Electrochemical Synthesis of 3-(Het)aryl-5-methylthioisothiazoles from β-Oxodithioesters via β-amino-α,β-unsaturated dithioesters

Abstract

In this study, an efficient and sustainable electrochemical strategy for the synthesis of 3-(het)aryl-5-methylthioisothiazoles from readily accessible β-oxodithioesters is described. The protocol proceeds via a highly regioselective condensation of β-oxodithioesters with ammonium acetate to generate β-amino-α,β-unsaturated dithioesters, which undergo intramolecular oxidative cyclisation mediated by electrochemically generated iodine. A catalytic amount of tetra-n-butylammonium iodide serves as the iodine source, while constant-current electrolysis was carried out using reticulated vitreous carbon (RVC) as the anode and platinum as the cathode. This electrochemical approach provides an operationally simple and environmentally benign alternative to conventional oxidative cyclisation methods by eliminating the requirement for stoichiometric chemical oxidants and significantly reducing waste generation. This method unveils an attractive protocol for the synthesis of isothiazoles and overcomes limitations of traditional methods such as need of stoichiometric amounts of oxidants and generation of waste.