Advancing Flow Chemistry Scale-Up Through Integrated Chemical Engineering

Introduction

In simple terms, flow chemistry, or continuous processing, is the reaction of two or more chemicals within a “pipe” or continuous reactor moving at a constant flow rate in a “plug flow” resulting in the formation of a new product (1).
Flow chemistry or continuous processing has gained significant traction in the last decade with many commercial examples (2) now coming to fruition and, most importantly, with endorsement from pharmaceutical regulatory bodies (3).

Flow chemistry opens a whole new scalable toolbox for organic chemists, enabling the synthesis of chemicals and active pharmaceutical ingredients (APIs) using challenging reaction classes, including those that are typically deemed forbidden or unsafe for batch reactions. These chemistries have become accessible thanks to the intrinsic low volume of flow reactions, coupled with enhanced control and excellent heat and mass transfer. This means that reactions can be safely conducted under continuous processing conditions, significantly minimising the risks associated with traditional batch processes. As highlighted in Figure 1, flow chemistry offers a myriad of benefits. Environmentally, it helps minimise waste generation and enhances safety. It also enables the exploration of new or challenging functional group exchanges; this is particularly advantageous in scenarios involving high pressure, high energy, oxidations, or photochemical transformations, where traditional methods might fall short.