Title of Invention	PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRAZOLE COMPOUND OF GENERAL FORMULA ( I )
Abstract	A process for the preparation of a compound of general formula (I) CF3S(0) (I) wherein R1 is CN or CSNH2; R2 is hydrogen or chloride; and R3 is halogen or haloalkyl or haloalkoxy or SF5; said process comprises reacting a compound of formula (II) where R1, R2 and R3 are as denned above; with a proton source.

Full Text

FORM 2 THE PATENTS ACT, 1970 [39 OF 1970] COMPLETE SPECIFICATION [See Section 10; Rule 13] "PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRAZOLE COMPOUND OF GENERAL FORMULA (I)" BAYER CROPSCIENCE S.A., a French body corporate of 55 Avenue Rene Cassin-69009 Lyon, France, The following specification particularly describes the nature of the invention and the manner in which it is to be performed:- The present invention relates to a process for the preparation of substituted pyrazole compound of general formula (I). Pyrazoles such as 5-Amino-l-aryl-3-cyanopyrazole compounds and derivatives thereof, for example Fipronil, form an important class of insecticides. Certain substituted 5-N-alkyl-N-alkoxyacetylamino-l-aryl-3-cyanopyrazole compounds have valuable pesticidal properties as disclosed in WO 00/35884 and US Patent 5,556,873. We have developed a new synthesis route for the production of intermediate compounds useful in the preparation of substituted pyrazole pesticide compounds. Accordingly, the present invention provides a process for the preparation of a compound of general formula (I) (I) wherein R1 is CN or CSNH2;. R2 is hydrogen or chloride; and R3 is halogen or haloalkyl or haloalkoxy or SF5 which process comprises reacting a compound of formula (II) CF3S(0) 10 15 20 (II) where R1, R2and R3 are as defined above; with a proton source. The proton source used in the process of the present invention is preferably an aqueous acidic solution for example aqueous hydrogen chloride. The reaction is suitably carried out in a suitable solvent or in a solvent which may or may not be partially miscible with water. Suitable solvents include hydrocarbon solvents such as toluene or xylene. The amount of proton source used in the reaction is suitably from 0.1 to 2 equivalents, preferably from 0.5 to 1.0 equivalents. The reaction may suitable be carried out at a temperature of from minus 50 to 200 °C, preferably from 50 to 100°C. With regard to R1, R2 and R3 , R1 is preferably CN, R2 is preferably chloride and R3 is preferably a haloalkyl, especially triffuoromethyl. Compound (IT) may be prepared by a novel synthesis route and according to another aspect of the present invention there is provided a process for the preparation of compound (II) as defined above which process comprises reacting a compound of general formula (III) —O CF3S(0) (III) wherein Rl, R2 and R3 are as previously defined; with a quaternary ammonium 5 salt The quaternary ammonium salt may be a tetraalkylammonium halide such as the iodide or the bromide, preferably tetraalkylammonium bromide. Suitable tetraalkylammonium bromide include tetrabutylammonium Bromide. The amount of the halide salt used in the reaction is suitably from 0.01 to 2 10 equivalents, preferably from 0.1 to 0.5 equivalents. The reaction may be carried out in the presence of an organic solvent which may or may not be partially miscible with water. Suitable solvents include hydrocarbon solvents such as toluene or xylene. The reaction is suitably carried out at a temperature of from 50 to 100°C. 15 Compound (III), as defined above, may be prepared by the known synthesis route which comprises reacting a pyrazole compound known as fipronil having the formula (IV) 20 with trimethylorthoformate. This reaction may be carried out the presence of an acidic catalyst. Suitable catalyst include para-toluene sulphonic acid. Compound (III) may also be treated with the quaternary ammonium salt followed by acidic treatment to produce directly compound (I) without isolating compound (II). Compound (I) may also be prepared by reacting fipronil (compound IV) with formaldehyde or a formaldehyde trimer or the chemical equivalent thereof to produce an intermediate compound (V) 10 CF3S(0) (V) 15 20 25 where Rl, R2, R3 are as defined above. Intermediate compound (V) may then be reacted with a reducing agent to provide compound (I). A suitable reducing agent includes sodium borohydride. The reducing agent may be present in an amount of from 1 to 5 equivalents. Certain compounds according to formulae (II), (III) and (V) are novel compounds and in particular according to another aspect of the present invention there is provided novel compounds: 3-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-5-N-formyl-N-methylamino-4-trifluoromethylsulfinylpyrazole (Compound II). 