Ester Enolates

O O

C C
R C OR'
H H

The preparation and reactions of -dicarbonyl

compounds, especially -keto esters, is the
main focus of this chapter.
 -H is Acidic carbanion is stabilized by enolate resonance
involving both carbonyl groups.

O O

C C
R C OR' pKa ~ 11
H H
–
CH3CH2O
•• • ••
•• O
–• •• • •O••
O• • O• •

C •• C C C
R –C OR' R C OR'

H H
 The Claisen Condensation
Synthesis of -Keto esters

O O O
1. NaOR'
2RCH2COR' RCH2CCHCOR' + R'OH
2. H3O +

-Keto esters
R

O O O
1. NaOCH2CH3
2CH3COCH2CH3 CH3CCH2COCH2CH3
2. H3O+
(75%)
ethyl acetoacetate or acetoacetic ester.
 Mechanism

Step 1: Form nucleophile by removing acidic -H.

•• •
O•
•• • –
CH3CH2 O• H CH2 COCH2CH3
••

•• •
O•
•• –
•• CH
CH3CH2 O H 2 COCH2CH3
••
Mechanism

•• • •• •
O• O•
–
• CH
CH3COCH2CH3 • 2 COCH2CH3

Step 2: Nucleophile formed from

one ester attacks carbon of • •• • – •• •
a second ester molecule • O • O•

CH3C CH2 COCH2CH3

•• OCH CH
2 3
••
Mechanism

Step 3: •• • –
•• O •• •
• O•
Leaving
group CH3C CH2 COCH2CH3
leaves
•• OCH CH
2 3
••

•• • •• •
O• O•
– • ••
CH3C CH2 COCH2CH3 + • OCH2CH3
••
Acid Base
 Mechanism
Step 4: Acid-base reaction
•• • •• •
O• O•
– • ••
CH3C CH2 COCH2CH3 + • OCH2CH3
••
•• • •• •
O• O•
– ••
CH3C CH COCH2CH3 + H OCH2CH3
•• ••

Step 5: Add acid to protonate negative ion.

 Another example O

2CH3CH2COCH2CH3
Reaction involves 1. NaOCH2CH3
bond formation
2. H3O+
between the -
carbon atom of one
ethyl propanoate O O
molecule and the
carbonyl carbon of CH3CH2CCHCOCH2CH3
the other.
CH3

(81%)
Another example
Intramolecular Claisen Condensation:
The Dieckmann Reaction

O O

CH3CH2OCCH2CH2CH2CH2COCH2CH3

1. NaOCH2CH3
2. H3O+

O O

COCH2CH3

(74-81%)
Step 1; Form Nucleophile by abstracting acidic -H
•• •
O• O

CH3CH2OCCH2CH2CH2CH2COCH2CH3

NaOCH2CH3

•• • •• •
O• O•
–
CH3CH2OCCH2CH2CH2CHCOCH2CH3
••
Step 2: Intramolecular reaction; Nu attacks electrophilic carbon
•• •O•• •–
CH3CH2O • •
•• •
•• O•
C
H2C CHCOCH2CH3

H2C CH2

•• • •• •
O• O•
–
CH3CH2OCCH2CH2CH2CHCOCH2CH3
••
Step 3; Reform carbonyl group; leaving group leaves
•• •• •–
•O
CH3CH2O • •
•• •
•• O•
C
H2C CHCOCH2CH3

H2C CH2

••
•• O
•• •
O•
C
•• •–
CH3CH2O • + H2C CHCOCH2CH3
••
H2C CH2
Mixed Claisen Condensations
work best when the reaction mixture contains
one compound that can form an enolate and
another that cannot.

O O O O

HCOR ROCOR ROC COR

These esters
O
cannot form
an enolate. COR
Example
O O

COCH3 + CH3CH2COCH3

1. NaOCH3
2. H3O+

O O

CCHCOCH3 (60%)

CH3
 Acylation of Ketones with Esters
O
O

CH3CH2OCOCH2CH3 +

1. NaH
2. H3O+
Esters that cannot
O
form an enolate can O
be used to acylate COCH2CH3
ketone enolates.
(60%)
Example
O O

COCH2CH3 + CH3C

1. NaOCH2CH3
2. H3O+

O O

CCH2C

(62-71%)
Example
O O

CH3CH2CCH2CH2COCH2CH3

1. NaOCH3
2. H3O+

O O

CH3
(70-71%)
 Ketone Synthesis via -Keto Esters

O O
1. NaOR' heat
2RCH2COR' RCH2CCHH
2. H3O +

1. Form -keto ester from two esters.

2. Add water to hydrolyze ester and form -
keto acid.
3. Decarboxylate (-CO2) -ketoester.
 O O O
1. NaOR'
2RCH2COR' RCH2CCHCOR' + R'OH
2. H3O +

Step 1: Form -keto ester from two esters.

Step 2: Hydrolysis of Ester to form -keto acid.

O O
H+
RCH2CCHCOR' + H2O

O O

RCH2CCHCOH + R’OH

R
Step 3: Decarboxylation (-CO2) to form Ketone

O O O
heat
RCH2CCHCOH RCH2CCHH
R R

+ CO2
Example; Step 1- Formation of -ketoester
O

2 CH3CH2CH2CH2COCH2CH3

1. NaOCH2CH3
2. H3O+
O O

CH3CH2CH2CH2CCHCOCH2CH3

CH2CH2CH3
(80%)
Example(cont): step 2: Hydrolysis to form b-keto acid

O O

CH3CH2CH2CH2CCHCOCH2CH3 1. KOH, H2O, 70-80°C

2. H3O+
CH2CH2CH3

O O

CH3CH2CH2CH2CCHCOH

CH2CH2CH3
Example (cont): Step 3: Decarboxylation to form ketone

O O

CH3CH2CH2CH2CCHCOH

CH2CH2CH3

70-80°C

CH3CH2CH2CH2CCH2CH2CH2CH3

(81%)