Title of Invention

PROCESS FOR THE PREPARATION OF PESTICIDAL OXIME ESTERS"

Abstract

A process for the prepARAtion of novel pesticidal oxime esters of formula I, RI/ARA-CH=N-OCOR2/ArB, and formula II, Rl/ARA-CH=N-OCO-Arc-COO-N=CH-ARA/RI chARActerized by the reaction of compounds containing an oxime moiety Rl,MA-CHN-O- with compounds comprising of an acyl moiety RI/ArBCO- wherein the reaction is carried out in an organic solvent in a need based presence of a base as catalyst at 15 to 100 0C, and wherein MA, MB and Arc represent substituted or unsubstituted aryl, alkyl, ARAlkyl, alkylaryl group(s), and R1 and R2, substituted or unsubstituted pARAfinic, olefinic or acetylenic group(s), to yield geometrically isomeric compounds of formulae I and II. The configuration around the oxime double bond CH=N, in the molecule being Z or E or both. The application also describes the pesticidal compositions based on the above esters for use in combating mosquito (Culex fatigans), agricultural insect pests namely Spodoptera litura, and Helicoverpa armigera besides some phytophagous fungi and nematodes infecting agricultural crops.

Full Text

This invention relates to a process for the prepAR+Ation of novel pesticidal oxime esters as agents for protection against pest infestation. More particularly it relates to substituted oxime esters as effective novel pesticides such as insecticides, insect growth regulators, fungicides, nematicides and the like. Prior art Biologically active novel aliphatic and aromatic oxime ethers having alkoxy, phenoxy, benzodioxole groups are known in the prior art. These are well known for their pest control properties. The reported products are insecticides (Bull MJ, Davies HJ, Robert JG, Henry SC and Henry AC (1980) Pestic. Sci 44: 249-256., Nanjyo K, Katsuyama N, Kariya A, Yamamura T, Hyeon S, Suzuki A, and Tamura S (1980), Agril Biol Chem 44(1) 217-218), insect growth regulators (Niwa A, Iwamura H, Nakagawa, Y and Fuj ita T (1988), J Agric Food Chem 36: 378-84., Choudhury H, Saxena VS and Walia S (1998), JAgric Food Chem 46 (2) 731-736.) or insecticide synergists (Walia S, Saxena VS and Mukerjee SK (1985) JAgric Food Chem 33, 308-3 10). In the prior art US patent 4,468,397 describes insecticidal oxime ethers formed as a result of the reaction of oxime(s) with alkyl halides, and hydroxamic acid esters also referred to as oxime cArBamates formed as a result of reaction of oxime(s) with methyl isocynate. Number of oxime derivatives such as ethers (US patent 4,514,406, 5,055,471 and 5,446,067), unsaturated ethers (US patent 6,303,818), aromatic ethers (US patent 6,407,100), O-benzyloxime ethers (US patent RE 37,839), 1-azolyl substituted oxime ethers (JP-A 60-87269) have also been described as potential insecticides and/or fungicides. Hydroximic acid derivatives useful as pesticides (US patent 5,919,825) and cyclohexenone oxime ethers suitable as herbicide (US patent 5,604,183) have also been described. A recent US patent 6,680,410 describes the process for providing oxime ethers by alkylation of oximes with dimethylsulphate in aprotic solvents such as dimethlformamide, tert-butyl methyl ether, or acetone containing potassium cArBonate. Some other US patents 4,414,743, 4,518,536 and 4,548,756 describe a variety of oxime ethers with plant growth stimulating and herbicide safener activity without any disadvanl:age to cultivated crops. Oxime ester group of compounds reported in this invention are formed as a result of reaction of aldoximes/ ketoximes with substituted or un-substituted aromatic/aliphatic acid chlorides. Such compounds have not been investigated earlier for their pest control property. This invention reports the synthesis and pesticidal activity of such oxime esters. Background of invention Literature is replete with examples of oxime ether group of compounds exhibiting insect growth inhibitory activity. No literature was however, available employing oxime ester group of compounds for pest control