1-Substituted-4-Nitroimidazole Compound and Method for Preparing the Same

Abstract

The present invention relates to a 1-substituted-4-nitroimidazole compound represented by the general formula (1) or a salt thereof, (wherein R is a hydrogen atom, a lower alkoxy group-substituted lower alkyl group, a phenyl-lower alkoxy group-substituted lower alkyl group, a cyano-substituted lower alkyl group, a phenyl-lower alkyl group which may have lower alkoxy groups as the substituents in the phenyl ring or a group of the formula —CH 2 R A ; X is a halogen atom or a group of the formula —S(O)n-R 1 ) and method for preparing the same. The compound of the formula (1) is a useful compound as an intermediate for synthesis of various pharmaceutical and agricultural chemicals, particularly, as intermediates for antitubercular agents.

1 - 3 . (canceled) 
     
     
         4 . A method for preparing a 1-substituted-4-nitroimidazole compound represented by the general formula (10), 
       
         
           
           
               
               
           
         
         [wherein R A  is a group of the formula 
       
       
         
           
           
               
               
           
         
         wherein R B  is a hydrogen atom or a lower alkyl group; and X is a halogen atom or a group of the formula —S(O) n —R 1 ; n is 0 or an integer of 1 or 2; R 1  is a phenyl group which may have 1 to 3 substituents, selected from the group consisting of a nitro group, a halogen atom and a lower alkyl group, in the phenyl ring], characterized by reacting a 4-nitroimidazole compound represented by the general formula (2), 
       
       
         
           
           
               
               
           
         
         [wherein X is the same as defined above], with a glycidyl benzenesulfonate represented by the general formula (11), 
       
       
         
           
           
               
               
           
         
         [wherein R A  is the same as defined above; and R c  is a group of the formula, 
       
       
         
           
           
               
               
           
         
         wherein R D  is a nitro group; R E  is a halogen atom or a lower alkyl group; and a is 0 or an integer of 1 or 2; provided that when a is 2, then two of R E  may be the same or different]. 
       
     
     
         5 . (canceled) 
     
     
         6 . A method for preparing a 4-nitroimidazole compound represented by the general formula (2b), 
       
         
           
           
               
               
           
         
         [wherein R 1  is a phenyl group which may have 1 to 3 substituents, selected from the group consisting of a nitro group, a halogen atom and a lower alkyl group, in the phenyl ring], which is characterized by rearranging a 1-nitroimidazole compound represented by the general formula (26), 
       
       
         
           
           
               
               
           
         
         [wherein R 1  is the same as defined above]. 
       
     
     
         7 . A method for preparing a 4-nitroimidazole compound represented by the general formula (25a), (2c) or (10d), 
       
         
           
           
               
               
           
         
         [wherein R 1  is a phenyl group which may have 1 to 3 substituents, selected from the group consisting of a nitro group, a halogen atom and a lower alkyl group, in the phenyl ring; R is a hydrogen atom, a lower alkoxy group-substituted lower alkyl group, a phenyl-lower alkoxy group-substituted lower alkyl group, a cyano group-substituted lower alkyl group, a phenyl-lower alkyl group which may have a lower alkoxy groups as the substituents in the phenyl ring, or a group of the formula —CH 2 R A ; R A  is a group of the following formula, 
       
       
         
           
           
               
               
           
         
         wherein R B  is a hydrogen atom or a lower alkyl group; and n 1  is 1 or 2], which is characterized by oxidizing a 4-nitroimidazole compound represented by the general formula (25), (2b) or (10c), 
       
       
         
           
           
               
               
           
         
         [wherein R 1  and R are the same as defined above]. 
       
     
     
         8 . A method for preparing a 4-nitroimidazole compound represented by the general formula (15a), 
       
         
           
           
               
               
           
         
         [wherein X 1  is a halogen atom], which is characterized by nitrating an imidazole compound represented by the general formula (15), 
       
       
         
           
           
               
               
           
         
         [wherein X 1  is the same as defined above] in the presence of a nitronium halogenated borate. 
       
     
     
         9 . The method for preparing the 4-nitroimidazole compound according to  claim 8 , wherein the nitronium halogenated borate is nitronium tetrafluoroborate. 
     
     
         10 . The method for preparing 4-nitroimidazole compound according to  claim 9 , wherein the nitration is conducted in nitromethane. 
     
     
         11 . A method for preparing 1-substituted-4-nitroimidazole compound represented by the general formula (10c), 
       
         
           
           
               
               
           
         
         [wherein R 1  is a phenyl group which may have 1 to 3 substituents, selected from the group consisting of a nitro group, a halogen atom and a lower alkyl group, in the phenyl ring; and R A  is a group of the formula, 
       
       
         
           
           
               
               
           
         
         wherein R B  is a hydrogen atom or a lower alkyl group], which is characterized by nitrating a 1-substituted imidazole compound represented by the general formula (27), 
       
       
         
           
           
               
               
           
         
         [wherein R 1  and R A  are the same as defined above]. 
       
     
     
         12 - 16 . (canceled)