Resolution Of Alpha-Cyano-Benzyl Acetate Via Lipase-Catalyzed Asymmetric Alcoholysis In Organic Media

Enantiopure cyanohydrin compounds are useful intermediates in organic synthesis and their derivatives, such asa-hydroxy acids, α-hydroxy ketones and aldehydes and β -hydroxy amines, are important for the production of pharmaceuticals and agrochemicals. The method of lipase-catalyzed asymmetric alcoholysis of α-cyano-benzyl acetate in organic media was tried to obtain the satisfied product as follows:Through screening, the preferable system for the asymmetric reaction were: Lipase Alcaligenes sp., tetrahydrofuran and methanol. Effects of various parameters were studied to deduce the kinetics and mechanism of the reaction. The optimal temperature was 40 ℃. The external diffusion limitation could be excluded by raising the rotation speed and the internal diffusion could be ignored. The experimental results indicated that the decomposition of the mandelonitrile was the main reason of the decrease of the yield and e.e. value and benzaldehyde could greatly inhibit the enzyme activity. The kinetics was found to obey the Ping-Pong bi-bi mechanism with substrate inhibition of methanol. The initial rate equation is as follow:Where v0: the initial rete, [A]: methanol concentration, [B]: (S)-α-cyano-benzyl acetate The parameter values and R2 value of the simulated initial rate equation were calculated: Vm= 169.11(mmol/L/hr), KA=0.01 (mmol/L), KB= 1536.86 (mmol/L), KiA=796.98 (mmol/L), R2= 0.969, and the simulated values correspond to the experimental value quite well.