OP-II-3

OP-III-A-10LIPASE-CATALYZED REACTION IN A DOWN FLOW CONTINUOUSREACTOR IN ORGANIC SOLVENTSSerap Sahin, Päivi Mäki-Arvela, Kari Eränen,Tapio Salmi, Dmitry Yu. MurzinProcess Chemistry Center, Åbo Akademi University, Turku, FI-20500, Finland;E-mail: ssahin@abo.fiUtilization of cascade methodology in which the intermediate product is convertedin the forthcoming consecutive reactions without any separation in the same pot [1]has great potential for use in chemical industry. Enzymatic reactions can be favoredover chemical catalysis due to the fact that enzymes display high enantioselectivity[2]. The vast majority of the enzymatic processes was performed in a batch mode [3-5]. However, there are only a few examples of processes carried out in continuousflow systems. The aim of this work was to study the kinetic resolution (KR) of racemic1-phenylethanol (R/S)-1 (Fig 1b) in a continuous flow reactor (Fig 1a).The KR of (R/S)-1 with ethyl acetate was performed in a down flow continuousreactor. The internal diameter and the length of the reactor are 1 cm and 12 cm,respectively. The reactor was filled with 3.5 cm quartz sand (> 355 μm) from thebottom on top of a 1 cm quartz wool layer. The catalyst bed containing a mixture of0.125 g immobilized lipase, Novozym 435, and 1.5 g quartz sand had a height of2.9 cm. The uppermost quartz layer which dimension is 3.5 cm in length distributesthe liquid flow above the catalyst bed. The KR of (R/S)-1 with ethyl acetate at themolar ratio of 1:3 in 400 mL toluene was perfomed at 70 °C. The solution wassaturated with argon proir pumping into the reactor. The liquid flow rate was varied ina range of 1.5 mL min –1 -3 mL min –1 . The immobilized lipase was kept at 4 °Covernight between the experiments.a) b)T emp eraturesensorOHO+O CH 3ArgonflowSubstrate pumpS - phenylethanol ethyl acetateOHOimmoblized+O CH 3 lipaseCH 3OOLipase-filledcontinuous flow reactorR- phenylethanolethyl acetateR - 1- phenylethyl aRacemic 1-phenylethanol withethyl acetate in toluene at 70 o CChiral productFigure 1. a) Simplified illustration of the experimental apparatus (~~: temperature controlunit), b) enantioselective enzymatic esterification of R-phenylethanol with ethyl acetate asacyl donor.169