Novel Quinazolinone–Isoxazoline Hybrids: Synthesis, Spectroscopic Characterization, and DFT Mechanistic Study
Yassine Rhazi,
Mohammed Chalkha,
Asmae Nakkabi,
Imad Hammoudan,
Mohamed Akhazzane,
Mohamed Bakhouch,
Samir Chtita,
Mohamed El Yazidi
Affiliations
Yassine Rhazi
Engineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, Fez P.O. Box 1796, Morocco
Mohammed Chalkha
Engineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, Fez P.O. Box 1796, Morocco
Asmae Nakkabi
Engineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, Fez P.O. Box 1796, Morocco
Imad Hammoudan
Laboratory Physical Chemistry, Faculty of Sciences of Tetouan, Abdelmalk Essaadi University, Tetouan P.O. Box 93002, Morocco
Mohamed Akhazzane
Cité de l’Innovation, Université Sidi Mohamed Ben Abdellah, Route Immouzer, Fez P.O. Box 2626, Morocco
Mohamed Bakhouch
Laboratory of Bioorganic Chemistry, Department of Chemistry, Faculty of Sciences, Chouaïb Doukkali University, El Jadida P.O. Box 24, Morocco
Samir Chtita
Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca P.O. Box 7955, Morocco
Mohamed El Yazidi
Engineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, Fez P.O. Box 1796, Morocco
Quinazolinone and isoxazoline systems have attracted much 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, in the present work we report the synthesis and spectroscopic characterization of new quinazolinone–isoxazoline hybrids. The target compounds were obtained via 1,3-dipolar cycloaddition reactions 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 that 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 density functional theory (DFT) to support the experimental results in regard to the regiochemistry of the studied reactions. The computational mechanistic study was in good agreement with the experimental data.
