An efficient one-pot three-component synthesis of thiadiazole N-nucleosides with high atom economy from β-D-ribosylhydrazine, aryl thiamide, and aromatic aldehyde promoted by (diacetoxyiodo)benzene under microwave irradiation is reported. The strategy involves formation of thiourea derivatives by microwave-assisted addition of an arylisothiocyanate formed in situ by (diacetoxyiodo)benzene-promoted oxidative rearrangement of an aryl thiamide with Schiff bases of β-D-ribosylhydrazine and a substituted/unsubstituted aromatic aldehyde. The thiourea intermediate on intramolecular heterocyclization yielded thiadiazole N-nucleosides, 2-(arylimino)-3-(β-D-ribosyl)-5-aryl-1,3,4-thiadiazoles. The whole reaction sequence proceeded with quantitative transformation of reactants into thiadiazole N-nucleosides at an ambient temperature. The reaction sequence is supported by isolation of Schiff bases and their quantitative conversion into final product by reaction with arylisothiocyanate under the same reaction conditions.

Synthesis of Thiadiazole N-Nucleosides. -Title compounds (IV) are efficiently synthesized by an environmentally benign three-component one-pot cyclization procedure via Hofmann rearrangement of thiamide (II). A tentative reaction mechanism is given. -(SIDDIQUI*, I. R.; SIDDIQUI, N. A.; SHAMIM, S.; SHIREEN; SRIVASTAVA, A.; Nucleosides, Nucleotides Nucleic Acids 32 (2013) 8, 453-463, http://dx.