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Forbidden chemistries go flow in API synthesis


Bernhard Gutmann, C. Oliver Kappe
Institute of Chemistry, University of Graz, NAWI Graz,
Heinrichstrasse 28, 8010 Graz, Austria


The application of continuous flow microstructured reactors for the production of complex molecules has gained significant momentum in recent years. Conventionally, a chemical process is designed to accommodate the limits of the available reactionware. Thus, reactions are often done under non-ideal conditions due to restraints imposed by the equipment. The small internal volumes of microreactors and their high surface area-to-volume ratios enable reactions to be run under conditions not easily accessible in traditional batch reactors. Furthermore, reactions previously impractical (“forgotten chemistry”) or virtually impossible (“forbidden chemistry”) to perform can be operated in these devices with little risk at various scales. In this review selected examples from the recent literature highlighting the above mentioned advantages of continuous processing are discussed.


Flow chemistry is a very well-established technique for the large scale production of commodity chemicals. Continuous production eliminates the extra labor and cost of starting up and shutting down of a chemical process, thereby minimizing the formation of off-quality material during non steady-state operation and maximizing throughput. The repeated cycling of temperature and pressure from starting and stopping of a conventional batch production unit does not only decrease product quality and process reliability, but it is energy and time consuming and increases the complexity of the process. In contrast, a continuous reactor can be kept running 24/7. Furthermore, continuous processes can be closely controlled and are relatively easily automated and, thus, often require only few w ... ...