Towards Versatile Continuous‐Flow Chemistry and Process Technology Via New Conceptual Microreactor Systems

Abstract

In the past decade, microreaction technology has been attracted much attention to the scientific community as one of the subareas in chemical synthesis. The microreactor improves the yield with higher selectivity, and also facilitates the reactions by simple, safe, fast, and green approaches. This review gives an overview on our contributions to develop versatile continuous-flow syntheses and process technology by exampling gas-liquid binary phase in modified PDMS microreactors, and process intensification for safe operation of toxic/hazardous chemistry by generating hazardous chemicals to end utilization via various separation techniques in newly devised systems as well as ordinary capillary reactors. Furthermore, it covers process technology for ultrafast organic synthesis such as submillisecond control of short-lived intermediates in a polyimide chip reactor. These works provide outlooks for integrated and automated flow chemistry via one-flow/feed to end concept, i.e., useful in pharmaceutical industry, toward enabling new and innovative chemistry beyond limits of a batch reactor.

Fast‐Synthesis of α‐Phosphonyloxy Ketones as Drug Scaffolds in a Capillary Microreactor

“…Continuous‐flow microreactors have recently attracted much attention as an important technique for synthesizing organic molecules including drug intermediates/molecules in a very short time under mild reaction conditions A high surface area to volume ratio in this microfluidic system promotes mass and heat transfer, leading to selectivity and conversion much superior to the levels obtainable by conventional batch processes . Owing to their many complex issues such as inefficient mixing, non‐uniformity in heat, and safety in the scale‐up of batch process, in recently, flow approach is more attractive and reliable in both academia and industry , .…”

“…From all these experiments, it was observed that the reaction time could surprisingly be decreased to 3.93 s from 5 min in flask (Table , entry 3) at a total flow rate of 3 mL/min to attain the identical chemical performance of the desired product 3 in 67 % yield and the side products 4 & 5 in 5 % & 21 %, respectively, which is consistent with the results of the reaction in flask (entry 8, Table ). Notably, the use of larger diameter PFA capillary (1.0 mm) significantly decreased the yield of product 3 (52 %), presumably owing to lowered mixing efficiency, (Table , entry 7). Excellent mixing efficiency throughout the confined reaction space of the microfluidic reactor, which is provided by a high surface‐area‐to‐volume ratio, lowered the synthesis time to several seconds (3.9 s) from several minutes (5 min).…”

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

“…Flow chemistry as a branch of organic synthesis has been reviewed extensively through several informative and educational articles [14][15][16][17][18][19][20][21] and books [22][23][24][25][26][27]. As such our aim is not to include a comprehensive review here but to simply highlight the principle characteristics and direct the reader to the listed references for further consultation.…”

Membrane Microreactors for the On‐Demand Generation, Separation, and Reaction of Gases

“…[9,14] Kim and co-workersd eveloped ad ual-channel microreactor strategy for performingg as-liquid transformations ( Figure 1b). [15] The microreactor is fitted with ah ydrophobic poly(dimethylsiloxane) (PDMS)m embrane (45 mmt hickness) which allowsd iffusion of gases but is impermeablet ot he other reaction components. Ag as flows along one channel passing through the membrane into the second channel containing the liquid phase for the organic transformation.T he system was first reported for reactions involving O 2 .…”

“…Kim and co‐workers developed a dual‐channel microreactor strategy for performing gas–liquid transformations (Figure b) . The microreactor is fitted with a hydrophobic poly(dimethylsiloxane) (PDMS) membrane (45 μm thickness) which allows diffusion of gases but is impermeable to the other reaction components.…”