CHEMY421 (Organic
Chemistry III)
Carbonyl
Condensation
Reactions
1st sem 2023-2024, Dr. Suad AlRashdan
Aldol condensation
• Carbonyl
reactions
condensation
are
the
between
two
compounds
and
reactions
carbonyl
involve
a
combination of Nu- addition
and α-substitution steps.
• The general mechanism is as
follow:
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Mechanism of Aldol Condensation
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Carbonyl condensation versus Alpha substitutions
• Both carbonyl condensation and alpha substitution reaction take place in
basic conditions and involve enolation intermediates.
• Alpha substitution reactions require full equivalent of strong base and the
E+ is added rapidly to ensure that enolate ion is quenched quickly.
• Carbonyl condensation reactions require only a catalytic amount of a weak
base.
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Dehydration of Aldol Products: Synthesis of Enones
• The β-hydroxy aldehydes and β-hydroxy ketones formed in aldol reactions
are easily dehydrated to yield ,-unsaturated products, or conjugated enones
(ene -one). It’s this loss of water that gives the aldol condensation its
name.
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Dehydration of Aldol Products: Synthesis of Enones
• Most alcohols are resistant to dehydration by dilute acid or base because hydroxide
ion is a poor leaving group, but β-hydroxy carbonyl compounds dehydrate easily
because of the carbonyl group.
• Under basic conditions, a hydrogen is abstracted and the resultant enolate ion expels
the OH leaving group in an E1cB reaction). Under acidic conditions, an enol is
formed, the OH group is protonated, and H2O is then expelled in an E1 or E2
reaction.
• Conjugated enones are more stable than nonconjugated eneons.
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Dehydration of Aldol Products: Synthesis of Enones
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Intramolecular Aldol Reactions
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Intramolecular Aldol Reactions
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Mixed Aldol Reactions
• A mixed Aldol reaction leads to a mixture of different products.
• Mixed Aldol reaction can lead to a single product if either of the two
conditions is met:
If one of the carbonyl compound contains no alpha hydrogen. Neither
benzaldehyde nor formaldehyde can form an enolate ion.
If one of the carbonyl compounds is much more acidic than the other
and so it transformed into its enolate ion in preference to the other.
Example:
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Mixed Aldol Condensation Reaction
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Condensations of Esters:
The Claisen Condensation Reaction
• Esters are weakly acidic. When an ester with an α-hydrogen is treated with a
base such as sodium ethoxide, a carbonyl condensation
• reaction occurs to yield a -keto ester. This reaction between two ester
molecules is known as the Claisen condensation reaction.
• Example:
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Claisen Condensation Mechanism
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Intramolecular Claisen Reactions
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Intramolecular Claisen Reactions
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Conjugate carbonyl addition: Michael Addition
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Michael Reaction
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Michael Addition Reaction
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Carbonyl Condensation with Enamines:
Stork Reaction
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Stork Reaction Mechanism
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Carbonyl Condensation with Enamines: Stork Reaction
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The Robinson Annulation Reaction
The Robinson Annulation is a
useful reaction for the formation
of
six-membered
rings
in
polycyclic compounds, such as
steroids.
It
combines
two
reactions:
the
Michael
Addition
and
the
Aldol
Condensation.
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