purposes. The present invention reports the process for the prepAR+Ation of novel oxime ester compounds bearing alkyl, aryl, hydroxy, alkoxy, phenoxy, aryloxy, methylenedioxy substituents and (or) related moieties. These esters are structurally different from those reported in US patents 4,414,743, 4,468,397, 4,514,406, 4,518,536, 4,548,756 5,446,067, 6,303,818, 6,407,100, RE 37,839, 5,919,825, 5,604,183 as well as other literature. Those described in US patent 4,468,397 are esters of hydroxamic acid (generally known as oxime cArBamates) formed as a result of the reaction of the oxime with methyl isocynate, or oxime ethers formed as a result of the reaction of the oxime with alkyl halides. Unlike these, the compounds described in this invention are oxime esters formed as a result of the reaction of oximes with substituted/unsubstituted aromatic/aliphatic acid chlorides. Such compounds have not been reported earlier and have now been found particularly effective as insecticides, insect bioregulator, nematicide and fungicide for the control of agricultural or veterinary pests, and as mosquitocide for the control of public health pest. Object of invention An object of the invention is to prepare novel oxime esters with pest control properties. Another objective is to establish the pesticidal potential of these novel derivatives against various pests such as insects., nematode, fungi and others. The invention According to this invention, there is provided a process for the prepAR+Ation of pesticidal oxime esters of the formulae I Rl/AR+A-CH~=N-O-COR2/ArB and II Rl/AR+A-CH=N-OOCAr+C-COO-N=CH-AR+A /R1 chAR+Acterized by the reaction of compounds containing an oxime moiety RI/AR+A-CH=N-O- with compounds comprising of an acyl moiety RI/ArBCO- to form a link CH=N-O-CO- between Rl,AR+A-CH=N-O- and —COR2/ArB to yield compounds of formula I RI/AR+A-CH~N-O-COR2/ArB, and between RI/AR+A-CH=N0- and -CO-Ar+CCO- to yield compounds of formula II RI/AR+A-CH=N-OOC-Ar+C-COON=CH-AR+A/RI wherein the reaction is carried out in an organic solvent in a need based presence of a base as catalyst at 15 to 100 0C, and wherein AR+A, ArB and Ar+C represent substituted or unsubstituted aryl, alkyl, AR+Alkyl, alkylaryl group, and R1 and R2 substituted or unsubstituted pAR+Afinic, olefinic or acetylenic group, to yield geometrically isomeric compounds of formulae I and II Preferred oxime esters of formula I, RJ/AR+A-CH=N-O-COR2/ArB, according to this invention are those in which R1 and R2 represents substituted alkyl, alkenyl, cycloalkyl of varying chain length group with one or more of hydroxy, methoxy, ethoxy, alkenyloxy or phenoxy or halogen substituents, AR+A and M~ represent phenyl, aryl, benzalkyl, phenoxyphenyl, substituted 2-phenyl-3-methylbutyl, or aromatic ring with one or more of hydroxy, methoxy, ethoxy, alkenyloxy, phenoxy or halo sub stituents, The configuration of the groups about the double bond is either Z or E or mixture of both Z and E isomers. AR+A is preferably a phenoxy, benzyl or phenyl group substituted by halogen, methylenedioxy, phenoxy or alkoxy at the ortho, meta, and/or pAR+A position(s). In formula II, RI/AR+A-CH=N-OCO-Ar+C-COO-N=CH-AR+A/RI, AR+A group may be unsubstituted phenyl group or phenyl group substituted with one or more of alkoxy, phenoxy or halogen especially at 3-position. Compound(s) comprising a moiety AR+CH=N-O- and a compound comprising a moiety COR or COAr are reacted together to form a link between -CH=N-0- and COR/Ar as shown in formulae I and II. The species Ar/R is generally present in the form of alkyl/aryl, /substituted benzoyl halide for example acetyl/cyclopropyl/ benzoyl/ terphthalloyl or phenoxybenzoyl chloride. Typical reactions for the prepAR+Ation of the said compounds of types I and II are given below. (Structure Removed) The oximes Rl/MA-CH=N-OH and acid chlorides [RCOCl, Ar+COCL or C6H4(COCI)2J used as starting materials are either known or can be prepared by known methods Oximes for examples can be