2. Knoevenagel condensation is 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.
Knoevenagel reaction is a modification of Aldol condensation
reaction.
The active hydrogen compound used should be of the form
Z-CH2-Z or Z-CHR-Z where Z is an electron withdrawing
group.
3. Eg: Diethyl malonate, Malonic acid and ethyl acetoacetate
H5C2OOC-CH2-COOC2H5
Diethyl malonate
HOOC-CH2-COOH
Malonic acid
Z must be powerful enough to facilitate deprotonation 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.
4. The carbonyl group is an aldehyde or a ketone.
Eg: Acetaldehyde (CH3CHO), Acetone (CH3CO CH3)
The catalyst is usually a weakly basic amine.
Eg: Pyridine (C5H 5N)
5. Knoevenagel condensation is 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.
6. The condensation of carbon acid compounds with aldehydes to
afford α,β-unsaturated compounds.
The Doebner Modification, which is possible in the presence of
carboxylic acid groups, includes a pyridine-induced
decarboxylation
7. Step:1: An enol intermediate is formed initially.
8. Step:2: The enol formed reacts with aldehyde, and the
resulting aldol undergoes based induced elimination.
9. With malonic compounds the reaction product can lose
a molecule of carbon dioxide in a subsequent step. The
base is pyridine. For example, the reaction product of
acrolein (allyl aldehyde) and malonic acid in pyridine is
trans-2,4-Pentadienoic acid with one carboxylic acid
group and not two.
Acrolein
Malonic acid
trans-2,4-Pentadienoic acid
10. The Knoevenagel condensation is a key step in the
commercial production of the antimalarial drug
lumefantrine.
Knoevenagal reaction is used in the synthesis of conjugated
enones which serve as key intermediates in various
reactions.
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.
