Sulfur‐ and Amine‐ Promoted Multielectron Autoredox Transformation of Nitromethane: Multicomponent Access to Thiourea Derivatives

Abstract

Thiourea derivatives are in‐demand motifs in organic synthesis, medicinal chemistry and material science, yet redox methods for the synthesis that start from safe, simple, inexpensive and readily available feedstocks are scarce. In this article, we disclose the synthesis of these motifs using elemental sulfur and nitromethane as the starting materials. The method harnesses the multi‐electron auto‐redox property of nitromethane in the presence of sulfur and amines, delivering thiourea products without any added oxidant or reductant. Extension of this reaction to cyclizable amines and/or higher homologues of nitromethane led to a wide range of nitrogen heterocycles and thioamides. Operationally simple, the reactions are scalable, tolerate a wide range of functional groups, and can be employed for the direct functionalization of natural products. Mechanistically, the nitro group was found to act as an oxidant leaving group, being reduced to ammonia whereas sulfur, along with the role of a sulfur building block for the thiocarbonyl group, behaved as a complementary reductant, being oxidized to sulfate.

Sulfur-Promoted Access to 3-Arylquinoxalin-2-ones by Oxidative Coupling of o-Phenylenediamines with Arylacetates

“…While these aromatic amines have been known to be readily oxidizable when other oxidants were used, elemental sulfur and/or DMSO have shown to be excellent oxidants for the functionalization of acetophenones, 8 dialkylketones, 9 phenylacetylenes, 10 malonic acids, 11 and nitroalkanes. 12 In continuing our development of synthetic methodology involving this versatile and user-friendly element, we report herein our results on the synthesis of 3-arylquinoxalin-2-ones 3 via sulfur-promoted oxidative coupling of o-phenylenediamines 1 with arylacetates 2. For this purpose, we carried out a series of screening reactions using o-phenylenediamine 1a (1 mmol) and ethyl phenylacetate 2a (1.2 equiv) as model substrates.…”

“…Recently, we have developed elemental sulfur S 8 as a selective oxidant for C–H functionalization using aromatic amines, such as o -phenylenediamines, o -aminophenols, o -aminothiophenols, and anilines, as the nucleophiles. While these aromatic amines have been known to be readily oxidizable when other oxidants were used, elemental sulfur and/or DMSO have shown to be excellent oxidants for the functionalization of acetophenones, dialkylketones, phenylacetylenes, malonic acids, and nitroalkanes …”