CH689421A5 - Aromatic aldimine and ketimine oxime ether(s) - Google Patents

Abstract

Aromatic oxime ethers of formula (I) are new, where R1 = 1-4C alkyl; Y-X = CH2=, 1-2C alkylthio CH=, or 1-2C alkyl ON=; Z = aldimino or hetimino. 14 Cpds. (I) are specifically claimed, including 2-(alpha-(((alpha-methyl-3-trifluoromethylbenzyl)imino)oxy) -O-tolyl)-3-methylthio-acrylic acid methyl ester (Ia).

Description

       

  
 



  The present invention relates to intermediates for oxime ethers of the general formula
EMI1.1
 
 



  wherein
 R1 means C1-4 alkyl,
 (Y-X) C1-2-alkyl-ON = means and
 Z stands for an aldimino or ketimino group, in particular for a group
EMI1.2
 
 



  wherein
 R2 is hydrogen, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, C1-2 alkoxymethyl, C1-2 alkylthiomethyl, C1-4 alkylsulfonyl , C1-3 alkoxy, C1-3 alkylthio or cyano and
 R3 C1-6 alkyl, aryl C1-4 alkyl, heteroaryl C1-4 alkyl, C2-12 alkenyl, aryl C2-4 alkenyl, aryloxy C1-4 alkyl, heteroaryloxy C1-4 alkyl, heteroaryl-C2-4-alkenyl, C3-6-cycloalkyl, aryl, heteroaryl, C2-5-alkanoyl, aroyl or heteroaroyl, or
 R2 and R3 together with the carbon atom to which they are attached form an optionally substituted, optionally containing an oxygen atom, sulfur atom and / or nitrogen atom containing a four- to seven-membered saturated or unsaturated ring which may also have an optionally substituted fused benzene ring.



  The compounds of formula I, in which (YX) can also mean CH2 =, C1-2-alkylthio-C =, in accordance with EP-B 460 575, have fungicidal properties and are suitable as fungicidal active ingredients, in particular for use in agriculture and in horticulture.



  In the above formula 1 and below all groups "alkyl" and "alkenyl", as such or as part of larger groups, e.g. Heteroarylalkyl, depending on the number of carbon atoms, be straight-chain or branched. In addition, the alkenyl groups can have one or more double bonds. Halogen as a substituent means fluorine, chlorine, bromine or iodine, with fluorine, chlorine and bromine being preferred. A haloalkyl group can have one or more identical or different halogen substituents. Aryl is to be understood in particular as phenyl, naphthyl, phenanthryl or fluorenyl. Heteroaryl means a heterocyclic group with an aromatic character and 1-3 heteroatoms N, O and / or S. Preferred are triazole or other five-membered rings and six-membered rings with 1-2 heteroatoms, which in turn may additionally have one or two fused benzene rings.



  Examples which have no limiting meaning, but which are to be referred to as "group Het *" in the following, are pyrrolyl, pyridyl, furyl, thienyl, isoxazolyl, thiazolyl, pyrazinyl, pyridazinyl, imidazolyl, pyrimidinyl or triazolyl, or such a group Group with condensed benzene, e.g. Quinolinyl, Quinoxalinyl, Benzofuryl, Benzothienyl or Dibenzofuryl called. Analogously, this also applies to "aryl" or "heteroaryl" as part of a larger group, e.g. Aralkyl or heteroarylalkyl. The aryl and heteroaryl groups can each have one or more of the following substituents:



  Halogen, C1-4-alkyl, C1-4-haloalkyl, aryl-C1-4-alkyl, aryloxy-C1-4-alkyl, C2-4-alkenyl, aryl-C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, aryl, C1-4-alkoxy, C1-4-haloalkoxy, aryl-C1-4-alkoxy, C1-4-alkylthio, aryloxy, cyano, nitro, C2-4-haloalkenyl, C2-4- Haloalkynyl, C2-4-alkenyloxy, C2-4-haloalkenyloxy, C3-4-alkynyloxy, C3-4-haloalkynyloxy, cyclopropylmethoxy, cyclopropyl (optionally substituted one to three times by halogen and / or methyl), cyanomethoxy (-OCH2CN), C1-4 alkoxymethyl, C1-4 alkylthiomethyl, C1-4 alkylsulfinylmethyl, C1-4 alkyl sulfonylmethyl, arylthio, thiocyanato, C1-4 alkoxyiminomethyl, C1-4 alkanoyloxy, C1-4 alkoxycarbonyl;



  and also a heteroaryl radical, a heteroaryl C1-4 alkyl radical, a heteroaryloxy C1-4 alkyl radical, a heteroaryl C2-4 alkenyl radical, a heteroaryl C1-4 alkoxy radical or a heteroaryloxy radical; where the term heteroaryl is to be understood as a representative of the above-mentioned "group Het *".



