Theoretical studies on the reactivity of mono-substituted imidazole ligands

Abstract

The global and local quantum chemical reactivity descriptors of a series of imidazole derivatives substituted at 2, 4, and 5 positions with different groups including electron-donating and electron-withdrawing substituents have been calculated using the B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) methods. The substituents have been selected to cover a wide range of electronic effects. Considering the calculated Fukui functions, both imidazole derivatives and their anions are found to be suitable nucleophilic sites in the gas phase. For the most substituents it was observed that the calculated Fukui function \(f_{\text{k}}^{ - }\) values at the N-site are small in case of electron-releasing substituents indicating a preferred N-site for hard reaction. In contrast, large \(f_{\text{k}}^{ - }\) values in case of electron-attracting groups indicate a preferred N-site for soft reaction. These two local descriptors predicted the reactivity of the electron-rich imidazole sequence to be 2-substituted imidazoles > 5-substituted imidazoles > 4-substituted imidazole where reactivity toward electrophilic attack at a pyridine nitrogen atom is enhanced by electron donor substituents elsewhere in the molecule, due to resonance effect.