Multi-step continuous-flow synthesis

Abstract

Organic chemistry is continually evolving to improve the syntheses of value added and bioactive compounds. Through this progression, a concomitant advancement in laboratory technology has occurred. Many researchers now choose to mediate transformations in continuous-flow systems given the many benefits over round bottom flasks. Furthermore, reaction scale up is often less problematic as this is addressed at the inception of the science. Although single-step transformations in continuous-flow systems are common, multi-step transformations are more valuable. In these systems, molecular complexity is accrued through sequential transformations to a mobile scaffold, much like an in vitro version of Nature's polyketide synthases. Utilizing this methodology, multi-step continuous-flow systems have improved the syntheses of active pharmaceutical ingredients (APIs), natural products, and commodity chemicals. This Review details these advancements while highlighting the rapid progress, benefits, and diversification of this expanding field.

Continuous flow (micro-)reactors for heterogeneously catalyzed reactions: Main design and modelling issues

“…Several examples of continuous flow multistep reactions, often catalytically mediated, have been recently reviewed [8,51]. Very versatile configurations of micromixers, microreactors, heaters, pumps, membrane separators, etc.…”

Integrated Micro‐Flow Synthesis Based on Photochemical Wolff Rearrangement

“…[10][11][12][13][14][15][16][17][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] (1) Precise control of short reaction times (<1 sec) can be achieved.…”

“…[7,8] In addition, in order to reduce the risks involved in handling these dangerous compounds, the reactor should be as small as possible. [9] From this point of view, integrated microflow synthesis [10][11][12][13][14][15][16][17] is ideal for the preparation of compounds 1 and their Wolff rearrangement.…”

Organic oxidations promoted in vortex driven thin films under continuous flow

“…7,10 Alternative options such as air or molecular oxygen, 11,12 hypochlorous acid and sodium hypochlorite (chlorine bleach), 13 and hydrogen peroxide 14,15 have been identified as green oxidants because of their attractive safety profile, high atom economy, and the generation of innocuous by-products such as water or sodium chloride. 16 To this end, continuous flow reactors have been shown to address safety, scalability and efficiency of many transformations, 17,18 including these oxidations. 19,20 These advances notwithstanding, such continuous flow reactors often suffer from high overhead cost, complex operation, the use of organic solvents and channel blocking associated with the formation of emulsions, salts and other insoluble material.…”