Chemoenzymatic synthesis of the chiral herbicide: (S)-metolachlor

Abstract

A chemoenzymatic approach for the production of (S)-metolachlor, one of the most widely used herbicides, has been developed. The starting material (S)-N-(2-ethyl-6-methylphenyl)alanine was obtained by the use of lipase-catalyzed hydrolytic kinetic resolution. Under the optimal conditions, the good activity and excellent enantioselectivity of lipase B from Candida antarctica (CAL-B,E > 100) are achieved in diethyl ether – water (15% v/v), which is about 9.7-fold more enantioselective than that in a pure buffered aqueous solution (E = 12.1). After a simple extraction procedure is used to separate the acid product from the remaining ester, the remaining ester is racemized, providing the basis for the continuous resolution process. Then (S)-metolachlor is synthesized by a simple chemical method using the enantiomerically pure (S)-acid.Key words: (S)-metolachlor, herbicide, CAL-B, (S)-N-(2-ethyl-6-methylphenyl)alanine, resolution.