chapter 21 ester enolates
DESCRIPTION
Chapter 21 Ester Enolates. O. O. C. C. R. C. OR'. H. H. Introduction. The preparation and reactions of b -dicarbonyl compounds, especially b -keto esters, is the main focus of this chapter. - PowerPoint PPT PresentationTRANSCRIPT
Chapter 21Chapter 21Ester EnolatesEster Enolates
IntroductionIntroduction
The preparation and reactions of The preparation and reactions of -dicarbonyl -dicarbonyl compounds, especially compounds, especially -keto esters, is the -keto esters, is the main focus of this chapter.main focus of this chapter.
A proton on the carbon flanked by the two A proton on the carbon flanked by the two carbonyl groups is relatively acidic, easily and carbonyl groups is relatively acidic, easily and quantitatively removed by alkoxide ions.quantitatively removed by alkoxide ions.
CCCCRR
CCOR'OR'
HH HH
OO OO
IntroductionIntroduction
CCCCRR
CCOR'OR'
HH HH
OO OO
CCCCRR
CCOR'OR'
HH
OO OO
••••––
ppKKaa ~ 11 ~ 11
CHCH33CHCH22OO––
IntroductionIntroduction
The resulting carbanion is stabilized by The resulting carbanion is stabilized by enolate resonance involving both carbonyl enolate resonance involving both carbonyl groups.groups.
CCCCRR
CCOR'OR'
HH
OO OO
••••––
•••• ••••••••••••
CCCCRR
CCOR'OR'
HH
OO OO–– •••• ••••••••
••••••••
IntroductionIntroduction
The resulting carbanion is stabilized by The resulting carbanion is stabilized by enolate resonance involving both carbonyl enolate resonance involving both carbonyl groups.groups.
CCCCRR
CCOR'OR'
HH
OO OO
••••––
•••• •••••••••••• •••• ••••
CCCCRR
CCOR'OR'
HH
OO OO––
•••• ••••••••
21.121.1
The Claisen CondensationThe Claisen Condensation
The Claisen CondensationThe Claisen Condensation
-Keto esters are made by the reaction shown, -Keto esters are made by the reaction shown, which is called the Claisen condensation.which is called the Claisen condensation.
Ethyl esters are typically used, with sodium Ethyl esters are typically used, with sodium ethoxide as the base.ethoxide as the base.
2RCH2RCH22COR'COR'
OO1. NaOR'1. NaOR'
2. H2. H33OO++++ R'OHR'OH
OO OO
RCHRCH22CCHCOR'CCHCOR'
RR
ExampleExample
Product from ethyl acetate is called Product from ethyl acetate is called ethylethyl acetoacetateacetoacetate or or acetoaceticacetoacetic esterester..
2CH2CH33COCHCOCH22CHCH33
OO1. NaOCH1. NaOCH22CHCH33
2. H2. H33OO++
OO OO
CHCH33CCHCCH22COCHCOCH22CHCH33
(75%)(75%)
MechanismMechanism
Step 1:Step 1:
CHCH33CHCH22 OO––•••• ••••
••••
••••
COCHCOCH22CHCH33
OO
CHCH22HH
••••
MechanismMechanism
Step 1:Step 1:
CHCH33CHCH22 OO––•••• ••••
••••
••••
COCHCOCH22CHCH33
OO
CHCH22HH
••••
––••••
••••
COCHCOCH22CHCH33
OO
CHCH22CHCH33CHCH22 OO••••
••••HH
••••
MechanismMechanism
Step 1:Step 1:
––••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
––••••
COCHCOCH22CHCH33
OO
CHCH22
•••• ••••
Anion produced is Anion produced is stabilized by electron stabilized by electron delocalization; it is the delocalization; it is the enolate of an ester.enolate of an ester.
MechanismMechanism
Step 2:Step 2:
––••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
CHCH33COCHCOCH22CHCH33
OO ••••••••
MechanismMechanism
Step 2:Step 2:
––••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
CHCH33COCHCOCH22CHCH33
OO ••••••••
CHCH33CC
––OO•••• ••••••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
OCHOCH22CHCH33••••••••
MechanismMechanism
Step 2:Step 2:
CHCH33CC
––OO•••• ••••••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
OCHOCH22CHCH33••••••••
MechanismMechanism
Step 3:Step 3:
CHCH33CC
––OO•••• ••••••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
OCHOCH22CHCH33••••••••
––OCHOCH22CHCH33••••
••••••••
CHCH33CC
OO•••• ••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
++
MechanismMechanism
––OCHOCH22CHCH33••••
••••••••
CHCH33CC
OO•••• ••••
••••
COCHCOCH22CHCH33
OO
CHCH22
••••
++
Step 3:Step 3:
The product at this point is ethyl acetoacetate.The product at this point is ethyl acetoacetate.
