Synthesis of novel 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones derivatives

Authors

  • A. A. Safonov Zaporizhzhia State Medical University, Ukraine,
  • A. V. Nevmyvaka Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2020.1.198087

Keywords:

1, 2, 4-triazole, thiones, acids, salts, heterocyclic compounds

Abstract

 

A wide range of biological activity of 1,2,4-triazole derivatives (anti-inflammatory, antiviral, antitumor, immunostimulating, etc.) and the availability of sources for their preparation determine the prospects of using compounds of this class to create modified derivatives based on them and, as a result, medicines. Derivatives of 1,2,4-triazole have already established themselves both in the agricultural sector and in veterinary medicine and pharmacy.

The aim of work was to synthesize 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones, 2-((5-(2-bromophenyl)-4-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acids and their salts.

Materials and methods. 3-(2-Bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones (4a-4c) were synthesized by refluxing 1 mol 2-(2-bromobenzoyl)-N-substitutedhydrazinecarbothioamides (3a-3c) with 2 mol KOH in water medium and after cooling neutralized with acetic acid.

2-((5-(2-Bromophenyl)-4-substituted-4H-1,2,4-triazole-3-yl)thio)acetic acids (5a-5c) were obtained by refluxing the solution of 0,1 mol NaOH and substances 4a-4c respectively. It was dissolved in 2-propanol medium with 0,1 mol 2-chloroacetic acid. 2-((5-(2-Bromophenyl)-4-substituted-4H-1,2,4-triazole-3-yl)thio)acetic acid salts (6a-6o) were synthesized by adding organic amines or inorganic salts to substances 5a-5c respectively in 2-propanol or water medium. The elemental analysis of synthesized compounds was established by the universal analyzer Elementar Vario L cube (CHNS). The 1H spectra (at 400 MHz and 100 MHz) were recorded in DMSO-d6 on a Varian MR-400 spectrometer and analyzed with the ADVASP™ Analyzer program. The completeness of the reactions and the individuality of the resulting compounds were controlled by the gas chromatograph Agilent 7890B with a 5977B mass spectrometry detector.

 

Results. It was synthesized new 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thionesand there derivatives, the structure of compounds was confirmed using Elemental analysis (CHNS), 1HNMR and Chromatographic mass spectral analysis.

Conclusions. As a result, 21 novel compounds of 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones were synthesized and characterized.

References

El-Wahab, H. A. A., Hamdy, A. -R. M., Gamal-Eldin, S. A., & El-Gendy, M. A. (2011). Synthesis, biological evaluation and molecular modeling study of substituted 1,2,4-triazole-3-acetic acid derivatives. Der Pharma Chemica, 3(6), 540-552. http://derpharmachemica.com/archive.html

Kaplaushenko, A. H., Knysh, E. H., Panasenko, O. I, Sameliuk, Yu. H., Kucheriavyi, Yu. M., Shcherbak, M. O., … Hulina, Yu. S. (2016). Praktychne znachennia ta zastosuvannia pokhidnykh 1,2,4-triazolu [Practical value and application of derivatives of 1,2,4-triazole]. Zaporizhzhia. [in Ukrainian].

Hulina, Yu. S., & Kaplaushenko, А. G. (2018). Synthesis, physical and chemical properties of 5-((1Н-tetrazole-1-yl)methyl)-4-R-4Н-1,2,4-triazole-3-thiols and their chemical transformations. Biopharmaceutical journal, 1(10), 26-30.

