Chapter 12 Aldehydes and Ketones
Nucleophilic Addition to
Carbonyl Group
12.1
12.2
12.3
12.4
Nomenclature
Structure of Carbonyl Group
Preparation of aldehydes and ketones
Nucleophilic addition of aldehydes and
ketones
12.4.1 Hydration of aldehydes and ketones
12.4.2 The addition of hydrogen cyanide
12.4.3 The addition of alcohols
12.4.4 The addition of amines
12. 5 The Addition of Ylides:
the Wittig Reaction
12.5.1 Ylides (叶立德)and Preparation of
phosphorous ylides
12.5.2 Mechanism of the Wittig reaction
12.5.3 Synthesis of alkenes by
Wittig reactions
12.6 Oxidation of Aldehydes and ketones
12.6.1 Oxidation of Aldehydes
12.6.2 Baeyer-Villiger oxidation of ketones
12.7 Spectroscopic analysis of aldehydes
and ketones
Aldehydes and Ketones
O
C
O
O
O
H C H
R C H
R C R
Carbonyl group Formaldehyde Aldehyde Ketone
羰基
甲醛
12.1 Nomenclature
O
O
O
C
C
C H
O
R C
Formyl
Ar
Acyl
Aroyl
醛基
酰基
酮
醛
芳酰基
Ph
Benzoyl
芳酰基
General role:
• The longest continuous chain with
carbonyl group is as a parent, suffix:
e al or one. To ketones, numbered
the number of carbonyl group.
O
O
CH3CHCH2C H
CH3
P284
9.3
CH3
CH3CH2CCHCH2CH3
O
CH3
3-Methylbutanal 4-Methyl-3-hexanone
3-甲基丁醛
4-甲基-3-己酮 4-Methylcyclohexanone
4-甲基环己酮
O
CHO
C
CH2 CHCH CH C H
CH3 CH3
O
Benzophenone
Benzaldehyde
二苯甲酮
2,3-Dimethyl-4-pentenal
2,3-二甲基-4-戊烯醛
苯甲醛
O
2. When –CHO is attached to a ring, CH2CCH2CH3
suffix is -aldehyde or -carbaldehyde
(以甲醛为母体)
Benzyl ethyl ketone
乙基苄基甲酮
3. Alkyl groups are as substitutes,
“ketone” are as parent
12.2 Structure of Carbonyl Group
C O
C C
sp2- hybridized
πbond
Trigonal plane
¦Ä
C
¦Ä
O
Acetaldehyde
(乙醛)
Polarized
Dipole moment
μ = 2.3 ~ 2.9D
Resonance
structures:
C
O
C O
Electron
delocalization
O
CH3 C CH3
Polar solvent
-
O
+C
Acetone
Nucleophilic
H+,E+
Electrophilic
-
OH-,Nu:
(丙酮)
P283,
9.2
Reaction sites and
reactions of aldehydes and ketones
Nucleophilic addition
Oxidation
And reduction
O
C C
H
Reaction of
α -hydrogen
R (H)
12.4 Nucleophilic Addition of Aldehydes
−
and Ketones
Nu
:
Nu:
¦Ä
¦Ä
H Nu + C
O
C O H OH−, H− , R C − ,
3
H2O, NH3, ROH
Nu
H Nu
Nu
C
O
sp2
sp3
Intermediate:
an alkoxide ion
The trigonal planar structure of
C=O is relatively open to attack
from above or below by Nu−:.
