Knoevenagel Condensation

In 1894, German chemist Emil Knoevenagel reported that diethyl malonate and formaldehyde condensed in the presence of diethylamine to form a bis-adduct. He later discovered that the same type of bis-adduct was produced when formaldehyde and other aldehydes were condensed with ethyl benzoylacetate or acetylacetone in the presence of primary and secondary amines. In 1896, he conducted further experiments, reacting benzaldehyde with ethyl acetoacetate at 0°C using piperidine as the catalyst to form ethyl benzylidene acetoacetate as the single product. The reaction of aldehydes and ketones with active methylene compounds in the presence of a weak base to produce α,β-unsaturated dicarbonyl or related compounds is now known as the Knoevenagel condensation reaction.

One of the general features of this reaction is that aldehydes react much faster than ketones. Additionally, the active methylene groups require two electron withdrawing groups, with typical examples including malonic esters, acetoacetic esters, malonodinitrile, or acetylacetone. Both the solvent and the nature of the catalyst employed are important. As the by-product of the reaction is water, removing the generated water by azeotropic distillation or by the addition of molecular sieves helps to shift the equilibrium to favor the formation of the product.