Nitrogen atom, protonation site

The (3-carbon atom of an enamine is a nucleophilic site because of conjugation with the nitrogen atom. Protonation of enamines takes place at the (3-carbon, giving an iminium ion. 

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). 

Consider a nucleus that can partition between two magnetically nonequivalent sites. Examples would be protons or carbon atoms involved in cis-trans isomerization, rotation about the carbon—nitrogen atom in amides, proton exchange between solute and solvent or between two conjugate acid-base pairs, or molecular complex formation. In the NMR context the nucleus is said to undergo chemical exchange between the sites. Chemical exchange is a relaxation mechanism, because it is a means by which the nucleus in one site (state) is enabled to leave that state. 

Even without a cage effect, the entropy effect will be somewhat more favorable for ortho reaction when hydrogen bonding to an azine-nitrogen atom generates the necessary nucleophile. The possibility of proton transfers between the solvent molecules (MeOH) near the reaction site and the more distant MeO is expected to produce a favorable increase (relative to other solvents) in the entropy of activation, which can reinforce the effect of a favorable point of... 

Assignment of the isotropically shifted signals observed for the CuNiSOD example discussed in the previous paragraph has been achieved by means of anion titrations (not discussed here) and nuclear Overhauser enhancement spectroscopy (NOESY), to be discussed next. In Figure 3.24B the CuNiSOD active site is depicted with histidine nitrogens and protons identified for the discussion of the NOESY results. The copper(II) ion is coordinated to the N ligand atoms of his46... 

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