Optimization and kinetic modeling of lipase catalyzed enantioselective N-acetylation of ( ± )-1-phenylethylamine under microwave irradiation

Abstract

BACKGROUND: Optically pure amines are used in the fine chemical industry as resolving agents, chiral auxiliaries, and chiral synthetic building blocks for pharmaceuticals as well as agrochemicals. Lipase-catalyzed kinetic resolution of ( ± )-1-phenylethylamine with ethyl acetate as an acyl donor was achieved using immobilized lipase (Novozyme 435) as a biocatalyst under microwave irradiation. RESULTS: Response surface methodology was employed with a four-factor-three-level Box-Behnken design to evaluate the effect of synthesis parameters (speed of agitation, enzyme loading, temperature and acyl donor:amine molar ratio) on conversion, enantiomeric excess, enantioselectivity and initial rate. The optimum reaction conditions obtained were mole ratio of acyl donor:amine 1:1, temperature 49.86 °C, 0.03 g of catalyst loading and 345 rpm speed of agitation, giving 49.12% conversion, 78.83% enantiomeric excess and an enantioselectivity of 38.21. R-stereopreference of lipase was analyzed in detail from the aspects of enzymatic kinetic mechanism and reaction activation energy of both enantiomers. CONCLUSION: Novozyme 435 was found to be the most active chiral catalyst for resolution of ( ± )-1-phenylethylamine under microwave irradiation. Statistical analysis was satisfactorily used to determine the optimum reaction conditions. It was found that lipase has R-stereopreference and the reaction matches the Ping Pong Bi Bi mechanism with dead-end inhibition of 1-phenylethylamine. Copyright © 2011 Society of Chemical Industry