Reliable sizing-up of the 3D curved circular microchannel reactor for continuous flow synthesis of a zidovudine intermediate†

Abstract

Herein, we report a size scale-up method for a 3D curved circular microchannel reactor (3D-CCMR), based on a rule of keeping fluid velocity and residence time constant during sizing-up and validated via computational fluid dynamics simulation with mixing index as the key evaluation indicator. The energy dissipation rate was also investigated via simulation to evaluate the energy consumption during sizing-up. Then, a scaled-up microreactor (3D-CCMR-2), aiming at a throughput scale-up factor of 4, was manufactured, and it was proved experimentally that the mass and heat transfer performance was not deteriorated in 3D-CCMR-2 as compared to the original microreactor (3D-CCMR-1). Ultimately, the continuous flow synthesis of the intermediate of anti-AIDS drug zidovudine was performed in both 3D-CCMRs and an actual throughput scale-up factor of 4.0 was achieved. The work in this paper represents the first key step for the scale-up of continuous flow synthesis of zidovudine, and the sizing-up strategy proposed in this paper could offer good guidelines for the size scale-up of microreactors.