A PROCESS FOR SYNTHESIS OF HIGH PURITY l-[3-(TRIFLUOROMETHYL)PHENYL]ETHANONE OXIME

Abstract

A process for preparation of 3-Trifluoromethyl acetophenone oxime of formula I includes reacting an isomeric mixture of halo benzotrifluoride with Mg metal in an organic solvent in presence of a catalyst to obtain a Grignard complex. The Grignard complex is reacted with a ketene in hydrocarbon solvent in presence of transition metal ligand-acid complex to obtain an isomeric mixture of trifluoromethyl acetophenone. Finally, the isomeric mixture of trifluoromethyl acetophenone is reacted with hydroxylamine salt to obtain compound of formula I.

Claims

1. A process for preparation of 3-Trifluoromethyl acetophenone oxime of formula I comprising: a) reacting an isomeric mixture of halo benzotrifluoride with Mg metal in an organic solvent in presence of a catalyst to obtain a Grignard complex b) reacting the Grignard complex with a ketene in hydrocarbon solvent in presence of transition metal ligand-acid complex to obtain an isomeric mixture of trifluoromethyl acetophenone; and c) reacting the isomeric mixture of trifluoromethyl acetophenone with hydroxylamine salt to obtain compound of formula I.

2. The process as claimed in claim 1, wherein the isomeric mixture in is a mixture of meta:para:ortho halo benzotrifluoride in the ratio of 96:3:1.

3. The process as claimed in claim 1, wherein the catalyst is one selected from a group consisting of iodine, ethylene dibromide and other alkyl magnesium bromide.

4. The process as claimed in claim 1, wherein the transition metal ligand is one selected from a group consisting of Fe(AcAc)3, Ir(AcAc)3, Ru(AcAc′)3 and Cr(AcAc)3.

5. The process as claimed in claim 1, wherein the acid complex is an organic aliphatic acid selected from a group consisting of acetic acid, propionic acid, butanoic acid of and isobutanoic acid.

6. The process as claimed in claim 1, wherein th-a ratio of Grignard complex to ketene is in the range of 1:0.95-1.25 molar equivalents.

7. The process as claimed in claim 1, wherein the hydrocarbon solvent in b) is one selected from a group consisting of toluene, xylene and mesitylene.

8. The process as claimed in claim 1, wherein the hydroxylamine salt in c) is one selected from a group consisting of a sulphate salt or a chloride salt.

9. The process as claimed in claim 1 further comprising simple solvent purification to obtain the compound of the formula I with a purity higher than 99%.

Description

EXAMPLES

[0025] The following experimental examples are illustrative of the invention but not limitative of the scope thereof:

[0026] Preparation of Isomeric Mixture Trifluoromethyl Acetopheneone

[0027] To a mixture of Mg turnings (5.8 g), and dry THF (150 ml) under nitrogen atmosphere at room temperature in a 500 mL flask, catalytic iodine was added. Mixture of 2, 3 and 4 bromo (trifluoromethyl) benzene (50 g) was added gradually to it using a dropping funnel at ˜40-50° C. The reaction mixture was further stirred at 40-5° C. for 2-4 h to obtain the Grignard reagent. Completion of the Grignard formation was confirmed with the help of Gas liquid chromatography (GLC).

[0028] The Grignard reagent was gradually added into a solution of ketene (28.3 g,) in aromatic hydrocarbon (75 ml) in presence of complex prepared from catalytic amount of transition metal ligands preferably Fe ligands and organic aliphatic acid at 0 to −10° C. in a 500 mL flask under N2 atmosphere. The reaction mixture was further stirred at 0 to −10° C. for 2-3 h. A sample of the solution was analyzed by GLC. The overall process yield is 78 to 85%.

[0029] A second alternative of preparing the trifluoromethyl acetophenone was carried out as follows: The Grignard reagent was gradually added simultaneously along with solution of ketene (28.3 g) in a 500 mL flask under N2 atmosphere into a solution of complex prepared from catalytic amount of transition metal ligands preferably Fe ligands and aliphatic acid in aromatic hydrocarbon (75 ml) at 0 to −10° C. in such a way that reaction mass always has slight excess of ketene solution. The reaction mixture was further stirred at 0 to −10° C. for 2 -3 h. A sample of the solution was analyzed by GLC for completion of the reaction. The overall process yield is 75 to 81%.

[0030] Preparation of 3 Trifluoromethyl Acetopheneone Oxime

[0031] The isomeric mixture of trifluoromethyl acetophenone (30 gm) was dissolved in aliphatic alcohol (30 ml).To this solution, was added equivalent amount of hydroxylamine hydrochloride or hydroxyl amine sulphate under stirring. 30% NaOH solution (1-1.3 eq) was added gradually to this solution at ambient temperature. The reaction mixture was warmed and stirred at 40 to 45° C. for 5-7 h. The reaction progress was monitored on GLC. After reaction completion, product is extracted in dichloromethane solvent and isolated by solvent removal. The product thus obtained was purified using cyclic saturated hydrocarbons such as cyclopentane, cyclohaxane etc., by crystalizing out the required 3-trifluoromethyl acetopheneone oxime (3-TFMAP-oxime). The isolated yield of pure 3-TFMAP oxime after purification was ˜80-85%.

[0032] The foregoing description of the invention has been set merely to illustrate the invention and is not intended to be limiting. Since the modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to the person skilled in the art, the invention should be construed to include everything within the scope of the disclosure.