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Kilo-Scale Electrochemical Oxidation of a Thioether to a Sulfone: A Workflow for Scaling up Electrosynthesis

Cite this: Org. Process Res. Dev. 2022, 26, 8, 2423–2437
Publication Date (Web):July 1, 2022
https://doi.org/10.1021/acs.oprd.2c00111
Copyright © 2022 American Chemical Society
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Abstract

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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.

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This article is cited by 15 publications.

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