Synthesis and properties of 5-(((5-amino-1,3,4-thiadiazole-2-yl)thio)methyl)-4-phenyl-1,2,4-triazole-3-thione and its some S-derivatives


  • A. S. Hotsulia Zaporizhzhіa State Medical University, Ukraine,
  • S. O. Fedotov Zaporizhzhіa State Medical University, Ukraine,



5-aminothiadiazole, 1, 2, 4-triazole, physical-chemical properties



Increased attention to thiadiazole and 1,2,4-triazole derivatives is determined by the extensive structural modification capabilities of heterocyclic system derivatives and their high pharmacological potential. Synthesis of new molecules containing, along with the 1,2,4-triazole moiety, thiadiazole is a promising trend in the field of biologically active substances.The purpose of this work was to study the reaction of nucleophilic substitution of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione with haloalkanes and to establish the structure of the obtained compounds.

Materials and methods. Thiosemicarbazide was used as the key starting reagent. As a result of the reaction of the starting material with carbon disulfide in dimethylformamide, a thione was obtained which was further reacted with the iso-propyl ester of the chloroethane acid. The resulting ester was used for further transformations using hydrazinolysis reaction, nucleophilic addition, and intramolecular alkaline heterocyclization. The alkylderivatives of the obtained 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were synthesized by reaction with bromoalkanes, in an alcohol medium with an equimolecular amount of alkali. The structure of the synthesized compounds was confirmed by modern physical-chemical methods of analysis: 1H NMR spectroscopy, IR spectrophotometry, and elemental analysis data. The individuality of substances was established by means of high-performance liquid chromatography.

Results. The method of obtaining 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione has been optimized. The optimal conditions for the synthesis S-alkylderivatives of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were determined. The structure of the synthesized compounds was established and their physical properties were investigated.

Conclusions. A number of S-alkylderivatives of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were obtained and their structure was confirmed by modern physical-chemical methods of analysis


Abdelriheem, N. A., Mohamed, A. M. M., & Abdelhamid, A. O. (2017). Synthesis of Some New 1,3,4-Thiadiazole, Thiazole and Pyridine Derivatives Containing 1,2,3-Triazole Moiety. Molecules, 22(2), Article 268.

Altintop, M. D., Can, O. D., Ozkay, U. D., & Kaplancikli, Z. A. (2016). Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents. Molecules, 21(8), Article 1004.

Castelino, P. A., Dasappa, J. P., Bhat, K. G., Joshi, S. A., & Jalalpure, S. (2016). Some novel Schiff bases of 1,2,4 triazole bearing haloarene moiety-synthesis and evaluation of antituberculosis properties and neutrophil function test. Medicinal Chemistry Research, 25(1), 83-93.

El-Sherief, H. A. M., Youssif, B. G. M., Abbas Bukhari, S. N., Abdelazeem, A. H., Abdel-Aziz, M., & Abdel-Rahman, H. M. (2018). Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors. European Journal of Medicinal Chemistry, 156, 774-789.

Hotsulia А. S., Fedotov S. O. (2019). Synthesis and properties of some S-derivatives of 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione. Current issues in pharmacy and medicine: science and practice, 12(3), P. 245-249.

Kucukguzel, S. G., & Cikla-Suzgun, P. (2015). Recent advances bioactive 1,2,4-triazole-3-thiones. European Journal of Medicinal Chemistry, 97, 830-870.

Li, Y. S., Tian, H., Zhao, D. S., Hu, D. K., Liu, X. Y., Jin, H. W., Song, G. P., & Cui, Z. N. (2016). Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors. Bioorganic & Medicinal Chemistry Letters, 26(15), 3632-3635.

Oh, T., Hayat, F., Yoo, E., Cho, S. N., Sheen, Y. Y., Kim, D. K., & Choo, H. Y. P. (2015). Antitubercular Activities of the Novel Synthesized 1,2,4-Triazole Derivatives. Bulletin of the Korean Chemical Society, 36(1), 43-51.

Olesiejuk, M., Kudelko, A., Swiatkowski, M., & Kruszynski, R. (2019). Synthesis of 4-Alkyl-4H-1,2,4-triazole Derivatives by Suzuki Cross-Coupling Reactions and Their Luminescence Properties. Molecules, 24(3), Article 652.

Rao, D. V. N., Prasad, A. R. G., Spoorthy, Y. N., Rao, D. R., & Ravindranath, L. (2015). Synthesis, Characterization and Antimicrobial Evaluation of Substituted 1,2,4-Triazole Thiones Containing Pyrazole Moiety. Journal of Clinical and Analytical Medicine, 6(5), 590-595.

Saidov, N. B., Kadamov, I. M., Georgiyants, V. A., & Taran, A. V. (2014). Planning, Synthesis, and Pharmacological Activity of Alkyl Derivatives of 3-Mercapto-4-Phenyl-5-Arylaminomethyl-1,2,4-Triazole-(4H). Pharmaceutical Chemistry Journal, 47(11), 581-585.

Sayed, S., Khalil, M., & Raslan, M. (2014). Synthesis of pyrazole, 1,3-dithiolan and thiophene derivatives pendant to thiazolo[2,3-c]-1,2,4-triazole moiety. European journal of chemistry, 5(2), 356-362.

Seelam, N., Shrivastava, S. P., Prasanthi, S., & Gupta, S. (2016). Synthesis and in vitro study of some fused 1,2,4-triazole derivatives as antimycobacterial agents. Journal of Saudi Chemical Society, 20(4), 411-418.

Singh, R., Kashaw, S., Mishra, V., Mishra, M., Rajoriya, V., & Kashaw, V. (2018). Design and synthesis of new bioactive 1,2,4-triazoles, potential antitubercular and antimicrobial agents. Indian journal of pharmaceutical sciences, 80(1), 36-45.

Szulczyk, D., Tomaszewski, P., Jozwiak, M., Koziol, A. E., Lis, T., Collu, D., Iuliano, F., & Struga, M. (2017). Synthesis and Biological Activities of Ethyl 2-(2-pyridylacetate) Derivatives Containing Thiourea, 1,2,4-triazole, Thiadiazole and Oxadiazole Moieties. Molecules, 22(3), Article 409.

Tatar, E., Kucukguzel, S. G., Karakus, S., De Clercq, E., Andrei, G., Snoeck, R., Pannecouque, C., Oktem Okullu, S., Unubol, N., Kocagoz, T., Kalayci, S., Sahin, F., & Kucukguzel, I. (2015). Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents. Marmara Pharmaceutical Journal, 19(2), 88-102.


How to Cite

Hotsulia AS, Fedotov SO. Synthesis and properties of 5-(((5-amino-1,3,4-thiadiazole-2-yl)thio)methyl)-4-phenyl-1,2,4-triazole-3-thione and its some S-derivatives. Current issues in pharmacy and medicine: science and practice [Internet]. 2020Jul.3 [cited 2024Feb.26];13(2). Available from:



Original research