, together with the adjoining carbon atoms, form a 5-membered ring comprising 2 or 3 heteroatoms and an endocyclic double bond and are, independently, selected from NR9, N, C(O), or O, and wherein R9 is H or CH3; wherein R5 is H or C1haloalkyl; wherein T is selected from:
, or is a direct bond, R6 to R8 are independently selected from H, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, 2-(acetamid)ethyl,2-ethoxyethyl, oxolan-3-yl, thietan-3-yl, oxetan-3-yl, propen-2-yl, 2- methoxyethyl, 2,2-diethoxyethyl, oxan-4-yl, 3-methoxypropyl, 2-hydroxyethyl, 3,3- imethoxypropyl, 2-cyanoethyl or 2-methylsulfonylethyl, or R6 and R7 together with the nitrogen atom to which they are attached form an imidazole or morpholine group; Q is selected from
or is a direct bond; with the proviso that T and Q cannot both be a direct bond; A is a phenyl group, a C6cycloalkyl, or piperidine ring, wherein A is optionally substituted by one or more of halogen, C1-6alkyl, C1-6cycloalkyl, C1- 6alkoxy, C1-6haloalkyl, C1-6halocycloalkyl, C1-6haloalkoxy, or an agronomically acceptable salt, stereoisomer, enantiomer, tautomer and/or N-oxide of the compound of Formula (I).
2. The compound according to claim 1, wherein R1 to R4 are independently H, F, Cl, C1-3alkyl or C1-3haloalkoxy. 3. The compound according to claim 1 or 2, wherein W is phenyl, pyridine, thiophene, thiazole, or C1-4alkyl, wherein the ring of the phenyl, pyridine, thiophene, or thiazole is unsubstituted or independently substituted by 1, 2 or 3 fluorine or chlorine substituents. 4. The compound according to any of the preceding claims, wherein A1, A2 and A3, together with the adjoining carbon atoms, form a 5-membered ring comprising 3 heteroatoms and an endocyclic double bond. 5. The compound according to claim 5, wherein the 3 heteroatoms comprise two nitrogen atoms and an oxygen. 6. The compound according to any of the preceding claims, wherein R5 is trifluoromethyl, difluoromethyl or fluoromethyl. 7. The compound according to any of the preceding claims, wherein R6 to R8 are H or methyl. 8. The compound according to any of the preceding claims, wherein A is monosubstituted. 9. The compound according to claim 8 wherein A is monosubstituted by F, Cl, C1-3alkyl or C1- 3haloalkoxy, preferably in the para position. 10. A composition comprising a compound of formula I as defined in any of the preceding claims, one or more auxiliaries and diluent, and optionally one or more other active ingredient. 11. A method of combating and controlling one or more pests which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest a pesticidally effective amount of a compound of formula I as defined in any one of claims 1 to 9, or a composition as defined in claim 10. 12. A method for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula I as defined in any one of claims 1 to 9, or a composition as defined in claim 10. 13. A plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula I as defined in any one of claims 1 to 9, or a composition as defined in claim 10.
4. A process for making a compound of Formula (I) as defined in any one of claims 1 to 9 by reacting a compound of Formula (V)
with a compound of Formula (VI)
where R11 is H or CH3 and all other substituents as defined in claim 1.
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