Process for preparing pesticidal intermediates

Abstract: The invention relates to a process for the preparation of compounds of formula (I): wherein W, R 1 and R 2 are as defined in the description.

Description: The invention relates to novel processes for preparing intermediates useful in the preparation of pesticides. European Patent Publication Nos. 0295117 and 0234119 describe the preparation of pesticidally active phenylpyrazole compounds and of 5-amino-1-aryl-3-cyanopyrazole intermediate compounds used in their synthesis. Various methods for preparing these compounds are known. The present invention seeks to provide improved or more economical methods for the preparation of pesticides and the intermediate compounds useful in preparing them. Helv. Chim. Acta. Vol. 41, 1958, p306-309, describes on page 307 the oxidation of N-phenyl-N'-2-cyanoethyl-phenylhydrazine using (a) iron (III) sulphate and then (b) sodium hydroxide to produce 2-phenyl-3-aminopyrazole. The reaction scheme depicted in this reference shows azo-N-phenyl-N'-β-cyanoethyl as an intermediate product. That compound is depicted as being converted to the pyrazole via a postulated phenylhydrazono intermediate. The postulated route of the reaction is inferred from the failure of another possible intermediate (a pyrazoline) to dehydrogenate under similar conditions. The structure of the azo compounds in the postulated reaction scheme is only indicated as "probable" on the basis of analysis, UV and IR spectra. US Patent No. 4,824,960 describes the preparation of 5-amino-1-arylpyrazole derivatives of general formula: wherein Ar represents substituted phenyl or pyridyl, which can be used as intermediates in the preparation of compounds possessing herbicidal or pesticidal properties, by the reaction of arylhydrazines of formula: Ar-NH-NH 2 wherein Ar is as hereinbefore defined, with acrylonitrile of formula: NC-CH=CH 2 in a first stage in the presence of a diluent and optionally a catalyst to give the arylhydrazine compounds of the formula: Ar-NH-NH-CH 2 -CH 2 -CN wherein Ar is as hereinbefore defined, followed by oxidation and cyclisation in a second process stage. However if it is desired to Perform an oxidation of the above 3-arylhydrazinopropionitriles (without cyclisation to the 5-amino-1-arylpyrazoles) in order to obtain 3-arylhydrazonopropionitriles, which may then be further processed to provide important 5-amino-1-aryl-3-cyanopyrazole compounds which are valuable intermediates in the preparation of pesticides, a different process must be employed The present invention accordingly provides a process for the preparation of a compound of the formula (I): wherein W represents nitrogen or -CR 3 ; R 1 represents halogen, haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy), R 4 S(O) n -, or -SF 5 ; R 2 represents hydrogen or halogen (for example chlorine or bromine); R 3 represents halogen (for example chlorine or bromine); R 4 represents alkyl or haloalkyl; and n represents 0,1 or 2; which process comprises the oxidation of a compound of formula (II): wherein R 1 , R 2 and W are as hereinbefore defined; to prepare a compound of formula (III): wherein R 1 , R 2 and W are as hereinbefore defined; followed by the reaction of the compound of formula (III) with a source of hydrogen cyanide to prepare the compound of formula (I). Unless otherwise specified in the present specification "alkyl" means straight- or branched- chain alkyl having from one to six carbon atoms (preferably one to three). Unless otherwise specified "haloalkyl" and "haloalkoxy" are straight- or branched- chain alkyl having from one to six carbon atoms (preferably one to three) substituted by one or more halogen atoms selected from fluorine, chlorine or bromine. Suitable oxidants for the above reaction to form compounds of formula (III) include quinones such as benzoquinone, peroxides such as hydrogen peroxide, hypohalites such as sodium hypochlorite; or preferably a metal salt or oxide for example cupric chloride or mercuric oxide. The oxidation is generally conducted in a solvent. Solvents suitable for use include aromatic halogenated or non-halogenated hydrocarbons