GB2139213A - Heterocyclic amido derivatives - Google Patents

Abstract

Heterocyclic amido derivatives of formula: <IMAGE> in which R1 is a 6-membered heterocyclic group containing 1 or 2 nitrogen atoms; R2 is an optionally halogenated alkyl or phenyl group; and R<3> is a 5-membered heterocyclic group containing one hetero-atom, optionally substituted by a halogen atom and/or by an allyl group, exhibit herbicidal, fungicidal and plant-growth regulant properties.

Description

SPECIFICATION Heterocyclic amido derivatives This invention relates to certain heretocyclicamido derivatives, to a process fortheir preparation and to their use as herbicides, plant-growth regulants and fungicides.

Accordingly the invention provides heterocyclic amido derivatives offormula:

in which R1 represents a 6-membered heterocyclic group containing 1 or2 nitrogen atoms; R2 represents an optionally halogenated alkyl or phenyl group; and R3 represents a 5-membered heterocyclic group containing one hetero-atom, optionally substituted bya halogen atom and/or by an alkyl group.

Preferably R1 represents a pyridyl or pyrazinyl group; R2 represents an alkyl group of 1 to 6 carbon atoms, for example, methyl, t-butyl or dimethylpropyl, ora phenyl group optionally substituted by up to two chlorine atoms, for example, phenyl of dichlorophenyl; and R3 represents a thienyl orfuryl group optionally substituted bya bromine atom or by an alkyl group of 1 to 6 carbon atoms, for example, methyl.

The invention also includes a processforthe preparation ofthe heterocyclic amido derivatives of formula I, which comprises reacting a compound of formula: R1-NH-CH2-R3 II with an acid halide offormula: R2-CO-Hal Ill in which R1, R2 and R3 are as defined in relation to formula I, and Hal represents a halogen, preferably chlorine, atom, in the presence of a base. The base is preferably an organic base, such as a tertiary amine, a trialkylaminesuch astriethylamine being particularly preferred.The reaction is conveniently carried out in an inert solvent, for example, a liquid hydrocarbon such as xylene. Suitable temperatures forthe reaction are from 50 two 1500C.

The starting material offormula II may be prepared by methods analogous to those already known. For example, an amine of formula R1-NH2 may be condensed with an aldehyde offormula OHC-R3 and the resulting imino compound offormula R1- N=CH-R3maythen be reduced by conventional methods.

As mentioned above, the heterocyclic amido derivatives ofthe invention are biological active. When applied to plants they may, according to the dosage and plant species, exhibit phytotoxic (herbicidal) properties, or plant growth regulant properties, for example, plant growth suppression orthe production of very dark leaves (hyperchromism). They may also be used, usually at somewhat lower dosages than those required to produce herbicidal effects, to combat certain fungi in plants, in particular barley powdery mildew (Erysiphe graminis).

The invention therefore includes biologically active compositions comprising a heterocyclic amido de rivative ofthe invention together with a carrier.

Likewise the invention also includes a method of combating and/or regulating plant growth art a locus, or combating plantfungi at a locus infected, or subject two infection by such fungi, which comprises applying to the locus a biologically effective amount of a heterocyclic amido derivative or composition according to the invention.

Acarrierin a composition according to the invention is any material with which the active ingredient isformulated to facilitate application to the locus to be treated, orto facilitate storage, transport or handling. A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, and any ofthe carriers normally used in formulating agricultu ral compositions may be used. Preferablycomposi- tions according to the invention contain 0.5 to 95% by weight of active ingredient.

Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicate, for exam pletalcs; magnesium aluminium silicates,forexam ple attapulgites and vermiculites; aluminium sili cates,forexamplekaolinites, montmorillonitesand micas; calcium carbonate; calcium sulphate; ammo nium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates; elements, for example carbon and sulphur; natural and synthe tic resins, for example cou marone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes, for exam ple beeswax, paraffin wax, and chlorinated mineral waxes; and solid fertilizers, for example superphos phates.

Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones,for exam ple acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatichydrocarbons,forexample benzene, toluene andxylene; petroleum fractions, for example kerosine and light mineral oils; and chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene andtrichloroethane. Mixtures of different liquids are often suitable.

Agricultural compositions are often formulated and transported in a concentrated form which is subsequently diluted bythe user before application.

The presence of small amounts ofcarrierwhich is a surface-activeagentfacilitatesthis process of dilu tion. Thus preferably at least one carrier in a composition according to the invention is a surface active agent. For example the composition may contain at leasttwo carriers, at least one of which is a surface-active agent.

Formulae in the printed specification were reproduced from drawings submitted after the date of filing, in accordance with Rule 20(14) of the Patents Rules 1982.

A surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be nonionic or ionic. Examples of suitable surfaceactive agents include the sodium or calcium salts of polyacrylicacids and lignin sulphonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters of glycerol, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates ofthese condensation products; alkali or alkaline earth metal salts, preferably sodium salts, of sulphuric orsulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium alkylaryl sulphonates such as sodium dodecylbenzene sulphonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.

The compositions of the invention may for example be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates and aerosols. Wettable powders usually contain 25, 50or75%wofactive ingredient and usually contain in addition to solid inert carrier, 3-10%w of stabilizer(s) and/or other additives such as penetrants or stickers.Dusts are usuallyformulated asa dust concentrate having a similar composition to that ofawettable powder but without a dispersant. and are diluted in the field with furthersolid carrier to give a composition usually containing 1/2-10%w of active ingredient Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676-0.152 mm), and may be manufactured by agglomeration or impregnation techniques.

Generally, granules will contain 1/2-75%w active ingredient and 0-10%w of additives such as stabilizers, surfactants, slow release modifiers and binding agents. The so-called "dryflowable powders" consist of relatively small granules having a relatively high concentration of active ingredient. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, co-solvent, 10-50% w/v active ingredient, 2-20% w/v emulsifiers and 0-20% w/v of other additives such as stabilizers, penetrants and corrosion inhibitors.Suspension concentrates are usually compounded so as to obtain a stable, non-sedimentingflowable productand usually con- tain 10-75%w active ing redient, 0.5-15%wofdispers- ing agents,0.1-10%w of suspending agents such as protective colloids and thixotropic agents, 0.10%w of other additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formulation to assist in preventing sedimentation or as anti-freeze agents for water.

Aqueous dispersions and emulsions, for example compositions obtained by diluting awettable powder or a concentrate according to the invention with water, also lie within the scope ofthe present invention. The said emulsions may be of the water-inoil or the oil-in-watertype, and may have a thick 'mayonaise'-like consistency.

The compositions of the invention may also contain other ingredients, for example, other com pounds possessing herbicidal, insecticidal or fungi cidal properties.

The invention is further illustrated in the following Examples.

EXAMPLE 1 N- 05- bromothien -2- ylmethyl) - N- (trimethylacety I)aminopyrazine A. Preparation of starting material (i) Aminopyrazine (9.9 g) and 5 - bromothiophene 2 - aldehyde (20.0 g) in chloroform (200 ml) containing a few dissolved crystals of p -toluenesulphonic acid were heated together under reflux for three hours.

The reaction mixturewas then cooled, washed in turn with sodium carbonate solution and water, and dried.

The solventwas removed under reduced pressure and the residue was recrystallized from ethanol to give N - (5 - bromothien - 2 -ylmethylidene) iminopyrazine as darkyellow crystals m.p. 128-130 C.

(ii) N -(5- bromothien -2-ylmethylidene) iminopyrazine (20 g, prepared as (i) was dissolved in methanol (200 ml). This solution was stirred under nitrogen while sodium borohydride (5.65 9) was added portionwise. The mixture was reduced to small volume under reduced pressure and water (200 ml)wasthen added. The aqueous mixturewas extracted with dichloromethane (2 x 150 ml) and the extracts were dried. The solventwas removed under reduced pressure and the residue was recrystallized from ethyl acetate to give N - (5 - bromothien -2 ylmethyl) aminopyrazine as a white crystallinesolid m.p.99-100 C.

B. Preparation ofN- (5- bromothien- 2- ylmethy!)- N - (trimethylacetyl) aminopyrazine Trimethylacetyl chloride (4.5 g) andtriethylamine (3.75 g) in xylene (100 ml) were stirred together at ambienttemperature under nitrogen for 30 minutes.

N - (5 - bromothien - 2 - ylmethyl) aminopyrazine (5.0 g, prepared as in A(ii) )was then added and the mixture was heated under refluxwith stirring for 2 hours. The mixture was filtered and the solvent was removed from the filtrate under reduced pressure.

The residue was purified by column chromatography and then recrystallized from an ethyl acetate/cyclohexane mixture to give the required product as a white crystalline solid m.p. 105-106 C.

Analysis Calculated for C14H16 N3OSBr: C47.5%; H 4.5%; N 11.9% Found: C47.7%; H4.7%; N11.9% EXAMPLES2to 13 Further heterocyclic amido derivatives were prepared using similar proceduresto that of Example 1.

These compounds are identified, and their physical properties and analyses are given, in Table I.

