Process for the Sulfinylation of a Pyrazole Derivative

Abstract

The present invention relates to a process for the of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile (II) is reacted with a sulfinylating agent selected from trifluoromethylsulfinic acid, trifluoromethylsulfinic acid anhydride, and a trifluoromethylsulfinate alkaline or alkaline earth metal salt and mixtures of the acid and/or the salt(s), in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent.

1 . A process for the of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile (II) comprising reacting the compound with
 a sulfinylating agent selected from the group consisting of trifluoromethylsulfinic acid, trifluoromethylsulfinic acid anhydride, and a trifluoromethylsulfinate alkaline or alkaline earth metal salt and mixtures of the acid and/or the salt(s), in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid is p-toluenesulfonic acid, and   a halogenating agent.   
     
     
         2 . The process of  claim 1 , wherein said halogenating agent is selected from the group consisting of thionylchloride, thionylbromide, phosphoroxychloride, oxalylchloride, phosgen, triphosgen ((CCl 3 ) 2 C(═O)), chloroformiates, phosphorpentachloride, phosphortrichloride, trichloromethylchloromethanoat, and xylenesulfonic acid chloride. 
     
     
         3 . The process of  claim 1 , wherein said halogenating agent is a chlorinating agent selected from the group consisting of thionylchloride and phosphoroxychloride. 
     
     
         4 . The process of  claim 1 , wherein said amine of the amine acid complex is selected from the group consisting of the alkyl amines trimethylamine, triethylamine, tripropylamine, triisopropylamine, tributylamine, dimethyl ethyl amine, diethyl methylamine, dimethyl n-propyl amine, diisopropyl ethyl amine, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), DBN (1,5-diazabicyclo[4.3.0]non-5-ene), methyl morpholine, ethyl morpholine, N,N-dimethyl aniline, methyl piperidine, methyl pyrrolidine, methyl dibenzyl amine, and the aromatic amines pyridine, DMAP (dimethylamino pyridine), collidine, lutidine, pyrimidine, pyrazine, and piperazine. 
     
     
         5 . The process of  claim 1 , wherein said amine of the amine acid complex is selected from the group consisting of trimethylamine, triethylamine, dimethyl ethyl amine, dimethyl n-propyl amine and pyridine. 
     
     
         6 . The process of  claim 5 , wherein said amine is trimethylamine, triethylamine or pyridine. 
     
     
         7 . The process of  claim 1 , wherein at least one of the alkyl groups attached to the nitrogen atom of the amine is a methyl group. 
     
     
         8 . The process of  claim 1 , wherein the nitrogen atom of the amine group is sp 3 -hybridized and does not form a double bond with the neighbour atom. 
     
     
         9 . The process of  claim 1 , wherein said sulfinylating agent is selected from the group consisting of trifluoromethylsulfinic acid, trifluoromethylsulfinate sodium salt, and trifluoromethylsulfinate potassium salt, and mixtures of these. 
     
     
         10 . The process of  claim 1 , wherein said reaction is conducted in an organic solvent selected from the group consisting of toluene, benzene, xylene, trifluoromethylbenzene, monochlorobenzene, dichlorobenzene, and ethylbenzene. 
     
     
         11 . The process of  claim 1 , wherein said reacting comprises combining 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile with a reaction mixture of said sulfinylating agent, said amine acid complex and said halogenating agent. 
     
     
         12 . The process of  claim 1 , wherein 1.4 to 2.2 molar equivalents of said amine acid complex relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile are present. 
     
     
         13 . The process of  claim 1 , wherein 1.15 to 1.35 molar equivalents of said halogenating agent relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile are present. 
     
     
         14 . The process of  claim 1 , wherein 1.0 to 1.35 molar equivalents of said sulfinylating agent relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile are present. 
     
     
         15 . The process of  claim 1 , wherein said reacting comprises, after combining 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile, said sulfinylating agent, said amine acid complex, and said halogenating agent, the temperature is raised to 30° C. to 55° C., within 5 to 60 minutes. 
     
     
         16 . The process of  claim 1 , wherein said reacting comprises, after combining 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile, said sulfinylating agent, said amine acid complex, and said halogenating agent, the temperature is raised to 30° C. to 39° C., within 5 to 60 minutes. 
     
     
         17 . The process of  claim 1 , further comprising crystallizing 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile from a solution of monochlorobenzene, dichlorobenzene, ethylbenzene or toluene. 
     
     
         18 . The process of  claim 1 , further comprising formulating 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile into a pesticidal composition. 
     
     
         19 . The process of  claim 1 , further comprising formulating 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile into a veterinarily acceptable parasiticidal composition. 
     
     
         20 . 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile of  claim 1 . 
     
     
         21 . 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile of  claim 1 , which contains less than 20 ppm of bromine. 
     
     
         22 . 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile of  claim 1  which contains less than 10 ppm of the compound D 
       
         
           
           
               
               
           
         
       
     
     
         23 . 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile of  claim 1  and in an inert atmosphere, which contains less than 200 ppm of compounds containing sulfur in its oxidation state (IV). 
     
     
         24 . A pesticidal or parasiticidal composition comprising 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile of  claim 20 . 
     
     
         25 . A method for the control of insects, acarids or nematodes by contacting the insect, acarid or nematode or their food supply, habitat, breeding ground or their locus with a pesticidally effective amount of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile of  claim 20 . 
     
     
         26 . A method of protecting growing plants from attack or infestation by insects, acarids or nematodes by applying to the foliage or the seeds of the plants, or to the soil or water in which they are growing, a pesticidally effective amount of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile of  claim 20 . 
     
     
         27 . The method of  claim 25 , wherein 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile is applied in an amount of from 5 g/ha to 2000 g/ha. 
     
     
         28 . The method of  claim 26 , wherein 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile is applied in an amount of from 5 g/ha to 2000 g/ha. 
     
     
         29 . A method for treating, controlling, preventing or protecting animals against infestation or infection by parasites which comprises orally, topically or parenterally administering or applying to the animals or their habitat a parasiticidally effective amount of 5-amino-1-[2,6-dichloro-4-(trifluorornethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile of  claim 20 , or its veterinarily acceptable enantiomers or salts. 
     
     
         30 . A process for the preparation of a composition for treating, controlling, preventing or protecting animals against infestation or infection by parasites which comprises admixing 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile of  claim 20 , or its veterinarily acceptable enantiomers or salts with a veterinarily acceptable carrier. 
     
     
         31 . The process of  claim 30 , wherein 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)-pyrazole-3-carbonitrile or its veterinarily acceptable enantiomer or salt is present in a parasiticidally effective amount.