1. Chapter 16 Synthesis and Reactions of β- Dicarbonyl Compounds
(Ester Enolates)
16.1 β – Dicarbonyl compounds
16.2 Acidity of β – dicarbonyl compounds
16.3 The Claisen Condensation
16.4 Intramolecular Claisen condensation:
The Dieckmann Reaction
16.5 Mixed (crossed) Claisen Condensation
16.6 Acylation of ketones
16.7 Ketone synthesis via β- keto esters
16.8 The acetoacetic ester synthesis
The Malonic ester synthesis
16.10 α- Deprotonation of carbonyl
compounds by Lithium dialkylamides

2. 16.2 Acidity of β – Dicarbonyl compounds
α,β- diketone
α,β- keto ester
A malonic ester
Two carbonyl groups were separated
by an intervening carbon
16.2 Acidity of β – Dicarbonyl
compounds
pKa=9~11

3. 16.3 The Claisen Condensation
P369
11.10
16.3 The Claisen Condensation
On treatment with alkoxide base, esters
undergo self-condensation to give a
α,β- keto ester and an alcohol:
Ethyl acetate Ethyl acetoacetate (75%)
Ethyl 3-oxobutanoate

4. Mechanism of Claisen condensation
Step 1 Proton abstraction to give the ester
enolate ion
Step 2 Nucleophilic addition of ester enolate
ion to the carbonyl group of the ester or
Anion of
tetrahedral
intermediate
Ester
Ester enolate

5. Step 3 Dissociation of the tetrahedral
intermediate
Step 4 Deprotonation of β- keto ester
Step 5 Protonation of the anion to give
β- keto ester (Acidification)

6. The features of the reaction: One mole. of ester with two α- hydrogen:
RCH2COOR’
2. Deprotonation of β- keto ester
and acidification
3. The formation of C–C bond between
the α- carbon atom of one mole. and the
carbonyl carbon of another
4. The formation of a product with two
functional groups

7. 16.4 Intramolecular Claisen Condensation The Dieckmann Reaction
Ch.P407
Intramolecular Claisen condensation
The diesters
To form a five- or six- membered ring
Ethyl 2-oxocyclo-
pentanecarboxylate
(74-81%)
Diethyl hexanedioate
Dieckmann cyclization

8. as professor of chemistry
C. R. Hauser and B. E. Hudson,
Organic Reactions, 1, 274 (1942) D. E. Wolf and K. Folkers,
Organic Reactions, 6, 449 (1951) B. S. Thyagarajan, Chem. Revs.,
54,1029(1954) N. J. Leonard and C. W. Schimelpfenig,
J. Org. Chem., 23, 1708 (1958) H. H. House, Modern Synthetic Reactions,
p 261 (New York, 1965)
Walter Dieckman
( ) was
born in Harmburg,
Germany, and received
his Ph.D. at the
University of Munich
as professor of chemistry

9. 16.5 Mixed (crossed) Claisen Condensation
RCH2COOR’
Carry:P836, 21.3
Esters:
Formate
Ester
Carbonate
Oxalate
Benzoate

10. 16.6 Acylation of ketones The ketone containing two α- H at least
Carry:P837, 21.4
The ketone containing two α- H at least
reacts with esters, the ketone was acylated:
1. NaOEt
2. H3O+
Acylation of ketone is observed at the
presence of ester, instead of aldol addition
of ketones

11. 16.7 Ketone synthesis via β- keto esters
The decarboxylation of β- keto acids
Ch.P408,
(2)
The similar way as dicarboxylic acids
β- keto esters
β- keto acids
ketones
Synthesis of β- keto ester by Claisen
condensation.

12. Hydrolysis (Saponification) 16.8 The acetoacetic ester synthesis
Claisen
condensation
Decarbo-
xylation
16.8 The acetoacetic ester synthesis
Ch.P409,
(3)
Ethyl acetoacetic ester is a stronger acid:
The anion produced from acetoacetic ester
acts as a nucleophile: SN2 reaction with
alkyl halides.

13. Transformation of the functional groups: The acidity of α- H of
Alkylation of
α- carbon.
Transformation of the functional groups:
The acidity of α- H of
acetoacetic ester
2. Decarboxylation of β-
keto acids
Structural
unit – Synthon
Carry:P840

14. The synthesis of two substituted β- keto esters:
Dialkylation of β- keto esters:
3-Ethyl-5-
hexen-2-one (48%)
The other β- keto esters are also dialkylated:

15. Synthetic equivalent:
2-Allylcyclohexanone
(66%)
Synthetic equivalent:
R’–Ｘ
R”–Ｘ
Enolates of ketones C H 3 O E t R
Anion of acetoacetic ester
orβ- keto ester
is synthetic equivalent
to enolates of ketones

16. 16.9 The Malonic ester synthesis
The synthesis of mono- or
disubstituted acetic acids
Diethyl malonate
The precursor
The transformation of functional groups:
Synthon
P363

17. Hydrolysis, decarboxylation
Anion from malonic ester
Mono-alkylation
1.NaOH, H2O
2. H+, △
Hydrolysis,
decarboxylation
Dialkylation

18. Preparation of cycloalkane carboxylic acids:RX
R’COOH
1. By Grignard reagent 2.
3. By malonic ester
(80%)

19. Lithium diisopropylamide
16.10α- Deprotonation of carbonyl
compounds by Lithium dialkylamides
Carry:
P847,
21.10
Ester enolate
Alkoxide ions:
RO–
pKa= ~22
Lithium diisopropylamide
(LDA)
Basicity：

20. （92%）

21. Direct Alkylation of ketones, Esters,
and Nitriles
Lactone
Butyrolactone
(丁内酯 )
2-Methylbutyrolactone
(2-甲基丁内酯 )(88%)
Ester
Ethyl 2-methyl-
propanoate
Ethyl 2,2-dimethyl-
propanoate(87%)
Ketone
2-Methylcyclohexanone
2,6-Dimethylcyclohexanone
(56%)

22. Additional Problems:
Ch. P403
1. Predict the product(s) of the following
reaction:
(b)
(a)
(c)
(d)

23. (b) (a) (c) 2. How would you prepare the following
compounds using an acetoacetic ester
synthesis or a malonic ester synthesis?
(b)
(a)
(c) 3.
4. How would you synthesize the following
compounds from cyclohexanone? More
than one step may be required.

24. 5. How might the following compounds be
prepare using Micheal addition? Show
the nucleophilic donor and the electrophilic
acceptor in each case.
6. Fill in the missing reagents a-h in the following
scheme and give the name of each reaction.
7. How would you prepare the following
compounds from cyclohexanone?