Electrophilic substitution: pyrrole vs pyridine template

Attack at C2 of pyrrole gives a σ-complex with three resonance forms (one with the positive charge on N, every atom an octet), so C2 is favoured over C3. In pyridine, attack at C3 is the only position that keeps the positive charge off the electronegative nitrogen.

Mechanism step by step

Electron-rich pyrrole reacts fast at C2; electron-poor pyridine reacts slowly, and only at C3

1. Pyrrole: attack at C2 – The C2=C3 π bond attacks E⁺ (any electrophile)
2. Three resonance forms – The charge reaches C3, C5 and N; the N⁺ form has an octet on every atom
3. Loss of H⁺ – Aromaticity returns: 2-substituted pyrrole
4. Pyridine: attack at C3 – Pyridine reacts like nitrobenzene: slow, and only at C3 (C2 or C4 attack would put + on a 6-electron N)
5. σ-Complex from C3 attack – The charge sits on C2, C4 and C6 only, never on N
6. Pyridine in practice – Forcing conditions: bromine in oleum at 130 °C gives 3-bromopyridine (N is protonated, which slows it further)

Key points

• Pyrrole is a π-excessive heterocycle (6 π electrons on 5 atoms, the N lone pair is part of the aromatic sextet): it reacts like an enamine or phenol, far faster than benzene, so mild reagents are used (HNO₃/Ac₂O, not HNO₃/H₂SO₄, which polymerises it).
• C2 attack gives three resonance forms, C3 attack only two, so C2 substitution dominates (about 50 : 13 for nitration of pyrrole).
• Pyridine is π-deficient (the electronegative N, whose lone pair is not in the ring, pulls density away) and under acid it is protonated to the even less reactive pyridinium ion.
• Pyridine instead undergoes nucleophilic substitution at C2 and C4 (Chichibabin reaction), and pyridine N-oxide is used to bring electrophiles to C4.

Drawn with 109 atoms, 17 arrows, 8 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 29 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 11 Textbook