P288
9.6
12.4.1 Hydration of Aldehydes and
P290
O ketones
R C H (CH3) + H2O
[RCH(OH)2]
K=
[RCHO] [H2O]
O
>
CF3 C CF3 H C H
Khydr22,000
41
>
O
CH3 C H
OH
9.7
C
(CH3) H
OH
Geminal diol
Reversible
O
R
K
（同碳二醇）
Hydrate(水合物)
>
O
CH3 C CH3
>
O
(CH3)3C C C(CH3)3
1.8 × 10-2 4.1 × 10-3 2.5 × 10-5
Reactivity decreases
Factors affecting the reactivity:
1. Electronic effects of alkyl groups
Electron-donating effect of alkyl
O
Substituents stabilizes the carbonyl
CH3 C
group;
Electron-withdrawing effect destabilizes
OH
the carbonyl group
O
O
CF3 C
CF3
R C R
H2O
CH3
R C OH
R
2. Steric effect of
2 sp3
Hybridization:
sp
alkyl groups
The bond angle:
H < CH3 < tert-Butyl
120° 109.5°
The crowding in the products is increased
by the larger group
An aldehyde
A ketone
Mechanism of Hydration
The addition of water is subject to catalysis
by both an acid and a base.
The mechanism for the base-catalyzed
reaction:
Step 1
HO
H
+
C
H3C
A hydroxide
ion
O
slow
OH
H C
H3C
O
An alkoxide
ion
A hydroxide ion attacks the carbon of
the carbonyl group.
Nucleophile:
This step is rate-determining. HO－> H O
2
Step 2
OH
OH
H C O
H3C
+ H OH
fast
H C O H + OH
H3C
An alkoxide ion attracts a proton from
water, yielding geminal diol.
The mechanism for the acid-catalyzed reaction:
Step 1 R ¦Ä ¦Ä
fast R
H
C O + H O H
H
H
C O
+ H2O
H
Protonation of carbonyl group:
R
R
H
C
O
H
H
C
O
H
Step 2
R
H O
+
H
Slow
C O
H
H O
R C
H
O H
H
H
Water as a nucleophile attacks the protonated
carbonyl group
The step is rate-determining
Step 3
H
H O
H C
R
O H
O H
H
H O
H C
O H
R
Transformation of the proton
+
H O H
H
The mechanism for the base-catalyzed
reaction:
12.4.2 The addition of hydrogen cyanide
(氢氰酸)
－Cyanohydrin (氰基醇)formation
O
OH
R
C
R C H (CH3) + HCN
(CH3) H
CN
Characteristics of the reaction
1. Base-catalyzed,reagent: KCN
2. Formation of C－C bond
3. －CN
COOH, －NH2
O
CH3CH2 C CH3
OH
HCN
CH3CH2 C CN
CH3
95%H2SO4
¡÷
CH3CH2 C COOH
CH3
12.4.3 The addition of alcohols
Acid catalysis Aldehydes react with alcohols
to yeld hemiacetals (半缩醛) or acetals(缩醛)
O
+
R'OH / H
R C H
Aldehyde
R
H
OH
C
R'OH / H+
OR'
R
C
H
OR'
hemiacetal
acetal
O
C H + 2 CH3CH2OH
Benzaldehyde Ethanol
HCl
OR'
+ H2O
CH
OCH2CH3
OCH2CH3
Benzaldehyde
diethyl acetal
苯甲醛缩 二乙醇(60%)
Mechanism of the reaction:
R
H
R
C O + H O R'
¦Ä
R' O
H C
¦Ä
H
H
H
O H
O R'
H
H C
O H
+
H O R'
H
R
O R'
R
H
O R'
R
H C
C O H + O R'
O H
H O R'
H
O R'
H C
R
OH2
-H2O
H
C O R'
R
R'
H
R' O H
C
O
R'
H
R
O
H
C
O
R' O H
R'
R
H
O
R'
C
O
R' + R' OH 2
R
The position of equilibrium is favorable for
acetal formation from most aldehydes.
For most ketones, the position of equilibrium
is unfavorable.
excess alcohol as solvent
Diols react with aldehydes or ketones to form
cyclic acetals by removing the water:
O +
HOCH2
O CH2
O CH2
对甲苯磺酸
HOCH2
Acetals are susceptible to hydrolysis in
aqueous acid:
R
(R")H
C
OR'
OR'
+ H 2O
H
R
(R")H
C O + 2 R'OH
Acetal hydrolysis is favored by excess water.
