1. Chapter 15 Enols and Enolates
（烯醇与烯醇负离子）
15.1 The acidity of the αhydrogens of
carbonyl compounds: enolate ions
15.2 Keto and Enol tautomers
15.3 αHalogenation of aldehydes and
ketones
15.4 The Haloform Reaction
15.5 The Aldol Condensation（羟醛缩合）
Mechanism for the aldol addition
The features of aldol addition
Mixed aldol condensation
Claisen-Schmidt condensation

2. 15.6 Nucleophlic addiotion to αβ-unsaturate
aldehydes and ketones
,2 addition and 1,4 addition
The Micheal reaction
Conjugate addition of organocopper
reagents
15.7 Alkylation of enolate ions

3. The acidity of the αhydrogens of carbonyl compounds: enolate ions
αHydrogens are acidic:
βhydrogen
αhydrogen
Pka:
When a carbonyl compound
loses an αproton, the anion called enolate is
produced: A B
Enolate is stabilized
by resonance
Enolates (烯醇负离子）

4. Lithium diisopropylamide
p-πconjugation H -
Na+H -
Sodium hydride
(氢化钠)
Lithium diisopropylamide
(二异丙基氨基锂)
(LDA)
Cyclohexanone
Enolate ion(100%)

5. Table 15.1 Acidity Constants for Some Organic Compounds
Compound pKa
CH3COOH
CH2(COCH3)2
CH3COCH2CO2CH3
CH2(CO2CH3)2
H2O
CH3CH2OH
CH3COCl
CH3CHO
CH3COCH3
CH3CN
CH3CON(CH3)2
NH3 5 9 11 13
15.74 16 17 19 25 30 35
Table 15.1 Acidity Constants for
Some Organic Compounds
P361

6. Keto and Enol tautomerism
(酮式与烯醇式互变异构）
P353
Aldehydes and ketones containing α-
hydrogen are in equilibrium with their
enol isomers
Tautomerization
（互变异构）
Keto and enol form are called tautomers
Keto form Enol form
Acetaldehyde
(~100) (Extremely small)
Acetone
(>99%) (1.5×10-4)
Cyclohexanone
Keto Enol
(98.8%) (1.2%)
The bond of C=O
is stronger than
C=C

7. In β-dicarbonyl compounds, two carbonyl
groups are separated by one－CH2－group
2,4-Pentanedinone
（2,4-戊二酮）
(24%)
Enol form
(76%)
Resonance stabilization of the enol form

8. αHalogenation of aldehydes and ketones
Aldehydes and ketones react with halogens
by substitution of one of the αhydrogen
P356
11.3
Features of the reaction:
Acid –catalyzed
Regiospecific
Aldehydic hydrogen isn’t affected

9. Mechanism of αhalogenation of aldehydes
and ketones
Step 1 Acid-catalyzed formation of
an enol
Step 2 Reaction of the enol with halogen

10. The Haloform (卤仿)Reaction
Ch.P349
A methyl ketone react with a halogen in the
present of base, multiple halogenations
occur at the carbon of -CH3
The dissociation of the trihalomethylketone
in aqueous base, to produce carboxylate
（羧酸盐）and the haloform
CHI3 is yellow
Precipitate
(沉淀）
The haloform
reaction using I2
Indentification

11. 15.5 The Aldol Condensation(羟醛缩合)
2 Molecules of aldehydes
To form hydroxy
aldehyde
Dilute sodium hydroxide
P366
11.8
Acetaldehyde
3-hydroxybutanal
aldehyde + alcohol = aldol
Aldol addition , aldol reaction or aldol
condensetion
Mechanism for the aldol addition:
Step 1 Base-catalyzed formation of enolate
ion:
Enolate ion

12. Step 2 The nucleophilic addition of enolate
to carbonyl group:
Step 3 The alkoxide ion abstracts a proton
from water to form aldol:

13. 15.5.2 The features of aldol additions:
Carbon-carbon bond formation between
theα-carbon atom of one aldehyde and
the carbonyl group of another.
2. Dehydration of addition product
The addition product ( aldol + OH－）is
heated,hydration occurs to form α,β-
unsaturated aldehyde:
π-π
conjugation

14. 3. Reversible reaction. the equilibrium of
aldol reation for ketones is unfavorable.
Intra-molecular aldol condensation:
Bicyclo[5.3.0]dec-1(7)-
en-2-one(96%)
（二环[5.3.0]-1-癸烯-2-酮）
1.6-Cyclodecanedione
（1,6-环癸二酮）

15. 15.5.3 Mixed aldol condensation
4. The product with two functional groups:
Insect
repellent
Mixed aldol condensation
Only one of the reactant can form an enolate.
One of the reactant is more reactive toward
nuelophilic addition than other.

