Synthesis and structure of salts of 2-(((3-mercapto-5-methyl-4H-1,2,4-triazole-4-yl)imino)methyl)benzoic acid

Authors

  • T. V. Hlazunova Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2020.1.198113

Keywords:

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

Abstract

 

Modern pharmacy and medicine can offer a substantial number of highly effective synthetic medicines. A great portion of these medicines falls into the group of 1,2,4-triazole derivatives.

1,2,4-Triazoles are distinguished by important pharmacological properties, including antimicrobial, antifungal, anti-inflammatory, hypoglycemic, while also being capable of stimulating the central nervous system.

Undoubtedly, a constant increase of number of publications regarding the synthesis, characterization of biological, chemical, and physical properties of 1,2,4-triazole derivatives by both foreign and Ukrainian researchers promotes the search for promising compounds of this class of heterocyclic compounds globally.

The purpose of our work was to synthesize and characterize structures of salts of 2-(((3-mercapto-5-methyl-4H-1,2,4-triazole-4-yl)imino)methyl)benzoic acid, as potentially bioactive compounds.

Materials and methods. The physical-chemical characterization of the synthesized compounds was conducted according to the guidelines provided by the State Pharmacopoeia of Ukraine. The melting point was determined using MPA100 apparatus. Elemental analysis was held using Elementar Vario L.cube analyzer. 1H NMR spectra were recorded using Varian Mercury VX-200 spectrometer (1Н, 200 MHz). Chromatographic and mass-spectrometric data were obtained using Agilent 1260 Infinity LC system coupled with Agilent 6120 mass spectrometer.

Results and discussion. 2-(((3-Mercapto-5-methyl-4H-1,2,4-triazole-4-yl)imino)methyl)benzoic acid was used as the starting compound for the synthesis of the new structures. In order to afford the desired compounds, the starting material was subjected to salt formation reactions with ammonium hydroxide, sodium and potassium hydroxides, methylamine, ethylamine, dimethylamine, 1-propylamine, 2-propylamine, monoethanolamine, diethylamine, tert-butylamine, piperidine, piperazine, morpholine, 2-methylpiperidine, and 4-methylmorpholine whether in alcohol or water solutions.

Conclusions. The chemical experiments resulted in 16 new substances, salts of 2-(((3-mercapto-5-methyl-4H-1,2,4-triazole-4-yl)imino)methyl)benzoic acid. The chemical structure of the synthesized compounds was confirmed using instrumental methods, including 1H NMR spectroscopy, LC-MS, and elemental analysis. The obtained salts will be used in further pharmacological research.

References

Shcherbak, M. A., Kaplaushenko, A. G., Maletskiy, N. N., & Sharaya, Ye. A. (2014). Issledovaniya po sozdaniyu lekarstvennoi formy na osnove 3-(4-nitrofenil)-5-(nonilsul'fonil)-1,2,4-triazol-4-amina [The research on creation the dosage form based on 3-(4-nitrophenyl)-5-(nonylsulfonyl)-1,2,4-triazol-4-amine]. Zaporozhye Medical Journal, 4(85), 82-85. [in Russian].

Kaplaushenko, A. H. (2013). Doslidzhennia zi stvorennia novoho oryhinalnoho vitchyznianoho likarskoho zasobu na osnovi 1,2,4-triazolu [The research of creating a new original domestic drug based on 1,2,4-triazole]. Naukovyi zhurnal MOZ Ukrainy, 2(3), 115-121. [in Ukrainian].

Kravchenko, T. V., Panasenko, O. I., & Knish, E. G. (2016). Sytnez ta fizyko-khimichni vlastyvosti 4-((R)amino)-5-metyl-4H-1,2,4-tryazol-3-tioliv [Synthesis and physicochemical properties of 4-((R)amino)-5-methyl-4H-1,2,4-triazole-3-thiols]. Farmatsevtychnyi zhurnal, (6), 55-59. [in Ukrainian].

Shcherbyna, R. O. (2014) Analiz farmakolohichnoi aktyvnosti pokhidnykh 1,2,4-triazolu [Analysis of pharmacological activity of 1,2,4-triazole derivatives]. Farmatsevtychnyi chasopys, (4), 145-150. [in Ukrainian].

Ihnatova, T. V. Kaplaushenko, A. H., & Frolova, Yu. S. (2019). Stvorennia, doslidzhennia fizychnykh i khimichnykh vlastyvostei 2-((4-R-5-fenetyl-4H-1,2,4-triazol-3-il)tio)etanovykh(propanovykh, benzoinykh)kyslot i solei 2-((4-R-5-fenetyl-4H-1,2,4-triazol-3-il)tio)etanovykh kyslot [Creation, study of physical and chemical properties of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanоic(propanоic, benzoic)acids and salts of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic acid]. Current Issues in Pharmacy and Medicine: Science and Practice, 12(2), 123-128. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2019.2.170973

Shcherbyna, R. O., Panasenko, O. I., & Knysh, Ye. H. (2016). Vyvchennia antyoksydantnoi aktyvnosti solei 2-((4-R-3-(morfolinometylen)-4H-1,2,4-tryazol-5-il)tio)atsetatnykh kyslot [The studying of antioxidant activity of salts 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5-yl)thio)acetic acids]. Ukrainian Biopharmaceutical Journal, 1(42), 37-40. [in Ukrainian].