3-cyano-1 -(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxy methylideneamino-4-trifluoromethylsulfinyIpyrazole (Compound III) 3-cyano-l3(2,6-dichloro-4-trifluoromethylphenyl)-5-hydroxymemylarriino-4-trifluoromethylsulphinylpyrazole (Compound V). Compound (I) prepared according to the process of the present invention may be used as the starting material for a further important pyrazole which is known to have pesticidal properties and which is defined according to general formula (VI). 10 15 wherein Rl is CN or CSNH2; X is N or CR4; R2 and R4 are, each, independently hydrogen or chlorine; R3 is halogen, haloalkyl, haloalkoxy or -SF5; R5 and R6 are each independently an alkyl group; and n is 0, 1 or 2; The preparation of this compound from compound (I) is known from International Patent Application Number WO 00/35884 which is herein incorporated by reference. In particular compound (I) is reacted with ethoxy acetyl chloride in the presence of triethylamine to produce compound (VI). The present invention will now be illustrated by reference to the following non limiting examples: 20 25 Example 1: A substantial molar excess of trimethylorthoformat is reacted with fipronil (Compound IV) at reflux with 0.5 equivalents of paratoluensulfonic acid to provide 3-Cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-5- methoxymethylideneamino-4-trifluoromethylsulfinylpyrazole (Compound III). This product is immediately treadted with 0.1 equivalents of tetrabutylammoniurn iodide in xylenes at 100 degrees centigrade for 5 hours to provide 3-Cyano-l-(2,6-dichloro-4-triiluoromethylphenyl)-5-(N-formyl-N- methylamino)-4-trifluoromethylsulfmylpyrazole (Compound II). The medium is immediately reacted with aqueous hydrogen chloride and to provide 3-Cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-trifluoromethylsulfinylpyrazole as final product (Compound I). 5 Example 2: 5 equivalent of a sodium methylate (30% solution in methanol) was rapidly added to a suspension of 0.437g of Fipronil and 1.4 equivalent of paraformaldehyde in 3mL of methanol to provide the 3-Cyano-l-(2,6-dichloro-4- 10 trifluoromemylphenyl)-5-hydroxymethylamino-4-1xifluoromethylsulfilnylpyrazole (Compound V) after 3 hour at 20°C and 1 hour at 60°C. Then 1 equivalent of sodium borohydride was added to the medium which provide after classical extraction and chromatography separation the 3-Cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-trifluoromethylsulfinylpyrazole 15 (Compound I). WE CLAIM: 1. A process for the preparation of a compound of general formula (I) CF3S(0) (I) wherein R1 is CN or CSNH2; R2 is hydrogen or chloride; and R3 is halogen or haloalkyl or haloalkoxy or SF5; said process comprises reacting a compound of formula (II) where R1, R2 and R3 are as denned above; with a proton source. 2. A process as claimed in claim 1 wherein R1 is CN, R2 is chloride and R3 is trifluoromethyl. A process as claimed in claim 1 or claim 2 wherein the proton source is an aqueous acidic solution. A process as claimed in claim 3 wherein the aqueous acidic solution is aqueous hydrogen chloride. A process as claimed in any one of the preceding claims carried out in the presence of a solvent. A process as claimed in claim 5 wherein the solvent is toluene or xylene. A process for the preparation of compound of formula (I) as claimed in claim 1 wherein said compound II is prepared by a process comprises reacting a compound of general formula (III) (Ill) wherein R1, R2 and R3 are as defined in claim 1; with a quaternary ammonium salt A process as claimed in claim 7 wherein the quaternary ammonium salt is a tetraalkylammonium halide A process as claimed in claim 7 or 8 wherein the tetraalkylammonium halide is tetraalkylammonium bromide. 10. A process as claimed in any one of claims 7 to 9 wherein said process is carried out in the presence of an organic solvent. 11. A process as claimed in claim 10 wherein the solvent is toluene or xylene. 12. A process for the preparation of compound (I) as claimed in claim 1 wherein said process comprises reacting compound (III) with a quaternary ammonium salt followed by the addition of an acid. 13. Novel compound 3-cyano- 1 -(2,6-dichloro-4-trifluoromethylphenyl)-5-N-formyl-N-methylamino-4-triflucromethylsulfinylpyrazole. 14. Novel compound 3-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxy methylideneamino-4-trifluoromethylsulfinylpyrazole. Dated: 30/10/2002 [RANJNA MEHTA DUTT] REMFRY 8B SAGAR ATTORNEY OF THE APPLICANTS]

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