Crystallographic and Theoretical Analysis of a Spirohydantoin Derivative: 3-(4-tert-Butylbenzoyl)-1,3-diazaspiro[4.5]decane-2,4-dione

Providing structural information on drug-like compounds is a significant step in efforts to develop innovative drugs with balanced solubility, cell permeability and target binding. In this paper, a new cyclohexane-5-spirohydantoin tethered with a 4-tert-butylbenzoyl group was synthesized and its crystal structure was determined using the single crystal X-ray diffraction. The Hirshfeld surface analysis was used to gain a preliminary insight into the proportion and nature of the intermolecular interactions in the crystal structure, while their quantitative description is further presented in terms of a systematic analysis of dimeric motifs representing different recognition modes. A combination of N–H∙∙∙O and C(sp3)–H∙∙∙O hydrogen bonds, C(sp3)–H∙∙∙π, lone-pair∙∙∙π and π∙∙∙π stacking interactions links the molecules into a bilayer having two carbonyl O atoms exposed to the exterior. Further stacking of the bilayers occurs through C(sp3)–H∙∙∙O hydrogen bonds involving these O atoms as acceptors, C(sp3)–H∙∙∙π and π∙∙∙π stacking interactions between the phenyl groups. The molecular electrostatic potential surface map reveals that the carbonyl O atoms of the hydantoin ring and the phenyl ring are electrophilic centers, while the N1–H1 group is a nucleophilic center. The calculated HOMO and LUMO energies were used to semiquantitatively estimate the global reactivity descriptors suggesting the soft nature of the molecule.