Method for producing substituted anthranilic acid derivatives

Abstract

The present invention relates to a process for preparing substituted anthranilic acid derivatives of the formula (I) in which R 1 , R 2 , R 3 and R 4 are each as defined in the description, by conversion of compounds of the general formula (IV) in the presence of a palladium catalyst and carbon monoxide. The present invention likewise relates to compounds of the general formula (IV).

1 . Process for preparing a compound of formula (I) 
       
         
           
           
               
               
           
         
         in which 
         R 1  is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, or is a hetaryl radical of formula (II) 
       
       
         
           
           
               
               
           
         
         where 
         R 8  is C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, which may optionally be mono- or polysubstituted, identically or differently by fluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl, 
         Z is CH or N, 
         and 
         Y is hydrogen, fluorine, chlorine, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of formula (III) 
       
       
         
           
           
               
               
           
         
         where 
         R 9  is C 1 -C 5 -alkyl which may optionally be mono- or polysubstituted identically or differently by halogen, 
         R 2  is an OR 5  or NR 6 R 7  radical, 
         where 
         R 5 , R 6  and R 7  are each independently hydrogen, C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, 
         R 3  is hydrogen, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl, 
         R 4  is hydrogen, fluorine, chlorine, cyano, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino, (C 1 -C 4 -alkoxy)imino, (C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy)imino, SF 5  or C 3 -C 6 -trialkylsilyl, 
         comprising reacting a substituted anthranilamide derivative of the formula (IV) 
       
       
         
           
           
               
               
           
         
         in which the R 1 , R 3  and R 4  radicals are each as defined above 
         and X is chlorine, bromine or iodine, 
         in the presence of a palladium catalyst and optionally of a phosphine ligand simultaneously with carbon monoxide and a compound of formula (V)
   R 5 —OH   (V)
 
 
         in which R 5  is as defined above 
         or a compound of formula (VI)
   HNR 6 R 7    (VI)
 
 
         in which R 6  and R 7  are each as defined above. 
       
     
     
         2 . Process according to  claim 1 , wherein the compound of formula (IV) is prepared by reacting a Compound of formula (IX) 
       
         
           
           
               
               
           
         
         in which X, R 3  and R 4  are each as defined above 
         with acids of formula (VIII)
   R 1 COOH   (VIII)
 
 
         in which R 1  is as defined above. 
       
     
     
         3 . Process according to  claim 2 , wherein the compound of formula (IV) is prepared in the presence of a condensing agent and of a base. 
     
     
         4 . Process according to  claim 1 , wherein the palladium catalyst used is a palladium (II) salt and/or Pd(O) species. 
     
     
         5 . Process according to  claim 4 , wherein the palladium catalyst used is bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium bromide and/or palladium acetate. 
     
     
         6 . Process according to  claim 1 , wherein the phosphine ligand used is a compound of formula (X)
   PR 10 R 11 R 12    (X)
   where the R 10 , R 11  and R 12  radicals are each independently hydrogen, linear or branched C 1 -C 8 -alkyl, vinyl, aryl or heteroaryl selected from pyridine, pyrimidine, pyrrole, thiophene and furan, which may in turn be substituted by further substituents from the group of linear or branched C 1 -C 8 -alkyl or C 6 -C 10 -aryl, linear or branched C 1 -C 8 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear or branched C 1 -C 8 -alkyl or halogenated C 6 -C 10 -aryl, C 6 -C 10 -aryloxycarbonyl, linear or branched C 1 -C 8 -alkylamino, linear or branched C 1 -C 8 -dialkylamino, C 1 -C 8 -arylamino, C 1 -C 8 -diarylamino, hydroxyl, carboxyl, cyano and halogen,   or a chelating biphosphine.   
     
     
         7 . Process according to  claim 6 , wherein the chelating biphosphine is one or more selected from 1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)butane, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 1,1′-bis(diphenylphosphino)ferrocene. 
     
     
         8 . Process according to  claim 6 , wherein the phosphine ligand used is triphenylphosphine. 
     
     
         9 . Process according to  claim 6 , wherein 1-20 molar equivalents of phosphine are used, based on the amount of palladium catalyst used. 
     
     
         10 . Compound of formula (IV) 
       
         
           
           
               
               
           
         
         Where 
         R 1  is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, or is a hetaryl radical of formula (II) 
       
       
         
           
           
               
               
           
         
         where 
         R 8  is C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, which may optionally be mono- or polysubstituted, identically or differently by fluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl, 
         Z is CH or N, 
         and 
         Y is hydrogen, fluorine, chlorine, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of formula (III) 
       
       
         
           
           
               
               
           
         
         where 
         R 9  is C 1 -C 5 -alkyl which may optionally be mono- or polysubstituted identically or differently by halogen, 
         R 2  is an OR 5  or NR 6 R 7  radical, 
         where 
         R 5 , R 6  and R 7  are each independently hydrogen, C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, 
         R 3  is hydrogen, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl, 
         R 4  is hydrogen, fluorine, chlorine, cyano, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino, (C 1 -C 4 -alkoxy)imino, (C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy)imino, SF 5  or C 3 -C 6 -trialkylsilyl. 
       
     
     
         11 . Compound of formula (IV) according to  claim 10 , where
 R 1  is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, or is a hetaryl radical of the general formula (II)   
       
         
           
           
               
               
           
         
         where 
         R 8  is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl, 
         Z is CH or N, and 
         Y is hydrogen, fluorine, chlorine, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -fluoro- or -chloroalkyl, C 1 -C 6 -fluoro- or -chlorocycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoro- or -chloroalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -fluoro- or -chloroalkylthio, C 1 -C 4 -fluoro- or -chloroalkylsulphinyl, C 1 -C 4 -fluoro- or -chloroalkylsulphonyl, cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of the general formula (III) 
       
       
         
           
           
               
               
           
         
         in which 
         R 9  is C 1 -C 5 -alkyl which may be mono- or polysubstituted identically or differently by halogen, 
         R 3  is methyl, 
         R 3  is likewise chlorine, 
         R 4  is chlorine or cyano, 
         and 
         X is bromine or iodine. 
       
     
     
         12 . Compound of formula (IV) according to  claim 10 , where
 R 1  is a hetaryl radical of the general formula (II)   
       
         
           
           
               
               
           
         
         where 
         R 8  is fluorine or chlorine, 
         Z is N, 
         and 
         Y is hydrogen, fluorine, chlorine or a radical of the general formula (III) 
       
       
         
           
           
               
               
           
         
         where 
         R 9  is CF 3  or C 2 F 5 , 
         R 3  is methyl, 
         R 4  is chlorine or cyano, 
         and 
         X is bromine.