Neutralization strong/weak nitrogen bases

Protonation, if forced upon pyrrole, is found to take place not on nitrogen but on the a-carbon atom (19). This occurs because incorporation of the nitrogen atom s lone pair of electrons into the aromatic 6jre system leaves the N atom positively polarised protons tend to be repelled by it, and are thus taken up by the adjacent a-carbon atom. The basicity situation rather resembles that already encountered with aniline (p. 70) in that the cation (19) is destabilised with respect to the neutral molecule (18a). The effect is much more pronounced with pyrrole, however, for to function as a base it has to lose all aromatic character, and consequent stabilisation this is reflected in its related pKa (-0-27) compared with aniline s of 4-62, i.e. pyrrole is a very weak base indeed. It can in fact function as an acid, albeit a very weak one, in that the H atom of the NH group may be removed by strong bases, e.g. eNH2 the resultant anion (20) then retains the aromatic character of pyrrole, unlike the cation (19) ... 

Substituents which reduce the basicity of a pyridine nitrogen can also influence the susceptibility of the heterocycle to electrophilic susbtitution, in these cases by increasing the proportion of neutral (more reactive) pyridine present at equilibrium 2,6-dichloropyridine nitrates at C-3, as the free base, and only 10 times more slowly than 1,3-dichlorobenzene. As a rule-of-thumb it has been suggested that (i) pyridines with a pATa > 1 will nitrate as cations, slowly unless strongly activated, and at an a or (3 position depending on the position of the substituent, (ii) weakly basic pyridines, pA a < -2.5, nitrate as free bases, and at an a or / position depending on the position of the substituent. ... 

Nicotinamide riboside contains a quaternary nitrogen with a strongly ionized positive charge at neutral pH. Phosphorolysis yields nicotinamide, which is a weak base, and hydrogen ion. Consequently, the reaction proceeds practically to completion in buffered solutions at neutral pH. 

---