ENZYMATIC CATALYSIS IN scCO_2 FOR KINETIC RESOLUTION OF CHIRAL ALCOHOLS IN BATCH, CONTINUOUS AND SEMI CONTINUOUS MODE

摘要

Synthesis of enantiomerically pure compounds are becoming more and more important in pharmaceutical, agrochemical and fine chemical industry. The use of enzymes as enantioselective catalysts in kinetic resolution reactions is one of the most useful methods to obtain these pure enantiomers from racemic mixtures because enzymes can exhibit extreme high selectivity and yield. In this study a crystallized enzyme of Candida Antarctica lipase B (ChiroCLEC-CAB) is used in scCO_2-being a green environmentally friendly solvent- in a model esterification reaction of ±1-phenyl ethanol (1-PhEtOH) with vinyl acetate (AcOVi). In all tested conditions, the enantioselectivity of the enzyme exceeds 99%. Initial reaction rates in scCO_2 are up to three times higher than in a conventional organic solvent (hexane). The enzyme, however, was found to be sensitive to large and/or sudden pressure differences, making reuse of the catalyst in batch processing very difficult. In a (semi) continuous reactor setup the ChiroCLEC-CAB catalyst is kept in the reactor -at the desired process temperature and pressure- by using a suitable filter in the outlet of the reactor. The process was run, at the same conditions for a period of over 2 weeks without changing that catalyst at 40°C and 90 bar both in continuous and semi continuous mode. Over this period of time the activity dropped to about 30% of its original value. This deactivation process can however be reversed by adding a small amount of water to the reaction mixture. This indicates that during continuous and semi continuous processing, the (very) small amount of water -which is necessary for the enzyme to be active- is 'stripped' from the catalyst. However, adding a small amount of water regenerates the catalyst.