Preparation of Sulfonyl Chlorides by Oxidative Chlorination of Thiols and Disulfides using HNO3/HCl/O2 in a Flow Reactor

A continuous flow metal-free protocol for the synthesis of sulfonyl chlorides from thiols and disulfides in the presence of nitric acid, hydrochloric acid and oxygen was developed. The influence of the reaction parameters was investigated under batch and flow conditions. Online F-19 NMR was successfully implemented to investigate different reaction conditions within a single experiment. The sulfonyl chlorides were isolated (mostly in 70-81 % yield) after performing a simple aqueous washing procedure. In particular, the protocol was successfully operated for >6 hours to convert diphenyl disulfide to its corresponding sulfonyl chloride, achieving a throughput of 3.7 g h(-1). The environmental impact of the protocol was assessed and compared to an existing continuous flow protocol using 1,3-dichloro-5,5-dimethylhydantoin (DCH) as reagent. The process mass intensity (PMI) for the newly-developed flow protocol (15) compared favorably to the DCH flow process (20).