However, were nothing else to happen, the yield of ethyl However, were nothing else to happen, the yield of ethyl acetoacetate would be small because the equilibrium acetoacetate would be small because the equilibrium constant for its formation is small.constant for its formation is small.
Something else does happen. Ethoxide abstracts a Something else does happen. Ethoxide abstracts a proton from the CHproton from the CH22 group to give a stabilized anion. group to give a stabilized anion.
The equilibrium constant for this reaction is favorable. The equilibrium constant for this reaction is favorable.
MechanismMechanism
––OCHOCH22CHCH33••••
••••••••
CHCH33CC
OO•••• ••••
••••
COCHCOCH22CHCH33
OO
CCHH22
••••
++
Step 4:Step 4:
++ OCHOCH22CHCH33••••
••••HH
––
••••
COCHCOCH22CHCH33
OO ••••
CHCH33CC
OO•••• ••••
CCHH••••
MechanismMechanism
Step 5:Step 5:
––
••••
COCHCOCH22CHCH33
OO
CHCH33CC
OO•••• ••••
CCHH••••
In a separate operation, the reaction mixture is In a separate operation, the reaction mixture is acidified. This converts the anion to the isolated acidified. This converts the anion to the isolated product, ethyl acetoacetate.product, ethyl acetoacetate.
MechanismMechanism
++
Step 5:Step 5:
––
••••
COCHCOCH22CHCH33
OO
CHCH33CC
OO•••• ••••
CCHH••••
++OOHH ••••
HH
HH
OO
HH
••••
HH
••••CHCH33CC
OO•••• ••••
••••
COCHCOCH22CHCH33
OO
CCHH
••••
HH
Another exampleAnother example
Reaction involves Reaction involves bond formation bond formation between the between the --carboncarbon atom of one atom of one ethyl propanoate ethyl propanoate molecule and the molecule and the carbonyl carbon carbonyl carbon of of the other.the other.
2CH2CH33CHCH22COCHCOCH22CHCH33
OO
1. NaOCH1. NaOCH22CHCH33
2. H2. H33OO++
(81%)(81%)
OO OO
CHCH33CHCH22CCCCHCOCHHCOCH22CHCH33
CHCH33
21.221.2
Intramolecular Claisen Intramolecular Claisen
Condensation:Condensation:
The Dieckmann ReactionThe Dieckmann Reaction
CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CHCH22COCHCOCH22CHCH33
OO OO
1. NaOCH1. NaOCH22CHCH33
2. H2. H33OO++
ExampleExample
COCHCOCH22CHCH33
OO OO
(74-81%)(74-81%)
CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CCHH22COCHCOCH22CHCH33
OO OO
NaOCHNaOCH22CHCH33
viavia
CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CCHHCOCHCOCH22CHCH33
OO OO
••••
––
•••• ••••
•••• ••••
•••• ••••
viavia
CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CCHHCOCHCOCH22CHCH33
OO OO
••••
––
•••• •••••••• ••••
viavia
CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CCHHCOCHCOCH22CHCH33
OO OO
••••
––
•••• •••••••• ••••
CCHHCOCHCOCH22CHCH33
OO
––•••• ••••
CHCH22HH22CC
HH22CC
CC
OO•••• ••••••••CHCH33CHCH22OO
••••
••••
viavia
CCHHCOCHCOCH22CHCH33
OO
––•••• ••••
CHCH22HH22CC
HH22CC
CC
OO•••• ••••••••CHCH33CHCH22OO
••••
••••
viavia
CCHHCOCHCOCH22CHCH33
OO
––•••• ••••
CHCH22HH22CC
HH22CC
CC
OO•••• ••••••••CHCH33CHCH22OO
••••
••••
CHCH33CHCH22OO••••
••••••••––
•••• ••••
CCHHCOCHCOCH22CHCH33
OO
CHCH22HH22CC
HH22CC
CC
OO••••••••
++
21.321.3
Mixed Claisen CondensationsMixed Claisen Condensations
Mixed Claisen CondensationsMixed Claisen Condensations
As with mixed aldol condensations, mixedAs with mixed aldol condensations, mixedClaisen condensations are best carried outClaisen condensations are best carried outwhen the reaction mixture contains one when the reaction mixture contains one compound that can form an enolate and compound that can form an enolate and another that cannot.another that cannot.