prepared by reacting corresponding aldehyde or ketone with hydroxylamine hydrochloride in the presence of an organic solvent, prefereably methanol or ethanol, with or without the presence of a base such as sodium cArBonate, sodium acetate, in the temperature range of 0 to 100 0C. The product obtained after addition of water to the reaction mixture can be filtered or extracted with a suitable solvent and/or purified by recrystallisation. Acid chlorides can be prepared by reacting acids with thionyl chloride, POCl3 or PCI5, and neutralizing the emanating acidic gas vapors in saturated sodium hydroxide solution. Oxime esters of formulae I and II are prepared by reacting the oximes with slight excess of the molar quantities of mono- or dicArBoxylic acid chlorides in an inert organic diluent such as benzene, toluene, xylene, methylenechloride, chloroform, ethylacetate, acetone, ethylmethylketone or methyl isobutylketone with the addition of a catalytic amount of triethylamine or pyridine. The reaction is performed at a temperature between 15-80 0 Oxime esters of formulae II and I prepared as above are usually mixture of Z and £isomers. These can be conveniently sepAR+Ated by column chromatography to obtain pure Z and E isomers. The compounds of formulae I and II as such or in various prepAR+Ations have been found effective to combat insect, nematode and fungal infestation in agricultural crops, mosquito control and/or control of ectopAR+Asites and endopAR+Asites in veterinary health. The invention therefore includes pesticidal compositions comprising a compound of formulae I and II as active ingredients together with a carrier, diluent, or surfactant and (or) c)ther formulant(s). Suitable solid diluents such as pumice, gypsum, kaolin, bentonite, talc etc, liquid diluents such as ketonic as well as aliphatic and aromatic solvents, along with suitable swelling agent, dispersing agent or emulsifying agent, can be used to prepare various solid and liquid prepAR+Ations such as dusts, granules, emulsifiable concentrates, solutions, water dispersible powder etc. The composition may include a mixture of compounds of formulae I and II and/or other ingredients including another pesticide e.g. an insecticide, fungicide, nematicide etc. or adjuvants such as synergist etc. While the various compositions may preferably contain from 1 to 20% by weight of active ingredient, those applied after dilution may contain from 0.001 to 1% by weight of the active ingredient at the final application stage. The composition may conveniently be applied at an application rate of 1 to 500 g a. i. per hectare. The compound(s) have been found to be active in combating pests such as insects, fungi and nematodes. Examples Examples I-X describe the prepAR+Ation of m-phenoxybenzaldoxime esters of formulae I and 2. Example XI describes their pest control activity. The structures of these compounds have been confirmed by 1H NMR spectroscopy. PrepAR+Ation of series offormida 1 Example —I (m-Phenoxybenzaldoxime N-O-cyclopropane cArBoxilate (I) To a stirred solution of m-phenoxybenzaldoxime (1 .97g, 0.01 mole) in methylene chloride, xylene, or solvent ether (50m1), an aliphatic or alicyclic cArBoxylic acid chloride for example cyclopropane cArBoxylic acid chloride (1.04g, 0.01 mole) was added slowly at a temperature range of 10 to 300C. The reaction is best done at ambient temperature in the presence of a base such as triethylamine. After cooling, the solution was filtered and concentrated under reduced pressure. The residual product was subjected to prepAR+Ative thin layer chromatography (TLC) or column chromatography over silica gel using diethyl ether/hexane or methlene chloride/hexane (1:9) or distilled under reduced pressure to yield m-phenoxy benzaldoxime N-O-cyclopropane cArBoxilate.