Chichibabin reaction
| Chichibabin reaction | |
|---|---|
| Named after | Aleksei Chichibabin |
| Reaction type | Substitution reaction |
| Identifiers | |
| RSC ontology ID | RXNO:0000527 |
The Chichibabin reaction (pronounced ' (chē')-chē-bā-bēn) is a method for producing 2-aminopyridine derivatives by the reaction of pyridine with sodium amide. It was reported by Aleksei Chichibabin in 1914. The following is the overall form of the general reaction:
The direct amination of pyridine with sodium amide takes place in liquid ammonia. Following the addition elimination mechanism first a nucleophilic NH2− is added while a hydride (H−) is leaving.
Ciganek describes an example of an intramolecular Chichibabin reaction in which a nitrile group on a fused ring is the source of nitrogen in amination.
It is widely accepted that the Chichibabin reaction mechanism is an addition-elimination reaction that proceeds through an σ-adduct (Meisenheimer adduct) intermediate (the third structure). First, the nucleophilic NH2− group adds to the δ+ ring carbon pushing electrons onto the ring nitrogen and forming the anionic σ-adduct, which is stabilized by sodium. Electrons from the nitrogen are then pushed towards the ring forming a C=N bond and ejecting a hydride ion. The hydride ion abstracts a hydrogen from the positively charged nitrogen, forming hydrogen gas. The ring nitrogen then pushes electrons back into the ring, regaining aromaticity, the now negatively charged NH group abstracts a proton from water giving the product.
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