Exploring the structure and reactivity of organic crystals: a combined crystallographic and quantum chemical analysis of a 1,5-benzodiazepine-based heterocycle

Organic crystals, composed of small organic molecules held together by noncovalent intermolecular interactions, exhibit a diverse range of properties. Careful consideration of these interactions enables scientists to tailor crystal properties for specific applications. This study investigated the structural and electronic features of a 1,5-benzodiazepine-based heterocycle, 1-((3-(2-chlorophenyl)isoxazol-5-yl)methyl)-4-(2-hydroxyphenyl)-1H-benzodiazepin-2-one. Employing a multifaceted approach combining structural and quantum chemical methods, we elucidated the molecular geometry, crystal packing, and chemical reactivity in both mono- and dimeric forms. We revealed a network of noncovalent interactions governing the solid-state structure, including C–H⋯O and C–H⋯N hydrogen bonds, alongside π-interactions (C–H⋯π and π–π stacking). Multi-approach quantum mechanics analysis using dispersion-corrected DFT (ωB97X-D/aug-cc-pVTZ) unveiled the nature and energetics of these interactions, incorporating natural bond orbital analysis, quantum theory of atoms in molecules, and Hirshfeld surfaces. Conceptual DFT identified the studied heterocycle as a moderate electrophile and strong nucleophile in polar organic reactions, while Parr functions pinpoint favourable sites for electrophilic and nucleophilic attacks.