Synthesis and research of the physical-chemical properties of 5-((2-bromphenyl)-4-amino-4H-1,2,4-triazole-3-ylthio)acetic acid salts

Authors

  • Ye. S. Pruglo Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2018.1.123588

Keywords:

2-bromophenyl, 1, 2, 4-triazole, physical-chemical properties, synthesis

Abstract

At this stage of the development of modern science the scientists get a lot of questions in the field of medicine and pharmacy, and one of the most important among them is the study and search of new ways of synthesis of high-performance and low-toxic substances. Special attention is paid to 1,2,4-triazole and xanthine. On their basis some medical drugs were made, which are widely used in medicine.

The aim of this work was the synthesis and study of properties of salts of 5-(2-bromophenyl)-4-amino-4H-1,2,4-triazole-3-ylthio)acetic acid.

Methods and results. As starting material theophylline was selected. Through a number of stages 5-(2-bromphenyl)-4-amino-4H-1,2,4-triazole-3-thion was obtained. By the reaction of neutralization the salts with organic and inorganic bases were obtained. The physical-chemical properties of the compounds were determined. The structure of the substances was confirmed by elemental analysis on an Elementar Vario L cube (CHNS) instrument; IR spectra (4000–400 cm-1) were taken on the ALPHA-T modules of the Bruker ALPHA FT-IR spectrometer. The 1H NMR spectra of the compounds were recorded using a Varian Mercury VX 200 spectrometer (solvent – DMSO-d6, internal standard: tetramethylsilane). The formation of salts was confirmed by the signals of the corresponding protonated amines. Chromato-mass spectral studies were carried out on the LC MS: Agilent 1260 Infinity HPLC System , ionization method – chemical ionization at atmospheric pressure (APCI).

Conclusions. The interaction of the resulting thiol with monochloracetic acid in aqueous solution with double quantity of alkali and subsequent neutralization leads to corresponding carboxylic acid obtaining. It was confirmed that the greatest outputs of salts as the reaction products were observed when using water as the solvent with the subsequent replacement of acetone. the optimum conditions of obtaining salts of 5-(2-bromophenyl)-4-amino-4H-1,2,4-triazole-3-ylthio)acetic acid with inorganic and organic bases were determined.

References

Taylor, A. P., Robinson, R. P., Fobian, Y. M., Blakemore, D. C., Jones, L. H., & Fadeyi, O. (2016) Modern advances in heterocyclic chemistry in drug discovery. Organic & Biomolecular Chemistry, 14(28), 6611–6637. doi: 10.1039/c6ob00936k.

Brown, D. G., & Bostrom, J. (2016) Analysis of past and present synthetic methodologies on medicinal chemistry: where have all the new reactions gone? J. Med. Chem., 59, 4443. doi: 10.1021/acs.jmedchem.5b01409.

Murty, M.S.R., Kesur, R. Ram, Rayudu, Venkateswara Rao, Yadav, J. S., Janapal, Venkateswara Rao, Pamanji, R., & Velatooru, L. R. (2012) Synthesis of New S-alkylated-3-mercapto-1,2,4-triazole Derivatives Bearing Cyclic Amine Moiety as Potent Anticancer Agents. Letters in Drug Design & Discovery, 9, 276–281. doi :10.2174/157018012799129882.

Mir, I., Siddiqui, M. T., & Comrie, A. (1970) Antituberculosis agents-I: -[5- (2-furyl)- 1,2,4-triazol-3-ylthio] acethydrazide and related compounds. Tetrahedron, 26, 5235–5238. https://doi.org/10.1016/S0040-4020(01)98732-0.

Yale, H. L., & Piala, J. J. (1966) Substituted s-triazoles and related compounds. J. Med. Chem., 9, 42–46. doi: 10.1021/jm00319a010.

Burch, H. A., & Smith, W. O. (1966) Nitrofuryl heterocycles. III. 3-Alkyl-5- (5-nitro-2-furyl)-1,2,4-triazoles and intermediates. J. Med. Chem., 9, 405–408. doi: 10.1021/jm00321a033.

Rollas, S., Kalyoncuoglu, N., Sur-Altiner, D., & Yegenoglu, Y. (1993) 5-(4- Aminophenyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones: synthesis and antibacterial and antifungal activities. Pharmazie, 48, 308–309.

Rudnicka, W., Foks, H., Janowiec, M., & Zwolska-Kwiek, Z. (1986) Studies of pyrazine derivatives. XXI. Synthesis and tuberculostatic activity of 4-aryl-1-pyrazinoylthiosemicarbazides and the products of their cyclization to 1,2,4-triazole-3-thione derivatives. Acta Pol. Pharm., 43, 523–528.

Mhasalkar, M. Y., Shah, M. H., Nikam, S. T., Anantanarayanan, K. G.; & Deliwala, C. V. (1970) 4-Alkyl-5-aryl-4H-1,2,4-triazole-3-thiols as hypoglycemic agents. J. Med. Chem., 13, 672–674. doi: 10.1021/jm00298a021.

Eweiss, N. F., Bahajaj, A. A., & Elsherbini, E. A. (1986) Synthesis of heterocycles. Part VI. Synthesis and antimicrobial activity of some 4-amino-5-aryl-1,2,4-triazole-3-thiones and their derivatives. Journal of Heterocyclic Chemistry, 23(5), 1451–1458. doi: 10.1002/jhet.5570230540.

Xie, W., Zhang, J., Ma, X., Yang, W., Zhou, Y., Tang, X., et al. (2015) Synthesis and Biological Evaluation of Kojic Acid Derivatives Containing 1,2,4-triazole as Potent Tyrosinase Inhibitors. Chemical Biology and Drug Design, 86(5), 1087–1092. doi: 10.1111/cbdd.12577.

Khan, Mahmood-Ul-Hassan, Akhtar, Tashfeen, Yasin, Khawaja, A., Al-Masoudi, Najim, A., Jones, Peter, G., & Hameed, Shahid (2010) Design, synthesis, and urease inhibition studies of a series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones. Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 65(2), 178–184.

How to Cite

1.
Pruglo YS. Synthesis and research of the physical-chemical properties of 5-((2-bromphenyl)-4-amino-4H-1,2,4-triazole-3-ylthio)acetic acid salts. Current issues in pharmacy and medicine: science and practice [Internet]. 2018Feb.16 [cited 2024Dec.27];(1). Available from: http://pharmed.zsmu.edu.ua/article/view/123588

Issue

Section

Synthesis of the biologically active compounds