Mixed Claisen CondensationsMixed Claisen Condensations
These types of esters cannot form an enolate.These types of esters cannot form an enolate.
HCORHCOR
OO
ROCORROCOR
OO
ROCROC
OO
CORCOR
OO
CORCOR
OO
ExampleExample
1. NaOCH1. NaOCH33
2. H2. H33OO++
(60%)(60%)
CCOCHOCH33
OO
++ CHCH33CCHH22COCHCOCH33
OO
OO OO
CCCCHCOCHHCOCH33
CHCH33
21.421.4
Acylation of Ketones with EstersAcylation of Ketones with Esters
Acylation of Ketones with EstersAcylation of Ketones with Esters
Esters that cannot form an enolate can be Esters that cannot form an enolate can be used to acylate ketone enolates.used to acylate ketone enolates.
ExampleExample
1. NaH1. NaH
2. H2. H33OO++
(60%)(60%)
++CHCH33CHCH22OOCCOCHOCH22CHCH33
OO OO
OO
CCOCHOCH22CHCH33
OO
ExampleExample
1. NaOCH1. NaOCH22CHCH33
2. H2. H33OO++
(62-71%)(62-71%)
CCOCHOCH22CHCH33
OO
++
OO
CCHH33CC
OO
OO
CCCCHH22CC
ExampleExample
1. NaOCH1. NaOCH33
2. H2. H33OO++
(70-71%)(70-71%)
CHCH33CHCH22CCHCCH22CHCH22COCHCOCH22CHCH33
OO OO
OO
OO
CHCH33
21.521.5
Ketone Synthesis via Ketone Synthesis via -Keto -Keto
EstersEsters
Ketone SynthesisKetone Synthesis
-Keto acids decarboxylate readily to give -Keto acids decarboxylate readily to give ketones (Section 19.17).ketones (Section 19.17).
++
OO
RCHRCH22CCHCCH22RR
OO OO
RCHRCH22CCHCOHCCHCOH
RR
COCO22
Ketone SynthesisKetone Synthesis
-Keto acids decarboxylate readily to give -Keto acids decarboxylate readily to give ketones (Section 19.17).ketones (Section 19.17).
-Keto acids are available by hydrolysis of -Keto acids are available by hydrolysis of --keto esters.keto esters.
OO OO
RCHRCH22CCHCOR'CCHCOR'
RR
OO OO
RCHRCH22CCHCOHCCHCOH
RR
HH22OO++ R'OHR'OH
Ketone SynthesisKetone Synthesis
-Keto acids decarboxylate readily to give -Keto acids decarboxylate readily to give ketones (Section 19.17).ketones (Section 19.17).
-Keto acids are available by hydrolysis of -Keto acids are available by hydrolysis of --keto esters.keto esters.
-Keto esters can be prepared by the Claisen -Keto esters can be prepared by the Claisen condensation.condensation.
2RCH2RCH22COR'COR'
OO1. NaOR'1. NaOR'
2. H2. H33OO++++ R'OHR'OH
OO OO
RCHRCH22CCHCOR'CCHCOR'
RR
ExampleExample
1. NaOCH1. NaOCH22CHCH33
2. H2. H33OO++
(80%)(80%)
2 CH2 CH33CHCH22CHCH22CHCH22COCHCOCH22CHCH33
OO
CHCH33CHCH22CHCH22CHCH22CCHCOCHCCHCOCH22CHCH33
OO OO
CHCH22CHCH22CHCH33
ExampleExample
1. KOH, H1. KOH, H22O, 70-80°CO, 70-80°C
2. H2. H33OO++
CHCH33CHCH22CHCH22CHCH22CCHCOCHCCHCOCH22CHCH33
OO OO
CHCH22CHCH22CHCH33
CHCH33CHCH22CHCH22CHCH22CCHCOHCCHCOH
OO OO
CHCH22CHCH22CHCH33
ExampleExample
70-80°C70-80°C
(81%)(81%)
OO
CHCH33CHCH22CHCH22CHCH22CCHCCH22CHCH22CHCH22CHCH33
CHCH33CHCH22CHCH22CHCH22CCHCOHCCHCOH
OO OO
CHCH22CHCH22CHCH33