654
CHAPTER 17
ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION TO THE CARBONYL GROUP
A
ldehydes and ketones contain an acyl group bonded either to hydrogen or
to another carbon.
Although the present chapter includes the usual collection of topics designed to acquaint
us with a particular class of compounds, its central theme is a fundamental reaction type,
nucleophilic addition to carbonyl groups. The principles of nucleophilic addition to alde-
hydes and ketones developed here will be seen to have broad applicability in later chap-
ters when transformations of various derivatives of carboxylic acids are discussed.
17.1 NOMENCLATURE
The longest continuous chain that contains the group provides the base name for
aldehydes. The -e ending of the corresponding alkane name is replaced by -al, and sub-
stituents are specified in the usual way. It is not necessary to specify the location of
the group in the name, since the chain must be numbered by starting with this
group as C-1. The suffix -dial is added to the appropriate alkane name when the com-
pound contains two aldehyde functions.*
±CH
O
X
±CH
O
X
RCH
O
X
Aldehyde
HCH
O
X
Formaldehyde
RCRH11032
O
X
Ketone
RC±
O
X
* The -e ending of an alkane name is dropped before a suffix beginning with a vowel (-al) and retained be-
fore one beginning with a consonant (-dial).
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When a formyl group (±CH?O) is attached to a ring, the ring name is followed
by the suffix -carbaldehyde.
Certain common names of familiar aldehydes are acceptable as IUPAC names. A
few examples include
PROBLEM 17.1 The common names and structural formulas of a few aldehydes
follow. Provide an IUPAC name.
(a) (c)
(b) (d)
SAMPLE SOLUTION (a) Don’t be fooled by the fact that the common name is
isobutyraldehyde. The longest continuous chain has three carbons, and so the base
name is propanal. There is a methyl group at C-2; thus the compound is 2-methyl-
propanal.
2-Methylpropanal
(isobutyraldehyde)
CH
3
CHCH
O
CH
3
32
1
HO CH
CH
3
O
O
(vanillin)
HCCH
2
CH
2
CH
2
CH
O O
(glutaraldehyde)
C
6
H
5
CH CHCH
O
(cinnamaldehyde)
(CH
3
)
2
CHCH
O
(isobutyraldehyde)
HCH
O
Formaldehyde
(methanal)
CH
3
CH
O
Acetaldehyde
(ethanal)
CH
O
Benzaldehyde
(benzenecarbaldehyde)
CH
O
Cyclopentanecarbaldehyde
CH
O
2-Naphthalenecarbaldehyde
CH
3
CCH
2
CH
2
CH
OCH
3
CH
3
4,4-Dimethylpentanal
CHCH
2
CH
2
CH
2
CH
O
CH
2
5-Hexenal
HCCHCH
OO
2-Phenylpropanedial
17.1 Nomenclature 655
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With ketones, the -e ending of an alkane is replaced by -one in the longest con-
tinuous chain containing the carbonyl group. The chain is numbered in the direction that
provides the lower number for this group.
Although substitutive names of the type just described are preferred, the IUPAC
rules also permit ketones to be named by functional class nomenclature. The groups
attached to the carbonyl group are named as separate words followed by the word
“ketone.” The groups are listed alphabetically.
PROBLEM 17.2 Convert each of the following functional class IUPAC names to
a substitutive name.
(a) Dibenzyl ketone
(b) Ethyl isopropyl ketone
(c) Methyl 2,2-dimethylpropyl ketone
(d) Allyl methyl ketone
SAMPLE SOLUTION (a) First write the structure corresponding to the name.
Dibenzyl ketone has two benzyl groups attached to a carbonyl.
The longest continuous chain contains three carbons, and C-2 is the carbon of the
carbonyl group. The substitutive IUPAC name for this ketone is 1,3-diphenyl-2-
propanone.
A few of the common names acceptable for ketones in the IUPAC system are
(The suffix -phenone indicates that the acyl group is attached to a benzene ring.)
CH
3
CCH
3
O
Acetone
CCH
3
O
Acetophenone
C
O
Benzophenone
CH
2
CCH
2
O
123
Dibenzyl ketone
CH
3
CH
2
CCH
2
CH
2
CH
3
O
Ethyl propyl
ketone
CH
2
CCH
2
CH
3
O
Benzyl ethyl ketone
CH
2
O
CHCCH CH
2
Divinyl ketone
CH
3
CH
2
CCH
2
CH
2
CH
3
O
3-Hexanone
CH
3
CHCH
2
CCH
3
O
CH
3
4-Methyl-2-pentanone
CH
3
O
4-Methylcyclohexanone
656 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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17.2 STRUCTURE AND BONDING: THE CARBONYL GROUP
Two notable aspects of the carbonyl group are its geometry and its polarity. The car-
bonyl group and the atoms directly attached to it lie in the same plane. Formaldehyde,
for example, is planar. The bond angles involving the carbonyl group of aldehydes and
ketones are close to 120°.
At 122 pm, the carbon–oxygen double bond distance in aldehydes and ketones is sig-
nificantly shorter than the typical carbon–oxygen single bond distance of 141 pm in alco-
hols and ethers.
