Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous-flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.

Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

Alan Ford,† Hugues Miel, Aoife Ring,† Catherine N. Slattery,† Anita R. Maguire,*,†,‡ and M. Anthony McKervey* †Department of Chemistry and ‡School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland Almac Discovery Ltd., David Keir Building, Stranmillis Road, Belfast BT9 5AG, United Kingdom Almac Sciences Ltd., Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, United Kingdom

Modern Organic Synthesis with α-Diazocarbonyl Compounds

Over the last two decades, flow technologies have become increasingly popular in the field of organic chemistry, offering solutions for engineering and/or chemical problems. Flow reactors enhance the mass and heat transfer, resulting in rapid reaction mixing, and enable a precise control over the reaction parameters, increasing the overall process selectivity, efficiency and safety. These features allow chemists to tackle unexploited challenges in their work, with the ultimate objective making chemistry more accessible for laboratory and industrial applications, avoiding the need to store and handle toxic, reactive and explosive reagents. This review covers some of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions.

Taming hazardous chemistry by continuous flow technology

The continuous flow synthesis of active pharmaceutical ingredients, value-added chemicals, and materials has grown tremendously over the past ten years. This revolution in chemical manufacturing has resulted from innovations in both new methodology and technology. This field, however, has been predominantly focused on synthetic organic chemistry, and the use of biocatalysts in continuous flow systems is only now becoming popular. Although immobilized enzymes and whole cells in batch systems are common, their continuous flow counterparts have grown rapidly over the past two years. With continuous flow systems offering improved mixing, mass transfer, thermal control, pressurized processing, decreased variation, automation, process analytical technology, and in-line purification, the combination of biocatalysis and flow chemistry opens powerful new process windows. This Review explores continuous flow biocatalysts with emphasis on new technology, enzymes, whole cells, co-factor recycling, and immobilization methods for the synthesis of pharmaceuticals, value-added chemicals, and materials.

/pdf/continuous-flow-biocatalysis-4ydtviifqr.pdf

Federica Mastronardi

Papers

Continuous flow generation and reactions of anhydrous diazomethane using a Teflon AF-2400 tube-in-tube reactor.