An efficient synthesis of novel difenoconazole analogues is described. The synthetic route involves a Friedel-Crafts acylation on triclosan molecule followed by a sequential azide formation/CuAAC reaction in a single synthetic operation leading to 1-(2‑chloro-5-(2,4-dichlorophenoxy)-4-hydroxyphenyl)-2-(4-(1-hydroxycyclohexyl)-1,2,3-triazol-1-yl)ethan-1-one derivatives in 50–96% yields. Synthesized 1,2,3-triazoles were evaluated for activity against diverse strains including bacterial strains of Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 700891 and fungal strain Candida albicans ATCC 90028. A 1,2,3-triazole derivative bearing a CH(OH)CH3 group displayed a selective activity against Methicillin-resistant Staphylococcus aureus (MRSA) comparable to Gentamicin standard. This selectivity can be attributed to a conformation adopted by 5‑chloro-2-(2,4-dichloro-phenoxy)-phenol core enabling non-covalent interactions presenting a higher activity based on Fukui function on triazole ring.