N-Methylthiomethylation of benzimidazoles with DMSO and their chemoselective oxidation to sulfoxides with NaBiO3

Abstract

A straightforward one-step method for the N-methylthiomethylation of benzimidazoles has been developed employing DMSO as a solvent and as a reagent. This methodology has been applied for the synthesis of diverse N-methylthiomethyl derivatives of benzimidazoles. The products can be chemoselectively oxidized to the corresponding sulfoxides with NaBiO3 in acetic acid. Both the N-methylthiomethyl derivatives of benzimidazoles and their corresponding sulfoxides are important medicinal scaffolds.

N1‐Methylthiomethylation of (8‐Aza)6‐Chloropurine with DMSO through the Pummerer Rearrangement

“…Comparing with MTMCl, DMSO is undoubtedly a more facile, cheaper, environmentally friendly, and greener MTM reagent. Inspired from oxidation reactions, these methods used DMSO as MTM source generally required extra activators, such as NH 4 OAc, [36,37] AcOH, [12] TMSCl, [38] NMP, [39] COCl 2, [40] SOCl 2, [41] Ac 2 O, [42] TFAA, [43,44] t BuBr, [45] and DPPA. [11] The key intermediate sulfonium salt A is generated by activated DMSO through the Pummerer rearrangement, and the MTM products can be obtained after the nucleophilic addition by alcohols, thiols or amines (Scheme 1b).…”