Organic Chemistry
Chapter 23: Carbonyl Condensation Reactions
I.
Lecture Outline
CARBONYL CONDENSATION REACTIONS
Carbonyl condensation reactions occur between an enolate or enol generated from a carbonyl compound attacks the
electrophilic carbon of a second carbonyl group (of the same type of molecule or other type). A β-hydroxycarbonyl product is
formed which may undergo elimination to give an α, β− unsaturated carbonyl product.
A. The Aldol Condensation
Acid Catalyzed
H+
O
H
O
O
R
R
R
H
H
H
H
H
H
H
R
Enol
H
OH
R
OH
Base-Catalyzed
O
O
O
R
R
R
H
H
H
H
Resonance Stabilized Enolate
B
H
R
O
O
O
R
R
H
H
H
R
H
O
R
OH
H-OH
1.
2.
3.
4.
In a simple aldol condensation reaction occurs two molecules of an aldehyde react with each other. The reaction is
usually either acid or base-catalyzed.
One of the aldehyde molecules behaves as a nuleophile and the other aldehyde behaves as an electrophile.
The enol or enolate form of one aldehyde (the nucleophile) attacks the carbonyl carbon atom of the other aldehyde (the
electrophile)
The ß-hydroxyaldehyde which results after the aldol condensation often undergoes dehydration to form an α,ßunsaturated aldehyde.
B:
O
O
H
R
H
R
H
H
R
OH
β-hydroxycarbonyl
H
R
α,β-unsaturated carbonyl
Organic Chemistry
Chapter 23: Carbonyl Condensation Reactions
Lecture Outline
B. Condensation of Ketones
1. Condensation between two ketones occurs under acid or base catalysis.
2. Symmetrical ketones (like acetone) provide a single aldol product.
3. Unsymmetrical ketones results in mixtures of products since more than one enol or enolate can be generated.
C. Crossed or Mixed Aldol Condensation
Acetone
O
O
H
H
H
O
H
CH3
CH3
H
H
B
Enolate derived from acetone
O
H
O
H
H
CH3
HO
H
CH3
O
H
H
β−Hydroxyketone
1.
2.
Crossed aldol condensations occur between different aldehydes or ketones.
a. Crossed condensations can occur between two different aldehydes.
b. Crossed condensations can occur between two different ketones.
c. Crossed condensations can occur between an aldehyde and a ketone. The aldehyde usually behaves as the
electrophile unless the ketone cannot be enolized.
Complex mixtures of products often result in crossed condensation reactions.
D. Intramolecular Aldol Condensation
O
O
H
O
O
H
O
H
H
H
HO
O
1.
2.
3.
Intramolecular aldol condensation occurs between two carbonyl groups in the same molecule to generate a cyclic
product.
Dehydration usually occurs to give the ,ß-unsaturated product.
Usually five- and six-membered rings are formed. Very small rings may not form due to strain energy and entropy
may prevent very large ring formation.
Organic Chemistry
Chapter 23: Carbonyl Condensation Reactions
Lecture Outline
E. Claisen Condensation
O
O
O
R
R
R
OR'
OR'
OR'
H
Resonance Stabilized Enolate
B
OR'
R
O
O
O
R
R
H
OR'
OR'
+
O
R
1.
2.
3.
HOR"
O
R
The Claisen condensation is a condensation reaction between two molecules of the same ester. The reaction is usually
base catalyzed.
The reaction mechanism of the Claisen condensation is analogous to the aldol condensation.
A ß-ketoester product results from a Claisen condensation.
F. Crossed Claisen Condensation
1. A crossed Claisen condensation occurs between two different esters.
2. As in crossed aldol condensations, complex product mixtures result.
G. Diekmann Cyclization
O
O
O
H3CO
H3CO
OCH3
O
H3CO
O
1.
+
H3CO
H3 C
O
The Diekmann cyclization is a intramolecular Claien condensation
II. CONJUGATE ADDITIONS WITH ENOLS AND ENOLATES TO α, β-UNSATURATED CARBONYLS
(MICHAEL ADDITION)
A. CONJUGATE ADDITION OF ENOLS AND ENOLATES
1. Enols and enolates are nucleophiles that react with α,β-unsaturated carbonyls at the number "4" carbon.
2. The reaction between enols or enolats and α,β-unsaturated carbonyls is referred to as a Michael addition.
α,β-unsaturated carbonyl
E+
O
O
O
E
O
H
H
O
enolate
O
H
OH