Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenyl) methyl)-4R-4H-1,2,4-triazole-3-yl)thio)acetic acids and its salts

Today’s a creation of new domestic medicines is very important problem for pharmacy and medicine. Therefore, it is relevant to synthesize new domestic biologically active compounds. It is known that a large number of new 3-thio and 4-amino derivatives on the basis of 1,2,4-triazole have recently been synthesized, among which compounds with high pharmacological activity have been found. Based on the experience of previous studies and with the aim of creating new original drugs, our goal was to synthesize 2-((5-(hydroxy(phenyl)methyl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids series and to obtain salts on its basis, which have high indicators of pharmacological activity based on the literature data.


Introduction
Today a creation of new domestic medicines is very important problem for pharmacy and medicine. Therefore, the synthesis of new domestic biologically active compounds is relevant.
Over the last ten years, the number of publications about various aspects of chemistry and use of triazole has been doubled and continues to increase. Publications of recent years [1][2][3][4][5][6] show that the heterocycle with the 1,2,4-triazole nucleus was proven to be well-established as a broad spectrum of biologically active compounds. This fact points to the interest in these compounds as potential objects of the modern pharmaceutical market, namely, compounds that contain both heterocycles.

The aim and objectives of the study
The main aim of the work is the purposeful synthesis of potential low-toxic and highly effective compounds with a wide spectrum of pharmacological activity among derivatives of 5-(hydroxy(phenyl)methyl)-4-R-4H-1,2,4-triazole-3thione, confirmation of their individuality and structure, as well as the study of physical-chemical properties, which will provide prospects for further pharmacological screening.

Materials and methods of research
It is known that a large number of new 3-thio and 4-amino derivatives [7] were recently synthesized on the basis of 1,2,4-triazole, and compounds with high pharmacological activity are found among them. In planning the experiment, a generalization was made regarding the dependence of toxicity and pharmacological activity of substances, which have been synthesized recently on their structure [8,9]. Relying on the experience of previous studies [10] with the aim of creating new original drugs, the goal was to synthesize a series of 2-((5-(hydroxy(phenyl)methyl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids on the basis of which salt is obtained, which, according to literature [11], has high pharmacological activity.
The chemical names of the compounds are given in accordance with the IUPAC nomenclature (1979) and the IUPAC (1993) recommendations.
The study of some physical and chemical properties of the synthesized compounds was carried out in accordance with the methods presented in the State Pharmacopoeia of Ukraine (SPU, version 1). The melting temperature was determined by the capillary method (2.2.14) with the PTP (M) device.
Elemental composition of new compounds was established with elemental analyzer ELEMENTAR vario EL cube (sulfanilamide was a standard).
IR-spectra were recorded in tablets of potassium bromide (concentration of 1 %) with a Specord M-80 spectrophotometer in the area of 4000-500 cm -1 (scan condition: dense program 3.0, constant time -τ = 3 s, scan time 33 min.). The tablets were prepared by joint grinding 200 mg of potassium bromide and 2 mg of the test compound, followed by compression.

Problems of pharmacy
The solution was boiled to acid medium (5 hours), filtered, 50 ml of water was added and left for 24 hours. Precipitates of the reaction products were filtered and dried. White crystalline substances are slightly soluble in water, soluble in alkaline and alkaline metal carbonate solutions and in organic solvents. 2-((5-(hydroxy(phenyl) methyl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetic acids (3,4) were purified by recrystallization from 40 % ethanol for the analysis.
The yellow crystalline substance is soluble in water and in organic solvents. The compound (4) was recrystallized from a mixture of water:ethanol:acetone (1:1:1) for analysis.
Yellow crystalline substances are soluble in water and in organic solvents. Compounds (7,14,15) were recrystallized from a mixture of ethanol:acetone (1: 1) for analysis.
2. The structure of the synthesized substances was confirmed by elemental analysis and IR-spectrophotometry, and their individuality was confirmed by the chromatographic method.