such as toluene or chlorobenzene, nitriles such as acetonitrile or amides such as N,N-dimethylformamide. The reaction temperature is generally from 20°C to 150°C, and preferably from 50°C to 100°C. The molar ratio of oxidant to compound of formula (II) is generally from 0.01:1 to 5:1, preferably from1:1 to 3:1. In formulae (I), (II) and (III) and in the formulae depicted hereinafter, preferred values of the symbols are as follows:- R 1 represents haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy) or -SF 5 ; W represents -CR 3 ; and R 3 represents halogen. A most preferred compound of formula (III) is 3-(2,6-dichloro-4-trifluoromethylphenylhydrazono)propionitrile. The process of the invention represents in certain aspects an improvement over the prior art. Compounds of formula (III) may exist as a mixture of syn and anti isomers. Compounds of formula (I) may exist in the R- and S- forms. The source of hydrogen cyanide which may be used in the reaction to prepare compounds of formula (I) from compounds of formula (III) may be hydrogen cyanide gas itself, when the reaction is optionally performed in the presence of a base, for example pyridine; but it is preferably prepared in situ (to avoid the direct use of hydrogen cyanide) from a metal cyanide salt (generally an alkali metal cyanide, for example sodium cyanide or potassium cyanide), in the presence of an acid. Suitable acids include organic acids such as aliphatic carboxylic acids for example acetic acid, or halogenated aliphatic carboxylic acids such as chloroacetic acid or trifluoroacetic acid, or sulphonic acids such as benzenesulphonic acid, 4-toluenesulphonic acid or methanesulphonic acid; or inorganic acids such as hydrochloric acid or sulphuric acid. Alternative sources of hydrogen cyanide (which may be generated in situ ) are trimethylsilylcyanide in water, or a mixture of trimethylsilylcyanide and a Lewis acid for example tin (IV) tetrachloride, in a solvent such as dichloromethane or tetrahydrofuran, at a temperature of from 20°C to 100°C, preferably from 30°C to 60°C. The reaction is preferably performed under increased pressure which increases the speed of the reaction. The preparation of compounds of formula (I) from compounds of formula (III) may be effected in a polar or a non-polar solvent. Examples of polar solvents which may be used include water; alcohols such as methanol or ethanol; N,N-dimethylformamide; dimethylsulphoxide; or alkanoic acids such as acetic acid. Examples of non-polar solvents include hydrocarbons such as hexane, or ethers such as tetrahydrofuran or dioxane, or dialkyl ethers such as diethyl ether. When a metal cyanide salt is used in the presence of an acid, the prepared solvent is water or a mixture of water with a water miscible solvent. The reaction temperature is generally from 0°C to 100°C, preferably from 20°C to 50°C. Most preferably the compound of formula (I) is 2-(2,6-dichloro-4-trifluoromethylphenylhydrazino)succinonitrile. According to a further feature of the invention the compound of formula (II) used as starting material is prepared by the reaction of an arylhydrazine compound of formula (IV): wherein R 1 , R 2 and W are as hereinbefore defined; with acrylonitrile of formula (V): NC-CH=CH 2 to give a compound of formula (II) as defined above. Compounds of formula (IV) and (V) are known. The compounds of formula (I) obtained by the process of the invention may be used in the preparation of pesticidally active 5-amino 1-aryl-3-cyanopyrazole derivatives of formula (VI) obtained from intermediate compounds of formula (V) and (VII) according to the following reaction scheme: wherein the symbols used above are as hereinbefore defined. The following non-limiting examples illustrate the invention. NMR spectra are recorded using deuterochloroform as solvent. Example 1 Cupric chloride (0.673g, 2.5 equivalents) was added in one portion to a solution of 3-(2,6-dichloro-4-trifluoromethylphenylhydrazino)propionitrile (0591g, 2mmol) in chlorobenzene, and the mixture heated at 65°C for 50 minutes. The reaction was judged to be complete and was cooled, washed (water), dried (magnesium sulphate), evaporated and