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Chapter 17
Aldehydes and Ketones:
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Classes of Carbonyl Compounds
Resonance
• The first resonance is better because all atoms
complete the octet and there are no charges.
• The carbonyl carbon has a partial positive and will
react as an electrophile.
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Chapter 18
3
Aldehydes Nomenclature
• The aldehyde carbon is number 1.
• IUPAC: Replace -e with -al.
• If the aldehyde group is attached to a ring,
the suffix carbaldehyde is used.
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4
IUPAC Nomenclature of Aldehydes
O
when named as
a substituent
formyl group
C
H
when named
as a suffix
carbaldehyde or
carboxaldehyde
Ketone Nomenclature
• Number the chain so that the carbonyl carbon
has the lowest number.
• Replace the alkane -e with -one.
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Chapter 18
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Cyclic Ketone Nomenclature
• For cyclic ketones, the carbonyl carbon is
assigned the number 1.
• When the compound has a carbonyl and a
double bond, the carbonyl takes precedence.
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Functional Class IUPAC Nomenclature of Ketones
O
O
CH3CH2CCH2CH2CH3
O
H2C
CHC CH
CH2
CH2CCH2CH3
List the groups
attached to the
carbonyl separately in
alphabetical order, and
add the word ketone.
Functional Class IUPAC Nomenclature of Ketones
O
O
CH3CH2CCH2CH2CH3
ethyl propyl ketone
CH2CCH2CH3
benzyl ethyl ketone
O
divinyl ketone
H2C
CHC CH
CH2
Structure and Bonding:
The Carbonyl Group
Structure of Formaldehyde
planar
bond angles: close to 120°
C=O bond distance: 122 pm
Both C and O are sp2 hybridizes.
Bonding in Formaldehyde
The half-filled
2p orbitals on
carbon and
oxygen overlap
to form a  bond.
The Carbonyl Group
very polar double bond
O
1-butene
propanal
dipole moment = 0.3D
dipole moment = 2.5D
Carbonyl Group of a Ketone is More
Stable than that of an Aldehyde
heat of combustion
O
2475 kJ/mol
H
2442 kJ/mol
O
Alkyl groups stabilize carbonyl groups the same
way they stabilize carbon-carbon double bonds,
carbocations, and free radicals.
Resonance Description of
Carbonyl Group
••
•• –
O ••
•• O ••
C
C
+
Nucleophiles attack carbon;
electrophiles attack oxygen.
Physical Properties
Aldehydes and Ketones have Higher Boiling Points
than Alkenes, but Lower Boiling Points than Alcohols
boiling point
–6°C
O
49°C
OH
97°C
More polar than alkenes,
but cannot form
intermolecular hydrogen
bonds to other carbonyl
groups.
Sources of Aldehydes and Ketones
Table 17.1 Synthesis of Aldehydes and Ketones
from alkenes
A number of
reactions already
studied provide
efficient synthetic
routes to
aldehydes and
ketones.
ozonolysis
from alkynes
hydration (via enol)
from arenes
Friedel-Crafts acylation
from alcohols
oxidation
Ozonolysis of Alkenes
• The double bond is oxidatively cleaved by
ozone followed by reduction.
• Ketones and aldehydes can be isolated as
products under these conditions.
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Friedel–Crafts Reaction
• Reaction between an acyl halide and an
aromatic ring will produce a ketone.
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Chapter 18
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Hydration of Alkynes
• The initial product of Markovnikov hydration is an enol,
which quickly tautomerizes to its keto form.
• Internal alkynes can be hydrated, but mixtures of
ketones often result.
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22
Grignards as a Source for Ketones
and Aldehydes
• A Grignard reagent can be used to make an alcohol, and then
the alcohol can be easily oxidized.
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23
What About..?
aldehydes from carboxylic acids
R
1. LiAlH4
2. H2O
O
O
C
C
OH
R
H
PDC, CH2Cl2
RCH2OH
Example
Benzaldehyde from benzoic acid
O
O
COH
CH
1. LiAlH4
2. H2O
(81%)
CH2OH
PDC
CH2Cl2
(83%)
What About..?
Ketones from aldehydes
R
1. R'MgX
2. H3O+
O
O
C
C
R
H
OH
RCHR'
R'
PDC, CH2Cl2
Example
3-heptanone from propanal
O
O
C
CH3CH2
CH3CH2C(CH2)3 CH3
H
(57%)
1. CH3(CH2)3MgX
2. H3
O+
OH
CH3CH2CH(CH2)3 CH3
H2CrO4
Industrial Importance
• Acetone and methyl ethyl ketone are common industrial
solvents.
• Formaldehyde is used in polymers like Bakelite and many
other polymeric products.
• Also used as flavorings and additives for food.