Acetals as protecting groups Acetals are
O
stable in basic
CH2OH
O
C OC2H5 solution
O
(a) Protection of carbonyl group
O
O
O
C OC2H5
H+
HOCH2CH2OH
O
O
C OC2H5
(b) Reduction of the ester group
1) LiAlH4 / Et2O
2) H2O
O
O
CH2OH
(c) Unmasking of the carbonyl group
+ O
CH
OH
H
2
O
CH2OH
H2O
O
12.4.4 The addition of amines（胺）
1. Reaction with primary amines: imides (亚胺
Aldehydes and ketones react with primary
amines to yield imides N-Substituted imides:
Step 1. Nucleophlic addition Schiff’s bases (西佛碱)
H
H
R N H +
C
O
H
R N
C O
R N
H
Primary Aldehyde
amine or ketone
Step 2. Elimination
Carbinoamine
（氨基甲醇）
H
R N C OH
C OH
R N C
+ H2O
Imide
（亚胺）
Careful
control
of pH!
The reactions are accelerated by
acid-catalysis
(a) Protonation of carbonyl group
C
O + H+
C
OH
C
OH
(b) Nucleophile attacks carbonyl group
H
H
R
N
H +
C
OH
R
N
C
OH
-H+
R
C
OH
H
H
(c) Elimination with acid-catalysis
pH: 4~5
H
H
R N C OH
N
+H+
R N C OH
H
R N C
+ H2O
O + (CH3)2CHCH2NH2
Cyclohexanone
H+
NCH2CH(CH3)2
N-CyclohexylideIsobutylamine
Isobutylamine
（异丙胺）
（N-亚环己基异丙胺）
Reaction with derivatives of ammonia
Y
N
H +
C
O
C
N
Y
+ H2O
H
C O
H2N OH
C N OH + H2O
Hydroxylamine An oxime
（羟胺）
C O
H2N NH2
（肟）
C N NH2 + H2O
Hydrazine A hydrazone
（肼）
（腙）
C6H5
H
C O
H2NNH
O2N
NO2
C6H5
2,4-Dinitrophenyl
Hydrazine
（2,4-二硝基苯肼）
C NNH
H
O2N
NO2 £«H2O
2,4-dinitrophenyl
hydrazone (腙)
The products are insoluble and have
sharp characteristic melting point.
The reaction are often used to identify
unknown aldehydes and ketones.
O
O + H2NNHCNH2
Semicarbazine
（氨基脲）
O
NNHCNH2 + H2O
Semicarbazone
（缩氨基脲）
（半卡巴腙）
Reactions with secondary amines
Aldehydes and ketones react with secondary
amine (R2NH), to form enamines （烯胺）
OH
O
RCH2CR' + R"2NH
RCH2C
R'
-H2O
NR"2
RCH CR'
NR"
O
N
benzene
N
+ H2O
¡÷
H
N-(1-Cyclopentenyl)
Pyrrodine
（吡咯烷）
[N-(1-环戊烯基)吡咯烷]
Cyclopentanone Pyrrolidine
（环戊酮）
12. 5 The Addition of Ylides:
the Wittig Reaction
Aldehydes and ketones react with
phosphorous ylides to yield alkenes and
triphenyl phosphine oxide
（三苯基氧膦）
R
R
R"
C C
+ (C6H5)3P O
R"'
R'
O
DMSO
CH3 S CH3
R"
C O + (C6H5)3P C
R"'
R'
Solvents: THF,
The characteristics of Wittig
reaction: Regioselectivity
O
O + Ph3P
CH2
CH3SCH3
Dimethyl sulfoxide
（二甲亚砜）
CH2 + Ph3P
86%
O
14.5.1 Ylides and the Preparation of
Phosphorous Ylides Ch.P346(己)
Ylides (叶立德): Molecules with two
oppositely charged atoms
R"
(C6H5)3P C
R
R"
(C6H5)3P C
R
A hybrid of the two resonance structures
Preparation of phosphorous ylides:
Step1 Alkyl halides Triphenyphosphine
SN2 reaction
R"
(C6H5)3P +
CH X
R"'
(C6H5)3P
R"
CH X
R"
Substrates: 1°, 2°Alkyl halides
