Chichibabin reaction

The Chichibabin reaction ( also Chichibabin amine reaction ) is a nucleophilic aromatic substitution reaction for the preparation of 2 - and 4- aminopyridines or quinolines, and was first described in 1914 by Alexei Yevgenyevich Chichibabin.

Here, in an activated for nucleophilic attack heteroaromatics a hydrogen atom is substituted. The nucleophilic substitution is performed on heteroaromatics whose electron density is reduced by the inductive and mesomeric effects.

Mechanism

The reaction ( here the example of the synthesis of ortho meta or para substituted 2-aminopyridine ) proceeds via an addition - elimination mechanism:

• In step 1, the product derived from the sodium amide ion is attached to the carbon atom, the negative charge is stabilized by the nitrogen.
• In the next step, the elimination of a hydride, which is subsequently protonated by the amino group to hydrogen.
• Finally, the 2-aminopyridine is released by the addition of water from its anion.