Regioselective Synthesis of 2,5-Disubstituted-1,3,4-thiadiazoles and 1,3,4-Oxadiazoles via Alkyl 2-(Methylthio)-2-thioxoacetates and Alkyl 2-Amino-2-thioxoacetates

Abstract

An acid-catalyzed regioselective cyclization reaction of 2,5-disubstituted-1,3,4-thiadiazoles and 1,3,4-oxadiazoles has been developed. The synthetic precursors alkyl 2-(methylthio)-2-thioxoacetates/alkyl 2-amino-2-thioxoacetates react efficiently with acyl hydrazides, which transformed into a series of dehydrative and desulfurative products with employment of p-TSA and AcOH through a regioselective cyclization process. The alkyl 2-amino-2-thioxoacetate pathway generates excellent yield among the mentioned procedures. The reported methods are operationally simplistic and highly efficient with metal-free conditions and demonstrate significant functional group compatibility. Regioselective cyclized products were confirmed by single-crystal X-ray diffraction studies.

An efficient synthesis of mono-, di-, and tri-substituted 1,3-thiazoles employing functionalized thioamides as thiocarbonyl precursors

“…We prepared the desired alkyl 2-amino-2-thioxoacetates according to our previously reported protocol. 26 Thus, alkyl 2-(methylthio)-2-thioxoacetates 1 on treatment with stoichiometric amounts of ammonium chloride and anhydrous sodium acetate in DMF furnished alkyl 2-amino-2-thioxoacetates 2 (Scheme 1). Reaction conditions: 1 (10 mmol, 1 equiv.…”

Regioselective Synthesis of 2,4- and 2,5-Disubstituted 1,3-Thiazoles from 2-Oxo-2-(amino)ethanedithioates via Base-Catalyzed Cyclization

“…Paper / PSP / Special Topic Template for SYNTHESIS Thieme intermediates. [26][27][28][29][30][31][32] In the present study, synthesis of 2,4-and 2,5-disubstituted thiazoles, molecular geometry, FMOs, global and local reactive descriptors, MEP, NCI, and docking analysis were studied and reported.…”