In-Flow Generation of Thionyl Fluoride (SOF2) Enables the Rapid and Efficient Synthesis of Acyl Fluorides from Carboxylic Acids

Identifier:  imarina:9378983

Handle: https://hdl.handle.net/20.500.11797/imarina9378983

Authors:  Mazzarella, Daniele; Stanic, Jelena; Bernus, Miguel; Mehdi, Arad Seyed; Henderson, Cassandra J; Boutureira, Omar; Noel, Timothy

Abstract:
Herein, we report an approach for generating thionyl fluoride (SOF2) from the commodity chemicals thionyl chloride (SOCl2) and potassium fluoride (KF). The methodology relies on a microfluidic device that can efficiently produce and dose this toxic gaseous reagent under extremely mild and safe conditions. Subsequently, the in situ-generated thionyl fluoride is reacted with an array of structurally and electronically differing carboxylic acids, leading to the direct and efficient synthesis of highly sought-after acyl fluorides. Importantly, our investigation also highlights the inherent modularity of this flow-based platform. We demonstrate the adaptability of this approach by not only synthesizing acyl fluorides but also directly converting carboxylic acids into a diverse array of valuable compounds such as esters, thioesters, amides, and ketones. This versatility showcases the potential of this approach for a wide range of synthetic applications, underscoring its significance in the realm of chemical synthesis.