Process for Preparing Substituted Biphenylanilides

Abstract

The present invention relates to a process for preparing substituted biphenylanilides of the formula I which comprises reacting a compound of formula II in the presence of a base and of a palladium catalyst selected from the group of: a) palladium-triarylpliosphine or -trialkylphosphine complex with palladium in the zero oxidation state, b) salt of palladium in the presence of triarylphospine or trialkylphosphine as a complex ligand or c) metallic palladium, optionally applied to support, in the presence of triarylphosphine or trialkylphosphine, in a solvent, with a diphenylborinic acid according to formula (III)

1 . A process for preparing substituted biphenylanilides of the formula I 
       
         
           
           
               
               
           
         
       
       Het is a heterocyclyl-residue selected from 
       
         
           
           
               
               
           
         
         wherein “#” indicates the substituted position of the residue; 
       
       X is hydrogen fluorine or chlorine; 
       R 1  is C 1 —C 6 -haloalkyl; 
       R 2  is cyano, nitro, halogen, C 1 —C 6 -alkyl, C 1 —C 6 -alkenyl, C 1 —C 6 -alkynyl, C 1 —C 6 -alkoxy, C 1 —C 6 -haloalkyl, (C 1 —C 6 -alkyl)carbonyl or phenyl; 
       R 3  is C 1 —C 4 -alkyl, C 1 —C 4 -alkenyl or C 1 —C 4 -alkynyl; 
       n is 1 , 2 or 3, where in case that n is 2 or 3, the R 2  radicals may also be different, 
       which comprises reacting a compound of formula II 
       
         
           
           
               
               
           
         
         in which Hal is halogen and X and Het are as defined above, in the presence of a base and of a palladium catalyst selected from the group of: 
         a) palladium-triarylphosphine or -trialkylphosphine complex with palladium in the zero oxidation state, 
         b) salt of palladium in the presence of triaryiphospine or trialkylphosphine as a complex ligand or 
         c) metallic palladium, optionally applied to support, in the presence of triarylphosphine or trialkylphosphine, 
         in a solvent, with a diphenylborinic acid according to formula (III) 
       
       
         
           
           
               
               
           
         
         in which R 2  and n are as defined above, where the triarylphosphines or trialkylphosphines used may be substituted. 
       
     
     
         2 . The process according to  claim 1 , wherein the compound (II) used is selected from the group consisting of N-(2-chloro-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 2-chloro-N-(2-chlorophenyl)pyridine-3-carboxamide and 2-chloro-N-(2-bromo-phenyl)pyridine-3-carboxamide. 
     
     
         3 . The process according to  claim 1  or  2 , wherein the starting compound (III) is a diphenylborinic acid which is substituted in the 3- and 4-position. 
     
     
         4 . The process according to  claims 1  or  2 , wherein a diphenylborinic acid (III) is used which bears fluorine or chlorine in the 3- and 4-positions. 
     
     
         5 . The process according to  claims 1  or  2 , wherein the starting compound (III) is di(3,4-dichlorophenyl)borinic acid. 
     
     
         6 . The process according to  claims 1  to  5 , wherein the palladium catalyst a) according to  claim 1  used is tetrakis(triphenylphosphine)palladium or tetrakis(tri-tert.-butylphosphine)palladium. 
     
     
         7 . The process according to  claims 1  to  5 , wherein a palladium catalyst b) according to  claim 1  is used. 
     
     
         8 . The process according to  claims 1  to  5 , wherein the palladium catalyst c) according to  claim 1  used is metallic palladium on activated carbon in the presence of triphenylphosphine whose phenyl groups are substituted by a total of from 1 to 3 sulfonate groups. 
     
     
         9 . The process as claimed in  claim 7 , wherein the salt of the palladium catalyst b) used is palladium chloride, palladium acetate, palladium bisacetylacetonate (Pd(acac) 2 ) or bisacetonitrilepalladium chloride. 
     
     
         10 . The process according to  claim 7 , wherein a palladium catalyst b) is used for which from 6 to 60 equivalents of triphenylphosphine are used per equivalent of the palladium salt. 
     
     
         11 . The process according to  claim 1 , wherein from 0.001 to 1.0 mol % of the palladium catalyst is used, based on the amount of compound (II). 
     
     
         12 . The process according to  claim 1 , wherein the reaction is carried out at a temperature of from 50 to I20° C. 
     
     
         13 . The process according to  claim 1 , wherein the reaction is carried out in a mixture of water and an organic solvent. 
     
     
         14 . The process according to  claim 13 , wherein the organic solvent used is an ether. 
     
     
         15 . The process according to  claim 1 , wherein the reactions are carried out at a pressure of from 1 to 6 bar. 
     
     
         16 . The process according to  claim 1 , wherein compound (II) is N-(2-chloro-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and compound (III) is di(3,4-dichlorophenyl)borinic acid. 
     
     
         17 . The process according to  claim 1 , wherein compound (II) is N-(2-chlorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and compound (III) is di(3,4-dichlorophenyl)borinic acid. 
     
     
         18 . The process according to  claim 1 , wherein compound (II) is 2-chloro-N-(2-bromophenyl)pyridine-3-carboxamide and compound (III) is (4-chlorophenyl)borinic acid.