Everything about The Knoevenagel Condensation totally explained
The
Knoevenagel condensation reaction is an
organic reaction named after
Emil Knoevenagel. It is a modification of the
Aldol condensation .
A Knoevenagel condensation is a
nucleophilic addition of an
active hydrogen compound to a
carbonyl group followed by a
dehydration reaction in which a molecule of water is eliminated (hence
condensation). The product is often an 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
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.
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.
Doebner modification
With malonic compounds the reaction product can lose a molecule of
carbon dioxide in a subsequent step. In the so-called
Doebner modification the base required is
pyridine. For example the reaction product of
acrolein and
malonic acid in pyridine is
trans-2,4-Pentadienoic acid with one carboxylic acid group and not two
Scope
A Knoevenagel condensation is demonstrated in the reaction of
2-methoxybenzaldehyde 1 with the
barbituric acid 2 in
ethanol using
piperidine as a base . The resulting enone
3 is a
charge transfer complex molecule.
The Knoevelagel condensation is a key step in the commercial production of the antimalarial drug lumefantrine (a component of
Coartem) :
The initial reaction product is a 50:50 mixture of
E and Z isomers but because both isomers
equilibrate rapidly around their common
hydroxyl precursor, the more stable Z-isomer can eventually be obtained.
A
multicomponent reaction featuring a Knoevenagel condensation is demonstrated in this
MORE synthesis with
cyclohexanone,
malononitrile and
3-amino-1,2,4-triazole :
Further Information
Get more info on 'Knoevenagel Condensation'.
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