Computational Study on the Synthesis of 3,5- Disubstituted Isoxazoles from Nitrile Oxide and Therminal Acetylenes

In the present research, synthesis of 3,5-disubstituted isoxazoles in the presence of CuI catalyst has been modeled by means of density functional theory (DFT) [1] in terms of structural and thermochemical aspects in the gas phase. For this purpose, reaction of benzonitrile oxide with phenyl acetylene that led to produce two regioselective disubstituted isoxazoles has been modelled. In the next step, the thermochemical effect of two different solvents acetonitrile and water was examined via polarized continuum model (PCM) [2] calculations and assessed comparatively with the experimental observations. Then, the origins of regioselectivity was interpreted via modeling of corresponded transition states structures. In this respect, the structural, thermochemical and electronic properties of transition states were analyzed at M08- HX/6-311G** level of theory that was in a reliable agreement with the observed regioselectivity. Additionally, we concentrated on topological analysis of electron density for regioisomeric products and their corresponded transition states. In this line, quantum theory of atoms in molecule (QTAIM) [3] approach was employed to calculate the electronic density, its laplacian and electronic energy density indicators at some key bond critical points. The -electron delocalization of isoxazole rings was comparatively discussed by determination of rHOMA and HOMHED aromaticity indexes [4].