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Despite growing applications being reported both in academia and industry, continuous flow chemistry remains a relatively untaught field across most chemistry undergraduate courses. This is particularly true in laboratory practical classes, where it is often deemed simpler to carry out synthetic reactions in traditional batch mode using round-bottomed flasks. Herein, we report the development of an undergraduate project that utilises cheap and readily available materials to construct continuous flow reactors. The students compare the performance of different types of reactors and conditions in a biphasic selective acetylation of a symmetrical diamine. Throughout the investigation, the students can vary multiple parameters as they optimise the reaction, thus actively learning and readjusting them based on their improved understanding. The experiments give the students an appreciation of continuous flow techniques in comparison to batch.

Downstream purification of products and intermediates is essential for the development of continuous flow processes. Described herein, is a study on the use of a modular and reconfigurable continuous flow platform for the self-optimisation of reactive extractions and multi-step reaction-extraction processes. The selective extraction of one amine from a mixture of two similar amines was achieved with an optimum separation of 90%, and in this case, the black-box optimisation approach was superior to global polynomial modelling. Furthermore, this methodology was utilised to simultaneously optimise the continuous flow synthesis and work-up of N-benzyl-α-methylbenzylamine with respect to four variables, resulting in a significantly improved purity.

A universal multistage cascade CSTR has been developed that is suitable for a wide range of continuous-flow processes. Coined by our group the “Freactor” (free-to-access reactor), the new reactor integrates the efficiency of pipe-flow processing with the advanced mixing of a CSTR, delivering a general “plug-and-play” reactor platform which is well-suited to multiphasic continuous-flow chemistry. Importantly, the reactor geometry is easily customized to accommodate reactions requiring long residence times (≥3 h tested).

The demand for efficient and sustainable chemical process development has driven significant advancements in automated droplet flow platforms, which, when coupled with high-throughput experimentation, offer powerful solutions for generating synthetic libraries and optimising reaction parameters. Droplet flow platforms allow for reactions to take place on a microfluidic scale, enabling rapid and sustainable process optimisations. The size of the droplet is varied, with the technique of generating the droplet differing from multiple pumps to advanced robotics. Approaches to integrate multiple analytical tools, phase sensors and parallel reactors have been developed, broadening the capabilities and increasing the throughput of these platforms. Herein, we review recent advancements made within this field, highlighting the type of chemical reactions investigated and the digital technologies which have enabled closed-loop optimisations.

With increased efforts towards enzyme engineering and chemocatalysis in milder conditions, the combination of chemocatalysis and biocatalysis has seen a significant rise in interest. Continuous flow methods have also provided advantages to many catalytic processes, which have been increasingly explored by both academics and industry. This review highlights the different approaches for the combination of chemocatalysis and biocatalysis in continuous flow, together with the main advantages and challenges facing the development of this relatively new research area.