Process for the preparation of amides

Abstract

The invention relates to a process for the preparation of fungicidally active compounds such as tricyclic amine derivatives (I). The process involves coupling of a carboxylic acid e.g. a compound of formula (II) with an aniline, e.g. a compound of formula (III) in the presence of a boronic acid catalyst or an antimony catalyst wherein R1, R2, R3, R4, R5, R6, R7, X, Y and Het are defined in the specification.

1 - 16 . (canceled) 
     
     
         17 . A process for (a) the preparation of compounds of the formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         Het is pyrrolyl or pyrazolyl, either being substituted by groups R8, R9 and R10; 
         X is a single bond; 
         Y is (CR12R13)(CR14R15)m(CR16R17)n or C═C(A)Z in which A and Z are independently C 1-6  alkyl or halogen; 
         m is 0 or 1; 
         n is 0 or 1; 
         R1 is hydrogen; 
         R2 and R3 are each, independently, hydrogen, halogen, C 1-4  alkyl, C 1-4  alkoxy or C 1-4  haloalkoxy; 
         R4, R5, R6 and R7 are each, independently, hydrogen, halogen, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, hydroxymethyl, C 1-4  alkoxymethyl, C(O)CH 3  or C(O)OCH 3 ; 
         R8, R9 and R10 are each, independently, hydrogen, halogen, cyano, nitro, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy(C 1-4 )alkylene or C 1-4  haloalkoxy(C 1-4 )alkylene, provided that at least one of R8, R9 and R10 is not hydrogen; 
         R12 and R13 are each, independently, hydrogen, halogen, C 1-5  alkyl, C 1-3  alkoxy, CH 2 OH, CH(O), C 3-6  cycloalkyl, CH 2 O—C(═O)CH 3 , CH 2 —C 3-6  cycloalkyl or benzyl; 
         or R12 and R13 together with the carbon atom to which they are attached form the group C═O or a 3-5 membered carbocyclic ring; 
         or R12 and R13 together form C 1-5  alkylidene or C 3-6  cycloalkylidene; and 
         R14, R15, R16 and R17 are each, independently, H or CH 3 ; 
         comprising the step of reacting a carboxylic acid of formula (II) 
       
       
         
           
           
               
               
           
         
         wherein Het is as defined above 
         with an aniline of the formula (III) 
       
       
         
           
           
               
               
           
         
         wherein R1, R2, R3, R4, R5, R6, R7, X and Y are as defined above; 
         in the presence of a boronic acid catalyst or an antimony catalyst; 
         or (b) the preparation of compounds of the formula (IA) 
       
       
         
           
           
               
               
           
         
         wherein 
         Heta is pyrrolyl, pyrazolyl or thiazolyl, each being substituted by groups R4a, R5a, R6a; 
         R1a is hydrogen, fluoro, chloro or bromo; 
         R2a is hydrogen, fluoro, chloro or bromo; 
         R3a is optionally substituted C 2-12  alkyl, wherein, when present, each optional substituent is, independently, selected from fluoro, chloro, bromo, hydroxy, cyano, C 1-4  alkoxyC(═O), formyl, nitro, C 1-4  alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, HC(OR′)═N and R′R″NN═C(H); 
         optionally substituted C 2-12  alkenyl, wherein, when present, each optional substituent is, independently, selected from fluoro, chloro, bromo, hydroxy, cyano, C 1-4  alkoxyC(═O), formyl, nitro, C 1-4 -alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, HC(OR′)═N and R′R″NN═C(H); 
         optionally substituted C 2-12  alkynyl, wherein, when present, each optional substituent is, independently, selected from fluoro, chloro, bromo, hydroxy, cyano, C 1-4  alkoxyC(═O), formyl, nitro, C 1-4  alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, HC(OR′)═N and R′R″NN═C(H); 
         optionally substituted C 3-12  cycloalkyl, wherein, when present, each optional substituent is, independently, selected from C 1-3  alkyl, fluoro, chloro, bromo, hydroxy, cyano, C 1-4  alkoxyC(═O), formyl, nitro, C 1-4  alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, HC(OR′)═N and R′R″NN═C(H); optionally substituted phenyl, wherein, when present, each optional substituent is, independently, selected from C 1-6  alkyl, fluoro, chloro, bromo, hydroxy, cyano, C 1-4  alkoxyC(═O), formyl, nitro, C 1-4  alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, HC(OR′)═N and R′R″NN═C(H); or optionally substituted heterocyclyl, wherein, when present, each optional substituent is, independently, selected from C 1-6  alkyl, fluoro, chloro, bromo, hydroxy, cyano, C 1-4  alkoxyC(═O), formyl, nitro, C 1-4  alkoxy, C 1-4  haloalkoxy, C 1-4  alkylthio, C 1-4  haloalkylthio, HC(OR′)═N; 
         R′ and R″ are, independently, hydrogen or C 1-4  alkyl; and 
         R4a, R5a, and R6a are, independently, selected from hydrogen, fluoro, chloro, bromo, cyano, nitro, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy(C 1-4 )alkyl and C 1-4  haloalkoxy(C 1-4 )alkyl, provided that at least one of R4a, R5a, and R6a is not hydrogen. 
         comprising reacting a carboxylic acid of formula (IIA) 
       
