Chichibabin pyridine synthesis

Not to be confused with Chichibabin reaction.

The Chichibabin pyridine synthesis (/ˈtʃiːtʃiːˌbeɪbiːn/) is a method for synthesizing pyridine rings. The reaction involves the condensation reaction of aldehydes, ketones, α,β-unsaturated carbonyl compounds, or any combination of the above, with ammonia.^[1] It was reported by Aleksei Chichibabin in 1924.^[2][3] Methyl-substituted pyridines, which show widespread uses among multiple fields of applied chemistry, are prepared by this methodology.^[4]

Chichibabin pyridine synthesis
Named after	Aleksei Chichibabin
Reaction type	Ring forming reaction
Identifiers
RSC ontology ID	RXNO:0000526

Representative syntheses

The syntheses are presently conduced commercially in the presence of oxide catalysts such as modified alumina (Al₂O₃) or silica (SiO₂). The reactants are passed over the catalyst at 350–500 °C. 2-Methylpyridine- and 4-methylpyridine are produced as a mixture from acetaldehyde and ammonia. 3-Methylpyridine and pyridine are produced from acrolein and ammonia. Acrolein and propionaldehyde react with ammonia affords mainly 3-methylpyridine. 5-Ethyl-2-methylpyridine is produced from paraldehyde and ammonia.^[5]

Mechanism and optimizations

These syntheses involve many reactions such as imine synthesis, base-catalyzed aldol condensations, and Michael reactions.

Many efforts have been made to improve the method.^[6][1] Conducting the reaction in the gas phase in the presence of aluminium(III) oxide.^[4] zeolite (yield 98.9% at 500 K),^[7]

From nitriles

Of the many variations have been explored. one approach employs nitriles as the nitrogen source. For example, acrylonitrile and acetone affords 2-methylpyridine uncontaminated with the 4-methyl derivative. In another variation, alkynes and nitriles react in the presence of organocobalt catalysts, a reaction inspired by alkyne trimerization.^[5]

See also

• Chichibabin reaction
• Gattermann–Skita synthesis
• Hantzsch pyridine synthesis
• Ciamician–Dennstedt rearrangement