Inline purification in continuous flow synthesis – opportunities and challenges

Abstract

Continuous flow technology has become the method of choice for many academic and industrial researchers when developing new routes to chemical compounds of interest. With this technology maturing over the last decades, robust and oftentimes automated processes are now commonly exploited to generate fine chemical building blocks. The integration of effective inline analysis and purification tools is thereby frequently exploited to achieve effective and reliable flow processes. This perspective article summarizes recent applications of different inline purification techniques such as chromatography, extractions, and crystallization from academic and industrial laboratories. A discussion of the advantages and drawbacks of these tools is provided as a guide to aid researchers in selecting the most appropriate approach for future applications. It is hoped that this perspective contributes to new developments in this field in the context of process and cost efficiency, sustainability and industrial uptake of new flow chemistry tools developed in academia.

Advances in in situ and in-line liquid–liquid extraction for bioprocess intensification

“…A wide range of continuousflow reactions, such as organic, inorganic, and photochemical syntheses, have implemented the in-line separations for removing undesired byproducts and purifying key intermediates or products between steps. 73,74 Recently, researchers have also begun to adopt these tools in a continuous-flow biocatalytic reaction system (i.e., flow biocatalysis 75 ) (Fig. 5).…”

Merging Continuous Flow Technology, Photochemistry and Biocatalysis to Streamline Steroid Synthesis

“…[14] Unlike batch reaction telescoping (multiple transformations without purification of intermediates), continuous flow approaches permit in-line work-up and purification, and reagent loading is accomplished at set points in the continuous flow sequence. [15] In this regard, continuous flow multistep synthesis can be viewed as a machine that mimics the biological processes in realizing complex natural products. Plug flow conditions and reaction compartmentalization is generally employed to achieve higher performance.…”

Continuous flow synthesis of phenyl glucosazone and its conversion to 2H-1,2,3-Triazole building blocks

“…As such flow chemistry offers improved heat and mass transfer through reactor miniaturisation which leads to small footprint systems whose modular configuration provides for additional flexibility [9]. Modern flow reactors have been developed with integrated in-line analysis [10] and purification [11] tools to facilitate the safe and automatable operation of synthetic sequences providing robust access to numerous structures of interest for academic and industrial applications. Unsurprisingly, flow technology has been exploited for the use of biorenewable building blocks [12] and biocatalysts [13] leading to many attractive applications as reviewed recently.…”