Transcript Chapter 11: Reactions at an sp3 Hybridized Carbon III

Carbonyl Compounds III:
Chapter 13
Chapter 13
1
Contents of Chapter 13






Acidity of Alpha Hydrogens
Keto-enol Tautomers
Alkylation of Enolate Ions
Aldol Condensation
No Claisen, Malonic/Acetoacetic Ester, or
Decarboxylation
No Bioloogical Reactions
Chapter 13
2
Acidity of a Hydrogens
In the presence of a strong base, a proton a to
a carbonyl group can be removed to form an
enolate ion stabilized by electron
delocalization:
O
CH3
C
B
CH2
H
CH3
O
O
C
C
CH2
CH3
CH2
resonance-stabilized enolate ion
Chapter 13
3
Alkylation of Enolate
Ions
Enolate ions are alkylated (bonds made to carbon) at
the alpha carbon:
Chapter 13
4
Product Analysis
Polarize the alpha carbon negative and an alpha
hydrogen positive and swap partners with the
positive and negative fragments of the alkylating
reagent
Chapter 13
5
Acidity of a Hydrogens
Reprotonation of the enolate ion can give an enol:
O
C
CH3
CH2
keto form
B
H
CH3
O
O
C
C
CH2
CH3
CH2
resonance-stabilized enolate anion
BH
OH
C
CH3
CH2
enol form
This is Base-Catalyzed Enolization
Chapter 13
6
Keto–Enol Tautomerism



Under ordinary conditions, all aldehydes and
ketones are in equilibrium with the
corresponding enol forms.
Interconversion of these isomers is catalyzed
by acids or bases.
For most simple aldehydes and ketones, the
equilibrium lies on the side of the keto form
because the carbon–oxygen double bond is
stronger than a carbon–carbon double bond.
Chapter 13
7
Acid-Catalyzed Enolization
O
CH3
C
O
H
CH3
protonation
CH3
O
deprotonation
-H
CH3
C
Chapter 13
C
H
CH2 H
H
CH2
8
Sample Problem
Draw two enol forms for the following compound:
O
CH3
C
CH
CH3
CH3
OH
CH3
C
C
CH3
OH
CH3
CH3
CH
C
CH2
CH3
Chapter 13
9
The Aldol Reaction

The most important reaction of an
enolate anion derived from an aldehyde
or ketone is nucleophilic addition to the
carbonyl group of another carbonylcontaining compound.
O
CH3
C
O
+
H
CH3
C
NaOH
H
CH3
acetaldehyde
Chapter 13
OH
O
CH
C

CH2
a
3-hydroxybutanal (aldol)
(a -hydroxyaldehyde)
H
10
Mechanism of the Aldol
Addition

Step 1 – Deprotonation:
O
H CH2
C
OH
H
CH2
O
O
C
C
H
CH2
H
resonance-stabilized enolate anion
Chapter 13
11
Mechanism of the Aldol
Addition

Step 2 – Nucleophilic Addition of
Enolate Ion:
O
CH3
C
+
H
CH2
O
O
O
C
C
C
CH3
H
H
CH2
H
tetrahedral intermediate
Chapter 13
12
Mechanism of the Aldol
Addition

CH3
Step 3 – Reaction of alkoxide
anion with solvent (protonation):
O
O
C
C
H
CH2
H
O
H
H
CH3
Chapter 13
OH
O
C
C
H
CH2
H
aldol
13
Dehydration of Aldol Products
-Hydroxyaldehydes and hydroxyketones are very easily
dehydrated to give a,-unsaturated
aldehydes or ketones.
CH3
OH
O
CH
C
CH2
O
H2O
H
CH3
Chapter 13
CH

CH
a
C
H
14
Aldol Reaction Product
Analysis
•
•
•
To figure out dehydration product of aldol reaction place carbonyl O of
one molecule under 2 alpha H’s of the other molecule
Erase the H’s and the O
Extend the carbonyl double bond from the carbonyl C of the lower
molecule to the alpha carbon of the upper molecule
Chapter 13
15
Aldol Reaction Product
Analysis
Chapter 13
16
Retrosynthetic Analysis

Draw structural formulas for the two carbonylcontaining compounds that react to give
cinnamaldehyde:
Chapter 13
17