H3PO3 promoted reactions of thioamides with 2-substituted benzyl alcohols

Abstract

In this study, we have investigated the reactivity of thioamides with alcohols by utilizing H₃PO₃ as a low-toxicity, cost-effective Brønsted acid catalyst. This report includes a methodology for the synthesis of thioesters from thioamides and 2-hydroxyaryl alcohols. Thioesters are emerging as a notable class of organic molecules due to their biological relevance, extensive use in drug discovery, and industrial applications. The diversity of the reaction protocol was further demonstrated through the S-alkylation of benzo[d]oxazole-2(3H)-thione and benzo[d]thiaazole-2(3H)-thione by the nucleophilic substitution of hydroxy-embedded arylalcohols. In absence of phenolic –OH, the reaction results were inferior. Based on control experiments, a reaction mechanism was proposed in which phenolic –OH acts as a directing group in the presence of H₃PO₃. Additionally, the practical utility of the reaction protocol was explored through the synthesis of structurally diverse benzothiazines from arylthioamides and 2-aminobenzyl alcohols.