TABLE I

EX- R1 R2 R3 m.p.,b.p. Molecular Analysis ample C Formula %C 'N %N 2 pyraziny} t-butyl thien-2-yl 87 C14H17N3OS Calculated 61.1 6.2 15.3 Found 61.5 6.4 15.5 3 pyrazinyl t-butyl thien-3-yl 54 C14H17N30S Calculated 61.1 6.2 15.3 Found 61.1 6.4 15.3 4 pyrazinyl t-butyl ftr-2-yl 140 at C14H17N3O2 Calculated 64.9 6.6 16.2 0.05 mm Hg Found 64.9 6.7 16.0 5 pyrazinyl t-butyl 3-methylthien-2-yl 65-66 C15H19N305 Calculated 62.3 6.6 14.5 Found 62.4 6.9 14.5 6 pyrazinyl t-butyl 5-methylthien-2-yl 59-60 C15H19N305 Calculated 62.3 6.6 14.5 Found 62.4 6.7 14.5 Ex- R1 R2 R3 m.p./o.p. Molecular Analysis ample C Formula %C tN 'N 7 pyrazinyl 2,2iyl- 5-methylthien-2-yl 2-yl 165 at C16H21N3OS Calculated 63.4 7.0 propyl 0.05 mm Hg Found 64.4 7.2 8 pyrazinyl t-butyl 5-methylfur-2yl 200 at C15H19N3O2 Calculated 66.0 7.0 15.4 4 mm Hg Found 66.1 7.3 15.2 9 pyrazinyl methyl 5-bromothien-2-yl 190 at C11H10N3OSBr calculated 42.3 3.2 13.5 0.3 mm Hg Found 42.6 3.3 13.9 10 pyrazinyl 2,2 dimetyl- 5-bromothien-2-yl 190 at C15H18N3OSBr Calculated 48.9 4.9 11.4 prcWl 0.2saHg Found 50.1 5.3 10.9 11 pyrazinyl phenyl 5-bromothien-2-yl 80 C16H13N3OSBr Calculated 51.3 3.2 11.3 Found 51.3 3.0 11.3 12 pyrazinyl 2,4-dichloro 5-bromothien-2-yl oil C16H11N3058rC12 Calculated 43.4 2.2 9.5 phenyl Found 44.0 2.2 8.8 13 pyrid-3-yl t-butyl 5-bromothien-2-yl 230 at C12H12H2OSBr Calculated 51.0 4.8 7.9 10 mn Hg Found 51.1 4.7 7.2 EXAMPLE 14 HerbidicalActivity To evaluate their herbicidal activity, the heterocyc lic amido derivatives of the invention were tested using as a representative range of plants: maize, Zea mays (Mz); rice, Oryza sativa (R); barnyard grass, Echinochloa crusgalli(BG); oat, Avena sativa (0); linseed, Linum usitatissisum (L); mustard, Sinapsis alba (M); sugar beet, Beta vulgaris (SB) and soya bean, Glycine max (S).

The tests fall into two categories, pre-emergence and post-emergence. The pre-emergence tests involved spraying a liquid formulation of the com pound onto the soil in which the seeds ofthe plant species mentioned above had recently been sown.

The post-emergence tests involved two types of test, viz., soil drench and foliar spraytests. In the soil drench tests the soil in which the seedling plants of the above species were growing was drenched with a liquid formulation containing a compound of the invention, and in the foliar sprayteststhe seedling plants were sprayed with such a formulation.

The soil used in the tests was a prepared horticultural loam.

The formulations used in the tests were prepared by diluting with water, solutions of the test compounds in acetone containing 0.4% by weight of an alkylphenol/ethylene oxide condensate available underthetrade markTRITON X-1 55. The acetone solutions were diluted with water and the resulting formulations applied at dosage levels corresponding to 5 kg and/or 1 kg of active material per hectare in a volume equivalent to 600 litres per hectare in the soil spray and foliar spray tests, and at a dosage level equivalentto 10 kilograms of active material per hectare in a volume equivalent to approximately 3,000 litres per hectare in the soil drench tests.

In the pre-emergence tests untreated sown soil and in the post-emergence tests untreated soil bearing seedling plants were used as controls.

The herbicidal effects of the test compounds were assessed visually twelve days afterspraying the foliage and thesoil, and thirteen days after drenching the soil and were recorded on a 0-9 scale. A rating 0 indicates growth as untreated control, a rating 9 indicates death. An increase of 1 unit on the linear scale approximates to a 10% 0C7 & increase in the level of effect.

The results ofthe tests are set out in Table ll below.

