Knoevenagel, Emil

This reaction was first reported by Emil Knoevenagel in 1894. It is a nucleophilic addition of a compound with an active methylene component to a ketone or aldehyde, followed by the elimination of water to form an olefin. Therefore, it is generally known as... 

For an excellent essay about Emil Knoevenagel see B. List, Angew. Chem., Int. Ed. 2010, 49, 1730-1734. 

Bases, often amines, can generate significant amounts of enolates from the P-dicarbonyl compounds in Table 19.3, and similar molecules. In the presence of an acceptor ketone or aldehyde, condensation occurs to give, ultimately, the a,P-imsaturated diester shown in Figure 19.77. This reaction is called the Knoevenagel condensation after Emil Knoevenagel (1865-1921). 

In 1894, Emil Knoevenagel expanded on Hantzsch s work in two significant ways. First, he showed that this reaction could be promoted by any primary or secondary amine, not just the few primary amines demonstrated by Hantzsch. (In ICnoevenagel s hands, tertiary amines, such as pyridine, quinoline, diethylaniline or dimethylaniline were ineffective, although this was to be later revisited by Hann and Lapworth, vide infra). 

The Knoevenagel reaction is a base-catalyzed aldol-type reaction that can occur through two possible mechanisms, depending on the type of base used. When Emil Knoevenagel made his initial discovery of this reaction, it was already known that benzaldehyde could condense with two equivalents of piperidine to provide the benzylidine bispiperidine aminal 1 Therefore, he proposed the intermediacy of an aminal (or imine) in the condensation. 

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