Electrophilic substitution of pyridine: practice and mechanism
Pyridine is electron-poor and only undergoes SEAr under harsh conditions, and then at C3. At C2 and C4 the σ-complex would put a positive charge on the nitrogen.
Example
The electronegative ring nitrogen makes pyridine electron-poor, and in acid it is also protonated. SEAr only works under harsh conditions and at C3: attack at C2 or C4 would put a positive charge on N in the σ-complex.
Mechanism step by step
- 1
In strongly acidic medium (oleum) pyridine is protonated at N, making the ring even more electron-poor.
- 2
The electrophile (Br⁺, activated by SO₃) attacks C3 at high temperature.
- 3
Loss of H⁺ gives 3-bromopyridine; yields are often moderate.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Typical mistakes
- C2 is unfavourable for electrophilic substitution: the σ-complex would put the positive charge on the electronegative N. Nucleophiles, on the other hand, attack C2.
- C4 is also unfavourable for electrophiles (positive charge on N in the σ-complex). That leaves C3.
Often confused with: Aromatic bromination (SEAr) · Chichibabin reaction
Frequently asked questions
How does pyridine differ from benzene?
N is more electronegative than C and pulls electron density out of the ring: electrophiles react poorly (as with nitrobenzene), nucleophiles readily at C2 and C4. The lone pair on N lies in the ring plane and makes pyridine basic (pKa of pyridinium ≈ 5).
How can pyridine be substituted more easily?
Via the N-oxide: the O pushes electrons back into the ring and electrophiles then attack C4. Afterwards the N-oxide is reduced (e.g. with PCl₃).