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 CuIcatalyst has been modeled by means of density functional theory (DFT) [1] in terms of structuraland thermochemical aspects in the gas phase. For this purpose, reaction of benzonitrile oxidewith phenyl acetylene that led to produce two regioselective disubstituted isoxazoles has beenmodelled. In the next step, the thermochemical effect of two different solvents acetonitrile andwater was examined via polarized continuum model (PCM) [2] calculations and assessedcomparatively with the experimental observations. Then, the origins of regioselectivity wasinterpreted via modeling of corresponded transition states structures. In this respect, thestructural, 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 regioisomericproducts and their corresponded transition states. In this line, quantum theory of atoms inmolecule (QTAIM) [3] approach was employed to calculate the electronic density, its laplacianand electronic energy density indicators at some key bond critical points. The -electrondelocalization of isoxazole rings was comparatively discussed by determination of rHOMA andHOMHED aromaticity indexes [4].

Keywords:

3 , 5-disubstituted Isoxazoles , Density Functional Theory , Polarized ContinuumModel , QTAIM Analysis , -electron Delocalization