Synthesis, physical-chemical properties of 2-((5-(adamantan-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acid esters

Abstract

The nitrogen-containing heterocyclic systems from the class of 1,2,4-triazole derivatives, which exhibit wide range of actions, occupy special place among the variety of heterocyclic compounds. Derived biologically active substances are actively introduced into practice as new original and effective drugs. We were interested in esters of 2-((5-(adamantan-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids, which exhibit high biological activity and can be intermediates for the synthesis of amides, hydrazides, ylidenderivatives of corresponding acids.The aim of this work is the synthesis of new esters of 2-((5-(adamantan-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids and the establishment of their physical-chemical properties.Materials and methods. Melting point was determined by open capillary method on the device OptiMelt MPA100. The elemental composition of the synthesized compounds was determined on the universal analyzer ElementarVario ЕL cube (CHNS) (standard – sulfanilamide). 1H NMR spectra were recorded on spectrometer Varian Mercury VX-200 (1H, 200 MHz) in the solvent dimethyl sulfoxide-d6 (tetramethylsilane internal standard) and decoded using a program ADVASP(tm) Analyzer program (Umatek International Inc.). Chromato-mass-spectral studies were performed on hazarding chromatograph Agilent 1260 Infinity HPLC equipped with mass spectrometer Agilent 6120 (ionization electro-spray (ESI).The results and discussion. Synthesis of 11 new compounds, namely esters of 2-((5-(adamantan-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids was carried out by two methods. According to the A method the alkylation of previously synthesized 3-(adamantan-1-yl)-1H-1,2,4-triazole-5-thiol was performed with the use of corresponding methyl ester of 2-chloroacetic acid and the presence of equivalent amount of sodium hydroxide. The B method involves the etherification of 2-((5-(adamantan-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acid with the use of methyl, ethyl, i-propyl, n-propyl and n-butyl alcohols in the presence of concentrated sulfuric acid. Compounds, which were obtained by different methods, do not give depression of the melting point. It should be noted that the practical yield of the reaction according to the A method is a little bit higher in comparison with the B method. Conclusions. The study of 11 new synthesized compounds, namely esters of 2-((5-(adamantan-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids has been performed.The structure of the synthesized compounds has been confirmed by modern instrumental methods of analysis (1H NMR spectroscopy, IR spectrophotometry, gas chromatography-mass spectrometry and elemental analysis).