Redox-Mediated and Microwave-Assisted Thiol Activation: Two Approaches to Unsymmetrical Disulfides Synthesis

Abstract

Two approaches to synthesis of unsymmetrical disulfides based on different types of thiol activation, namely, an electrochemical method in the presence of a redox mediator and a microwave irradiation, were discussed. The mediated electrosynthesis procedures were carried out by the oxidative coupling of thiols or by the thiol-disulfide exchange in the presence of redox pairs – substituted o-aminophenol/o-iminobenzoquinone. It has been established that the formation of unsymmetrical disulfides under electrochemical conditions occurs as a result of both the oxidative coupling of sulfur-centered radicals, and a redox-mediator promoted thiol-disulfide exchange which led to a high yield of heterodimeric products (89–99%). The microwave-assisted synthesis made it possible to obtain the target products with yields of 13–86% depending on different irradiation parameters such as power, temperature, and irradiation duration. However, this method requires a rigorous selection of conditions for each reaction and is therefore inferior to the electrochemical approach.

The transformations of thiols and their dimers in the redox-mediated thiol-disulfide exchange reaction

“…In addition to processes of a radical nature, exchange reactions between a thiol and a disulfide can occur in an electrochemical cell via an ionic mechanism (Scheme 5), as was shown earlier in the study of thiol oxidative coupling [46]. The combination of these transformations leads to an effective accumulation of the target unsymmetrical disulfide.…”

“…We have previously showed that thiol oxidative coupling can occur in the presence of sterically hindered o-aminophenol as a redox mediator and lead to R 1 SSR 2 [45]. Besides, undesirable reaction products (homodimers) participate in the TDE side process promoted by the o-aminophenol/o-iminobenzoquinone under electrochemical conditions [46]. The aim of the present work is to study TDE reactions in the presence of redox mediators 1-12 (Scheme 1) to promote exchange interaction.…”