Synthesis and studies of triazolothiadiazines. An approach toward new biologically active heterocyclic compounds

The first synthesis of the 1,2,4-triazolo[5,1-b][1,3,5] thiadiazine and some of its analogues, possessing a thiadiazino-s-triazole bicyclic ring system was performed starting from 2-benzyltriazole-5-thiol. The title compounds 6a-g were synthesized via double Mannich reaction in one step in high yields. The route employed the nucleophilic addition of two moles of CH2O onto the NH and SH groups of the triazole ring followed by cyclocondensation with elimination of two H2O molecules to form the thiadiazine derivatives. Examination of the biological activity against the selected fungi and bacteria is the main goal of this article. The tested compounds against fungi revealed that the title compounds were active against most strains of fungi, while the tested compounds were inactive against Gram +Ve and Gram -Ve bacteria. All new synthesized compounds were confirmed using the spectral analyses and the direction of the cyclization was confirmed using the molecular mechanics calculations.