Amide‐Linked Oxadiazole–Diacylhydrazide Derivatives: Synthesis, Characterization, and Antibacterial Evaluation

ABSTRACT A series of novel amide‐linked 1,3,4‐oxadiazole–diacylhydrazide conjugates were synthesized through EDC/DMAP‐mediated amide coupling between alkoxybenzoyl hydrazides ( IXa–d ) and acetamido‐functionalized 1,3,4‐oxadiazolethiol derivatives ( Xa–d ). This convergent synthetic strategy employed mild reaction conditions and afforded the target compounds in good yields. The structures of all synthesized compounds were unambiguously confirmed by comprehensive spectroscopic analysis, including IR, 1 H NMR, and 1 3 C NMR. Characteristic chemical shifts and coupling patterns in NMR spectra confirmed the successful formation of the amide linkage and the integrity of both heterocyclic moieties. The molecular architecture features an electron‐rich alkoxybenzene ring coupled to an electron‐deficient oxadiazole scaffold via a flexible diacylhydrazide‐amide linker, representing a unique structural motif. Preliminary structure‐activity relationship analysis based on antibacterial screening revealed selective activity against Gram‐positive bacteria ( Staphylococcus aureus and Enterococcus faecalis ), suggesting that the electronic and structural properties of the hybrid scaffold influence biological selectivity. This work provides a practical and efficient synthetic route to multifunctional oxadiazole–diacylhydrazide derivatives with potential applications in medicinal chemistry.