Sites of protonation of N2-substituted N1,N1-dimethyl formamidines from regional reactivity indices

N1,N1-dimethyl-N2-alkyl-formamidines and alkenyl, alkynyl and heteroalkyl derivatives present two potential sites for protonation reactions in the gas phase, namely, the amino (N1) and imino (N2) nitrogen atoms and eventually, a third potential protonation site at the N2 substituents. The protonation sites in polyfunctional molecules may be directly identified by using local reactivity indices. In this work, we present a theoretical analysis to predict protonation sites using the condensed or regional Fukui function formalism associated with a local hard and soft acids and bases (HSAB) principle. Our method correctly assesses the site of protonation in a wide series of N1,N1-dimethyl-N2-formamidines. The imino N2 site is predicted to be the preferred site for protonation, in close agreement with experimental data. Predicted proton affinities evaluated at the preferred (N2) site and obtained from HF/6-31G(d) calculations correlate well with the experimental values. The method is also tested against a short series of nicotinic acid derivatives that present closer values of proton affinity.