Efficient and Regioselective Synthesis of Phenothiazine via Ferric Citrate Catalyzed C-S/C-N Cross-Coupling

Abstract

Efficient C-S and C-N cross-coupling reactions have been developed for regioselective, scalable and environmentally benign synthesis of substituted phenothiazine derivatives. Cross-coupling reactions were demonstrated on various challenging substrates using non-toxic, highly economical, readily available ferric citrate as a catalyst to get desired product with high regioselectivity. Atom economy is the added advantage of this protocol since additional N-protection step before coupling and eventual deprotection of the same to obtain the desired product arenot required. To the best of our knowledge, this is the first report on the use of inexpensive ferric citrate as a catalyst without involving any ligand for the synthesis of regioselectively substituted phenothiazine.

Recent Advances in the Synthesis of Sulfonylureas

“…Methods for the synthesis of sulfonylureas normally involve coupling of sulfonamides to suitable carbon‐centered electrophiles such as isocyanates or activated carbamoyls bearing good leaving groups at the electrophilic carbonyl (Scheme 2). [16] In order to reinforce the nucleophilicity of sulfonamides they are usually deprotonated by a stoichiometric base albeit protocols not requiring the salification step have also been proposed in the literature [17,18] . A two‐step base‐mediated reaction between sulfonamides and isocyanates features the commercial, patented syntheses of sulfonylurea drugs.…”

Hydroxylamine‐Derived Reagent as a Dual Oxidant and Amino Group Donor for the Iron‐Catalyzed Preparation of Unprotected Sulfinamides from Thiols

“…Sulfonamides, sulfoximines and sulfimides (Scheme 1) are highly relevant for medicinal chemistry and crop protection because they exhibit interesting bioactivities [1, 7–10] . These exciting applications have been enabled by the development of efficient strategies for their synthesis [7, 8, 11–19] …”

“…The potential of sulfinamides thus seem to be far reaching and highlights the critical demand for the development of novel, practical methods to access them to facilitate their application in the various fields of medicinal chemistry, biology, and organic synthesis. However, such reactions clearly lag behind the development of countless methods to access other sulfur analogues such as sulfoximines, sulfonamides, sulfoxides, and sulfones [8, 17, 18, 51, 52] . Common procedures for synthesis of sulfinamides usually involve harsh multistep processes and start from less easily accessible starting materials, [53–68] whereas methods starting from commercially available thiols remain poorly developed [44, 61, 69, 70] .…”

Direct sulfonamidation of (hetero)aromatic C–H bonds with sulfonyl azides: a novel and efficient route toN-(hetero)aryl sulfonamides

“…7 Traditional synthesis of N-(hetero)aryl sulfonamides involves the reaction of sulfonyl chloride derivatives with aromatic amines, which suffers from the necessity for a strong base and generation of halide salts as the by-products. 8 Lately, new procedures towards the greener synthesis of the titled compounds have been developed, such as cross-coupling of primary sulfonamides and aryl electrophiles, 9 oxidative coupling of anilines with sodium sulfonates, 10 reduction coupling of nitroarenes with sodium sulfonates, 11 and direct sulfonamidation of aromatic C-H bonds with sulfonyl azides. Among others, transition-metal catalyzed denitrogenative coupling of arenes with sulfonyl azides offers prominent advantages of easily accessible starting materials, high efficiency, and no formation of toxic by-products (Fig.…”