Method for producing sulfonamides

Abstract

A process for preparing sulfonamides I where the variables are each as defined in the description, by reacting m-nitrobenzoyl chlorides II with amino sulfones III, under the influence of B equivalents of base IV, wherein, in step a), the amino sulfone III is reacted with B1 equivalents of base IV, and, in step b), the reaction mixture resulting from step a) is reacted with m-nitrobenzoyl chlorides II and B2 equivalents of base IV; where B, B1 and B2 are each as defined in the description.

1 . A process for preparing a fluorinated m-nitrobenzoyl chloride of formula IIA 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3  and R 4  are each hydrogen, halogen, cyano, nitro, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; 
         wherein at least one of the R 1  to R 4  radicals is fluorine,
 by reacting a fluorinated m-nitrobenzoic acid of formula VIIA 
 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3  and R 4  are each hydrogen, halogen, cyano, nitro, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; 
         wherein at least one of the R 1  to R 4  radicals is fluorine; 
         with a chlorinating agent, 
         wherein the reaction takes place in the presence of catalytic amounts of a phosphine derivative IX 
       
       
         
           
           
               
               
           
         
         wherein: 
         R a , R b , R c  are each C 1 -C 6 -alkyl or phenyl, which may optionally be substituted by C 1 -C 4 -alkyl; 
         X is oxygen or two single-bonded chlorine atoms; 
         n is 0 or 1. 
       
     
     
         2 . The process according to  claim 1 , wherein
 R 1  is hydrogen;   R 2  is hydrogen or halogen;   R 3  is hydrogen; and   R 4  is hydrogen or halogen;   wherein at least one of the R 2  and R 4  radicals is fluorine.   
     
     
         3 . The process according to  claim 1 , wherein the chlorinating agent is selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, thionyl chloride and phosphoryl chloride (POCl 3 ). 
     
     
         4 . The process of  claim 3 , wherein the ratio of the chlorinating agent to the fluorinated m-nitrobenzoic acid VIIA is 1.5 to 1. 
     
     
         5 . The process of  claim 4 , wherein the phosphine derivative IX is selected from the group consisting of triphenylphosphine, triphenylphosphine oxide and tri(C 1 -C 6 -alkyl)phosphine oxide. 
     
     
         6 . The process of  claim 1 , wherein the reaction is effected additionally in the presence of a Lewis acid. 
     
     
         7 . The process of  claim 6 , wherein the Lewis acid is selected from the group consisting of boric acid, tri-C 1 -C 4 -alkyl borate and cyclic boric esters. 
     
     
         8 . A process for preparing sulfonamides I 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3  and R 4  are each hydrogen, halogen, cyano, nitro, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; 
         wherein at least one of the radicals R 1  to R 4  is fluorine, 
         R 5  and R 6  are each hydrogen, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkenyl, C 1 -C 6 -alkoxy, phenyl or benzyl;
 wherein a fluorinated m-nitrobenzoyl chloride IIA prepared according to  claim 1  is reacted with an amino sulfone III
   H 2 N—SO 2 NR 5 R 6   III,
 
 
 
         wherein: 
         R 5  and Ware each hydrogen, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkenyl, C 1 -C 6 -alkoxy, phenyl or benzyl. 
       
     
     
         9 . The process according to  claim 8 , wherein
 R 1  is hydrogen;   R 2  is hydrogen or halogen;   R 3  is hydrogen;   R 4  is hydrogen or halogen;   wherein at least one of the R 2  and R 4  radicals is fluorine; and   R 5  and R 6  are each C 1 -C 6 -alkyl.   
     
     
         10 . A process for preparing a fluorinated m-nitrobenzoyl chloride IIA 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3  and R 4  are each hydrogen, halogen, cyano, nitro, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; 
         wherein at least one of the radicals R 1  to R 4  is fluorine, by hydrolyzing a fluorinated m-nitrobenzotrichloride XA 
       
       
         
           
           
               
               
           
         
         wherein the variables R 1 , R 2 , R 3  and R 4  are each as defined above; 
         wherein the reaction takes places in the presence of a catalyst or in a weakly acidic medium and at temperatures less than 80° C. 
       
     
     
         11 . The process of  claim 10 , wherein the hydrolysis is carried out solvent-free in the melt.