Synthesis, characterization and computational studies of new naphthoquinones fused isoxazoles by the regiospecific tandem sonogashira-cyclization reaction

The fast methodology of tandem Sonogashira-cyclisation reaction of 2-iodo-3‑methoxy-1,4-naphthoquinone with a series of alkynes followed by the addition of hydroxylamine hydrochloride provided a small library of seven novel 1,4-naphthoquinones fused with regiospecific NO isoxazole with moderate yield, up to 62%. The characterization by nuclear magnetic resonance (1H and 13C NMR), gas chromatography-mass spectrometry (GC-MS), and high-resolution electrospray ionization mass spectrometry (ESI-HRMS) was carried out with these seven compounds. The computational analyses were done by density functional theory (DFT) using B3LYP/6–311G* and the geometrical properties, the molecular electrostatic potential (MEP), the frontier molecular orbitals (FMO), and some global parameters were examined for the seven final compounds, the seven intermediaries of the reaction proposed in this study and the seven isomers ON of the isoxazole fused with the 1,4-naphthoquinone. The comparisons of the calculated parameters between the isomers ON and NO demonstrated the superior stability of the isomer NO and their higher tendency of polarizable that support the importance of the study and the potential to have biological activity.