Kilo-Scale Electrochemical Oxidation of a Thioether to a Sulfone: A Workflow for Scaling up Electrosynthesis
Cecilia Bottecchia, Dan Lehnherr, François Lévesque, Mikhail Reibarkh, Yining Ji, Vailankanni L. Rodrigues, Heather Wang, Yu‐hong Lam, Thomas P. Vickery, Brittany M. Armstrong, Keith Mattern, Kevin Stone, Michael K. Wismer, Andrew Singh, Erik L. Regalado, Kevin M. Maloney, Neil A. Strotman
Abstract
Organic electrosynthesis is a rapidly evolving field, providing powerful methods to assemble targets of interest in organic synthesis. Concerns around the scalability of electrochemical methods remain the biggest reason behind their scarce implementation in manufacturing routes for the pharmaceutical industry. To fill this gap, we report a workflow describing the key reaction parameters toward the successful scale-up of an organic electrosynthetic method from milligram to kilogram scale. The reaction used to demonstrate our workflow and scale-up in a flow setting was the oxidation of a thioether to its corresponding sulfone, a fragment of interest in an active pharmaceutical ingredient under development. The use of online flow nuclear magnetic resonance spectroscopy, offline ion chromatography, cyclic voltammetry, and density functional theory calculations provided insight into the reaction mechanism and side reactions.