Sailing the Stormy Seas of Sustainability: Flow vs. Batch in API Synthesis

Abstract

Given the numerous improvements in the flow synthesis of Active Pharmaceutical Ingredients (APIs), this approach has garnered significant attention both from academia and industry. Flow chemistry can indeed shorten synthesis steps and/or reaction time, increase productivity, and generally lead to the creation of new intellectual property. Compared with batch processes, continuous-flow protocols may also facilitate solvent utilisation and often eliminate the need for intermediate isolation, thereby reducing process waste. These features naturally suggest improved sustainability, though it is often expressed more qualitatively than quantitatively. Herein, we systematically compared batch and flow methods for API synthesis. The comparison is based on multiple levels of quantification, including mass-related green metrics (E-factor and unified RME), solvent safety and hazards, as well as space-time-yield, offering a quantitative insight into this subject.