The
validity of calculated NMR shifts to predict the outcome of
electrophilic aromatic substitution reactions on different heterocyclic
compounds has been examined. Based on an analysis of >130 literature
examples, it was found that the lowest predicted <sup>13</sup>C and/or <sup>1</sup>H chemical shift of a heterocycle correlates qualitatively
with the regiochemical outcome of halogenation reactions in >80%
of
the investigated cases. In the remaining cases, the site of electrophilic
aromatic substitution can be explained by the calculated HOMO orbitals
obtained using density functional theory. Using a combination of these
two methods, the accuracy increases to >95%
