Knoevenagel condensation

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The Knoevenagel condensation reaction is an organic reaction named after Emil Knoevenagel. It is a modification of the Aldol condensation ^[1].

A Knoevenagel condensation is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by an dehydration reaction in which a molecule of water is eliminated (hence condensation). The product is often a alpha, beta conjugated enone.

In this reaction the carbonyl group is an aldehyde or a ketone.The catalyst is usually a weakly basic amine. The active hydrogen component has the form

• Z-CH₂-Z or Z-CHR-Z for instance diethyl malonate, Meldrum's acid, ethyl acetoacetate or malonic acid.
• Z-CHR₁R₂ for instance nitromethane.

where Z is an electron withdrawing functional group. Z must be powerful enough to facilitate hydrogen abstraction to the enolate ion even with a mild base. Using a strong base in this reaction would induce self-condensation of the aldehyde or ketone.

With malonic compounds the reaction product can lose a molecule of carbon dioxide in a subsequent step. The Hantzsch pyridine synthesis, the Gewald reaction and the Feist-Benary furan synthesis all contain a Knoevenagel reaction step. The reaction also led to the discovery of CS gas.

[edit] Example reactions

A Knoevenagel condensation is demonstrated in the reaction of 2-methoxybenzaldehyde 1 with the barbituric acid 2 in ethanol using piperidine as a base ^[2]. The resulting enone 3 is a charge transfer complex molecule.

A multicomponent reaction featuring a Knoevenagel condensation is demonstrated in this MORE synthesis with cyclohexanone, malononitrile and 3-amino-1,2,4-triazole ^[3]:

[edit] References

1. ^ E. Knoevenagel, "Condensation von Malondiure mit Aromatiachen Aldehyden durch Ammoniak und Amine", Chemische Berichte, 1898 (31), 2596-2619.
2. ^ 1,3-Diethyl-5-(2-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione Abdullah Mohamed Asiria, Khaled Ahmed Alamrya Abraham F. Jalboutb, Suhong Zhang Molbank 2004, M359 [1] publication.
3. ^ Mild and ecofriendly tandem synthesis of 1,2,4-triazolo[4,3-a]pyrimidines in aqueous medium Arkivoc 2007 (06-2251BP) Anshu Dandia, Pritima Sarawgi, Kapil Arya, and Sarita Khaturia Link