Reactions of Aldehydes and
Ketones:
A Review and a Preview
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Table 17.2 Reactions of Aldehydes and Ketones
Already covered in earlier chapters:
Reduction of C=O to CH2
Clemmensen reduction
Wolff-Kishner reduction
Reduction of C=O to CHOH
Addition of Grignard and organolithium reagents
Catalytic Hydrogenation
• Widely used in industry
• Raney nickel is finely divided Ni powder
saturated with hydrogen gas.
• It will attack the alkene first, then the carbonyl.
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Deoxygenation of Ketones and
Aldehydes
• The Clemmensen reduction or the Wolff–
Kishner reduction can be used to
deoxygenate ketones and aldehydes.
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Clemmensen Reduction
Wolff–Kishner Reduction
• Forms hydrazone, then heat with strong base like
KOH or potassium tert-butoxide
• Use a high-boiling solvent: ethylene glycol, diethylene
glycol, or DMSO.
• A molecule of nitrogen is lost in the last steps of the
reaction.
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Sodium Borohydride
• NaBH4 can reduce ketones and aldehydes, but not
esters, carboxylic acids, acyl chlorides, or amides.
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Lithium Aluminum Hydride
OH
O
R
R(H)
LiAlH4
ether
R
H
R(H)
aldehyde or ketone
• LiAlH4 can reduce any carbonyl because it is
a very strong reducing agent.
• Difficult to handle
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Principles of Nucleophilic Addition:
Hydration of Aldehydes and
Ketones
Hydration of Ketones and
Aldehydes
• In an aqueous solution, a ketone or an aldehyde is in
equilibrium with its hydrate, a geminal diol.
• With ketones, the equilibrium favors the unhydrated
keto form (carbonyl).
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Acid-Catalyzed Hydration of
Carbonyls
• Hydration occurs through the nucleophilic addition
mechanism, with water (in acid) or hydroxide (in base)
serving as the nucleophile.
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Base-Catalyzed Hydration of
Carbonyls
• The hydroxide ion attacks the carbonyl group.
• Protonation of the intermediate gives the hydrate.
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Cyanohydrin Formation
• The mechanism is a base-catalyzed nucleophilic
addition: Attack by cyanide ion on the carbonyl group,
followed by protonation of the intermediate.
• HCN is highly toxic.
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Example
Cl
Cl
O
Cl
OH
NaCN, water
Cl
CH
CHCN
then H2SO4
2,4-Dichlorobenzaldehyde
cyanohydrin (100%)
Example
O
CH3CCH3
OH
NaCN, water
then H2SO4
CH3CCH3
CN
(77-78%)
Acetone cyanohydrin is used in the synthesis
of methacrylonitrile.
Acetal Formation
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Some reactions of aldehydes and ketones progress
beyond the nucleophilic addition stage
Acetal formation
Imine formation
Enamine formation
Compounds related to imines
The Wittig reaction
Recall Hydration of Aldehydes and Ketones
R
C
O ••
••
R'
HOH
R
••
HO
••
C
R'
••
O
••
H
Alcohols Under Analogous Reaction
with Aldehydes and Ketones
R
O ••
C
••
R'
R”OH
R
••
R"O
••
C
R'
••
O
••
H
Product is called
a hemiacetal.
Hemiacetal reacts further in acid to yield an acetal
R
••
R"O
••
C
••
Product is called
an acetal.
OR”
••
R'
R”OH, H+
R
••
R"O
••
C
R'
••
O
••
H
Product is called
a hemiacetal.
Example
O
CH + 2CH3CH2OH
HCl
CH(OCH2CH3)2
+ H2O
Benzaldehyde diethyl acetal (66%)
Diols Form Cyclic Acetals
O
CH3(CH2)5CH
+
HOCH2CH2OH
benzene
p-toluenesulfonic acid
H2C
CH2
O
O
+ H2O
C
(81%)
H
(CH2)5CH3
In general:
Position of equilibrium is usually unfavorable
for acetal formation from ketones.
Important exception:
Cyclic acetals can be prepared from ketones.
Example
O
C6H5CH2CCH3 +
HOCH2CH2OH
benzene
p-toluenesulfonic acid
H2C
CH2
O
O
(78%)
C6H5CH2
C
CH3
+ H2O
Mechanism for Hemiacetal
Formation
• Must be acid-catalyzed.
• Adding H+ to carbonyl makes it more reactive
with weak nucleophile, ROH.
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Acetal Formation
Hydrolysis of Acetals
OR"
R
C
O
C
R' + H2O
OR"
mechanism:
R
reverse of acetal formation;
hemiacetal is intermediate
application:
Aldehydes and ketones can be
"protected" as acetals.
+
R'
2R"OH
Acetals as Protecting Groups
Example
The conversion shown cannot be carried out
directly...
O
CH3CCH2CH2C
CH
1. NaNH2
2. CH3I
O
CH3CCH2CH2C
CCH3
because the carbonyl group and the
carbanion are incompatible functional
groups.
