Synthesis and physical-chemical properties of 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5yl)thio)acetic acid
DOI:
https://doi.org/10.14739/2409-2932.2014.3.30016Keywords:
Synthesis, Derivatives, 1, 2, 4-triazolesAbstract
The creation and improvement of the original domestic medicines is anactual problem of medical and pharmaceutical industries. Chemistry of heterocyclicsystems attracts scientists all over the world, as it is associated with a number of properties of this class of compounds which allow to use them for various purposes. It is known that the morpholine salts of 2-((4-R-5-R1-4H-1,2,4-triazoles-3-yl)thio)acetic acids exhibit low toxicity and pronounced pharmacological effect. The additional morpholine moiety in the 1,2,4-triazole’s nucleusshould lead to compounds with high biological activity.
The aim of researchis the synthesis of 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5-yl)thio)aceticacidsand determination of its physical-chemical properties.
Materials and methods.The determinationof physical-chemical propertiesof the obtained compounds has been carried out according to the methods listed in the State Pharmacopoeia of Ukraine. The determinationof melting temperature has been performed for the synthesized compounds (device OptiMelt Stanford Research Systems MPA100). The structure of the compoundshas been confirmed by 1H NMR spectroscopy (Mercury 400), chromatography-mass spectrometry (Agilent 1260 Infinity device with mass detector Agilent 6120 LC / MS) and elemental analysis (ElementarVario L cube).
Results.14 new synthesized compounds, namely isopropyl 2-morpholinoacetate, 2-morpholinoacetohydrazide, N-R-2-(2-morpholinoacetyl)hydrazinecarbothioamides, 2-(2-morpholinoacetyl)-hydrazinecarbothioamide, 3-(morpholinomethyl)-4-R-4H-1,2,4-triazole-5-thiolesand2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5-yl)thio)aceticacid(where, R=H, CH3, C2H5,C6H5) have been studied.The fragmentation of 2-((4-ethyl-3-(morpholinomethyl)-4H-1,2,4-triazol-5-yl)thio)acetic acid has been carried out usingmethod of LC/MS and fragment ions have been identified. The structure of the synthesized compounds in all cases has been confirmed by modern instrumental methods of analysis, and data connections can be used in further biological studies.
Conclusion.The preparative methods of synthesis of 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5-yl)thio)aceticacidsthat can be used for chemical modeling of new biologically active compounds are described. The structure of the synthesized compounds has been established by complex modern methods of investigation, namely: 1H NMR-spectroscopy, chromatography-mass spectrometry and element analysis.
References
Shcherbyna, R. O. (2014). Syntez, peretvorennia, fizyko-khimichni ta biolohichni vlastyvosti pokhidnykh 2-(4N-1,2,4-triazol-3-iltio)atsetaldehidu. (Dis…kand. farm. nauk). [Synthesis, transformation, physico-chemical and biological properties of derivatives of 2-(4H-1,2,4-triazoles-3-iltio) acetaldehyde Dr. farm. sci. diss.]. Zaporozhye. [in Ukrainian].
Popiolek, L., Kosikowska, U., Mazur, L., Dobosz, M., & Malm, A. (2013). Synthesis and antimicrobial evaluation of some novel 1,2,4-triazole and 1,3,4-thiadiazole derivatives. Medicinal Chemistry Research, 22(7), 3134–3147. doi: 10.1007/s00044-012-0302-9.
Sajdov, T., Sverdlova, O., & Bakhshiev, N. (1995). Prakticheskoe rukovodstvo po molekulyarnoj spektroskopii [A Practical Guide to Molecular Spectroscopy]. Saint Petersnurg: Izd-vo Sankt-Peterburgskogo universiteta. [in Russian].
Kazicyna, L., & Kupleckaya, N. (1979) Primenenie UF-, IK-, YaMR- i MASS-spektroskopii v organicheskoj khimii [Application of UV, IR, NMR and mass spectroscopy in Organic Chemistry].Moskow: University of Moscow. [in Russian].
Kaplaushenko, A. (2012). Syntez, budova i biolohichna aktyvnist pokhidnih 4-mono- ta 4,5-dyzamishchenykh 1,2,4-triazol-3-tionu. (Dis… dokt. farm. nauk). [Synthesis, structure and biological activity of 4-mono-and 4,5-disubstituted 1,2,4-triazoles-3-thione. Dr. farm. sci. diss.]. Zaporozhye. [in Ukrainian].
Kaplaushenko, A., Parchenko, V., Scherbyna, R., Panasenko, O., Knysh, Y., Belienichev, I., & Pavlov, S. (2012). Use of morpholinium 2-(5-(4-pyridyl)-4-(2-methoxyphenyl)-1,2,4-triazole-3-ylthio)acetate or piperidinium 2-(5-(furan-2-yl)-4-phenyl-1,2,4-triazole-3-ylthio)acetate as neurotropic agents. 76334. Biul. 24. [in Ukrainian].
Kumar, S., Prasad, R., & Chandrashekar, S. (2013). Synthesis and pharmacological evaluation of novel 4-isopropylthiazole-4-phenyl-1,2,4-triazole derivatives as potential antimicrobial and antitubercular agents. Medicinal Chemistry Research, 22(2), 938–948. doi: 10.1007/s00044-012-0092-0.
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