Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities

BAYRAK H., DEMİRBAŞ A., Karaoglu S. A., DEMİRBAŞ N.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.44, no.3, pp.1057-1066, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 3
  • Publication Date: 2009
  • Doi Number: 10.1016/j.ejmech.2008.06.019
  • Journal Name: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1057-1066
  • Keywords: Isonicotinic acid hydrazide, 1,2,4-Triazole, 1,3,4-Oxadiazole, 1,3,4-Thiadiazole, Antimicrobial activity, ANTIBACTERIAL ACTIVITY, DERIVATIVES, ANTICANCER, AGENTS, ACID
  • Karadeniz Technical University Affiliated: Yes

Abstract

4-Phenyl-5-pyridin-4-yl-4H-1,2,4-triazole-3-thiol (3) was obtained in basic media via the formation of 2-isonicotinoyl-N-phenylhydrazine-carbothioamide (2), and converted to some alkylated derivatives (4a,b) and Mannich base derivatives (5a-c). 2-[(4-Phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]acetohydrazide (7) that was obtained by using compound 3 as precursor in two steps was converted to thiosemicarbazide derivative (8), Schiff base derivatives (9) and 5-([(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl)-1,3,4-oxadiazole-2-thiol (10). Moreover, 5-([(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl)-3-{[(2-morpholin-4-ylethyl)amino]methyl}-1,3,4-oxadiazole-2(3H)-thione (11) was synthesized via reaction of compound 10 with 2-(4-morpholino)ethylamine. The treatment of compound 8 with NaOH gave 4-(4-methylphenyl)-5-{[(4-phenyl-5-pyridine-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-4H-1,2,4-triayole-3-thiol (12), while the acidic treatment of compound 8 afforded 5-{[(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-2(4-methylphenyl)-amino-1,3,4-thiadiazole (14). N-Methyl derivative of compound 14 and a Mannich base derivative of compound 12 were synthesized from the reactions of these precursors with methyl iodide and methyl piperazine, respectively. 

All newly synthesized compounds were screened for their antimicrobial activities. The antimicrobial activity study revealed that all the compounds screened showed good or moderate activity except compounds 3, 5c, 7, 9c, 9e, 9g, 9h, 11, and 13. (C) 2008 Elsevier Masson SAS. All rights reserved.

4-Phenyl-5-pyridin-4-yl-4H-1,2,4-triazole-3-thiol (3) was obtained in basic media via the formation of 2-isonicotinoyl-N-phenylhydrazine-carbothioamide (2), and converted to some alkylated derivatives (4a,b) and Mannich base derivatives (5a-c). 2-[(4-Phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]acetohydrazide (7) that was obtained by using compound 3 as precursor in two steps was converted to thiosemicarbazide derivative (8), Schiff base derivatives (9) and 5-([(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl)-1,3,4-oxadiazole-2-thiol (10). Moreover, 5-([(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl)-3-{[(2-morpholin-4-ylethyl)amino]methyl}-1,3,4-oxadiazole-2(3H)-thione (11) was synthesized via reaction of compound 10 with 2-(4-morpholino)ethylamine. The treatment of compound 8 with NaOH gave 4-(4-methylphenyl)-5-{[(4-phenyl-5-pyridine-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-4H-1,2,4-triayole-3-thiol (12), while the acidic treatment of compound 8 afforded 5-{[(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-2(4-methylphenyl)-amino-1,3,4-thiadiazole (14). N-Methyl derivative of compound 14 and a Mannich base derivative of compound 12 were synthesized from the reactions of these precursors with methyl iodide and methyl piperazine, respectively.