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 N -O isoxazole with moderate yield, up to 62%. The characterization by nuclear magnetic resonance (H-1 and C-13 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 O-N of the isoxazole fused with the 1,4-naphthoquinone. The comparisons of the calculated parameters between the isomers O-N and N-O demonstrated the superior stability of the isomer N-O and their higher tendency of polarizable that support the importance of the study and the potential to have biological activity. (c) 2023 Elsevier B.V. All rights reserved.

Automated summary

A fast tandem reaction was used to synthesize a series of novel 1,4-naphthoquinones fused with specific N -O isoxazole, with moderate yield (up to 62%). The compounds were characterized by NMR, GC-MS, and ESI-HRMS. Computational analyses revealed the superior stability and polarizability of the N-O isomers, supporting the importance of this study and their potential biological activity.