Lipase catalyzed kinetic resolution of (±)-1-(1-naphthyl) ethanol under microwave irradiation

Abstract

1-(1-Naphthyl) ethanol is an important chiral building block for the synthesis of active pharmaceutical intermediates (APIs). In this work, lipase catalyzed kinetic resolution of (RS)-1-(1-naphthyl) ethanol via transesterification was studied under microwave irradiation with different acyl donors. Vinyl acetate was the most effective and hence used as the acyl donor. Three different commercially available immobilized lipases were used, among which Candida antarctica lipase B, immobilized on acrylic resin (Novozym 435) was found to be the best catalyst in n-heptane as solvent. The effect of various parameters was studied in a systematic manner. The reaction was intrinsically kinetically controlled. Maximum conversion of 47.74% with enantiometric excess of substrate (ees) of 90.05% and enantiomeric ratio (E) of 433.39 was obtained in 3 h using 30 mg of enzyme loading with equi-molar ratio of alcohol to ester at 60 °C. From the progress curve analysis, the ping–pong bi–bi mechanism with inhibition by both substrates was found to fit the initial rates. Kinetic parameters were obtained by using non-linear regression. The process is efficient and easily scalable as compared to the chemical process.