The electrochemical oxidation of a thioether to form an API intermediate and the effects of substrate electronics on impurity formation

Abstract

Electrochemistry was explored as a means of oxidising a thioether to form a sulfone API intermediate. A design of experiments approach was employed to enable the scale up of the reaction, sacrificing a few percent of the yield to triple the throughput. During the course of this investigation a chloroalkyl sulfoxide was unexpectedly formed, and analysis of the substrate scope found that electron rich substrates are more susceptible to this reaction pathway. Even though electrochemical oxidation was not selected as a viable route, the results reported within will help to inform as to the suitability of this approach for different substrates in the future.