Russian Journal of Physical Chemistry A, Vol 90, No 11 (2016)

The quantum chemical study of the reactivity of a series of oxazole derivatives substituted at 2, 4, and 5 positions was performed using B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory. Different substituents have been applied to cover a wide range of electronic effects. On the basis of Fukui functions, oxazole derivatives in the gas phase are found to be suitable nucleophilic sites. For the most of studied substituents, it was observed that the calculated Fukui function f_k^- values at the N-position are small in case of electron-withdrawing substituents, resulting a preferred N-position for hard reactions. In contrast, large f_k^- values in case of electron-donating groups show a preferred N-position for soft reactions. These two local reactivity descriptors predicted the reactivity of the electron-rich oxazoles sequence to be 2-substituted oxazoles > 5-substituted oxazoles > 4-substituted oxazoles, where due to resonance effect, the reactivity toward electrophilic attack at the pyridine nitrogen atom is enhanced by electron donor substituents.