Process for preparing substituted biphenylanilides

1. A process for preparing a substituted biphenylanilide of formula (I),

wherein

X is hydrogen, fluorine or chlorine;

R 1 is —NH(CO)R 3 or —N═CR 4 R 5 ; and

R 3 , R 4 , R 5 independent from each other represent hydrogen, —C 2 —(C═O)CH 3 , C 1 -C 8 -alkyl, C 1 -C 8 -alkenyl, C 1 -C 8 -alkynyl or C 6 -C 18 -aryl; or

R 4 , R 5 together with the carbon atom to which they are attached form a five- or six-membered ring comprising one, two or three hetero atoms selected from the group consisting of N, O, and S;

R 2 is cyano, nitro, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl, C 1 -C 6 -alkynyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkyl, (C 1 -C 6 -alkyl)carbonyl or phenyl; and

n is 1, 2 or 3, where in case that n is 2 or 3, the R 2 radicals may also be different,

which comprises reacting a compound of formula (II)

in which Hal is halogen and X is as defined above, in the presence of a base and a palladium catalyst selected from the group consisting of:

a) palladium-triarylphosphine or -trialkylphosphine complex with palladium in the zero oxidation state,

b) salt of palladium in the presence of triarylphospine or trialkylphosphine as a complex ligand, and

c) metallic palladium, optionally applied to support, in the presence of triarylphosphine or trialkylphosphine;

in a solvent, with an organoboron compound of formula (III)

selected from the group consisting of:

(i) a boronic acid of formula (III)

wherein

m is 2,

each Q is a hydroxyl-group,

R 2 and n are as defined above,

or the anhydrides, dimers or trimers formed thereof;

(ii) a boronic acid derivative of formula (III), wherein

m is 2,

p is 1,

each Q is independently selected from the group consisting of F, Cl, Br, I, C 1-4 -alkyl-, C 6-10 -aryl, C 1-4 -alkoxy- and C 6-10 -aryloxy-residues,

R 2 and n are as defined above;

(iii) a bonnie acid of formula (III),

wherein

m is 1,

p is 2,

Q is selected from the group consisting of OH, F, Cl, Br, I, C 1-4 -alkyl-, C 6-10 -aryl-, C 1-4 -alkoxy- and C 6-10 -aryloxy-residues,

R 2 and n are as defined above;

(iv) a cyclic boronic acid ester of formula (III),

wherein

m is 2,

p is 1,

each Q is independently C 1-4 -alkoxy residues which together with the boron atom they are attached form a 5- or 6-membered ring which may be substituted by C 1-4 -alkyl-residues,

R 2 and n are as defined above;

(v) a boronate of formula (III)

wherein

m is 3,

p is 1,

R 2 and n are as defined above;

each Q is independently selected from the group consisting of OH, F, Cl, Br, I, C 1-4 -alkyl-, C 6-10 -aryl-, C 1-4 -alkoxy- and C 6-10 -aryloxy-residues,

and wherein the negative charge of the boronate anion is compensated by a cation;

(vi) a triarylborane of formula (III),

wherein

m is 0,

p is 3,

R 2 and n are as defined above; and

(vii) a tetraarylborate of formula (III),

wherein

m is 0,

p is 4,

R 2 and n are as defined above,

and wherein the negative charge of the boronate anion is compensated by a cation; and

where the triarylphosphines or trialkylphosphines used may optionally be substituted.

2. The process according to claim 1 , wherein the compound (II) is selected from the group consisting of N-(2-bromo-4-fluorophenyl)acetamide, N-(2-chloro-4-fluorophenyl)acetamide, N-(2-bromo-phenyl)acetamide, N-(2-chlorophenyl)acetamide, N-(2-chlorophenyl)-3-oxobutanamide, N-(2-bromophenyl)-3-oxobutanamide, N-(2-chloro-4-fluorophenyl)-3-oxobutanamide, N-(2-bromo-4-fluorophenyl)-3-oxobutanamide, 2-bromo-N-(propan-2-ylidene)aniline, 2-chloro-N-(propan-2-ylidene)aniline, 2-bromo-4-fluoro-N-(propan-2-ylidene)aniline, and 2-chloro-4-fluoro-N-(propan-2-ylidene)aniline.

3. The process according to claim 1 , wherein the starting compound (III) is a diphenylborinic acid which is substituted in the 3- and 4-position.

4. The process according to claim 3 , wherein the diphenylborinic acid (III) bears fluorine or chlorine in the 3- and 4-positions.

5. The process according to claim 4 , wherein the compound of formula (III) is di(3,4-dichlorophenyl)borinic acid.

6. The process according to claim 1 , wherein the palladium catalyst a) according to claim 1 used is tetrakis(triphenylphosphine)palladium or tetrakis(tri-tert.-butylphosphine)palladium.

7. The process according to claim 1 , wherein a palladium catalyst b) is used.

8. The process according to claim 1 , wherein the palladium catalyst c) used is metallic palladium on activated carbon in the presence of triphenylphosphine wherein the phenyl groups in triphenylphosphine are substituted by a total of from 1 to 3 sulfonate groups.

9. The process as claimed in claim 7 , wherein the salt of the palladium catalyst b) used is palladium chloride, palladium acetate or bisacetonitrilepalladium chloride.

10. The process according to claim 7 , wherein from 6 to 60 equivalents of triphenylphosphine are used per equivalent of the palladium salt.

11. The process according to claim 1 , wherein from 0.001 to 1.0 mol % of the palladium catalyst is used, based on the amount of the compound of formula (II).

12. The process according to claim 1 , wherein the reaction is carried out at a temperature of from 20 to 80° C.

13. The process according to claim 1 , wherein the reaction is carried out in a mixture of water and an organic solvent.

14. The process according to claim 1 , wherein the organic solvent used is an ether.