  Almost all of the substituents mentioned for aryl and heteroaryl groups can occur once or twice, preferably once, with the exception of C1-4-alkyl, which can be used as a substituent up to four times, and halogen, which can be up to three times in the case of Fluorine can also occur up to five times.



  The preferred aryl group is phenyl, regardless of whether it appears alone or as part of another substituent. Accordingly, aroyl is preferably benzoyl.



  C2-alkanoyl means acetyl. Haloalkyl is to be understood as meaning alkyl groups which are substituted by F, Cl, Br and / or J up to six times the same or different. Examples of haloalkyl groups alone or as part of another substituent (such as haloalkoxy) are CH2Cl, CHCl2, CCl3, CHBr2, CH2CH2Cl, CHCI-CHCl2, CF2Cl, CH2J, CF3, C2F5, CF2-CF2Cl, CHF2, CH2F, CF2CHFCF3.



  Trifluoromethyl, difluoromethoxy and trifluoromethoxy are preferred.



  In addition, the aryl groups (in particular phenyl) can carry a five-, six- or seven-membered saturated or unsaturated ring containing one or two oxygen atoms, which ring may optionally contain one or more methyl, methoxy, phenyl, halogen, cyano or oxo (C = O) can be substituted. Examples of such groups are 5-benzofuryl, 6-benzodioxanyl and 5- (1,3-benzodioxolyl).



  In the event that R2 and R3 together with the carbon atom to which they are attached form an optionally substituted ring, as described in more detail above, come as substituents on the ring
EMI4.1
 
 



  in particular C1-6 alkyl or optionally substituted phenyl in question. Any fused-on benzene ring may also be substituted. Possible substituents for the phenyl group or the benzene ring itself are those mentioned above in connection with the aryl group.



  If asymmetric carbon atoms are present in the compounds of formula 1, the compounds appear in optically active form. The compounds appear in the [E] or [Z] form solely because of the presence of the aliphatic or imino double bond X = C and the imino double bond of the aldimino or ketimino group Z. Atropisomerism can also occur. The formula is intended to cover all of these possible isomeric forms and their mixtures, e.g. racemic mixtures and any [E / Z] mixtures.



  In the compounds of the formula I, R1 preferably denotes methyl; and independently of it (Y-X) preferably methylene, methylthiomethylene (CH-SCH3) or methoxyimino (N-OCH3); Compounds in which R is methoxyimino are particularly preferred.



  In the group (R2) (R3) C = N-, R2 is preferably hydrogen, C1-4-alkyl (in particular methyl or ethyl), C1-4-haloalkyl (in particular trifluoromethyl) or C3-6-cycloalkyl (in particular cyclopropyl) and R3 is preferably optionally substituted phenyl, naphthyl (in particular beta -naphthyl) or benzyl, any substituents preferably having up to three identical or different halogen atoms (in particular fluorine, chlorine and / or bromine), C1-4-alkyl groups (in particular methyl), C1- 4-haloalkyl groups (in particular trifluoromethyl), C1-4-haloalkoxy groups (in particular trifluoromethoxy) and alkylenedioxy (in particular 3,4-methylenedioxy), or heteroaryl, in particular furyl optionally substituted with up to two methyl groups, optionally thienyl substituted with chlorine or methyl, Pyridyl or benzofuryl.



  If R3 is heteroaryl, R2 is preferably methyl.



  Other representatives of compounds of the formula I are:
 those compounds of formula 1 in which R, methyl, (YZ) CH2, Z is a group (R2) (R3) C = N-, R2 methyl and R3 3-trifluoromethyl-benzyl, 4-chloro-3-trifluoromethyl-benzyl, phenyl , 3-chlorophenyl, 3,5-dichlorophenyl, 2-fluoro-5-methylphenyl, 3-trifluoromethoxyphenyl or 5-chloro-2-thienyl;



  The process for the preparation of the compounds of formula 1 is characterized in that an oxime Z-OH, in particular an oxime of the general formula
EMI5.1
 
 



  wherein R2 and R3 have the meanings given above, with a benzyl alcohol derivative of the general formula
EMI5.2
 
 



  wherein R1 and Y-X have the meanings given above and U represents a leaving group, brings about the reaction.



  This reaction is a nucleophilic substitution which can be carried out under the reaction conditions customary in this regard. The leaving group U present in the benzyl alcohol derivative of the formula III is preferably chlorine, bromine, iodine, mesyloxy, benzenesulfonyloxy or tosyloxy. The reaction is conveniently carried out in an inert organic diluent such as a cyclic ether, e.g. Tetrahydrofuran or dioxane, acetone, dimethylformamide or dimethyl sulfoxide, in the presence of a base such as sodium hydride, sodium or potassium carbonate, a tertiary amine, e.g. a trialkylamine, especially diazabicyclononane or diazabicycloundecane, or silver oxide, at temperatures between -20 ° C. and 80 ° C., preferably in the temperature range from 0 ° C. to 20 ° C.



