Nitrogen atom, protonation site aniline

The effect of pH is rarely of use for pK measurement it is more often of use in identifying the site of protonation/deprotonation when several basic or acidic sites are present. Knowing the incremental substitutent effects Z of amino and ammonium groups on benzene ring shifts in aniline and in the anilinium ion (40), one can decide which of the nitrogen atoms is protonated in procaine hydrochloride (problem 24). 

It is a well established fact that the preferred site of protonation of aniline in solution is the nitrogen atom, due to the higher stabilization upon solvatation of the N-protonated species with respect to the ring protonated ion (/). In the gas phase however, the situation is less clear, and the preferred site of protonation has been the subject of many experimental and theoretical studies. Based on proton transfer equilibria at 600 K and upon correlation of the proton affinities... 

In summary, it is confirmed that while the nitrogen protonation in the unsubstituted ANI is favored marginally, by about 4 kJ mol-1, over the para-C4-protonation, the protonation sites in substituted anilines are essentially determined by the nature and position of the substituents. The halogen atoms consistently reduce the basicity whereas the alkyl groups enhance it. Substitution at meta positions induces a larger increment than that at ortho positions. The overall effects of substituents on PAs are essentially additive. 

The protonation of aniline is the object of our next example (see Scheme 3). Notwithstanding different experimental gas-phase studies [84-86] the question regarding the preferred protonation site on this molecule remains matter of controversy. The situation in solution is instead well defined. As it is shown in Table 1, both PWP and B3LYP calculations indicate that the protonation on the para-carbon is slightly favoured over that on nitrogen atom. 

Subsequently, Fuentealba et al. studied the regional Fukui functions for different sites of aniline and some of its substituents (see Figure 22). Aniline may be protonated at the nitrogen atom of the amino group and also at the aromatic ring para to the NH2 substituent. The presence of other substituents may change... 

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