Question

Please explain the reactivity and orientation effects observed in each heterocycle. a. Pyridine is less reactive than benzene in electrophilic aromatic substitutions and yields 3-substituted products. b. Pyrrole is more reactive than benzene in electrophilic aromatic substitutions and yields 2-substituted products.

Answer 1

Hetero aromatics contain heteroatoms (e.g. O, N, S) and the presence of the heteroatoms impact the reactivity compared to benzene.

a) Pyridine is less reactive than benzene in electrophilic substitutions and gives 3-substituted products (more like nitrobenzene) due to the electronegativity of Nitrogen atom, it is usually called as a p-electron defficient aromatic. Because of basic nature of the Nitrogen atom of pyridine often prevents and interacts with the electrophile E+ which further deactivates the system.

Electrophilic substitutions to pyridine at the 2- or 4-position generate an energetically unfavorable σ complex compare to 3-position. Electrophilic substitutions on pyridine normally either do not proceed or proceed only partially at 3-position.

b) Next 5-membered ring heterocycles means furan, pyrrole and thiophene are p-electron-rich aromatics because they have 6p electrons over 5 atoms because if this they are more reactive than benzene in electrophilic substitution reactions. For example furan is similarly acts as activated benzene-like methoxybenzene

Electrophilic substitution on Pyrroles normally generates C2 or C5 substituted pyrroles because of the highest degree of stability of the protonated intermediate compare to C3 or C4 position.