Aromatic and Saturated Heterocycles

Pyridine: An Aromatic Six-Membered Heterocyclic Compound

The structure of pyridine considerably resembles that of benzene. It may be formally derived from the structure of benzene through the exchange of one ring carbon for a nitrogen. However, is pyridine, which is structurally and electronically allied to benzene, also aromatic?.

Fig.1

Pyridine is aromatic based on the following facts. The protons of pyridine display chemical shifts in the NMR spectrum that are typical of aromatic protons. Furthermore, electrophilic substitutions at pyridine are possible. The nitrogen of pyridine is $sp2$-hybridized and possesses one lone electron pair. This electron pair is located in an $sp2$ orbital that is parallel to the ring plane. Therefore, in contrast to pyrrole, the nitrogen's lone electron pair of pyridine does not participate in the aromatic π electron system. As a result, pyridine can easily be protonated, yielding a pyridinium cation. Two valence electrons of the nitrogen are involved in the two σ bonds with the adjacent carbons. The fifth valence electron of the nitrogen occupies the p orbital that is perpendicular to the ring plane. Thus, analogous to the ring carbons, this electron takes part in the π electron system.

Fig.2
Comparison of benzene and pyridine.

Electrophilic substitutions at pyridine

As an aromatic compound, pyridine may participate in electrophilic substitutions as an electrophile. How easily and at which positions do these substitutions occur? In order to answer these questions, the pyridine's resonance structures, illustrated below, should be taken into account.

Fig.3
Resonance structures of pyridine.

In comparison to benzene, the lone electron pair of pyridine's nitrogen is incapable of considerably increasing the electron density of the π electron system and, thus, pyridine's nucleophilicity to any significant degree, as it does not participate in the π electron system, due to geometric reasons. Rather, the nucleophilicity of the π electron system is decreased by the electron-withdrawing effect of the highly electronegative nitrogen. This fact is indicated by the three resonance structures that contain positively charged carbons. As a result, the reaction rates of electrophilic substitutions at pyridine are much lower than that of electrophilic substiutions at benzene. Noticeable reaction rates may only be achieved under more drastic reaction conditions.

Fig.4
Chemical shifts of benzene's and pyridine's protons in the NMR spectra.

The electron deficiency at the carbons C-2, C-3, and C-6 of pyridine, which is indicated by the positions of the positive charges in the resonance structures, may be substantiated by the chemical shifts of the corresponding protons in the 1H NMR spectrum. Furthermore, electrophilic substitutions at pyridine preferably occur at C-3 and C-5, as they are the most electron-rich carbons of pyridine.

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