19.9:
Basicity of Heterocyclic Aromatic Amines
The basicity of heterocyclic amines is influenced by both the resonance and the hybridization effects.
To understand the resonance effect, consider two aromatic heterocyclic amines—pyridine and pyrrole. The nonbonded electrons of the pyridine nitrogen reside in an sp2 hybrid orbital. As they do not contribute to the aromatic sextet, they are available for protonation.
In pyrrole, the nonbonding electrons are present in a p orbital and are part of the aromatic π system. Here, protonation is unfavorable as aromaticity is lost in the conjugated acid.
As the pKa of the protonated pyrrole is less than pKa of the protonated pyridine, pyridine is more basic than pyrrole.
For the hybridization effect, consider the hybridization of the amine nitrogen. As the percent s character increases, the nonbonded electrons are held more tightly and are less available for protonation.
With less s character of the sp3-hybridized piperidine nitrogen, it is easily protonated with a higher pKa value of the conjugate acid. Thus, piperidine is more basic than pyridine.
19.9:
Basicity of Heterocyclic Aromatic Amines
Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
Figure 1. The comparison of the basicity of piperidine and pyridine.
This difference in basicity may be attributed to the state of hybridization of orbitals containing a lone pair of electrons on the N atom, as depicted in Figure 2. In the case of piperidine, the lone pair resides in an sp3-hybridized orbital having lower s character, making the lone pair more available for exhibiting basicity towards acid. On the other hand, in piperidine, the lone pair resides in an sp2-hybridized orbital containing a much higher s character. Consequently, the lone pair is more tightly bound to the aryl ring and less available for exhibiting basicity towards acid.
Figure 2. The effect of the hybridized orbitals on the basicity.
Pyrrole is much less basic than pyridine, having a pKb value of 15. The lone pair of electrons on the N atom shown in Figure 3 resides in a pure p orbital and are perfectly aligned with the p orbitals of C atoms, which participate in the ring’s aromaticity. Therefore, the lone pair of electrons on the N atom of pyrrole is delocalized by resonance throughout the ring. Conversely, the lone pair on the N atom of pyridine being in an sp2 hybridized orbital is aligned perpendicular to the other sp2 orbitals of C atoms taking part in resonance. So, the lone pair of electrons on the N atom of pyridine is much more available than that in pyrrole, resulting in higher basicity of pyridine.
Figure 3. The Lewis structure of pyrrole.
Imidazole contains two N atoms in a five-membered ring and is a vital heterocycle found in many proteins. This heterocyclic amine with a pKb of 7 is more basic than pyridine by a factor of 100. The N atom resembling that in pyrrole is non-basic. The other N atom is basic and abstracts H from acid giving rise to its conjugated acid, which is stabilized by the resonance, as illustrated in Figure 4. This resonance stabilization of the conjugate base results in the increased basicity of imidazole relative to pyridine.
Figure 4. The resonance stabilization in imidazolium ions.
Basicity of amines provides a valuable practical tool to separate amines from a mixture containing other neutral compounds. This is achieved by dissolving the impure mixture in ether and shaking it with water in a separatory funnel. After the two layers separate, draining the water layer removes the salt and most inorganic impurities. When dilute aqueous acid is added to the organic layer, amines are selectively protonated into the corresponding acid and dissolve in the aqueous layer. Draining the organic layer removes the neutral organic impurity. Slow basification of the aqueous layer again regenerates the free amine, which could be extracted using a fresh volume of ether. The subsequent evaporation of ether yields a pure amine.