Synthesis, structure and properties of N-R-amides and hydrazides of 2-[4-R-5-(theophylline-7ʹ-yl)-1,2,4-triazole-3-ylthio]acetic acid
DOI:
https://doi.org/10.14739/2409-2932.2017.3.112748Keywords:
theophylline, 1, 2, 4-triazole, amides, hydrazide, synthesis, physical propertiesAbstract
One of the most important tasks of modern pharmaceutical science is the search for new biologically active substances, which have high efficacy and low toxicity. Derivatives of 1,2,4-triazole and theophylline are a promising class of compounds for synthesis of biologically active substances on their basis, due to a wide range of biological activity of these heterocycles’ derivatives
The purpose of work is the development of efficient methods for synthesis of new amides and hydrazides of 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid (R = CH3, C2H5, C6H5) with variation of the reactions conditions and the study of physical properties of the obtained compounds.
Materials and methods. As a key source of reagents we used 7'-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline and esters of 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid, which were obtained by known methods from readily available raw materials. By heating in ethanol medium the corresponding amines (ammonia, methylamine, ethylamine, monoethanolamine, diethanolamine), n-propyl ether 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid a series of amides of 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid were obtained. Hydrazide of 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid was synthesized by interaction of corresponding esters of 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid with an aqueous solution of hydrazine hydrate in ethanol medium. The structure of the obtained compounds is confirmed by data of elemental analysis, 1H NMR spectroscopy and IR-spectrophotometry. The individuality of substances is established by using high performance liquid chromatography with diode-array and mass spectrometric detection.
Results. Optimal methods of obtaining amides and hydrazides of 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid have been developed. Getting investigated amides by two alternative ways of synthesis, it was established that the initial interaction of thiol with 2-chloracetamide proceeds with high yield product of the reaction compared to the reaction between a corresponding ester with ammonia.
Conclusions. 15 amide and 3 hydrazide 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acids have been synthesized, their structure has been established and physical properties have been studied.
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