Hypervalent Iodine(III) Mediated Synthesis of 3-Substituted 5-Amino-1,2,4-thiadiazoles through Intramolecular Oxidative S–N Bond Formation

Abstract

An efficient synthesis of 3-substituted-5-arylamino-1,2,4-thiadiazoles through intramolecular oxidative S-N bond formation of imidoyl thioureas by phenyliodine(III) bis(trifluoroacetate) is reported. The protocol features a metal-free approach, broad substrate scope, very short reaction times, good to excellent yields, and simple starting materials.

Sunlight‐Driven Synthesis of 1,2,4‐Thiadiazoles via Oxidative Construction of a Nitrogen‐Sulfur Bond Catalyzed by a Reusable Covalent Organic Framework

“…Previous reports state that an ionic mechanism always involves oxidative N−S bond formation via cross‐dehydrogenative coupling of N−H and S−H bonds. However, based on the above control experiments, a radical mechanism is suggested for this transformation under sunlight‐driven aerobic oxidative conditions (Scheme ) .…”

“…Using our developed protocol, the 2D‐COF catalyst shows good recyclability and easy separation; and 3,5‐disubstituted 1,2,4‐thiadiazoles are smoothly prepared in water . Furthermore, a radical mechanism for this transformation is proposed by the results of control experiments, although an ionic mechanism always involves direct N−S bond formation via CDC process of N−H and S−H bonds by previous reports …”

Building 1,2,4‐Thiadiazole: Ten Years of Progress

“…Synthesis of 1,2,4‐thiadiazoles 20 through PIFA‐promoted oxidative S–N bond formation in imidoyl thioureas 19 …”

“…[28] One of the most recent and standout works concerning the synthesis of 1,2,4-thiadiazoles was carried out by Mariappan and collaborators. [29] Basically, this research led to the development of an efficient methodology to produce 3-substituted 5-(arylamino)-1,2,4-thiadiazoles 20 through intramolecular oxidative S-N bond formation in imidoylthioureas 19 through the action of phenyliodine(III) bis(trifluoroacetate) (PIFA). The cyclization protocol features a metal-free approach, broad substrate scope, very short reaction times, good to excellent yields (71-86 %), and simple starting materials (Scheme 8).…”

A continuous flow synthesis and derivatization of 1,2,4-thiadiazoles

“…The synthesis of 1,2,4-thiadiazoles can be accomplished by a variety of methods including oxidative ring closure, 11,12 multicomponent reactions 13 or [3+2]-cycloadditions. 14 A further option which is more amenable to subsequent functionalization on the heterocyclic scaffold is based on reacting various amidines with trichloromethane sulfenylchloride (5, Scheme 1).…”