Synthesis and transformation in the series of 2-((5-(2,4- and 3,4-dimethoxyphenyl)-3H-1,2,4-triazole-3-yl)thio)acetic acids
Keywords:2-((5-(2,4- and 3,4-dimethoxyphenyl)-3H-1,2,4-triazole-3-yl)thio)acetic acids, esters, toxicity indicators
The aim of the work is to develop preparative methods for the synthesis of 2-((5-(2,4- and 3,4-dimethoxyphenyl)-3H-1,2,4-triazole-3-yl)thio)acetic acids, to study the esterification reaction in this regard, to study physical and chemical properties of the obtained substances, and to predict their toxicity.
Materials and methods. Compounds were synthesized using reagents and solvents qualified as “ch.p.”. The IUPAC nomenclature as supplemented was used during the preparation. The melting temperature was determined with the capillary method according to HFC (2.2.14) on the device PTP (M). Elemental analysis was determined with the ELEMENTAR vario EL cube analyzer (manufactured in Germany) (standard – sulfonamide). IR spectra were recorded using spectrophotometer Specord M-80 (manufactured in Germany) within the range of 4000–500 cm-1 (scanning was performed under the following conditions: slot program 3.0, time constant – τ = 3 s, scanning time 34 min, samples were analyzed in the form of tablets with potassium bromide). 1H NMR spectra were recorded using Varian VXR-300 spectrophotometer (manufactured in the USA), dimethyl sulfoxide-D6 solvent, and tetramethylsilane was used as an internal standard. The spectra were decoded using the computer program ADVASP 1.43. Thin layer chromatography was performed using Sorbfil plates (analytical, size 10 × 15 cm, base: polymer substrate, sorbent: silica gel STX-1A, grain: 5–17 μm, layer thickness: 110 m combination – silicazole).
Results. The synthesis of new 2-((5-(2,4- and 3,4-dimethoxyphenyl)-3H-1,2,4-triazole-3-yl)thio)acetic acids was carried out. These products became a basis for synthesis of a number of relevant esters. Physical and chemical properties were investigated for the synthesized compounds. The structure of the obtained substances was confirmed by elemental analysis, IR-spectroscopy, 1H NMR-spectrometry, and their individuality were established by thin-layer chromatography. Computer GUSAR-online prediction of acute toxicity of 2-((5-(2,4- and 3,4-dimethoxyphenyl)-3H-1,2,4-triazole-3-yl)thio)acetic acids and their esters was performed.
Conclusions. Preparative methods for the synthesis of 2-((5-(2,4- and 3,4-dimethoxyphenyl)-3H-1,2,4-triazole-3-yl)thio)acetic acids have been developed, for which esterification reactions have been studied. Thus, physical and chemical properties of the received substances were investigated, and indicators of their toxicity were predicted.
Syntez ta doslidzhennia biolohichno aktyvnykh pokhidnykh 1,2,4-triazol-3-tionu, shcho mistiat metoksyfenilni zamisnyky. Dys. kand. farm. nauk: 15.00.02. [Synthesis and study of biologically active derivatives of 1,2,4-triazole-3-thione containing methoxyphenyl substituents] (Dissertation PhD). Zaporizhzhia State Medical University. [in Ukrainian].
Kaplaushenko, A. H., Knysh, E. H., Panasenko, O. I, Sameliuk, Yu. H., Kucheriavyi, Yu. M., Shcherbak, M. O., Kaplaushenko, T. M., Rud, A. M., & Hulina, Yu. S. (2016). Praktychne znachennia ta zastosuvannia pokhidnykh 1,2,4-triazolu [Practical significance and application of 1,2,4-triazole derivatives]. Zaporizhzhia: ZSMU. [in Ukrainian].
Kaplaushenko, A. G. (2009). Metody syntezu ta biolohichna aktyvnist 1,2,4-tryazol-3-tioniv [Synthesis methods and biological activity of 1,2,4-triazol-3-thions]. Ukrainskyi biofarmatsevtychnyi zhurnal, (4), 48-53. [in Ukrainian].
Kaplaushenko, A. G. (2015). Khimichni vlastyvosti amino- i tiozamishchenykh 1,2,4-triazoliv [Chemical properties of amino and thio-substituted 1,2,4-triazoles]. Current issues in pharmacy and medicine: science and practice, (1). 101-106. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2015.1.41702
Kaplaushenko, A. G. (2013). Vykorystannia pokhidnykh 1,2,4-triazolu yak takykh, shcho shyroko zastosovuiut u medytsyni, ta stvorennia potentsiinykh likarskykh zasobiv na osnovi danoho heterotsyklu [The use of 1,2,4-triazole derivatives as those, that are widely used in medicine, and the creation of potential medicines based on this heterocycle]. Scientific journal of the Ministry of Health of Ukraine, (3), 152-159. [in Ukrainian].
Kazitsyna L. A., & Kupletskaya N. B. (1979). Primenenie UF-, IK-, YaMR- i mass-spektroskopii v organicheskoi khimii [Application of UV, IR, NMR and mass spectroscopy in organic chemistry]. Moscow: Moscow State University. [in Russian].
GUSAR-оnline. (n.d.). Way2Drug.com. http://www.way2drug.com/gusar/acutoxpredict.html
Sidorov, K. K. (1973). O klassifikatsii toksichnosti yadov pri parenteral'nykh sposobakh vvedeniya [About the poison toxicity classification in parenteral administration methods]. Toksikologiya novykh promyshlennykh veshchestv, 13, 45-71. [in Russian].
How to Cite
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)