K2S-Mediated Tandem Selenylation and Cyclization of CaC2 with Diselenides: Synthesis of 2-Methylbenzoselenazole

Abstract

A concise and efficient one-step strategy for the synthesis of 2-methylbenzoselenazoles has been developed using K2S-mediated reaction of diselenides with calcium carbide (CaC2) as a solid acetylene source. This method features a novel Se–S dynamic exchange mechanism, wherein K2S cleaves the Se–Se bond of diselenides through an S2–-mediated pathway to generate selenium anions. These anions subsequently react with in situ-generated acetylene to form vinyl selenides. The trisulfur radical anion (S3•–) derived from K2S then activates the vinyl group, facilitating the key intramolecular cyclization to afford 2-methylbenzoselenazole products. Mechanistic studies, including HRMS, 1H NMR, and control experiments, support the proposed pathway. Moreover, the demethylation of 6-methoxy-2-methylbenzoselenazole readily converts the methoxy group into a hydroxy functionality, enabling access to versatile building blocks bearing clickable alkynes, nucleophile-sensitive bromoalkyl groups, and hydrolyzable esters for advanced applications. This work represents the first application of a K2S-mediated dynamic interchange reaction of diselenides for constructing selenium-containing heterocycles, offering a promising and sustainable route to synthesize biologically relevant benzoselenazole derivatives.