Tetraarylborate process for the preparation of substituted biphenyls

1. A process for the preparation of a substituted biphenyl of formula (I)

in which

X 1 and X 2 , independently of one another, are halogen atoms or linear or branched C 1-12 -alkyl groups;

n is 0, 1 or 2;

m is 1, 2, 3, 4 or 5;

R 1 is selected from the group consisting of amino (NHR 2 ), nitro (NO 2 ), amide groups (R 2 —(CO)—NH—) and Schiff's bases (R 3 R 4 C═N—),

R 2 , R 3 and R 4 , independently of one another, are linear or branched C 1-12 -alkyl groups or cyclic C 3-8 -alkyl groups, benzyl groups, benzoyl groups, prazolyl groups of formula (Ia), or pyridyl groups of formula (Ib)

R 3 is a linear or branched C 1-12 -alkyl group or a C 1-6 -haloalkyl group having 1 to 6 halogen atoms,

comprising reacting an aryl halide of formula (II)

in which

Hal is selected from the group consisting of bromine, chlorine and iodine; and

R 1 , X 1 and n are as defined above,

in the presence of a base and a palladium catalyst in a solvent,

with a tetraarylborate of formula (III)

in which

X 2 and m are as defined above, and

M q+ is a cation selected from the group consisting of ammonium (q=1), alkali metal (q=1) and alkaline earth metal (q=2).

2. The process according to claim 1 , wherein

X 1 is 5-fluoro;

X 2 is 3/4-chloro;

n is 1;

m is 2;

R 1 is selected from the group consisting of amino (NH 2 ), nitro (NO 2 ), amide groups (R 2 —(CO)—NH—) and Schiff's bases (R 3 R 4 C═N—),

R 2 , R 3 and R 4 , independently of one another, are linear or branched C 1-12 -alkyl groups or cyclic C 3-8 -alkyl groups.

3. The process according to claim 1 , wherein

X 1 is hydrogen;

X 2 is 3,4,5-fluoro;

n is 1;

m is 3;

R 1 is selected from the group consisting of amino (NH 2 ), nitro (NO 2 ), amide groups (R 2 —(CO)—NH—) and Schiff's bases (R 3 R 4 C═N—),

R 2 , R 3 and R 4 , independently of one another, are linear or branched C 1-12 -alkyl groups or cyclic C 3-8 -alkyl groups.

4. The process according to claim 1 , wherein the aryl halide of formula (II) is selected from the group consisting of N—(2-bromo-4-fluorophenyl)acetamide, N-(2-chloro-4-fluorophenyl)acetamide, N-(2-bromophenyl)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-(prop-2-ylidene)aniline, 2-chloro-N-(prop-2-ylidene)aniline, 2-bromo-4-fluoro-N-(prop-2-ylidene)aniline, and 2-chloro-4-fluoro-N-(prop-2-ylidene)aniline.

5. The process according to any of claims 1 to 4 , wherein the tetraarylborate of formula (III) is selected from the group consisting of sodium tetrakis(3,4-dichlorophenyl)borate, potassium tetrakis(3,4-dichlorophenyl)borate, sodium tetrakis(4-chlorophenyl)borate, potassium tetrakis(4-chlorophenyl)borate, sodium tetrakis(3,4,5-trifluorophenyl)borate, and potassium tetrakis(3,4,5-trifluorophenyl)borate.

6. The process according to any of claims 1 to 4 , wherein the palladium catalyst is

a) palladium complexes comprising palladium in the oxidation state zero and phosphine ligands of formula PR′ 3 , in which R′, independently of one another, is selected from the group consisting of C 1-6 -alkyl, C 3-5 -cycloalkyl and C 6-12 -aryl and phosphinoferrocene ligands;

b) palladium salts in the presence of phosphine ligands of formula PR′ 3 , in which R′, independently of one another, is selected from the group consisting of C 1-6 -alkyl, C 3-5 -cycloalkyl and C 6-12 -aryl, or in the presence of phosphinoferrocene ligands; or

c) palladium metal which is optionally applied to a support and optionally added phosphine ligands of formula PR′ 3 , in which R′, independently of one another, is selected from the group consisting of C 1-6 -alkyl, C 3-5 -cycloalkyl and C 6-12 -aryl and phosphinoferrocene ligands.

7. The process according to claim 6 , wherein the palladium catalyst is selected from the group consisting of tetrakis(triphenylphosphine)palladium, tetrakis(tri-tert-butylphosphine)palladium, adamant-1-yl(adamant-2-yl)butylphosphinepalladium, biphenyl-2-yl(di-tert-butyl)phosphinepalladium, 1,1-bis(di-tert-butylphosphino)ferrocenepalladium, pentaphenyl(di-tert-butylphosphino)ferrocenepalladium, and 1,3-bis(di-tert-butylphosphinomethylene)phenylpalladium.

8. The process according to claim 6 , wherein the palladium catalyst is selected from the group consisting of palladium chloride, palladium acetate or bisacetonitrilepalladium chloride, palladium(II)dibenzylideneacetone, and bisacetylacetonatepalladium.

9. The process according to claim 1 , wherein 0.001 to 10.0 mol % of the palladium catalyst—based on the aryl halide of formula (II)—is used.

10. The process according to any of claims 1 to 4 , wherein the reaction is effected at a temperature of 20 to 100° C.

11. The process according to any of claims 1 to 4 , wherein the solvent is a mixture of water and at least one organic solvent.

12. The process according to claim 11 , the organic solvent is toluene.

13. The process according to claim 5 , wherein the palladium catalyst is

a) palladium complexes comprising palladium in the oxidation state zero and phosphine ligands of formula PR′ 3 , in which R′, independently of one another, is selected from the group consisting of C 1-6 -alkyl, C 3-5 -cycloalkyl and C 6-12 -aryl and phosphinoferrocene ligands;

b) palladium salts in the presence of phosphine ligands of formula PR′ 3 , in which R′, independently of one another, is selected from the group consisting of C 1-6 -alkyl, C 3-5 -cycloalkyl and C 6-12 -aryl, or in the presence of phosphinoferrocene ligands; or

c) palladium metal which is optionally applied to a support and optionally added phosphine ligands of formula PR′ 3 , in which R′, independently of one another, is selected from the group consisting of C 1-6 -alkyl, C 3-5 -cycloalkyl and C 6-12 -aryl and phosphinoferrocene ligands.

14. The process according to claim 13 , wherein the palladium catalyst is selected from the group consisting of tetrakis(triphenylphosphine)palladium, tetrakis(tri-tert-butylphosphine)palladium, adamant-1-yl(adamant-2-yl)butylphosphinepalladium, biphenyl-2-yl(di-tert-butyl)phosphinepalladium, 1,1-bis(di-tert-butylphosphino)ferrocenepalladium, pentaphenyl(di-tert-butylphosphino)-ferrocenepalladium, and 1,3-bis(di-tert-butylphosphinomethylene)phenylpalladium.

15. The process according to claim 13 , wherein the palladium catalyst is selected from the group consisting of palladium chloride, palladium acetate or bisacetonitrilepalladium chloride, palladium(II)dibenzylideneacetone, and bisacetylacetonatepalladium.