  Alternatively, the reaction can be carried out with phase transfer catalysis in an organic solvent, such as methylene chloride, in the presence of an aqueous basic solution, e.g. Sodium hydroxide solution, and a phase transfer catalyst, such as tetrabutylammonium hydrogen sulfate, take place at room temperature [see for example W.E. Keller, "Phase Transfer Reactions", Fluka Compendium Vol. I and II, Georg Thieme Verlag, Stuttgart (1986/1987), in which Chemistry Letters 1980, pages 869-870, is mentioned in particular].



  The compounds of the formula I thus prepared can be isolated and purified by methods known per se. Any isomer mixtures obtained, e.g. E / Z isomer mixtures into which pure isomers are separated, for example by chromatography or fractional crystallization.



  The oximes Z-OH used as starting materials in the process according to the invention, e.g. of formula II, are either known or can be prepared by methods known per se, for example by reacting the corresponding carbonyl compound R2R3C = O with hydroxylamine hydrochloride in the presence of a base, e.g. Sodium or potassium hydroxide or pyridine, further methods can be found in Houben-Weyl, "Methods of Organic Chemistry", Volume X / 4, pages 3-308 (1968) ("Production and Conversion of Oximes").



  Also the starting materials of formula III, i.e. the alpha - (2-UCH2-phenyl) acrylic acid alkyl esters of the formula IIIa, the alpha - (2-UCH2-phenyl) - beta - (C1-2-alkylthio) acrylic acid alkyl esters of the formula Illb and the 2- ( 2-UCH2-phenyl) -glyoxylic acid alkyl ester -O- (C1-2-alkyl) oxime of the formula IIIc
EMI7.1
 
 



  either known, or they can be prepared by methods known per se. Thus, in the European patent publication (EP) 348 766 the production of methyl alpha - (2-bromomethyl-phenyl) -acrylate, in EP 310 954 and in Angew. Chem. 71, 349-365 (1959) the production of alpha - (2-bromomethyl-phenyl) -beta-methylthio-acrylic acid methyl ester and in EP 363 818 and again in Angew. Chem. 71, 349-365 (1959) describes the preparation of methyl 2- (2-bromomethyl-phenyl) -glyoxylate-O-methyloxime.



  The still new compounds of formula IIIc form the subject of the present invention. The compound of the formula IIIc in which R, methyl, U bromine and C1-2-alkyl are methyl is known from EP-A 254 426.



  To prepare an alpha - (2-bromomethyl-phenyl) -beta-methylthio-acrylic acid C1-4-alkyl ester, one can also use a synthesis which deviates from the process described in EP 310 954 and which involves the bromination of the corresponding 3- (4-Bromo-benzenesulfonyloxy) -2- (o-tolyl) -acrylic acid C1-4-alkyl ester with N-bromosuccinimide to give 3- (4-bromo-benzenesulfonyloxy) -2- (2-bromomethyl-phenyl) -acrylic acid- C1-4 alkyl ester and, as a second step, the reaction of the latter ester with sodium methanethiolate to the desired end product. The starting material 3- (4-bromo-benzenesulfonyloxy) -2- (otolyl) acrylic acid methyl ester is described for example in EP 310 954.



  The compounds of the formula I have a fungicidal action and can accordingly be used to combat or prevent fungal attack in agriculture, in horticulture and in wood protection. They are particularly suitable for inhibiting growth or for destroying phytopathogenic fungi on parts of plants, e.g. Leaves, stems, roots, tubers, fruits or flowers, and on seeds and on harmful fungi that occur in the soil. Furthermore, wood-degrading and wood-staining fungi can be combated with the compounds of the formula I. The compounds of formula I are, for example, active in combating fungi of the classes Deuteromycetes, Ascomycetes, Basidiomycetes and Phycomycetes.



  The compounds of the formula I are particularly suitable for controlling the following pathogens:
 



  Powdery mildew (e.g. Erysiphe graminis, Erysiphe cichoracearum, Podosphaera leucotricha, Uncinula necator, Sphaerotheca spp.)
 Rust fungi (e.g. Puccinia tritici, Puccinia recondita, Puccinia hordei, Puccinia coronata, Puccinia striiformis, Puccinia arachidis, Hemileia vastatrix, Uromyces fabae)
 Scab fungi (e.g. Venturia inaequalis)
 Cercospora spp. (e.g. Cercospora arachidicola, Cercospora beticola)
 Mycosphaereila spp. (e.g. Mycosphaerella fijiensis)
 Alternaria spp. (e.g. Alternaria brassicae, Alternaria mali)
 Septoria spp. (e.g. Septoria nodorum)
 Heminthosporium spp. (e.g. Helminthosporium teres, Heiminthosporium oryzea)
 Plasmopara spp. (e.g. Plasmopara viticola)
 Pseudoperonospora spp. (e.g. Pseudoperonospora cubensis)
 Phytophthora spp. (e.g. Phytophthora infestans)
 Pseudocercosporella spp. (e.g. Pseudocercosporella herpotrichoides)
 Piricularia spp. (e.g.

