Abstract

Micro-Packed Bed Reactors for Continuous API Manufacturing

Jisong Zhang, Assistant Professor, Tsinghua University

The micropacked bed reactors (µPBRs) have attracted substantial attention for their safer, greener, and more efficient characteristics in multiphase reaction process. The hydrodynamics (pressure drop, residence time distribution and liquid holdup) and gas-liquid mass transfer in µPBRs were studied with an automated platform. The results show that capillary forces have a large effect on the pressure drop and liquid holdup, giving a large holdup of 0.65~0.85 compared with 0.05~0.25 in large scale trickle beds. The kLa values are in the range of 0.12~0.39 s-1, which is about one-to-two orders of magnitude larger than those of conventional trickle beds. A mathematical model describing hydrodynamics and an empirical correlation predicting kLa have been developed showing good agreement with experimental data. Based on these engineering understanding of µPBRs, several types of hydrogenation reactions have been performed, including deprotection, reduction of nitro, reductive amination and hydrodechlorination. The results demonstrate that hydrogenations in µPBRs always give higher yield, much less reaction time, less catalyst consumption compared with bath reactors. Furthermore, we did a scaling up of the microsystem to a capacity of 60 kg/day, which has been successfully applied for several API manufacturing, with the largest output of a ton.