Large-scale preparation of (Z)-3-hexen-1-yl acetate using candida antarctica-immobilized lipase in hexane

A kilogram-scale synthesis of (Z)-3-hexen-1-yl acetate, in hexane, on direct esterification of (Z)-3-hexen-1-ol with acetic acid in the presence of 2% (w/w reactants) of an immobilized lipase from Candida antarctica (Novozym 435) is reported. Conversion yields ranging from 92 to 96% were obtained after optimization of various parameters. In that respect, elimination of the water proved crucial. Using at both the laboratory large scale (preparation of 200-400 g of ester) and the pilot scale (1-5 kg) a "reflux" rotary evaporator equipped with a graduated decantation flask, we were able to trap the water evolved during esterification while at the same time monitor the time course of the reaction. As a consequence of both an efficient water trapping and of a gentle dispersion of the immobilized lipase into the reaction medium, the lifetime of the enzyme was significantly prolonged. At the laboratory large scale (LLS), the yield was still >/=90% after seven consecutive utilizations whereas at the pilot scale (PS), it reached 93% after reusing the enzyme four times. In those conditions, the amount of immobilized enzyme necessary to produce 1 kg of (Z)-3-hexen-1-yl acetate was 18 g (1. 8%) and 60 g (6%) at the LLS and the PS, respectively. Copyright 1998 John Wiley & Sons, Inc.