Synthesis, antimicrobial and antifungal activity of 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles

Abstract

To select a molecule that could become a promising pharmacological agent, chemists use already-known heterocyclic bases by adding pharmacologically active groups. One such heterocyclic system is 1,2,4-triazole base, on the basis of which a huge number of biologically active compounds have already been found. It is known that 1,2,4-triazole derivatives show a fairly high antimicrobial and antifungal effect while remaining low-toxic compounds and 5-alkylthio-1,2,4-triazoles exhibit antimicrobial and antifungal activity. Based on the literature search, it can be concluded that 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles are insufficiently studied.

The aim of the work was to synthesize and investigate antimicrobial and antifungal activity among 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles.

Materials and methods. It was used 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol as a starting substance, which was synthesized by previously described techniques. 3-(2-Bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles were obtained by alkylation of the starting thiol with halohenalkanes (according to the first method) and the addition of hydrochloric acid in an alcoholic medium, then subsequent heating in microwave synthesis system (by the second method). To study the antimicrobial and antifungal activity of the newly synthesized 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles, the method of serial dilutions was used according to guidelines.

Results. 3-(2-Bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles were obtained by two methods: a) an equivalent amount of halohenalkane was added to 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol (I) (solvent – KOH pre-dissolved in 2-propanol). Boiled to pH = 7; b) 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol (I) (solvent – methyl or 1-propyl alcohol and 10 drops of HCl) was heated in Milestone Flexi Wave microwave synthesis system. Reaction conditions: The mixture was heated for 45 minutes at a temperature of 150 °C, a pressure 14.4 bar, ΔMW ≈ 200 W. The completeness of the reaction was determined using a gas chromatograph Agilent 7890B with a mass spectrometric detector 5977B. Antimicrobial and antifungal activity of 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles (6 new compounds) was investigated. The most active compound with antifungal and antimicrobial effect was IIi. Substances IIa–IIe had moderate antimicrobial effect.

Conclusions. New 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles were synthesized by two methods. The antimicrobial and antifungal activity was investigated for the obtained compounds. The most active compound was 3-(2-bromophenyl)-5-(decylthio)-4-phenyl-4H-1,2,4-triazole (IIi). Some conclusions were drawn regarding the dependence of “structure – antimicrobial and antifungal effect”: the antimicrobial effect increased with the length of the carbon radical; changing the decyl radical to another one in the molecule 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazole reduced antifungal activity.