16. Claisen-Schmidt condensation Ketones react with aromatic aldehyde
in the presence of base, to give mixed aldol
condensation product:
benzaldehyde
acetone
4-Phenyl-3-buten-2-one
（4-苯基-3-丁烯-2-酮）(70%)
The enolate of ketone as a nucleophile
attacks the carbonyl group of aromatic
aldeyhyde.
2-Hydroxymethyl-
3-methylbutanal
(3-甲基-2-羟甲基丁醛)

17. Claisen, Ludwig Born: Köln (Germany), 1851 Died: Godesberg near Bonn
enc/fecs/Claisen.htm

18. Conjugate addition（共轭加成）
15.6 Conjugation addition to α,β-
unsaturated aldehydes and ketones
,2 addition and 1,4 addition
The nucleophilic addition of α,β- unsaturated
aldehydes or ketones
may be in two way:
1,2-addition
Direct addition
（直接加成）
The resonance
structure:
1,4-addition
Conjugate addition（共轭加成）

19. When the nucleophile is stronger base,
General roles:
When the nucleophile is stronger base,
1,2 addition is often observed: RMgX,
RLi, LiAlH4.
2. When the nucleophile is weaker base,
conjugate addition is observed:
(95%)

20. 15.6.2 The Micheal Reaction 3. 1,2 addition－Kinetic control
1,4 addtion－Thermodynamic control
1,2 addition product retains C=C bond,
1,4 addition product retains C=O bond.
carbon-oxygen double bonds are more stable
than carbon-carbon double bonds
The Micheal Reaction
Ch.P413
Conjugate additions of enolate ions
(or carbanions)to α,β-unsaturate carbonyl
compounds－Micheal addition(迈克尔加成)
or Micheal reaction.
Enolate ions or carbanions: derived from
β- dicarbonyl compounds.

21. Robinson annulation Intromecular aldol addition
2-Methyl-1,3-
Cyclohexanedione
（2-甲基-1,3-环己二酮）
Methyl
vinyl ketone
（甲基乙烯基甲酮）
2-Methyl-2-
(3’-oxobutyl)-
1,3-cyclohexanediol)
[2-甲基2-(3’-氧代丁基)-
1,3-环己二酮](85%)
(65%)
Robinson annulation
Intramolecular
Aldol addition
product
Micheal addition +
Intromecular aldol
addition

22. Micheal addition of stabilized anions 3-oxocyclohexylacetic acid
2-Cyclohexenone
（2－环己烯酮）
Diethyl,3-oxocyclohexyl-
malonate
(3-氧代环己基丙二酸二乙酯)
(90%)
3-oxocyclohexylacetic acid
(3-氧代环己基乙酸)
Problem:

23. Arthur Micheal Arthur Micheal(1853-1942) was
Arthur Micheal( ) was
born to a wealthy family in Buffalo,
New York. Although he received no
formal university degree,he studied
in Heidelberg,Berlin,and the École
de Médecine,Paris.Returning to the
United State, he became Professor
of Chemistry at Tufts University
and then at Harvard University
( ).Perhaps his most impor-
tant contribution to science was his
instrumental role in bring the
European model of gradual
education to the United State.
Arthur Micheal

24. United Kingdom University of Oxford Oxford, United Kingdom
Sir Robert Robinson
United Kingdom University of Oxford Oxford, United Kingdom
b d. 1975
The Nobel Prize in Chemistry 1947

25. Robinson received the 1947 Nobel Prize in Chemistry for his work
on the synthesis of natural products, especially the alkaloids.
His 1917 landmark one-step synthesis of tropinone from three
simple precursors at room temperature in dilute aqueous solution
was the forerunner of modern biomimetic syntheses. He did
structural and synthetic work on other alkaloids (strychnine,
morphine, brucine), on steroids (cholesterol), on wood dyes
(brazilin, haematoxylin), and on the coloring matter of flowers
(anthocyanins). In connection with steroid synthesis, he developed
a general method for constructing a six-membered ring onto a
ketone with an enolizable hydrogen (Robinson annulation).
In the mid-1920s, Robinson introduced his electronic theory
of organic reactions, and used it to rationalize orientation in
electrophilic aromatic substitution. The curved arrow used by
chemists to represent electron displacements was first used in
this way by Robinson (1924). Robinson wrote over 500 papers
and several books on natural products but in addition he was
an avid chess player who wrote "The Art and Science of Chess:
A Step-by-Step Approach".
HH_LName=Robinson

26. 15.6.3 Conjugate addition of organo- copper reagents
Organocopper reagents (CuLiR2) undergo
conjugate addition toα,β-unsaturated
carbonyl compounds:
98% %
Lithium dialkylcuprates adds predominantly
in the less-hindered way to give the product
with the alkyl groups trans to each other.

27. 15.7 Alkylation of enolate ions
Enolate ions derived from β- dicarbonyl
compounds react with alkyl halide by SN2
mechanism :
P362
11.6
2,4-Pentanedione
（2,4-戊二酮）
Iodo-
methane
3-Methyl-
2,4-pentanedione
Enolate ions of β- dicarbonyl compounds
are more stables than aldehydes or ketones.
p-π conjugation
2. Alkyl halide: CH3X,
RCH2X,