Recent Advances in Continuous-Flow Reactions Using Metal-Free Homogeneous Catalysts

Abstract

Developments that result in high-yielding, low-cost, safe, scalable, and less-wasteful processes are the most important goals in synthetic organic chemistry. Continuous-flow reactions have garnered much attention due to many advantages over conventional batch reactions that include precise control of short reaction times and temperatures, low risk in handling dangerous compounds, and ease in scaling up synthesis. Combinations of continuous-flow reactions with homogeneous, metal-free catalysts further enhances advantages that include low-cost and ready availability, low toxicity, higher stability in air and water, and increased synthetic efficiency due to the avoidance of the time-consuming removal of toxic metal traces. This review summarizes recently reported continuous-flow reactions using metal-free homogeneous catalysts and classifies them either as acidic catalysts, basic catalysts, or miscellaneous catalysts. In addition, we compare the results between continuous-flow conditions and conventional batch conditions to reveal the advantages of using flow reactions with metal-free homogeneous catalysts.

Process intensification of dendritic fibrous nanospheres of silica (DFNS) via continuous flow: a scalable and sustainable alternative to the conventional batch synthesis

“…Continuous flow reactors are emerging as promising alternatives for traditional batch reactors. [32][33][34][35][36] Extensive literature is present to support the performance of both homogeneous 37 and heterogeneous reactions 38 through flow. The important advantages of continuous flow methods when compared to batch/hydrothermal synthesis; include (a) large surface area to volume ratio which allows efficient heat transfer, thereby affording easy adaptation of exothermic reactions 39 (b) mixing small amounts of reagents per time making the process safer, 40 (c) better control over reaction kinetics and product selectivity because of precise control of variables such as temperature, pressure, residence time, and stoichiometry, 41,42 (d) easy availability of enhanced scaleup technology after lab-based flow optimizations without the need for extensive re-designing with scale-increase, 43 and much more.…”

Recent Advances in the Solid- and Solution-Phase Synthesis of Peptides and Proteins Using Microflow Technology

“…In this context, the thin reaction channels in microflow photoreactors enhance light penetration efficiency compared with batch photochemical reactions. − (4) Microflow reactors also have small reaction spaces that can contain only small amounts of compounds. This attribute minimizes the risks when manipulating explosive and/or toxic compounds. − (5) Another important advantage is the facile scalability of processes either by continuous running or by numbering-up the reactors. − Microflow reactions are also highly amenable for use in automated synthesis, − as control of the pumping and temperature control devices is required to realize the microflow. Notably, a combination of automated microflow synthesis with in-line monitoring technology , allows high-throughput data acquisition that drives the autonomous optimization of reaction conditions using machine learning technology. , …”

An integrated resource-efficient microfluidic device for parallelised studies of immobilised chiral catalysts in continuous flow via miniaturized LC/MS-analysis

“…In recent years, intensive studies have been conducted in the field of asymmetric organocatalysis, [1][2][3][4] reaching a new milestone in 2021 when Benjamin List and David W. C. MacMillan were awarded the Nobel Prize in Chemistry for their work on small molecules as metal-free asymmetric organocatalysts. 5 The performance of such catalysts offers an efficient alternative to enzyme-and metal-catalyzed reactions, [6][7][8] particularly impacting the pharmaceutical as well as the fine and functional chemicals industry, in which practically only enantiomerically pure APIs are required.…”