( yield 2.30g, 82%). It was a mixture of both Z and E isomers, which could be sepAR+Ated by column chromatography. Example —II .m-Phenoxybenzaldoxime N-O-acetate (II) The method of example —I was repeated using solution of m-phenoxybenzaldoxime (1.97 g, 0.01 mole) in methylene chloride (50 ml) and reacting with acetyl chloride (0.70g, 0.01 mole) to yield the title compound (yield 2.17g, 85%). Example —III m-Phenoxybenzaldoxime N-O-chloroacetate (III) The method of example —I was repeated using solution of m-phenoxybenzaldoxime (1.97g, 0.01 mole) in methylene chloride (50m1) and reacting with chloroacetyl chloride (1.12g, 0.01 mole) to yield the title compound (yield 2.13g, 74%). Example —IV m-Phenoxybenzaldoxime N-O-isobutyrate (IV) The method of example —I was repeated using solution of m-phenoxybenzaldoxime (1.97g, 0.01 mole) in methylene chloride (50 ml) and reacting with isobutyryl chloride(1.06g, 0.01 mole) to yield the title compound (yield 2.26g, 80%). Example V m-Phenoxybenzaldoxime N-O-m-phenoxybenzoate) (V) The method of example —1 was repeated using solution of m-phenoxybenzaldoxime (1 .97g, 0.01 mole) in methylene chloride (50 ml) and reacting with m-phenoxybenzoyl chloride, (2.32g, 0.01 mole) to yield the title compound (yield 3.lOg, 76%). Example —VI m-Phenoxybenzaldoxime N-O-phenoxyacetate (VI) The method of example —1 was repeated using solution of m-phenoxybenzaldoxime (1.97g, 0.01 mole) in methylene chloride (50m1) and reacting with phenoxyacetyl chloride (1.70g, 0.01 mole) to yield the title compound (yield 2.60g, 75%). Example-ViI m-Phenoxybenzaldoxime N-O-2,4-dichlorophenoxyacetate (VII) The method of example I was repeated using solution of m-phenoxybenzaldoxime (1.97g. 0.01 mole) in methylene chloride (50 ml) and reacting with 2,4-dichlorophenoxy acetyl chloride (2.38g, 0.1 mole) to yield the title compound (yield 2.98g, 70%). Example —VIII m-Phenoxybenzaldoxime N-O-phenylacetate (VIII) The method of example—I was repeated using solution of m-phenoxybenzaldoxime (l.97g, 0.Olmole) in methylene chloride (50m1) and reacting with phenylacetic acid chloride (1 .54g, 0.01 mole) to yield the title compound (yield 2.61g, 79%). Example —IX m-Phenoxybenzaldoxime N-O-dichlorobenzoate (IX) The method of example —I was repeated using solution of m-phenoxybenzaldoxime (1 .97g, 0.0 imole) in methylene chloride (SOml) and reacting with dichlorobenzoy] chloride (2.08g, 0.01 mole) to yield the title compound (yield 2.77g, 72%). Example—X m-Phenoxybenzaldoxime N-O-2-(4-chlorophenyl)-3-methylbutanoate (X) The method of example I was repeated using solution of m-phenoxybenzaldoxime (1.97g. 0.0 imole) in methylene chloride (50 ml) and reacting with 2-(4-chlorophenyl)-3- methylbutyric acid chloride (2.3g, 0.01 mole)] to yield the title compound (yield 3.05g. 75%). PrepAR+Ation of series of formula 2 Example XI Bis (m-phenoxybenzaldoxime)terphthalate (XI) The method of example I was repeated using solution of m-phenoxybenzaldoxime (3.94g. 0.2 mole) in methylene chloride (50 ml) and reacting with substituted ter-phthaloyl chloride (2.02g, 0.1 mole), to yield the title compound (yield 3.61g, 65%).. Bioassay Pesticidal activity was assessed against the mosquito Gulexfatigans and the agricultural insect pests namely Spodoptera litura, and Helicoverpa armigera. Mosquito (Culex fatigans): Laboratory reared mosquito larvae (C. fatigans) were used in the experiments. The test compounds were dissolved in emulsified water at four different concentrations) and 500 ml each of the solution was taken in glass troughs measuring 15 cm diameter. A known number of 3-day old mosquito larvae were released into the glass troughs containing insecticide solution. For each concentration, two replications were maintained. Observations were recorded for percent mortality at 24 hr after treatment. The results of the bioassay are reported in Table-I. Tobacco armyworm (Spodoptera litura) and gram pod borer (Helicoverpa arm igera): Laboratory cultures of S. litura and H. armigera were maintained on an artificial diet at 272 0C. Neonate larvae of 3rd 4th and 5"~ stage were used for bioassay. The test compounds were mixed with the artificial