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

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.

Fe/S-Catalyzed Redox Condensation of o-Nitrophenols with Isothiocyanates to 2-Aminobenzoxazoles.

As frequently encountered byproducts of isocyanate chemistry, hydrogen sulfide and related sulfur containing compounds should be treated in a safe way to lower their adverse health and environmental effects, especially in large scale syntheses. As a proof of concept, we report herein an example of in situ recycling of sulfur byproduct to reductant in the synthesis of bioactive 2-aminobenzoxazoles 3. Using an Fe/S catalytic system, this heterocyclic scaffold could be obtained from o-nitrophenols 1 with isothiocyates 2 via direct redox condensation consisting of reduction of the nitro group of 1 by the sulfur moiety of 2.

Synthesis of Thioureas, Thioamides, and Aza-Heterocycles via Dimethyl-Sulfoxide-Promoted Oxidative Condensation of Sulfur, Malonic Acids, and Amines.

Malonic acid and derivatives have been well-known to undergo monodecarboxylation under relatively mild conditions and have been exclusively used as a C2 synthon. We report herein their new application as a C1 synthon via double decarboxylation promoted by sulfur and dimethyl sulfoxide. In the presence of amines as nucleophiles, a wide range of thioureas and thioamides as well as N-heterocycles were obtained in good to excellent yields under mild heating conditions.