TABLE II

Compound of Soil Drench Dosage Foliar Spray Pre-emergence Example No. 10 kg/ha kg/ha Mz R BC O L M SB S Mz R BG O L M SB S Mz R BG O L M SB S 1 4 5 5 2 6 6 5 5 5 5 2 5 5 4 5 2 5 7 4 7 5 7 7 1 4 4 4 3 4 3 5 4 3 5 5 2 5 4 3 4 4 2 3 5 32 4 3 5 3 2 3 5 5 1 1 3 2 3 4 54 5 5 33 4 76 1 22 3 34 5 32 3 3 5 3 4 1 1 2 6 5 6 3 5 3 2 6 5 4 3 2 3 3 6 2 5 3 6 7 1 1 3 3 5 5 7 5 5 4 4 4 5 6 4 5 7 4 1 2 3 2 5 5 2 5 7 9 5 6 6 3 5 3 5 3 4 3 3 3 5 4 5 2 5 2 1 4 4 4 2 3 2 10 4 6 3 3 3 5 3 5 5 3 4 3 4 7 4 6 5 6 5 1 4 4 2 4 6 2 5 4 5 3 13 2 4 5 5 2 5 3 4 5 4 4 5 6 4 5 6 3 2 4 4 3 1 2 1 3 4 2 4 4 2 4 3 EXAMPLE 15 FungicidalActivity The fungicidal activity of the heterocyclic amido derivatives ofthe invention was tested against barley powdery mildew, Erysiphegraminis (Eg) in the following manner.

The test measures the direct anti-sporulant activity of compounds applied as a foliar spray. For each compound about 40 barley seedlings were grown to the one-leaf stage in a plastic pot of sterile potting compost. Inoculation was effected by dusting the leaves with conidia of Erysiphe graminis, spp. hordei.

24 hours after inoculation the seedlings were sprayed with a solution ofthe compound in a mixture of acetone (50%), surfactant (0.04%) and water using a track sprayer. The rate of application was equivalent to 1 kg of active material per hectare. First assessment of disease was made 5 days aftertreatment, when the overall level ofsporulation on the treated pots was compared with that on control pots.

The extent of disease control is expressed as a control rating as follows: 0 = less than 50% disease control 1 = 50-80% disease control 2 = greaterthan 80% disease control The results obtained are set out in Table Ill.

TABLE III

Compound of Control Rating Example against Eg 1 2 2 0 3 0 6 1 10 1 13 0

Claims (11)

1. CLAIMS 1. Heterocyclic amido derivatives of formula:

   in which R1 represents a 6-membered heterocyclic group containing 1 or 2 nitrogen atoms; R2 represents an optionally halogenated alkyl or phenyl group, and R3 represents a 5-membered heterocyclic group containing one hetero-atom, optionallysubstituted bya halogen atom and/or byan alkyl group.
2. 2. Heterocyclic amido derivatives as claimed in claim 1, in which R1 represents a pyridyl or pyrazinyl group; R2 represents an alkyl group of 1 to 6 carbon atoms or a phenyl group optionally substituted by up to two chlorine atoms; and R3 represents a thienyl or furyl group optionally substituted by a bromine atom or byan alkyl group of 1 to 6 carbon atoms.
3. 3. Heterocyclic amido derivatives as claimed in claim 2, in which R1 represents a pyridyl or pyrazinyl; R2 represents a methyl, t-butyl, dimethylpropyl, phenyl or dichlorophenyl group;and R represents a thienyl orfuryl group optionally substituted by a bromine atom or buy a methyl group.
4. 4. Heterocyclic amido derivatives as claimed in claim 1 specifically identified herein.
5. 5. A processforthe preparation of a heterocyclic amido derivative as claimed in claim 1,which comprises reacting a compound offormula: R--NH--CH2--R II with an acid halide offormula: R2-CHal III in which RX, R2 and R3 are as defined in claim 1 and Hat represents a halogen atom, in the presence of a base.
6. 6. A process as claimed in claim 5, in which Hal represents a chlorine atom.
7. 7. A process as claimed in claim 5or6, in which the base is a tertiary amine.
8. 8. A process as claimed in claimS, substantially as described with reference to Example 't B.
9. 9. Heterocyclicamido derivatives as claimed in claim 1, when prepared buy a process as claimed in any one ofthe claims 5to 8.
10. 10. Biologically active compositions comprising a heterocyclic amido derivative as claimed in any one of the claims 1 to4or9,togetherwith a carrier.
11. 11. A method of combating andior regulating plant growth at a locus, or combating plant fungi at a locus infected, or subject to infection, by such fungi, which comprises applying to the locus a biologically effective amount of a heterocyclic amido derivative as claimed in any one of the claims 1 to 4 or 9 or a composition as claimed in claim 10.