diet at different concentration of (0.025-2.5 mg/g dry weight of diet yielding 5-500 ppm levels. The carrier solvent was evaporated and two neonate larvae were placed in 1 g fresh weight of diet contained in cups. The treatments were incubated in a growth chamber and mortality/insect growth abnormalities recorded after specified intervals for calculating LC50/EC50 value. The results are reported in Table-I. Table 1. Insecticidal and insect bioregulatory activity ( mg U') of some potential pesticidal oxime esters. (Table Removed) 8 We claim A process for the prepARAtion of novel pesticidal oxime esters of formula I, RI/ARA-CH=N-O-COR2/ArB, and formula II, RI/ARA-CH=N-OCO-ArC-COON=CH-ARA/RI chARActerized by the reaction of compounds containing an oxime moiety Rl,ARA~CH=N~O~ with compounds comprising of an acyl moiety RI/ArBCO- to form a link CH=N-O-CO- between RI,ARA-CH=N-O- and -COR2/ArB to yield compounds of formula I RI/MA-CH=N-O-COR2/ArB, and between RI/ARA-CHN-O- and -CO-ArCCO- to yield compounds of formula II RI/ARA-CHN-OOC-ArC-COO-NCH-ARA/R1 wherein the reaction is carried out in an organic solvent in a need based presence of a base as catalyst at 15 to 100 0C, and wherein ARA, MB and ArC represent substituted or unsubstituted aryl. alkyl, Aralkyl, alkylaryl group, and R1 and R2, substituted or unsubstituted pARAfinic, olefinic or acetylenic group, to yield geometrically isomeric compounds of formulae I and II 2. A process as claimed in claim 1 wherein the configuration of the groups RI/MACH- and OCOR2/AR1 about the oxime double bond -CH=N- in the oxime ester molecule may be syn., anti or both. 3. A process as claimed in claim I wherein the MA and/or MB is/are unsubstituted phenyl group or phenyl group substituted with one or more of hydroxy, alkoxy, alkenyloxy, methylenedioxy, phenoxy, or halo group in both the formulae I and II of the compounds, and ArC is substituted or unsubstituted alkyl, aryl or Aralkylor alkylaryl group in formula II. 4. A process as claimed in claim 1 wherein the R1 is substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, alkynyl, cycloalkyl, or mono-, or sesquiterpene moiety in both the formulae, and R2 represents alkyl, alkenyl, cycloalkyl, haloalkyl, haloalkenyl or Aralkylgroup in compounds of formula I. 5. A process as claimed in claims 1 to 4 above wherein the phenyl group, whenever substituted is at at ortho, meta or pARA position or a combination of two or more of these positions. 6. A process as claimed in claims 1 to 5 above wherein the reacting moieties to obtain the said oxime esters are unsubstituted or substituted alkanaldoxime, benzaldoxime, and unsubstituted or substituted aliphatic /aromatic acid chloride. 7. A process as claimed in claim I wherein the reaction is performed in inert organic solvent(s) such as benzene, toluene, xylene, methylenechloride, chloroform, ethylacetate, acetone, ethylmethylketone or methyl isobutylketone. 8. A process as claimed in claim 1 wherein the reaction is performed in a need based presence of a base such as triethylamine, pyridine., or the like. 9 9. A process as claimed in claim 1 wherein the reactant oximes are products of a reaction of un-substituted/substituted aliphatic/aromatic aldehydes with hydroxylamine hydrochloride and are either syn or anti or mixture of both isomers. 10. A process as claimed in claims 1 to 7 wherein the acid chlorides employed in the reaction are those obtained by the action of aliphatic and/or aromatic acids such as C2-C10-alkanoic acids, chloroacetic-, cyclopropane cArBoxylic-, 2(4-chlorophenyl-3 -methylbutanoic-, substituted or unsubstituted benzoic, phenylacetic, or phenoxyacetic-, phenoxybenzoic or terphthallic acid(s) with thionyl chloride. 11. A process as claimed in any of the above claims and as exemplified in thebody of the specification to yield the pesticidal oxime esters substantially as herein describe with reference with foregoing examples.

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