21.6 The Acetoacetic Ester Synthesis
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21.6 21.6 The Acetoacetic Ester The Acetoacetic Ester Synthesis Synthesis
description
21.6 The Acetoacetic Ester Synthesis. O. O. C. C. H 3 C. C. OCH 2 CH 3. H. H. Acetoacetic Ester. Acetoacetic ester is another name for ethyl acetoacetate . The "acetoacetic ester synthesis" uses acetoacetic ester as a reactant for the preparation of ketones. O. O. C. C. H 3 C. - PowerPoint PPT Presentation
Transcript of 21.6 The Acetoacetic Ester Synthesis
21.621.6
The Acetoacetic Ester SynthesisThe Acetoacetic Ester Synthesis
Acetoacetic EsterAcetoacetic Ester
Acetoacetic ester Acetoacetic ester is another name for is another name for ethylethyl acetoacetateacetoacetate..
The "acetoacetic ester synthesis" uses The "acetoacetic ester synthesis" uses acetoacetic ester as a acetoacetic ester as a reactantreactant for the for the preparation of ketones.preparation of ketones.
CCCC
CCOCHOCH22CHCH33
HH HH
OO OO
HH33CC
Deprotonation of Ethyl AcetoacetateDeprotonation of Ethyl Acetoacetate
CHCH33CHCH22OOCCCC
CCOCHOCH22CHCH33
HH HH
OO OO
HH33CC++
––
ppKKaa ~ 11 ~ 11Ethyl acetoacetate Ethyl acetoacetate can be converted can be converted readily to its anion readily to its anion with bases such as with bases such as sodium ethoxide.sodium ethoxide.
Deprotonation of Ethyl AcetoacetateDeprotonation of Ethyl Acetoacetate
ppKKaa ~ 16 ~ 16
CHCH33CHCH22OOCCCC
CCOCHOCH22CHCH33
HH HH
OO OO
HH33CC++
CCCC
CCOCHOCH22CHCH33
HH
OO OO
••••––HH33CC ++ CHCH33CHCH22OHOH
––
ppKKaa ~ 11 ~ 11Ethyl acetoacetate Ethyl acetoacetate can be converted can be converted readily to its anion readily to its anion with bases such as with bases such as sodium ethoxide.sodium ethoxide.
KK ~ 10 ~ 1055
Alkylation of Ethyl AcetoacetateAlkylation of Ethyl Acetoacetate
CCCC
CCOCHOCH22CHCH33
HH
OO OO
••••––HH33CC
The anion of ethyl The anion of ethyl acetoacetate can be acetoacetate can be alkylated using an alkylated using an alkyl halide (Salkyl halide (SNN2: 2:
primary and primary and secondary alkyl secondary alkyl halides work best; halides work best; tertiary alkyl halides tertiary alkyl halides undergo elimination).undergo elimination).
RR XX
Alkylation of Ethyl AcetoacetateAlkylation of Ethyl Acetoacetate
CCCC
CCOCHOCH22CHCH33
HH
OO OO
••••––HH33CC
The anion of ethyl The anion of ethyl acetoacetate can be acetoacetate can be alkylated using an alkylated using an alkyl halide (Salkyl halide (SNN2: 2:
primary and primary and secondary alkyl secondary alkyl halides work best; halides work best; tertiary alkyl halides tertiary alkyl halides undergo elimination).undergo elimination).
RR XX
CCCC
CCOCHOCH22CHCH33
HH
OO OO
HH33CC
RR
Conversion to KetoneConversion to Ketone
Saponification and Saponification and acidification convert acidification convert the alkylated the alkylated derivative to the derivative to the corresponding corresponding -keto -keto acid.acid.
The The -keto acid then -keto acid then undergoes undergoes decarboxylation to decarboxylation to form a ketone.form a ketone.
CCCC
CCOCHOCH22CHCH33
HH
OO OO
HH33CC
RR
CCCC
CCOHOH
HH
OO OO
HH33CC
RR
1. HO1. HO––, H, H22OO2. H2. H++
Conversion to KetoneConversion to Ketone
Saponification and Saponification and acidification convert acidification convert the alkylated the alkylated derivative to the derivative to the corresponding corresponding -keto -keto acid.acid.
The The -keto acid then -keto acid then undergoes undergoes decarboxylation to decarboxylation to form a ketone.form a ketone.
CCCC
CCOHOH
HH
OO OO
HH33CC
RR
CCCHCH22RR
COCO22
OO
HH33CC++
ExampleExample
1. NaOCH1. NaOCH22CHCH33
2. 2. CHCH33CHCH22CHCH22CHCH22BrBr
OO OO
CHCH33CCHCCH22COCHCOCH22CHCH33
ExampleExample
(70%)(70%)
1. NaOCH1. NaOCH22CHCH33
2. 2. CHCH33CHCH22CHCH22CHCH22BrBr
OO OO
CHCH33CCHCCH22COCHCOCH22CHCH33
OO OO
CHCH33CCHCOCHCCHCOCH22CHCH33
CHCH22CHCH22CHCH22CHCH33
ExampleExample
(60%)(60%)
OO
CHCH33CCHCCH22CHCH22CHCH22CHCH22CHCH33
1. NaOH, H1. NaOH, H22OO
2. H2. H++
3. heat, -CO3. heat, -CO22
OO OO
CHCH33CCHCOCHCCHCOCH22CHCH33
CHCH22CHCH22CHCH22CHCH33
Example: Example: DialkylationDialkylation OO OO
CHCH33CCCCHHCOCHCOCH22CHCH33
CHCH22CHCH CHCH22
Example: Example: DialkylationDialkylation
1. NaOCH1. NaOCH22CHCH33
2. 2. CHCH33CHCH22II
OO OO
CHCH33CCCCHHCOCHCOCH22CHCH33
CHCH22CHCH CHCH22
OO
CHCH33CCCOCHCCCOCH22CHCH33
CHCH22CHCH CHCH22
OO
CHCH33CHCH22
(75%)(75%)
1. NaOH, H1. NaOH, H22OO
2. H2. H++
3. heat, -CO3. heat, -CO22
OO
CHCH33CCCOCHCCCOCH22CHCH33
CHCH22CHCH CHCH22
OO
CHCH33CHCH22
Example: Example: DialkylationDialkylation
CHCH33CCHCCH CHCH22CHCH CHCH22
OO
CHCH33CHCH22
Another Another ExampleExample OO OO
HH
COCHCOCH22CHCH33
-Keto esters other than ethyl acetoacetate -Keto esters other than ethyl acetoacetate may be used.may be used.
