Hirshfeld surface analysis and energy framework for crystals of quinazoline methylidene bridged compounds

Among the drugs used worldwide, 50-60% are isolated or produced from plants; about half of these drugs are alkaloids or nitrogen-containing compounds. Within the alkaloids, quinazoline derivatives are of particular interest as they have a wide range of biological activity [1,2]. Their versatility stimulates the synthesis of new compounds containing the quinazoline fragment, with the aim of even increased biological activity. Continuing our research in this direction [3], the crystal structures of 3- (3,4-dimethoxyphenylethylamino)-methylidene-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-9-one (1) and 4-(3,4-dimethoxyphenylethylamino)-methylidene-2,3,4,10-tetrahydro-1H-pyrido [2,1-b] -quinazolin-10-one (2) were studied. The structures of compounds 1 and 2 were established by single crystal X-ray diffraction. Their molecular and crystal structures were described in the context of intra and inter-molecular interactions and of stereoisomerism.

For molecular crystals, Hirshfeld surface analyses may provide insight into intermolecular interactions, and energy framework analyses allow to quantify different contributions to the overall energy. These analyses were performed to pinpoint intermolecular interactions in 1 and 2. According to our results, the molecules are associated by intra- and intermolecular hydrogen bonds, C—H···π and C—O···π stacking interactions. The three-dimensional Hirshfeld surface analysis and two-dimensional fingerprint plots revealed that the structures are dominated by H···H, H···C/C···H and H···O/O···H contacts. The intermolecular energy analysis revealed a significant contribution of electrostatic and dispersion components for the stabilization of molecular packing.