Substituent and Solvent Effects on Intermolecular Interactions in Crystals of N-Acylhydrazone Derivatives: Single-Crystal X-ray, Solid-State NMR, and Computational Studies

New crystalline forms of hydrated and anhydrous N-acylhydrazones are reported. The studied crystal structures were determined by single-crystal X-ray diffraction at 90 or 100 K. Transferred aspherical atom model (TAAM) structure refinements were performed with the aid of the most recent version of the University at Buffalo Databank (UBDB). The resulting crystal structures were analyzed in terms of molecular conformations, intermolecular interaction energies, and crystal packing motifs. For this purpose, solid-state NMR studies and theoretical calculations were conducted supplementarily. It was found that all studied hydrazones adopt the E configuration around the azine N-N bond and imino N=C function in the solid state, whereas the hydrazide N-N-C=O moiety exhibits the E and Z arrangement in the N-acyl and N-aroyl derivatives, respectively. The constrained energy scans confirmed the E conformation of the hydrazide unit and the E arrangement of pyridine and hydrazone N atoms as the most stable ones. The association modes in the studied crystals are dominated by strong hydrogen bonds of the N-H center dot center dot center dot O or N-H center dot center dot center dot N-type involving the amide group as a proton donor. Consequently, as indicated by lattice energy calculations, a significant increase in the crystal cohesive energy per asymmetric unit is observed when water molecules are incorporated into the crystal structure, because this enables efficient saturation of the hydrogen bond acceptor and donor atoms. On the other hand, a substantial contribution of pi center dot center dot center dot pi stacking interactions to the overall stabilization of the crystal nets was also found. Thus, when more bulky phenyl substituents are introduced, the cohesive energy becomes more favorable.