Selective Cyclisation of 2-(2-Hydroxy-phenyl)-2,3-dihydro-1H-quinazolin-4 one with Formaldehyde and Isolation of Two Isomeric Oxazines

A novel series of oxazine-quinazoline compounds was designed and synthesized via the cyclization of 2-(2-hydroxyphenyl)-2,3-dihydro-1H-quinazolin-4-one (1) with formaldehyde, affording 12,12a-dihydro-5-oxa-6a,12-diaza-benzo[a]anthracen-7-one (2) and 10b,11-dihydro-6-oxa-4b,11-diaza-chrysen-12-one (3) in toluene and tetrahydrofuran, respectively.After the products were isolated, elemental analysis, GC-MS, ¹H and ¹³C NMR spectroscopy were used to confirm their chemical structures. For the synthesised oxazines, DFT calculations and molecular docking have been studied.The synthesised compounds showed better binding affinities toward DNA gyrase (PDB ID: 1KZN) and dihydrofolate reductase (PDB ID: 8SRW) in molecular docking studies, suggesting their potential antibacterial activity. Molecular dynamics (MD) simulations further validated stable protein–ligand interactions, highlighting the structural appropriateness of these molecules for biological applications. Collectively, these novel oxazine–quinazoline hybrids represent promising potential as antibacterial and anticancer agents and require further biological investigation.