Continuous Flow Organic Chemistry: Successes and Pitfalls at the Interface with Current Societal Challenges

Abstract

This review intends to provide the reader with a clear and concise overview of how preparative continuous flow organic chemistry could potentially impact on current important societal challenges. These societal challenges include health/well‐being and sustainable development. Continuous flow chemistry has enabled significant advances for the manufacturing of pharmaceuticals, as well as for biomass valorization toward a biosourced chemical industry. Examples related to pharmaceutical production are herein focused on (a) the implementation of flow chemistry to reduce the occurrence of drug shortages, (b) continuous flow manufacturing of orphan drugs, (c) continuous flow preparation of active pharmaceuticals listed on the WHO list of essential medicines and (d) perspectives for the manufacturing of peptide‐based pharmaceuticals. Examples related to sustainable development are focused on the valorization of biosourced platform molecules. Besides positive impacts on societal challenges, this review also illustrates some of the potentially most threatening perspectives of continuous flow technology within the actual context of terrorism and drug abuse.

Nickel on nitrogen-doped carbon pellets for continuous-flow hydrogenation of biomass-derived compounds in water

“…Moreover, the mass and heat control guaranteed by the flow process can allow the tunability of the reaction products. 20,21 Additionally, the development of Fig. 1 Lignocellulosic biomass composition and hydrogenation of its derivatives, i.e., glucose (Glu) hydrogenation to Sorbitol (Sor) as cellulose-derived process, hemicellulose derived compounds, Xylose (Xyl) conversion to Xylitol (Xyt), and the hydrogenation of Vanillin (V), from lignin, to 2-methoxy-4methylphenol (MMP) through Vanillyl alcohol (VA).…”

The Use of Molecular Oxygen for Liquid Phase Aerobic Oxidations in Continuous Flow

“…The challenges associated with handling O 2 are better addressed by using continuous processing than multipurpose batch reactors [7,8]. There is a current paradigm shift in the pharmaceutical industry from traditional batch manufacturing to continuous processing for the preparation of active pharmaceutical ingredients (APIs) [9][10][11][12]. This paradigm shift is reflected by a new focus in the pharmaceutical industry on process intensification, sustainability, product quality, safety, energy usage and cost [13].…”

Continuous Flow Organophosphorus Chemistry

“…[23][24][25] With its potential to overcome some of the common issues encountered with batch protocols, flow chemistry has thrived in the many research areas inherent of or at the interface with Organic Chemistry, including methodology, medicinal chemistry, total synthesis, physical organic chemistry and process chemistry to name a few. [26][27][28][29][30][31][32][33][34][35][36] Organophosphorus reagents are widespread for a wide range of reference reactions and organophosphorus chemistry has so many ties towards industrial applications with immense markets and volumes, including pharmaceuticals and agrochemicals. It is therefore not surprising to witness a revisit of organophosphorus chemistry by flow chemists with unquestionable advantages.…”