Step 2 An acid-base reaction
R"
(C6H5)3P C H
R"
X
(C6H5)3P
C6H5 Li
R"
C + C6H6 + LiX
R"
The strong base: Alkyllithiun or phenyllithium
12.5.2 Mechanism of the Wittig reaction
(C6H5)3P CH3
Br
CH3
CH3 C +
O
C6H5 Li
H
C CH3
P(C6H5)3
H3C
(C6H5)3P CH2+ C6H6 + LiX
H
CH3 C C CH3
O P(C6H5)3
H3C
H
CH3 C C CH3
O P(C6H5)3
(内膦盐) Oxaphosphetane
Triphenyl
Aldehyde phosphonium A betaine
（氧膦烷）
or ketone yelid
(甜菜碱)
CH3
CH3
C C
H
+ O P(C6H5)3
CH3
Triphenlphosphine
Oxaide(三苯基氧膦）
12.5.3 Synthesis of alkenes by Wittig
reactions C6H5
X
CH3
CH3
C6H5CH CCH3
H
C O +
H
C6H5
C
CH3
CH3
+ O C
C
CH3
X
H
(CH3)2CHBr + (C6H5)3P
H
(C6H5)3P CH(CH3)2Br
RLi (C H ) P C(CH ) C6H5CHO C H CH
6 5
3 2
6 5 3
CH(CH3)2 + (C6H5)3P O
Synthesis of β-Carotene （β-胡萝卜 素）
CH P(C6H5)3
2
+ O
CH
CHO
Georg F. K. Wittig received the Nobel Prize in Chemistry
in 1979.
12.6 Oxidation of Aldehydes and ketones
O
RCH
O
Oxidize
O
CH
O
RCOH
K2Cr2O7
H2SO4,H2O
Furfural
（糠醛）
C
O
H
AgNO3
NH4OH
The strong oxidizing reagents:
K2Cr2O7 / H+, KMnO4 / OH-;
The
reagent:
O mild oxidizing
Ag2O/OH-. P287
O COH
9.5
Furoic acid
（糠酸）(75%) Tollens
O
C
OH + Ag
reagent
German chemist whose method of
synthesizing olefins (alkenes) from carbonyl
compounds is a reaction often termed the
Wittig synthesis. For this achievement he
shared the 1979 Nobel Prize for Chemistry.
Wittig was born in Berlin and studied at
Kassel and Marburg. He was professor
at Freiburg 1937-44, Tubingen 1944-56,
and Heidelberg 1956-67.
In the Wittig reaction, which he first
demonstrated 1954, a carbonyl compound
(aldehyde or ketone) reacts with an organic
phosphorus compound, an alkylidenetriphenylphosphorane, (C6H5)3P=CR2,
where R is a hydrogen atom or an organic
radical. The alkylidene group (=CR2) of the
reagent reacts with the oxygen atom of the
Georg Wittig
carbonyl group to form a hydrocarbon with
1/2 of the prize
University of Heidelberg a double bond, an olefin (alkene). In general:
Heidelberg, Federal (C6H5)3P=CR2 + R2'CO (C6H5)3PO +
Republic of Germany R2C=CR2The reaction is widely used in
b. 1897
organic synthesis, for example to make
d. 1987
squalene (the synthetic precursor of
cholesterol) and vitamin D3
Bernhard Tollens
Was born in Hamburg,
Germany, received
His Ph.D. at University
of Göttingen,and then
became professor
at the same institution.
Bernhard Tollens
(1841-1918)
12.6.2 Baeyer-Villiger oxidation of ketones
Ketones react with peroxy acides
to give esters:
C6H5
O
O
C CH3 + RCOOH
CH3
O
O
C O C6H5 + RCOH
The oxygen atom is inserted between
the carbonyl group and the larger of
two groups attached to it.
