Chichibabin pyridine synthesis


The Chichibabin pyridine synthesis 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. It was reported by Aleksei Chichibabin in 1924.
Methyl-substituted pyridines, which show widespread uses among multiple fields of applied chemistry, are prepared by this methodology.

Representative syntheses

The syntheses are presently conducted commercially in the presence of oxide catalysts such as modified alumina or silica. 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 reacting with ammonia affords mainly 3-methylpyridine. 5-Ethyl-2-methylpyridine is produced from paraldehyde and ammonia.

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. Conducting the reaction in the gas phase in the presence of aluminium(III) oxide or zeolites has been shown to improve conversion and selectivity.

From nitriles

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.