Process for preparing chlorinated biphenylanilides and biphenylanilines

Abstract

The present invention relates to a process for preparing substituted biphenylanilides of the formula (I) in which R 1 is selected from a protected amino group, NO 2 , NH 2 and NHR 3 , in which a compound of the formula II is reacted in the presence of a base and of a palladium salt, in the presence of a phosphine ligand of the formula (V) as complex ligand or a salt thereof, in a solvent, with an organoboron compound of the formula (III) in which all the substituents are as defined in the description.

1 . Process for preparing a halogenated biphenylanilide of formula (I) 
       
         
           
           
               
               
           
         
         in which 
         X is selected from hydrogen, fluorine and chlorine; 
         R 1  is selected from —NH(CO)R 3 , —N═CR 4 R 5 , NO 2 , NH 2  and NHR 3 ; 
         R 2  is chlorine; 
         R 3 , R 4 , R 5  are each independently selected from hydrogen, —CH 2 —(C═O)CH 3 , C 1 -C 8 -alkyl, C 1 -C 8 -alkenyl, C 1 -C 8 -alkynyl and C 6 -C 18 -aryl; or 
         R 4 , R 5 , together with the carbon atom to which they are bonded, may form a 5- or 6-membered ring containing 1, 2 or 3 heteroatoms selected from N, O and S; 
         n is selected from 1, 2 and 3, 
         by reacting a compound of the formula (II) 
       
       
         
           
           
               
               
           
         
         in which 
         Hal is selected from bromine and iodine; and R 1  and X are each as defined above, 
         in the presence of a base and a palladium catalyst selected from the group consisting of: 
         a) a complex consisting of palladium in the 0 oxidation state and a phosphine ligand of the formula (V) or a salt thereof, 
         b) a palladium salt in the presence of a phosphine ligand of the formula (V) or a salt thereof and 
         c) metallic palladium, optionally applied to a support, in the presence of a phosphine ligand of the formula (V) or a salt thereof, 
         where the phosphine ligand of the formula (V) is defined as follows: 
       
       
         
           
           
               
               
           
         
         where 
         R 6  is selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, phenyl and NR 7  and 
         R 7  is selected from (C 1 -C 4 -alkyl) 2 , 
         or a salt thereof, 
         in a solvent, with an organoboron compound of the formula (III) 
       
       
         
           
           
               
               
           
         
         selected from the group consisting of: 
         (i) boronic acids of the formula (III) in which
 m is 2, 
 p is 1, 
 Q 1  and Q 2  are each hydroxyl groups, 
 R 2  and n are each as defined above, 
 or the anhydrides, dimers or trimers formed from the boronic acids of the formula (III); 
 
         (ii) boronic acid derivatives of the formula (III) in which
 m is 2, 
 p is 1, 
 Q 1  and Q 2  are each independently selected from F, Cl, Br, I, C 1-4 -alkyl-, C 6-10 -aryl-, C 1-4 -alkoxy- and C 6-10 -aryloxy, 
 R 2  and n are each as defined above; 
 
         (iii) borinic acids of the formula (III) in which
 m is 1, 
 p is 2, 
 Q is selected from OH, F, Cl, Br, I, C 1-4 -alkyl, C 6-10 -aryl, C 1-4 -alkoxy and C 6-10 -aryloxy radicals, 
 R 2  and n are each as defined above; 
 
         (iv) cyclic boronic esters of the formula (III) in which
 m is 2, 
 p is 1, 
 Q 1  and Q 2  are each independently selected from C 1-4 -alkoxy radicals which, together with the boron atom to which they are bonded, form a 5- or 6-membered ring which may be substituted by C 1-4 -alkyl radicals, 
 R 2  and n are each as defined above; 
 
         (v) boronates of the formula (III) in which
 m is 3, 
 p is 1, 
 R 2  and n are each as defined above, 
 Q 1  to Q 3  are each independently selected from OH, F, Cl, Br, I, C 1-4 -alkyl, C 6-10 -aryl, C 1-4 -alkoxy and C 6-10 -aryloxy radicals, 
 and in which the negative charge of the boronate anion is compensated for by a cation; 
 
         (vi) triarylboranes of the formula (III) in which
 m is 0, 
 p is 3, 
 R 2  and n are each as defined above; 
 
         (vii) tetraarylborates of the formula (III) in which
 m is 0, 
 p is 4, 
 R 2  and n are each as defined above, 
 and in which the negative charge of the boronate anion is compensated for by a cation. 
 
