Synthesis, Characterization and Antimicrobial Analysis of a Novel Thioether via S-Alkylation of Methyl-4H-1,2,4-Triazole-3-Thiol with Methyl Iodide

Abstract

The development of structurally novel antimicrobial compounds remains important because of the continuing emergence of antimicrobial resistance and the limited effectiveness of some existing therapeutic agents. Heterocyclic compounds containing the 1,2,4-triazole nucleus have attracted considerable attention because of their diverse chemical and biological properties. In the present study, a novel sulfur-containing 1,2,4-triazole derivative, designated Compound AP, was prepared through S-alkylation of methyl-4H-1,2,4-triazole-3-thiol with methyl iodide under basic conditions. The synthesized compound was characterized by melting-point determination, Fourier-transform infrared spectroscopy (FT-IR), gas chromatography-mass spectrometry (GC-MS), proton nuclear magnetic resonance (¹H NMR), and carbon-13 nuclear magnetic resonance (¹³C NMR) spectroscopy. The Compound exhibited a melting range of 112–114 °C. The FT-IR spectrum showed characteristic absorptions associated with triazole C–H, aliphatic C–H, C=N, ring vibrations, and methyl deformation. GC-MS showed a molecular ion at m/z 129 together with characteristic fragment ions at m/z 114, 85, 72, 70, 59, and 58. The ¹H NMR spectrum displayed signals at δ 8.37, 7.79, 3.72, and 2.75 ppm, with the signal at δ 2.75 ppm assigned to the newly introduced S–CH₃ group. The ¹³C NMR spectrum showed resonances at δ 144.997, 141.342, 32.079, and 15.084 ppm, supporting the proposed molecular structure. Antimicrobial screening demonstrated concentration-dependent inhibition against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. The largest inhibition zones at 200 µg/mL were observed against B. subtilis (13 mm), followed by S. aureus and C. albicans (12 mm each). The reported MIC values ranged from 64–256 µg/mL, while MBC/MFC values ranged from 128–512 µg/mL. These findings indicate that S-alkylation of a methyl-1,2,4-triazole-3-thiol framework can produce a structurally defined thioether with measurable broad-spectrum antimicrobial activity and provide a basis for further structural optimization and biological investigation.