Rud, A. M., Kaplaushenko, A. G., & Yurchenko, I. O. (2018). Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenyl)methyl)-4R-4H-1,2,4-triazole3-yl)thio)acetic acids and its salts. Zaporozhye medical journal, 20(1), 105-109. https://doi.org/10.14739/2310-1210.2018.1.122126

Wu, J. W., Yin, L., Liu, Y. Q., Zhang, H., Xie, Y. F., Wang, R. L., & Zhao, G. L. (2019). Synthesis, biological evaluation and 3D-QSAR studies of 1,2,4-triazole-5-substituted carboxylic acid bioisosteres as uric acid transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia associated with gout. Bioorganic & Medicinal Chemistry Letters, 29(3), 383-388. https://doi.org/10.1016/j.bmcl.2018.12.036

Hassan, A. A., Mohamed, N. K., Aly, A. A., Tawfeek, H. N., Brase, S., & Nieger, M. (2019). Eschenmoser-Coupling Reaction Furnishes Diazenyl-1,2,4-triazole-5(4H)-thione Derivatives. Chemistryselect, 4(2), 465-468. https://doi.org/10.1002/slct.201802870

Moreno-Fuquen, R., Arango-Daravina, K., Becerra, D., Castillo, J. C., Kennedy, A. R., & Macias, M. A. (2019). Catalyst- and solvent-free synthesis of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide through a microwave-assisted Fries rearrangement: X-ray structural and theoretical studies. Acta Crystallographica Section C-Structural Chemistry, 75, 359-371. https://doi.org/10.1107/s2053229619002572

Hulina, Yu. S., & Kaplaushenko, A. G. (2016). Syntez i fizyko-khimichni vlastyvosti 2-(5-(1H-tetrazol-1-ilmetyl)-4-R-4H-1,2,4-triazol-3-iltio)-atsetatnykh(propanovykh),2-,4-(5-(1H-tetrazol-1-ilmetyl)-4-fenil-4H-1,2,4-triazol-3-iltiometyl)-benzoinykh kyslot ta yikh solei [Synthesis and physical-chemical properties of 2-(5-(1Н-tetrazol-1-ylmethyl)-4-R-4Н-1,2,4-triazol-3-yltio)-acetic (propanoic),2-,4-(5-(1Н-tetrazol-1-ylmethyl)-4-phenyl-4Н-1,2,4-triazol-3-yltiometil)-benzoic acids and their salts]. Current issues in pharmacy and medicine: science and practice, 2, 32-37. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2016.2.71115

Bushueva, I. V., Parchenko, V. V., Shcherbyna, R. O., Safonov, A. A., Kaplaushenko, A. G., Gutyj, B. V., Hariv, I. I.(2017). Trifuzol - new original veterinary grug. Journal of Faculty of Pharmacy of Ankara University, 41(1), 42-49. https://doi.org/10.1501/Eczfak_0000000594

Tkachenko, A., Zazharsky, V., Bilan, M., & Kovaleva, L. (2010). Some peculiarities of bovis tuberculosis display in long not favourably farm. News of Dniproptrovsk State Agrarian and Economic University, (1), 100-103.

Aksonova, I. I., Shcherbyna, R. O., Panasenko, O. I., Knysh, Y. H., & Aksonov, I. V. (2014). Doslidzhennia riststymuliuiuchoi aktyvnosti pokhidnykh 1,2,4-tryazolu na prykladi nasinnia soniashnyka prostoho [The investigation of growth-stimulating activity of derivatives of 1,2,4-triazole on seeds of sunflower simple]. Ukrainskyi biofarmatsevtychnyi zhurnal, (6), 78-82. [in Ukrainian].

Rud, A. M., Kaplaushenko, A. G., Pruglo, Ye. S., & Frolova, Yu. S. (2018). Vstanovlennia pokaznykiv diuretychnoi dii (3-tio-4-R-4N-1,2,4-triazol-5-il)(fenil) metanoliv ta yikh pokhidnykh [Establishment of diuretic activity indicators for (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols and their derivatives]. Current issues in pharmacy and medicine: science and practice, 11(2), 215-219. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2018.2.134004

Downloads

How to Cite

1.
Safonov AA, Nevmyvaka AV. Synthesis of novel 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones derivatives. Current issues in pharmacy and medicine: science and practice [Internet]. 2020Mar.10 [cited 2024May24];13(1). Available from: http://pharmed.zsmu.edu.ua/article/view/198087

Issue

Section

Original research