Novel benzoyl and acetyl pyrazine-2-carbohydrazonamide hybrid derivatives: Experimental and theoretical insights

• Synthesis of Novel benzoyl and acetyl pyrazine-2-carbohydrazonamide derivatives using metallic Na-assisted interaction. • E- and Z-isomeric forms of some complexes in DMSO‑ d 6 have been studied, providing insights into their isomerization behavior. • Characterization using FTIR, 1 H NMR, and UV–vis spectroscopy, along with X-ray diffraction and Hirshfeld surface analysis. • Theoretical studies highlight the dominant role of hydrogen bonding interactions in governing the crystal packing. A series of novel benzoyl and acetyl pyrazine-2-carbohydrazonamide hybrid derivatives, namely N’ -benzoylpyrazine-2-carbohydrazonamide ( 1 ), N’ -(4-methylbenzoyl)pyrazine-2-carbohydrazonamide ( 2 ), N’ -(2-phenylacetyl)pyrazine-2-carbohydrazonamide ( 3 ) and N’ -(2-(1 H -indol-3-yl)acetyl)pyrazine-2-carbohydrazonamide ( 4 ), were readily obtained using a metallic Na-assisted interaction of 2-cyanopyrazine with benzohydrazide, 4-methylbenzohydrazide, 2-phenylacetohydrazide or 2-(1 H -indol-3-yl)acetohydrazide in dry MeOH. Compounds 1–4 were studied by a set of physical measurements, including FTIR, 1 H NMR and UV–vis spectroscopy, while their crystal structures were elucidated by single crystal X-ray diffraction and the corresponding crystal packing was further studied in detail using the Hirshfeld surface analysis. Compounds 3 and 4 were found to adopt both the E - and Z -isomeric forms in DMSO‑ d 6 . Molecules of the title compounds are linked via N H⋯O and N H⋯N hydrogen bonds and π⋯π interactions, yielding supramolecular aggregates. As it was found by the Hirshfeld surface analysis, molecules of 1–4 mainly interact through the H⋯X (X = H, C, N and O) and C⋯X (X = C and N) contacts. The molecular interactions were quantified and compared using DFT calculations, molecular electrostatic potential (MEP) analysis and quantum theory of atoms in molecules (QTAIM) analysis, highlighting the dominant role of hydrogen bonding interactions in governing the crystal packing.