Reactivity and regioselectivity of five-membered heterocycles in electrophilic aromatic substitution: A theoretical investigation

A theoretical study of the reactivity and regioselectivity of some five-membered heterocycles in electrophilic aromatic substitution is carried out at the B3LYP/6-311G(d,p) computational level. The relative reactivity of these systems is rationalized by means of the global nucleophilicity index recently proposed by Domingo's group [J. Org. Chem. 73 (2008) 4615-4624; J. Mol. Struct. (THEOCHEM) 865 (2008) 68-72]. The positional selectivity, namely α or β, is predicted by means of the local nucleophilicity indices proposed by the same group [J. Mol. Struct. (THEOCHEM) 895 (2009) 86-91]. The present study shows that the experimental trends of the relative reactivities and regioselectivities of these reactions are correctly predicted using these empirical reactivity indexes.