Novel quinazolinone-isoxazoline hybrids: synthesis, structural elucidation and theoretical DFT mechanistic study

Abstract Quinazolinone and isoxazoline systems have attracted more attention due to their interesting pharmacological properties. The association of these two pharmacophores in a single hybrid structure can boost the biological activity or bring a new one. Inspired by this new paradigm, we report in the present work, the synthesis and spectroscopic characterization of a new quinazolinone-isoxazoline hybrids. The target compounds were obtained via 1,3-dipolar cycloaddition reaction of arylnitriloxides and N-allylquinazolinone. The synthesized compounds were characterized using spectroscopic techniques such as: IR, 1D NMR (1H and 13C), 2D NMR (COSY and HSQC), and high-resolution mass spectrometry (HRMS). The spectral data show that this reaction leads only to the 3,5-disubstituted isoxazoline regioisomer and the observed regiochemistry is not affected by the nature of the substituents in the phenyl ring of the dipole. In addition, a theoretical study was performed using the density functional theory (DFT) to support the experimental results regarding the regiochemistry of the studied reactions. The computational mechanistic study is in perfect agreement with experimental data.