Another Another ExampleExample OO OO
HH
COCHCOCH22CHCH33
1. NaOCH1. NaOCH22CHCH33
2. 2. HH22CC CHCHCHCH22BrBr
OO OO
CHCH22CHCH
COCHCOCH22CHCH33
CHCH22(89%)(89%)
Another Another ExampleExample
OO OO
COCHCOCH22CHCH33
CHCH22CHCH CHCH22
Another Another ExampleExample OO
HH
OO OO
COCHCOCH22CHCH33
CHCH22CHCH CHCH22
1. NaOH, H1. NaOH, H22OO
2. H2. H++
3. heat, -CO3. heat, -CO22
CHCH22CHCH CHCH22 (66%)(66%)
21.721.7
The Malonic Ester SynthesisThe Malonic Ester Synthesis
Malonic EsterMalonic Ester
Malonic ester Malonic ester is another name for is another name for diethyldiethyl malonatemalonate..
The "malonic ester synthesis" uses diethyl The "malonic ester synthesis" uses diethyl malonate as a malonate as a reactantreactant for the preparation of for the preparation of carboxylic acids.carboxylic acids.
CCCC
CCOCHOCH22CHCH33
HH HH
OO OO
CHCH33CHCH22OO
An AnalogyAn Analogy
OO OO
CHCH33CCHCCH22COCHCOCH22CHCH33
OO OO
CHCH33CHCH22OCCHOCCH22COCHCOCH22CHCH33
OO
CHCH33CCHCCH22RR
OO
HOCCHHOCCH22RR
The same procedure by which ethyl The same procedure by which ethyl acetoacetate is used to prepare ketones acetoacetate is used to prepare ketones converts diethyl malonate to carboxylic acids. converts diethyl malonate to carboxylic acids.
ExampleExample
1. NaOCH1. NaOCH22CHCH33
OO OO
CHCH33CHCH22OCCHOCCH22COCHCOCH22CHCH33
HH22CC CHCHCHCH22CHCH22CHCH22BrBr2.2.
CHCH22CHCH22CHCH22CHCH22CHCH
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33
(85%)(85%)
ExampleExample
(75%)(75%)
1. NaOH, H1. NaOH, H22OO
2. H2. H++
3. heat, -CO3. heat, -CO22
CHCH22CHCH22CHCH22CHCH CHCH22
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33
OO
HOCCHHOCCH22CHCH22CHCH22CHCH22CHCH CHCH22
DialkylationDialkylation
1. NaOCH1. NaOCH22CHCH33
OO OO
CHCH33CHCH22OCCHOCCH22COCHCOCH22CHCH33
2. 2. CHCH33BrBr
CHCH33
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33 (79-83%)(79-83%)
DialkylationDialkylation
1. NaOCH1. NaOCH22CHCH33
OO OO
CHCH33CHCH22OCCCOCHOCCCOCH22CHCH33
2. 2. CHCH33(CH(CH22))88CHCH22BrBr
CHCH33CHCH33(CH(CH22))88CHCH22
CHCH33
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33
DialkylationDialkylation OO OO
CHCH33CHCH22OCCCOCHOCCCOCH22CHCH33
CHCH33
OO
CHCH33(CH(CH22))88CHCH22CHCOHCHCOH
CHCH33CHCH33(CH(CH22))88CHCH22
1. NaOH, H1. NaOH, H22OO
2. H2. H++
3. heat, -CO3. heat, -CO22
(61-74%)(61-74%)
Another Another ExampleExample
1. NaOCH1. NaOCH22CHCH33
OO OO
CHCH33CHCH22OCCHOCCH22COCHCOCH22CHCH33
2. Br2. BrCHCH22CHCH22CHCH22BrBr
CHCH22CHCH22CHCH22BrBr
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33
Another Another ExampleExample
This product is not isolated, but cyclizes in the This product is not isolated, but cyclizes in the presence of sodium ethoxide.presence of sodium ethoxide.
CHCH22CHCH22CHCH22BrBr
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33
Another Another ExampleExample
NaOCHNaOCH22CHCH33
CHCH22CHCH22CHCH22BrBr
OO OO
CHCH33CHCH22OCCHCOCHOCCHCOCH22CHCH33
OO OO
CHCH33CHCH22OCCCOCHOCCCOCH22CHCH33
HH22CC CHCH22
CCHH22
(60-65%)(60-65%)
Another Another ExampleExample
OO OO
CHCH33CHCH22OCCCOCHOCCCOCH22CHCH33
HH22CC CHCH22
CCHH22 1. NaOH, H1. NaOH, H22OO
2. H2. H++
3. heat, -CO3. heat, -CO22
HH22CC CHCH22
CCHH22
CC
HH COCO22HH
(80%)(80%)
