METHOD FOR SYNTHESIZING 2-ALKYL-4-TRIFLUOROMETHYL-3-ALKYLSULFONYLBENZOIC ACIDS

Abstract

A process for preparing 2-alkyl-4-trifluoromethyl-3-alkylsulfonylbenzoic acids of the formula (I) is described.

##STR00001##

Here, the substituents are radicals such as alkyl and substituted phenyl.

Claims

1. A process for preparing 2-alkyl-4-trifluoromethyl-3-alkylsulfonylbenzoic acids of formula (I), wherein a) reacting a 1,3-dichloro-2-alkyl-4-trifluoromethylbenzene with a cyanide source in the presence of a nickel compound, a phosphine ligand and a further metal to form a benzonitrile, b) reacting the benzonitrile with a thiolate in the presence of a phase transfer catalyst to form the corresponding thioether, c) hydrolyzing the nitrile group to a carboxyl group, d) oxidizing the thio group, optionally in the presence of an oxidation catalyst, ##STR00006## and e) where the substituents are defined as follows: R.sup.1 and R.sup.2 are each, independently of one another, C.sub.1-C.sub.4-alkyl or phenyl substituted by s radicals from the group consisting of chloro, fluoro, methoxy and ethoxy, M is lithium, sodium or potassium, n is 1 or 2, s is 1, 2 or 3.

2. The process as claimed in claim 1, wherein R.sup.1 and R.sup.2 are each methyl.

3. The process as claimed in claim 1, wherein sodium cyanide, potassium cyanide, zinc cyanide, potassium hexacyanoferrate(II) or acetone cyanohydrin is used as cyanide source.

4. The process as claimed in claim 1, wherein the cyanide source is used in a molar ratio of from 1:1 to 1.5:1, based on the compound of formula (II).

5. The process as claimed in claim 1, wherein nickel(II) chloride or nickel(II) bromide in an amount of from 0.5 to 5 mol percent and the phosphine ligand in an amount of from 0.5 to 10 mol percent based on the compound of formula (II) are used for producing the nickel catalyst.

6. The process as claimed in claim 1, wherein bis(2-diphenylphosphinophenyl) ether (dpephos), bis(diphenylphosphino)ferrocene (dppf) or rac-2,2-bis(diphenylphosphino)-1,1-binaphthyl (BINAP) is used as phosphine ligand in a molar ratio of from 1.5:1 to 3:1, based on the nickel compound.

7. The process as claimed in claim 1, wherein bis(2-diphenylphosphinophenyl) ether (dpephos) is used as phosphine ligand.

8. The process as claimed in claim 1, wherein from 2 to 10 mol percent of zinc, based on the compound of formula (II), are used as reducing agent.

9. The process as claimed in claim 1, wherein Na.sub.2WO.sub.4 is used in an amount of from 5 to 15 mol percent as oxidation catalyst and hydrogen peroxide is used in an amount of from 3 to 8 molar equivalents, in each case based on the compound of formula (Va).

10. A compound of formula (IIa): ##STR00007## wherein R.sup.1* is ethyl, n-propyl or phenyl.

11. A compound of formula (IIIa): ##STR00008## wherein R.sup.1* is methyl, ethyl, n-propyl, isopropyl or n-butyl.

12. The compound as claimed in claim 11, wherein R.sup.1* is methyl.

13. A compound of formula (V), ##STR00009## wherein R.sup.1 is methyl and R.sup.2 is methyl or ethyl.

Description

WORKING EXAMPLES OF THE PREPARATION OF COMPOUNDS OF THE FORMULA (II)

Example 1: Preparation of 2,4-dichloro-3-methylbenzotrifluoride

[0071] A 1 molar solution of lithium diisopropylamide in THF (0.6 mol) was slowly added dropwise to a solution of 2,4-dichlorobenzotrifluoride (107 g, 0.5 mol) and dimethyl sulfate (75.6 g, 0.6 mol) in 500 ml of THF at 50 C. The mixture was stirred at 50 C. for 2 hours and warmed to 20 C. 200 ml of 1 N HCl as aqueous solution were then slowly added dropwise and the THF was subsequently removed under reduced pressure at 40 C. The product was extracted with 300 ml of hexane, the extract was washed with water and dried over MgSO.sub.4. The hexane was removed under a vacuum of 40 mbar. This gave 110 g of a mixture which, according to GC/MS analysis, contained 78% of 2,4-dichloro-3-methylbenzotrifluoride, 10% of 2,4-dichlorobenzotrifluoride (starting material) and 12% of 2,4-dichloro-3-ethylbenzotrifluoride. The desired product can be obtained in pure form by crystallization from methanol at 30 C.

[0072] Yield: 73 g (64% of theory). M.p. 30-32 C. B.p. 82-84 C./8 mbar.

Example 2: Preparation of 2,4-dichloro-3-ethylbenzotrifluoride (Variant 1)

2,4-Dichloro-3-ethylbenzotrifluoride

[0073] A 1 molar solution of lithium diisopropylamide in THF (1.1 mol) was slowly added dropwise to a solution of 2,4-dichlorobenzotrifluoride (107 g, 0.5 mol) and dimethyl sulfate (138 g, 1.1 mol) in 500 ml of THF at 50 C. The mixture was stirred at 50 C. for 2 hours and warmed to 20 C. 100 ml of 1 N HCl as aqueous solution were then slowly added dropwise and THF was subsequently removed under reduced pressure at 40 C.

[0074] The product was extracted with 300 ml of hexane, the extract was washed with water and dried over MgSO.sub.4. The solution was concentrated in a vacuum of 40 mbar. This gave 125 g of a mixture which, according to GC/MS analysis, contained 25% of 2,4-dichloro-3-methylbenzotrifluoride, 5% of 2,4-dichlorobenzotrifluoride (starting material) and (70%) of 2,4-dichloro-3-ethylbenzotrifluoride. The desired product can be purified by distillation under reduced pressure using a Vigreux column.

[0075] Yield: 69 g (58% of theory). B.p. 114-118 C./15 mbar.

Preparation of 2,4-dichloro-3-methylbenzotrifluoride (Variant 2)

[0076] A 1 molar solution of lithium diisopropylamide in THF (0.6 mol) was slowly added dropwise to a solution of 2,4-dichlorobenzotrifluoride (107 g, 0.5 mol) and diethyl sulfate (92.4 g, 0.6 mol) in 500 ml of THF at 50 C. The mixture was stirred at 50 C. for 2 hours and warmed to 20 C. 100 ml of 1 N HCl as aqueous solution were then slowly added dropwise and THF was subsequently removed under reduced pressure at 40 C.

[0077] The product was extracted with 300 ml of hexane, the extract was washed with water and dried over MgSO.sub.4. The solution was concentrated in a vacuum of 40 mbar. This gave 116 g of a mixture which, according to GC/MS analysis, contained 78% of 2,4-dichloro-3-ethylbenzotrifluoride. The desired product can be purified by distillation under reduced pressure using a Vigreux column.