The migratory aptitude of groups:
H > phenyl > 3°alkyl > 2°alkyl
> 1°alkyl > methyl
O
O
CCH3 + PhCOOH
CHCl3
O
O
OCCH3 + PhCOH
(67%)
Mechanism of the Baeyer-Villiger oxidation:
CH3
O
C
O
H
+ O O C R
(1)
O
O H
C O O C R
CH3
C6H5
C6H5
(2) H+
CH3
O H
O H
C O O C R
C6H5
phenyl
migration
(3b)
O
-RC OH
(3a)
CH3
C6H5
O
C NH
CH3CH2
C
C
CH3CH2
C NH
O
O
+
+
H
C
H
CH3C O
6 5
O H
C O
O
Babiturate
(巴比妥)
Adolf von Baeyer was awarded
the Nobel Prize in Chemistry in 1905.
A great German organic chemist of his
time, he received the 1905 Nobel Prize in
Chemistry for his researches on organic
dyes and hydroaromatic compounds.
Most famous were his researches on the
constitution and synthesis of the plant
pigment indigo (1883), the discovery of
barbituric acid (1863) phenolphthalein
and fluorescein (1871), and the "strain
theory" of triple bonds and small carbon
rings.Three of his students (E. Fischer,
E. Büchner, R. Willstätter)
received Nobel prizes.
Johann Friedrich Wilhelm
Adolf von Baeyer
Germany Munich University
b. 1835
d. 1917
12.7 Spectroscopic analysis of
O
aldehydes and ketones
C
1665 ~ 1780 cm -1 (s) Stretching vibration
RCHO ~1730 cm-1
ArCHO 1695 ~1715 cm-1
O
Ch.P336
(四)
C
C H
RCOR 1705 ~1720 cm-1
ArCOR 1680 ~1700 cm-1
C CHO 1680~1690 cm-1
C
C COR 1665~1690cm-1
2820, 2720 cm -1 (m) Stretching vibration
When the carbonyl groups conjugate with
carbon-carbon double bond, the location of
the pick shifts to the direction of lower
frequency （低频）
O
O
(CH3)2CHCH2 C CH3
σ / cm -1
1717
O (CH3)2C CH C CH3
1715
1690
O
C
1700
H
O
–CHO
C
O
CH3CH2CH2CH2CH2CH2CH2C H
IR Spectrum of octyl aldehyde
O
CCH3
O
C
IR Spectrum of Acetophenone
Strentching vibration of C = O : 1683 cm -1
The characteristic absorption of
aldehydic proton:
O
C
1H
H
1H
NMR, δ: 9 ~ 10 ppm
NMR spectrum of acetaldehyde
1H
O
C CH3
O
C
CH2
NMR Spectrum of Butanone
1H NMR
δ：2.2 ppm
δ：2.5 ppm
13C
NMR :
The signal for the carbon of C=O in
aldehydes And ketones appears at very
low field:
CH2
CH2 CH
3
CH2
CH2
CH3
190-220 ppm
O
CH3CH2CCH2CH2CH2CH3
O
C
200
180
160
140
120
100
80
Chemical shift (δ, ppm)
60
40
20
0
Problems to Chapter 12
P303
9.21(b),(e),(f),(g),(h)
9.25(b),(c),(e)
9.29(b)~(d)
9.32(a),(b)
9.34((b),(d)
9.36(c)
9.38(b)
9.39(c)
9.40(b)
9.41(b),(c)
9.44
9.45
9.48*
9.49
9.50
9.51
Ch.P363
(十四)
(十五)
(十六)(B)
Additional Problems:
1. Show how the Wittig reaction might
be used to prepare the following alkene.
Identify the alkyl halide and the carbonyl
components that would be used.
(a) C6H5CH CH CH CHC6H5
(b)
(c)
CH CH2