Use of anilines in the petasis reaction: Dft mechanistic study

Abstract

Five 2-[(4-R-anilino)(phenyl)methyl]phenols with potential anticancer activity were synthesized by the Petasis reaction. Three of these compounds were previously unknown. All compounds were characterized by H-1 and C-13 NMR spectroscopy. Correlation analysis was performed between the C-13 NMR chemical shifts and Hammett substituent constants. The HOMO and LUMO energies were also calculated by the DFT B3LYP method using 6-311++G(d,p) basis set. In addition, electronic and structural characteristics such as molecular electrostatic potential (MEP) and Mulliken atomic charges, as well as thermodynamic parameters (rotation constants, entropy, thermal energy, thermal capacity), were calculated. A correlation between the theoretical electrophilicity index, which provides information on biological properties of compounds, and the substituent nature was analyzed. Molecular docking study was performed for 2-[(4-bromoanilino)(phenyl)methyl]phenol against the Borealin-Survivin complex from E. coli (PDB: 2RAW), and the binding energy was estimated at -6.8 kcal/mol.