       
     
     
         2 . Process according to  claim 1 , wherein the compound (II) is selected from the group consisting of N-(2-bromo-4-fluorophenyl)acetamide, N-(2-bromophenyl)acetamide, N-(2-bromophenyl)-3-oxobutanamide, N-(2-bromo-4-fluorophenyl)-3-oxobutanamide, 2-bromo-N-(propan-2-ylidene)aniline, 2-bromo-4-fluoro-N-(propan-2-ylidene)aniline, 2-bromo-4-fluoroaniline, 2-bromoaniline. 
     
     
         3 . Process according to  claim 1 , wherein the compound of the formula (III) is selected from the group consisting of bis(3,4-dichlorophenyl)borinic acid, bis(2,3-dichlorophenyl)borinic acid, bis(3-dichlorophenyl)borinic acid, bis(4-dichlorophenyl)borinic acid, 4-chlorophenylboronic acid, 3-chlorophenylboronic acid, 2-chlorophenylboronic acid, 3,4-dichlorophenylboronic acid and 2,3-dichlorophenylboronic acid. 
     
     
         4 . Process according to  claim 1 , wherein the base is selected from alkali metal hydroxides, alkali metal carbonates and alkali metal hydrogencarbonates. 
     
     
         5 . Process according to  claim 1 , wherein the palladium catalyst a) is a complex of palladium in the 0 oxidation state and a phosphine ligand of the formula (V) or a salt thereof. 
     
     
         6 . Process according to  claim 1 , wherein a palladium catalyst b) is used. 
     
     
         7 . Process according to  claim 1 , wherein a palladium catalyst c) is used, and this palladium catalyst c) comprises or consists of metallic palladium on activated carbon in the presence of a phosphine ligand of formula (V) or a salt thereof. 
     
     
         8 . Process according to  claim 6 , wherein the salt of the palladium catalyst b) is selected from the group consisting of palladium chloride, palladium acetate, palladium acetylacetonate and bis(acetonitrile)palladium chloride. 
     
     
         9 . Process according to  claim 1 , wherein the phosphine ligand of formula (V) is selected from di(tert-butyl)phenylphosphine, di-tert-butyl-p-[4-(trifluoromethyl)phenyl]phosphine, 4-(di-tert-butylphosphino)-p-N,N-dimethylaniline and di-tert-butyl-p-(4-methylphenyl)phosphine. 
     
     
         10 . Process according to  claim 1 , wherein a palladium catalyst b) is used, where the molar ratio of the palladium salt to the phosphine ligand of formula (V) or a salt thereof is 1:1 to 1:5. 
     
     
         11 . Process according to  claim 1 , wherein 0.001 to 1.0 mol % of the palladium catalyst is used, based on the amount of the compound of the formula (II). 
     
     
         12 . Process according to  claim 1 , wherein the reaction is conducted at a temperature of 20° C. to 100° C. 
     
     
         13 . Process according to  claim 1 , wherein the reaction is conducted in a mixture of water and an organic solvent. 
     
     
         14 . Compound of the formula (V) 
       
         
           
           
               
               
           
         
         where 
         R 6  is selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, phenyl and NR 7  and 
         R 7  is selected from (C 1 -C 4 -alkyl) 2 . 
       
     
     
         15 . Salt of the formula (V-i) 
       
         
           
           
               
               
           
         
         where 
         R 6  is selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, phenyl and NR 7  and 
         R 7  is selected from (C 1 -C 4 -alkyl) 2  and 
         Y is selected from the group consisting of BF 4   − , perchlorate and hydrogensulphate.