Continuous enantioselective hydrogenation in fixed-bed reactor: towards process intensification

Abstract

The platinum-catalyzed enantioselective hydrogenation of ethyl pyruvate (EP) has been studied in a continuous fixed-bed reactor working under trickle bed conditions. The alumina-supported platinum catalyst was chirally modified by continuous dosing of small amounts of cinchonidine (CD) to the reactor feed containing EP and hydrogen dissolved in acetic acid. A parametric sensitivity study, including CD/EP ratio, hydrogen pressure, temperature, solvent/EP ratio and total liquid feed rate indicated significant dependence of reaction rate and enantiomeric excess (ee) on these parameters. Optimization using the Box Wilson method with hydrogenation rate as objective function and ee>90% as boundary condition afforded a site–time–yield, expressed as average turnover frequency (TOF), of 84 000 h −1. The space–time–yield was found to be approximately one order of magnitude higher than that achieved in a batch reactor (autoclave) under otherwise similar conditions. These findings indicate that the continuous fixed-bed reactor operation may provide an interesting opportunity for process intensification of this type of asymmetric catalytic hydrogenations.