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

• Main Authors: D. V. Dovbnia, A. H. Kaplaushenko, Yu. S. Frolova
• Format: Article
• Language: English
• Published: Zaporozhye State Medical University 2021-03-01
• Series: Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki
• Subjects: 2-((5-(2; 4- and 3; 4-dimethoxyphenyl)-3h-1; 2; 4-triazole-3-yl)thio)acetic acids; esters; toxicity indicators
• Online Access: http://pharmed.zsmu.edu.ua/article/view/226741/226514
• ISSN: 2306-8094; 2409-2932

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.