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

Abstract

We herein report efficient methods for synthesis of 2,4- and 2,5-disubstituted-1,3-thiazoles 3(a-i) and 5(a-k) by the cyclization of 2-oxo-2-(amino)ethanedithioates with TosMIC and α-haloketones in high yields. The structures 3a and 5a were confirmed based on X-ray crystallographic studies. In addition, investigation of ground state geometry, electronic and molecular structural properties, FMOs, global reactivity descriptors, MEP and NCI analyses predicted to access the information related to the stability, reactivity, and strength of the interactions present in the molecules by quantum chemical calculations. Further, the potency of derivatives tested against the SARS-Cov2 receptor (PDB ID: 7mc6) via molecular docking approach with binding scores of –6.0 to –8.4 kcal/mol.

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

“…In addition to our on-going work on the synthesis of novel heterocyclic molecules and unique synthetic techniques utilizing a variety of intermediates such as methyl dithiocarboxylates, xanthate esters, and 2-oxo-2-(amino) ethanedithioates, [16][17][18][19][20][21][22][23][24][25] herein, we developed an operationally simple and novel method for the synthesis of mono-, di-and tri-substituted thiazoles using alkyl 2-amino-2-thioxoacetates intermediates.…”