Synthesis of some new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole derivatives and investigation of their antimicrobial activities

DEMİRBAŞ A., Sahin D., DEMİRBAŞ N., Karaoglu Ş.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.44, no.7, pp.2896-2903, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 7
  • Publication Date: 2009
  • Doi Number: 10.1016/j.ejmech.2008.12.005
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2896-2903
  • Keywords: 1,2,4-Triazole, 1,3,4-Thiadiazole, Mannich base, Schiff base, Antimicrobial activity, ANTIBACTERIAL ACTIVITY, MANNICH-BASES, ANTITUMOR ACTIVITIES, AGENTS, OXAZOLIDINONES, INHIBITORS
  • Recep Tayyip Erdoğan University Affiliated: Yes


4-Amino-2-[(5-arylamino-4,5-dihydro-1,3,4-thiadiazol-2-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones(3a-c) were obtained in acidic media via the formation of 2-[(4-amino-3-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetyl]-N-arylhydrazinecarbothioamides (2a-c), and then, compound 3b was converted to methylated derivative, 4. The basic treatment of carbothioamide derivatives, 2a-c, afforded 4-amino-2-[(4-aryl-5-sulphanyl-4H-1,2,4-triazol-3-yl)methyl]-5-(4-methylphenyl)-2,4-dihyro-3H-1,2, 4-triazol-3-ones (5a-c). The alkylation reactions of compounds 4H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one derivatives (Sa-c) were performed by using methyl iodide or ethyl bromide in the presence of sodium ethoxide, while the treatment of the same intermediates, 5a-c, with aromatic aldehydes produced 2-{[4-(4-aryl)-5-sulphanyl-4H-1,2,4-triazol-3-yl]methyl}-4-(arylmethylene)amino-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (8a-d). The synthesis of 4-amino-(or arylideneamino)-5-(4-methylphenyl)-2-{[(4-methylpiperazin-1-yl or morpholin-4-ylethyl)methyl]-4-aryl-5-thioxo-4,5 -dihydro-1H-1,2,4-triazol-3-yl}methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones (7a, b and 9) was performed by a one pot three-component Mannich reaction involving the corresponding compounds, 4-(substituted)amino-4H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one derivatives 5a, b and 8a, methylpiperazine or 2-(4-morpholino)ethylamine and formaldehyde. The newly synthesized compounds were well characterized by elemental analyses, IR, (1)H NMR, (13)C NMR and mass spectral studies. They were also screened for their microbial activities. The antimicrobial activity study revealed that some of which 2a, c, 3c, 5a-c, 8a-d showed good activity against a variety of microorganisms. (C) 2008 Elsevier Masson SAS. All rights reserved.