Shcherbyna, R. O., Kapelyanovych, Ye. V., Pruhlo, Ye. S., Panasenko, O. I., & Knysh, Ye. H. (2014). Doslidzhennia aktoprotektornoi aktyvnosti pokhidnykh 4-R-3-(morfolinometylen)-1,2,4-triazol-5-tiolu [The studying of actoprotective action of 4-R-3-(morpholinomethylene)-1,2,4-triazole-5-thiole derivatives]. Odeskyi medychnyi zhurnal, 6(146), 19-22. [in Ukrainian].

Aksyonova, I. I., Shcherbyna, R. O., Panasenko, O. I., Knysh, Ye. H., & Aksyonov, 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] Ukrainian Biopharmaceutical Journal, 6(35), 78-82. [in Ukrainian].

Murty, M. S. R., Ram, K. R., Rao, R. V., Yadav, J. S., Rao, J. V., & 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(3), 276-281. https://doi.org/10.2174/157018012799129882

Shcherbyna, R. O. (2017). Syntez i fizyko-khimichni vlastyvosti v riadu solei 2-((4-R-3-(morfolinometylen)-4H-1,2,4-triazol-5-il)tio)atsetatnykh kyslot [Synthesis, physical and chemical properties of 2-((4-R-3-(morfolinomethylen)-4H-1,2,4-triazole-5-yl)thio)acetic acid salts]. Current Issues in Pharmacy and Medicine: Science and Practice, 10(1), 4-8. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2017.1.93424

Shcherbyna, R. O., Panasenko, O. I., Knysh, Ye. H., & Varynskyy, B. О. (2014). Syntez i fizyko-khimichni vlastyvosti 2-((4-R-3-(morfolinometylen)-4H-1,2,4-triazol-5-il)tio) atsetatnykh kyslot [Synthesis and physical-chemical properties of 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5yl)thio)acetic acid]. Current Issues in Pharmacy and Medicine: Science and Practice, 3(16), 18-21. [in Ukrainian].

Hulina, Yu. S., & Kaplaushenko, A. H. (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-(1N-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-ylthio)-acetic(propanoic),2-,4-(5-(1Н-tetrazol-1-ylmethyl)-4-phenyl-4Н-1,2,4-triazol-3-yltiomethyl)-benzoic acids and their salts]. Current Issues in Pharmacy and Medicine: Science and Practice, 2(21), 32-37. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2016.2.71115

Samelyuk, Yu. H., & Kaplaushenko, A. H. (2015). Hostra toksychnist 5-(2-, 3-, 4-metoksyfenil, (3,4,5-trymetoksyfenil)-)-1,2,4-triazol-3-tioniv ta yikh tiopokhidnykh [Acute toxicity of 5-(2-, 3-, 4-methoxyphenyl, (3,4,5-trimethoxyphenyl)-)-1,2,4-triazole-3-thiones and their thioderivatives]. Current Issues in Pharmacy and Medicine: Science and Practice, 3(19), 57-60. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2015.3.52660

Saidov, T. V., & Sverdlova, O. V. (1995). Prakticheskoe rukovodstvo po molekulyarnoi spektroskopii [Practical guide to molecular spectroscopy]. Izdatel'stvo Sankt-Peterburgskogo Universiteta. [in Russian].

Kazitsyna, L. A. (1979). Primenenie UF-, IK-, YaMR- i MASS-spektroskopii v organicheskoi khimii [Application of UV, IR, NMR and mass spectroscopy in organic chemistry] (2th ed.). Izdatelstvo Moskovskogo Universiteta. [in Russian].

Varynskyy, B. О., Knysh, Ye. H., Parchenko, V. V., Panasenko, O. I., & Kaplaushenko, A. H. (2015). Vyvchennia zakonomirnostei utrymuvannia potentsiinykh likarskykh substantsii riadu 1,2,4-tryazol-3-iltioatsetatnykh kyslot ta yikh solei metodom VERKh/DMD-MS [The study of retention regularities for the potential drug substances of 1,2,4-triazol-3-ylthioacetic acids and their salts series by the method of HPLC/DAD-MS]. Zhurnal orhanichnoi ta farmatsevtychnoi khimii, 13(4), 68-75. [in Ukrainian].

Downloads

How to Cite

1.
Hlazunova TV. Synthesis and structure of salts of 2-(((3-mercapto-5-methyl-4H-1,2,4-triazole-4-yl)imino)methyl)benzoic acid. Current issues in pharmacy and medicine: science and practice [Internet]. 2020Mar.10 [cited 2024Mar.29];13(1). Available from: http://pharmed.zsmu.edu.ua/article/view/198113

Issue

Section

Original research