Structural and thermal properties of 3-substituted quinazolinone Schiff base conjugates†

Abstract

Quinazolinone Schiff base conjugates have recently attracted considerable attention from the scientific community due to their potential application as anti-cancer drugs and promising multidentate ligands. Unfortunately, reports dealing with the structural characterization of these compounds are incomprehensibly scarce. To explore the supramolecular features of these perspective compounds we have prepared and crystallized four quinazolinone Schiff base conjugates (1 = 3-{(E)-[(2-chlorophenyl)methylidene]amino}-2-methylquinazolin-4(3H)-one, 2 = 3-{(E)-[(2,4-dihydroxyphenyl)methylidene]amino}-2-methylquinazolin-4(3H)-one, 3 = 3-{(E)-[(2,3-dihydroxyphenyl)methylidene]amino}-2-methylquinazolin-4(3H)-one and 4 = 3-[(E)-benzylideneamino]-2-methylquinazolin-4(3H)-one). Single crystals were obtained by recrystallization of crude products from different solvents, and crystal structures were determined by single crystal X-ray diffraction. Considering their molecular structure, these compounds are similar, with the most pronounced difference being the dihedral angle between the two aromatic systems. In the crystal state, compounds with –OH groups on the benzene ring (2 and 3) are primarily connected by strong O–H⋯N hydrogen bonds, and unsubstituted (4) and Cl-substituted (1) compounds via N–H⋯O and C–H⋯O hydrogen bonds. Thermal analysis results have shown that among these compounds the 2,4-OH substituted 2 (226 °C) has the highest melting point, followed by 2,3-OH substituted 3 (201 °C), unsubstituted 4 (192 °C), and the Cl-substituted 1 (159 °C). Additional Hirshfeld surface analysis and intermolecular energy calculations indicate that hydrogen bonds have the largest impact on thermal stability and that dispersive interactions are important for stability, but can be sterically hindered by bulky substituents on aromatic systems.