separated by chromatography on silica gel to give 3-(2,6-dichloro-4-trifluoromethylphenylhydrazono)propionitrile, NMR 3.37 (d, 2H), 7.03 (t,1H), 7.5 (s, 2H), 7.75 (s,1H) (35% yield), and 3-(2,6-dichloro-4-trifluoromethylphenylazo)propionitrile, NMR 3.0 (t,2H), 4.6 (t,2H), 7.6 (s,2H) (60% yield). Example 2 Preparation of 2-(2,6-dichloro-4-trifluoromethylphenylhydrazino)succinonitrile 2-(2,6-Dichloro-4-trifluoromethylphenylhydrazono) propionitrile (0.296g, 1mmol), sodium cyanide (0.196g, equivalents), water (1ml) and acetic acid (5ml) were added successively to a tube, which was sealed and reacted at 20°C for 40 hours. The mixture was added to saturated sodium bicarbonate solution, extracted (dichloromethane), washed (water), dried (magnesium sulphate) and evaporated to give a mixture which contained 40% of the desired title compound, NMR 3.1 (m, 2H), 4.5 (m,1H), 5.89 (m, 1H), 6.94 (d,1H), 7.71 (s,2H), together with 60% of unchanged starting hydrazone. Reference Example i) Preparation of 2-(2,6-dichloro-4-trifluoromethylphenylhydrazono)succinonitrile A mixture of 2-(2,6-dichloro-4-trifluoromethylphenylhydrazino) succinonitrile (0.323g) and cupric chloride (0.175g) was heated in chlorobenzene at 60°C for 6 hours. After filtration and evaporation the title compound and 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole were obtained as a 7:1 mixture Column chromatography on silica gel eluting with dichloromethane gave the pure title compound, obtained as a mixture of syn and anti isomers, NMR (anti isomer) 3.6 (s,2H), 7.57 (s,2H), 8.82 (s,1H, exchangeable with D 2 O), NMR (syn isomer) 3.56 (s,2H), 7.59 (s,2H), 8.27 (s,1H, exchangeable with D 2 O). ii) Preparation of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole Ammonia (20 microlitres of an 8% ammonia solution in water) was added to a mixture of the above 2-(2,6-dichloro-4-trifluoromethylphenylhydrazono) -succinonitrile (0.077g) in ethanol (1ml) and water (0.2ml) at 0 °C. After 10 minutes the mixture was extracted (dichloromethane) and evaporated to give 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (0.076g, 97% yield). Purity 98% (by hplc).

Claims: A process for the preparation of a compound of formula (I): wherein W represents nitrogen or -CR 3 ; R 1 represents halogen, haloalkyl, haloalkoxy, R 4 S(O) n- or -SF 5 ; R 2 represents hydrogen or halogen; R 3 represents halogen; R 4 represents alkyl or haloalkyl; and n represents 0,1 or 2; which process comprises the oxidation of a compound of formula (II): wherein R 1 , R 2 and W are as hereinbefore defined; to prepare a compound of formula (III): wherein R 1 , R 2 and W are as hereinbefore defined; followed by the reaction of the compound of formula (in) with a source of hydrogen cyanide to prepare the compound of formula (I). A process according to claim 1 in which the oxidant is a metal salt or oxide. A process according to claim 1 or 2 in which the oxidation is conducted in a solvent. A process according to any one of claims 1 to 3 in which the molar ratio of oxidant to compound of formula (II) is from 0.01:1 to 5:1. A process according to claim 4 in which the ratio is from 1:1 to 3:1. A process according to any one of the preceding claims, in which the compound of formula (II) is prepared by the reaction of a compound of formula (IV): wherein R 1 , R 2 and W are as defined in claim 1, with acrylonitrile of formula (V): NC-CH=CH 2 A process according to any one of the preceding claims wherein: R 1 represents haloalkyl, haloalkoxy or -SF 5 ; W represents -CR 3 ; and R 3 represents halogen. A process according to any one of the preceding claims wherein in the definition of R 1 haloalkyl is trifluoromethyl and haloalkoxy is trifluoromethoxy; and in the definitions of R 2 and R 3 halogen is chlorine or bromide. A process according to any one of the preceding claims wherein: R 1 represents trifluoromethyl; W represents -CR 3 ; and R 2 and R 3 represent chlorine.

Inventors: ANCEL JEAN ERICK, ANCEL, JEAN ERICK
Applicants: BASF AGRO B V ARNHEM NL WAEDEN, BASF AGRO B.V., ARNHEM (NL), WAEDENSWIL-BRANCH
Application year: 1998
Main classification: C07C255
IPC codes: C07C253, C07C255, C07D213