       
         
           
           
               
               
           
         
         with an aniline of the formula (IIIA) 
       
       
         
           
           
               
               
           
         
         in the presence of a boronic acid catalyst or an antimony catalyst. 
       
     
     
         18 . The process according to claim  1  wherein the boronic acid catalyst is an aryl boronic acid. 
     
     
         19 . The process according to claim  1  wherein the boronic acid catalyst is 2-(N,N-dimethylaminomethyl)phenylboronic acid, boric acid or 3,5-trifluoromethylphenyl boronic acid. 
     
     
         20 . The process according to claim  1  wherein the antimony catalyst is Sb(OEt) 3 . 
     
     
         21 . The process according to claim  1  wherein the catalyst is employed in an amount of between 1 and 15 mol % based on the amount of carboxylic acid (II) or (IIA). 
     
     
         22 . The process according to claim  1  wherein the catalyst is employed in an amount of between 1 and 15 mol % based on the amount of aniline (III) or (IIIA). 
     
     
         23 . The process according to claim  1  wherein the molar ratio of acid (II) or (IIA):aniline (III) or (IIIA) is in the range of from 2:1 to 1:2. 
     
     
         24 . The process according to claim  1  wherein Het is a group of formula (VIIA) 
       
         
           
           
               
               
           
         
         in which R7a is selected from CF 3  and CHF 2 ; 
         and/or wherein Y is CHCH(CH 3 )CH 3  or C═CCl 2 ; 
         and/or wherein R2, R3, R4, R5, R6, R7 are independently selected from hydrogen. 
       
     
     
         25 . The process according to claim  1  wherein Y is CHCH(CH 3 )CH 3 . 
     
     
         26 . The process according to claim  1  wherein Y is C═CCl 2 . 
     
     
         27 . A process according to claim  1  for the preparation of a compound of formula (VI) 
       
         
           
           
               
               
           
         
         comprising reacting a carboxylic acid of formula (IV) 
       
       
         
           
           
               
               
           
         
         with an aniline of formula (V) 
       
       
         
           
           
               
               
           
         
         in the presence of a boronic acid catalyst or an antimony catalyst. 
       
     
     
         28 . A process according to claim  1  for the preparation of a compound of formula (VIII) 
       
         
           
           
               
               
           
         
         comprising reacting a carboxylic acid of formula (IV) 
       
       
         
           
           
               
               
           
         
         with an aniline of formula (VII) 
       
       
         
           
           
               
               
           
         
         in the presence of a boronic acid catalyst or an antimony catalyst. 
       
     
     
         29 . The process according to claim  1 , wherein Heta is a group of formula (VIIA) 
       
         
           
           
               
               
           
         
         in which R7a is selected from CF 3  and CHF 2 ; 
         and/or wherein R3a is a group of the formula (VIIIA) 
       
       
         
           
           
               
               
           
         
         in which R8 is H or C1-6 alkyl. 
       
     
     
         30 . A process according to claim  1  for the preparation of a compound of formula (IXA) 
       
         
           
           
               
               
           
         
         comprising reacting a carboxylic acid of formula (IV) 
       
       
         
           
           
               
               
           
         
         with an aniline of formula (XIA) 
       
       
         
           
           
               
               
           
         
         in the presence of a boronic acid catalyst or an antimony catalyst.