Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using Purine Nucleoside Phosphorylase.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task.

Syntheses, crystal structures and Hirshfeld surface analysis of 2-(benzyl-sulfan-yl)-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole and 2-[(2-chloro-6-fluoro-benz-yl)sulfan-yl]-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole.

The title compounds were synthesized by alkyl-ation of 5-[(4-di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole-2-thiol with benzyl chloride or 2-chloro-6-fluoro-benzyl chloride in the presence of potassium carbonate. The yields of 2-(benzyl-sulfan-yl)-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole, CHNOS (I), and 2-[(2-chloro-6-fluoro-benz-yl)sulfan-yl]-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole, CHClFNOS (II), were 96 and 92%, respectively. In the crystal structures of (I) and (II), C-H⋯π inter-actions are observed between neighboring mol-ecules.

DFT and TD-DFT study of isomeric 5-(pyridyl)-1,3,4-oxadiazol-2-thiones and 2-methylthio-5-(pyridyl)-1,3,4-oxadiazoles.

Internal rotations of pyridine fragment around single bond of isomeric 5-(2', 3' and 4'-pyridyl)-1,3,4-oxadiazol-2-thiones and 2-methylthio-5-(2', 3' and 4'-pyridyl)-1,3,4-oxadiazoles have been performed by DFT (B3LYP) and MP2 methods with RHF/6-31G(d,p) basis set. It was found that the MP2 barrier height lies a few below than DFT barrier heights for all studied compounds. In the molecule of 2-methylthio-5-(2'-pyridyl)-1,3,4-oxadiazole an anomeric effect detected due to a lone pair-lone pair interaction of pyridine and N4 oxadiazole nitrogen atoms.