   Piricularia oryzae)



  Furthermore, the compounds of the formula I act, for example, against fungi of the genera Tilletia, Ustilago, Rhizoctonia, Verticillium, Fusarium, Pythium, Gaeumannomyces, Scierotinia, Monilia, Botrytis, Peronospora, Bremia, Gloeosporium, Cercosporidium, Penicillium, Ceratochorpor, Rhynocospora, Rhynocospora Ramularia and Leptosphaeria. Certain representatives of the compounds of the formula I also have activity against wood-damaging fungi, such as, for example, the genera Coniophora, Gloeophyllum, Poria, Merulius, Trametes, Aureobasidium, Sclerophoma and Trichoderma.



  The compounds of formula 1 are characterized by prophylactic and curative, but above all by clear systemic effects.



  They act against phytopathogenic fungi under greenhouse conditions even at concentrations of 0.5 mg to 500 mg of active ingredient per liter of spray mixture. In the field, dosages of 20 g to 1 kg of active ingredient of the formula I per hectare and treatment are advantageously used. To control seed or soil-borne fungi in the pickling process, doses of 0.001 g to 1.0 g of the active ingredient of the formula per kg of seed are advantageously used.



  The following examples illustrate the invention.


 I. Preparation of the Active Ingredients of Formula I:
 


 example 1
 



  To a suspension of 0.24 g sodium hydride (55-60% in \ l) in 20 ml dimethylformamide is added dropwise at 5-10 ° C. 0.637 g 2- (2-bromomethylphenyl) acrylic acid methyl ester under gassing with argon and 0. 5 g of 3-trifluoromethyl-acetophenone oxime in 2 ml of dimethylformamide. The reaction mixture is stirred for a further 30 minutes. When the reaction has ended, the mixture is poured onto water and the aqueous mixture is extracted with three portions of ethyl acetate. The combined organic phases are washed twice with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining \ l is then purified chromatographically on silica gel using n-hexane / methylene chloride (1: 1) as the eluent.



  In this way, the 2- [alpha - [(E / Z-alpha-methyl-3-trifluoromethyl-benzyl) imino] oxyÜ-o-tolyl] acrylic acid methyl ester is obtained as colorless \ l.


 Example 4
 



  To a suspension of 0.78 g of sodium hydride (80% in \ l) in 20 ml of dimethylformamide, 5 g of methyl 2- (2-bromomethylphenyl) -glyoxylate-O-methyloxime and 3.2 g of beta-methoxide are added at 0 ° C. under argon gas -Acetonaphthonoxime added dropwise in 80 ml of dimethylformamide, and the reaction mixture is stirred at 0 ° C. for 4 hours. When the reaction has ended, the mixture is hydrolyzed with saturated ammonium chloride solution and extracted three times with diethyl ether. The combined organic phases are dried over anhydrous sodium sulfate and the solvent is distilled off. The remaining \ l is purified chromatographically on silica gel using diethyl ether / n-hexane (1: 1) as the eluent, and the product is crystallized from methylene chloride / diethyl ether / n-hexane.



  In this way, the methyl 2- [alpha - [(1- [beta-naphthyl] ethyl) imino] oxyÜ-o-tolyl] -glyoxylate-O-methyloxime is obtained as white crystals, mp. 97-98 ° C. .



  The following methoximinoglyoxylic acid derivatives can be obtained in the same way, predominantly by the method of Example 4:
EMI11.1
 
 
EMI12.1
 
 
EMI13.1
 
 
EMI14.1
 
 



   
EMI15.1
 
 
EMI16.1
 
 
EMI17.1
 
 


 Examples 133-141
 



  Analogously to the process described in Example 1 (“Method 1”), the compounds of the formula I listed in Table 3 below are obtained from the corresponding o-substituted benzyl bromide of the formula III (U = Br) and the corresponding oxime of the formula II
EMI17.2
 
 
EMI18.1
 
 



   


    

Claims (2)

    1. Compounds of the general formula EMI19.1        wherein  R1 C1-4 alkyl and  U is a leaving group, with the proviso that R1 and C1-2-alkyl do not simultaneously mean methyl when U is bromine. 2. Compounds according to claim 1, characterized in that leaving group U represents chlorine, bromine, iodine, mesyloxy, benzenesulfonyloxy or tosyloxy.