Синтез і дослідження властивостей 3-тіосульфонілпохідних 4-(2-метоксифеніл)-5-алкіл(арил)-1,2,4-тріазолу

Abstract

Introduction. 1,2,4-Triazoles derivatives are known to a number of scientists thanks to the valuable properties that appear in the antimicrobial, antifungal, analgesic, anticancer, antiviral, antituberculosis, anti-inflammatory, anticonvulsant and antidepressant activities and effects on the central nervous system. Thus, 5-thiosulfonyl 1,2,4-triazole derivatives are a sufficiently light known class of compounds.Analysis of literature showed the perspective for pharmacology impact of the 1,2,4-triazolе fragment and sulfonic group combination within a single molecule.The aim of the study was the synthesis and properties of substances among 1,2,4-triazoles 3-thiosulfonyl derivatives.The 4-(2-methoxyphenyl)-5-methyl-1,2,4-triazole-3-thiol and 4-(2-methoxyphenyl)-5-phenyl-1,2,4-triazole-3-thiol were used as starting materials, which were synthesized by known methods, namely, nucleophilic substitution reactions (esterification, hydrazinolysis), nucleophilic addition and intramolecular cyclization.Investigations of reaction with sulfochlorides (4-toluensulfochloride, benzensulfochloride, 3-nitrobenzensulfochloride, 2-naphtholsulfohloride, butane-1-sulfochloride and other) were conducted before the studies to determine the optimal conditions for subsequent work. Materials and methods of the researchResearches of the compounds’ physical-chemical properties we conducted according to methods, described in the State Pharmacopoeia of Ukraine. The melting point defined by the open capillary method on the ITM (M) instrument. The structure of the compounds is confirmed by elemental analysis instrument Elementar Vario L cube (CHNS), IR spectra (4000-400 cm-1) have been removed on  the ALPHA-T (KBr, CHCl3/HPLC) module  by Bruker ALPHA FT-IR spectrometer. 1H NMR spectra of compounds have been recorded by means of “Mercury 400” (solvent - DMSO-d6 or DMSO-d6 + CCl4 spectrometer, the internal standard - tetramethylsilane). Chromatography-mass spectral researches have been conducted on the Agilent 1100 Series LC/MSD System instrument, the ionization method - chemical ionization at atmospheric pressure (APCI).Investigation of antimicrobial and antifungal action has been performed by disco-diffusion method on Mueller-Hinton medium using the following test strains of microorganisms: gram-positive cocci (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212), gram-negative bacillus (Enterobacter aerugenes, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922), facultative anaerobic gram-negative bacillus (Klebsiella pneumonia 12) and fungi (Candida albicans ATCC 885-653).ConclusionsIt was determined, that the best option of  the alkylation reactions passing of 4- (2-metoxyphenyl)-5-R-1,2,4-triazoles-3-thiol sulfochloride is a reception of the intermediate potassium salt output compound, with it’s next dissolving it in water and gradual addition of appropriate  sulfochloride in acetone to a solution.Microbiological screening results showed that the synthesized compounds do not show antibacterial and antifungal activity relatively the number of test-strains of microorganisms.  Исследованы реакции получения 3-тиосульфонилпроизводных 4-(2-метоксифенил)-5-метил-1,2,4-триазола и 4-(2-метоксифенил)-5-фенил-1,2,4-триазола. Изучены физико-химические свойства и антимикробная активность синтезированных соединений.Дослідили реакції отримання 3-тіосульфонілпохідних 4-(2-метоксифеніл)-5-метил-1,2,4-тріазолу та 4-(2-метоксифеніл)-5-феніл-1,2,4-тріазолу. Вивчили фізико-хімічні властивості й антимікробну активність синтезованих сполук