Method of friedel-crafts acylation of anilides

Abstract

An anilide is reacted with an acylating agent by using as a catalyst a tri (perfluoroalkane sulfonate) compound of any of the elements belonging to groups 3 to 5 and groups 13 to 15 in periods 4 to 6 of the periodic table, thereby bonding an acyl group to the benzene ring. Thus, ketoaniline derivatives, which are useful as physiologically active compounds or intermediates in synthesizing the same, are synthesized in high reaction yield by catalytic acylation.

1 . A method for Friedel-crafts acylation of anilide, which comprises reacting an anilide with an acylating agent, using as a catalyst a tri(perfluoroalkane sulfonate) compound of an element that belongs to any one of periods 4 to 6 of the periodic table, that also belongs to any one of groups 3 to 5 or groups 13 to 15 of the periodic table, thereby bonding an acyl group to a benzene ring.  
     
     
         2 . The method for Friedel-Crafts acylation of anilide of  claim 1 , wherein the catalyst is one or more tri(perfluoroalkane sulfonate) compound(s) of an element selected from the group consisting of Ga, Sc, In, Y, Lanthanoids, Zr, Hf, Sn, Pb, Nb, Ta, Sb and Bi.  
     
     
         3 . The method for Friedel-Crafts acylation of anilide of  claim 1  or  2 , wherein the reaction is performed in a nitroalkane solvent containing a perchlorate or a halogenated hydrocarbon solvent.  
     
     
         4 . The method for Friedel-Crafts acylation of anilide of  claim 3 , wherein the perchlorate is an alkali metal perchlorate.  
     
     
         5 . The method for Friedel-Crafts acylation of anilide of any one of  claims 1  to  4 , wherein the acylating agent is an acid anhydride, an acid halide, an ester or a carboxylic acid.  
     
     
         6 . The method for Friedel-Crafts acylation of anilide of any one f  claims 1  to  5 , wherein an anilide represented by the following formula (1)  
       
         
           
           
               
               
           
         
       
       (wherein R 1  and R 2  each represent a hydrogen atom, a hydrocarbon group that may contain a substituent, or an acyl group represented by Ra—CO—, Ra—SO 2 — or Ra—OCO—, in which Ra represents a hydrocarbon group that may contain a substituent, at least one of R 1  and R 2  being the aforementioned acyl group; R 3  represents a substituent bonded to the benzene ring, and R 3  may be absent) with an acylating agent represented by the following formula (2)  
       
         
           
           
               
               
           
         
       
       (wherein R 4  represents a hydrocarbon group that may contain substituent; and R 5  represents —O—CO—Rb, in which Rb is a hydrocarbon group that may contain a substituent, a halogen atom or —OH)  
       thereby synthesizing an acylanilide represented by the following formula (3)  
       
         
           
           
               
               
           
         
       
       (therein R 1 , R 2 , R 3  and R 4  are as defined above).