Knoevenagel condensation

Knoevenagel reaction or Knoevenagel condensation is an important reaction in organic chemistry. It is a special case of the aldol reaction, in which ketones (R2 = Organylgruppe, R3 = Organylgruppe ) or aldehydes (R2 = H, R3 = H or Organylgruppe ), particularly with CH -acidic compounds (R1 = Organylgruppe ), eg malonic acetoacetic ester or nitromethane are reacted. This produces unsaturated condensation products.

A special reaction of the Knoevenagel reaction is their Doebner variant. In it, the aldehyde / ketone with free malonic acid in pyridine and in the presence of an amine catalyst ( frequently pyrrolidine or piperidine ), is reacted. The resulting unsaturated dicarboxylic acid decarboxylated it. In this way, for example, cinnamic acids are very easily accessible.

It was named after its discoverer, the reaction Emil Knoevenagel.

Reaction mechanism

In the first step, the CH -acidic compound (R1 = Organylgruppe ) by the added base as a catalyst, in this case a secondary amine deprotonated. The resulting anion nucleophilically attacks the carbanion the carbonyl carbon of the carbonyl compound as the oxygen of the carbonyl group is protonated. The result is an alcohol which is also isolated as intermediate. With elimination of water, eventually forming the unsaturated end product.

The Doebner variant offers easy access to α, β -unsaturated carboxylic acids such as cinnamic acids (R: various substituents in different positions, for example,- OCH3):

In the above reaction formula, the radical R can be in the ortho, meta or para position on the phenyl ring (see the substitution pattern ).