Knoevenagel condensation
Abstract
The Knoevenagel condensation involves active methylene compounds, such as a β-dicarbonyl or a malonitrile, reacting with a ketone or an aldehyde. This reaction is typically catalyzed by an amine base, such as piperidine or pyridine.
Keywords
β-dicarbonyl, Aldehyde, Ketone, α,β-unsaturated carbonyl compound
Category
Aldehyde/Ketone
Mechanism
The amine base first deprotonates the hydrogen in α-position of the electron-withdrawing group (EWG) of the activated methylene compound, generating a stabilized carbanion. This nucleophile then attacks the carbonyl carbon of the aldehyde or ketone, forming a β-hydroxy intermediate. The base subsequently deprotonates the α-position again, promoting the elimination of the hydroxyl group, yielding the α,β-unsaturated product.
Recent review
Heravi, M. M.; Janati, F.; Zadsirjan, V. Applications of Knoevenagel condensation reaction in the total synthesis of natural products. Monatsh. Chem. 2020, 151, 439-482.