O
CH3CCH2CH2C
C:
–
Strategy
1) protect C=O
2) alkylate
3) restore C=O
Example: Protect
O
CH3CCH2CH2C
CH +
HOCH2CH2OH
benzene
p-toluenesulfonic acid
H2C
CH2
O
O
C
CH3
CH2CH2C
CH
Example: Alkylate
H2C
CH2
O
O
C
CH3
1. NaNH2
2. CH3I
CH2CH2C
CCH3
H2C
CH2
O
O
C
CH3
CH2CH2C
CH
Example: Deprotect
H2C
CH2
O
O
H2O
C
CH3
CH2CH2C
CCH3
HCl
O
HOCH2CH2OH
+
CH3CCH2CH2C
(96%)
CCH3
Reaction with Primary Amines:
Imines
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Formation of Imines
• Ammonia or a primary amine reacts with a ketone or
an aldehyde to form an imine.
• Imines are nitrogen analogues of ketones and
aldehydes with a C═N bond in place of the carbonyl
group.
• Optimum pH is around 4.5.
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Example
O
CH + CH3NH2
CH=NCH3 + H2O
N-Benzylidenemethylamine (70%)
Example
O
CH + CH3NH2
OH
CH
NHCH3CH3
CH=NCH3 + H2O
N-Benzylidenemethylamine (70%)
Mechanism of Imine Formation
Acid-catalyzed addition of the amine to the carbonyl
compound group
Acid-catalyzed dehydration
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Other Condensations with Amines
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Example
O
CH3(CH2)5CH
+ H2NOH
NOH
CH3(CH2)5CH
+ H2O
(81-93%)
Example
O
C
+ H2NNH2
NNH2
C
(73%)
+ H2 O
Example
O
CCH3
+ H2NNH
phenylhydrazine
NNH
CCH3
a phenylhydrazone (87-91%)
+ H2 O
Example
O
O
CH3(CH2)9CCH3 +
H2NNHCNH2
semicarbazide
O
NNHCNH2
CH3(CH2)9CCH3
+
H2O
a semicarbazone (93%)
17.11
Reaction with Secondary Amines:
Enamines
Enamine Formation
H
H C
••
R2NH
O ••
C
••
••
R2N
C
••
R2N
C
(enamine)
+ H2O
C
C
••
O
••
H
Example
O
N
H
(heat in benzene)
+
N
(80-90%)
N
via
OH
The Wittig Reaction
 The Wittig reaction converts the carbonyl
group into a new C═C double bond where no
bond existed before.
 A phosphorus ylide is used as the nucleophile
in the reaction.
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Preparation of Phosphorus Ylides
 Prepared from triphenylphosphine and an
unhindered alkyl halide.
 Butyllithium then abstracts a hydrogen from
the carbon attached to phosphorus.
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Mechanism of the Wittig Reaction
Betaine formation
Oxaphosphetane formation
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Mechanism for Wittig
 The oxaphosphetane will collapse, forming
alkene and a molecule of triphenyl phosphine
oxide.
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Retrosynthetic Analysis
R
A
C
R'
C
B
There will be two possible Wittig routes to
an alkene.
Analyze the structure retrosynthetically.
Disconnect the doubly bonded carbons. One
will come from the aldehyde or ketone, the
other from the ylide.
Retrosynthetic Analysis of Styrene
O
C6H5CH
+
C6H5CH
+
(C6H5)3P
CH2
–
CHC6H5
••
+
••
Both routes
are acceptable.
O
+
(C6H5)3P
–
CH2
HCH
Oxidation of Aldehydes
Aldehydes are easily oxidized to carboxylic acids.
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Infrared (IR) Spectroscopy
 Very strong C═O stretch around 1710 cm-1 for
ketones and 1725 cm-1 for simple aldehydes
 Additional C—H stretches for aldehyde: Two
absorptions at 2710 cm-1 and 2810 cm-1
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IR Spectra
 Conjugation lowers the carbonyl stretching
frequencies to about 1685 cm-1.
 Rings that have ring strain have higher C═O
frequencies.
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Proton NMR Spectra
 Aldehyde protons normally absorb between
d9 and d10.
 Protons of the α carbon usually absorb
between d2.1 and d2.4 if there are no other
electron-withdrawing groups nearby.
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1H
NMR Spectroscopy
 Protons closer to the carbonyl group are more
deshielded.
 The a, b, and g protons appear at values of d that
decrease with increasing distance from the carbonyl
group.
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Carbon NMR Spectra of Ketones
 The spin-decoupled carbon NMR spectrum of
2-heptanone shows the carbonyl carbon at 208 ppm
and the α carbon at 30 ppm (methyl) and 44 ppm
(methylene).
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Mass Spectrometry (MS)
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MS for Butyraldehyde
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