The carbonyl group makes aldehydes and ketones rather polar, with molecular
dipole moments that are substantially larger than those of comparable compounds that
contain carbon–carbon double bonds.
Bonding in formaldehyde can be described according to an sp
2
hybridization model
analogous to that of ethylene, as shown in Figure 17.1.
Figure 17.2 compares the electrostatic potential surfaces of ethylene and formalde-
hyde and vividly demonstrates how oxygen affects the electron distribution in formalde-
hyde. The electron density in both the H9268 and H9266 components of the carbon–oxygen dou-
ble bond is displaced toward oxygen. The carbonyl group is polarized so that carbon is
partially positive and oxygen is partially negative.
In resonance terms, electron delocalization in the carbonyl group is represented by
contributions from two principal resonance structures:
C O
H9254H11001 H9254H11002
or C O
CH
3
CH
2
CH CH
2
1-Butene
Dipole moment: 0.3 D
CH
3
CH
2
CH O
Propanal
Dipole moment: 2.5 D
C
O
HH
116.5°
121.7°121.7°
Formaldehyde
C
O
HH
3
C
117.5°
118.6°123.9°
Acetaldehyde
C
O
CH
3
H
3
C
117.2°
121.4°121.4°
Acetone
17.2 Structure and Bonding: The Carbonyl Group 657
(a) Ethylene (b) Formaldehyde
FIGURE 17.1 Similari-
ties between the orbital hy-
bridization models of
bonding in (a) ethylene and
(b) formaldehyde. Both mol-
ecules have the same num-
ber of electrons, and carbon
is sp
2
-hybridized in both. In
formaldehyde, one of the
carbons is replaced by an sp
2
-
hybridized oxygen (shown
in red). Oxygen has two
unshared electron pairs;
each pair occupies an sp
2
-
hybridized orbital. Like the
carbon–carbon double bond
of ethylene, the carbon–oxy-
gen double bond of
formaldehyde is composed
of a two-electron H9268 compo-
nent and a two-electron H9266
component.
Verify their geometries by
making models of formalde-
hyde, acetaldehyde, and ace-
tone. Make sure you execute the
minimization routine.
Compare the dipole mo-
ments and electrostatic potential
maps of 1-butene and propanal
on Learning By Modeling.
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Of these two, A, having one more covalent bond and avoiding the separation of positive
and negative charges that characterizes B, better approximates the bonding in a carbonyl
group.
Alkyl substituents stabilize a carbonyl group in much the same way that they sta-
bilize carbon–carbon double bonds and carbocations—by releasing electrons to sp
2
-
hybridized carbon. Thus, as their heats of combustion reveal, the ketone 2-butanone is
more stable than its aldehyde isomer butanal.
The carbonyl carbon of a ketone bears two electron-releasing alkyl groups; an aldehyde
carbonyl group has only one. Just as a disubstituted double bond in an alkene is more
stable than a monosubstituted double bond, a ketone carbonyl is more stable than an
aldehyde carbonyl. We’ll see later in this chapter that structural effects on the relative
stability of carbonyl groups in aldehydes and ketones are an important factor in their rel-
ative reactivity.
17.3 PHYSICAL PROPERTIES
In general, aldehydes and ketones have higher boiling points than alkenes because they
are more polar and the dipole–dipole attractive forces between molecules are stronger.
But they have lower boiling points than alcohols because, unlike alcohols, two carbonyl
groups can’t form hydrogen bonds to each other.
Aldehydes and ketones can form hydrogen bonds with the protons of OH groups. This
makes them more soluble in water than alkenes, but less soluble than alcohols.
CH
3
CH
2
CH CH
2
1-Butene
H110026°C
Negligible
bp (1 atm)
Solubility in
water (g/100 mL)
CH
3
CH
2
CH O
Propanal
49°C
20
CH
3
CH
2
CH
2
OH
1-Propanol
97°C
Miscible in all
proportions
CH
3
CH
2
CH
2
CH
O
Butanal
2475 kJ/mol (592 kcal/mol)
CH
3
CH
2
CCH
3
O
2-Butanone
2442 kJ/mol (584 kcal/mol)Heat of combustion:
C
H11001
H11002
O
B
C O
A
658 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
The chemistry of the car-
bonyl group is considerably
simplified if you remember
that carbon is partially posi-
tive (has carbocation charac-
ter) and oxygen is partially
negative (weakly basic).
Physical constants such as
melting point, boiling point,
and solubility in water are
collected for a variety of
aldehydes and ketones in
Appendix 1.
(a) Ethylene (b) Formaldehyde
FIGURE 17.2 Differ-
ences in the electron distribu-
tion of (a) ethylene and
(b) formaldehyde. The region
of highest electrostatic po-
tential (red ) in ethylene lies
above and below the plane
of the atoms and is associated
with the H9266 electrons. The re-
gion close to oxygen is the
site of highest electrostatic
potential in formaldehyde.
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17.4 SOURCES OF ALDEHYDES AND KETONES
As we’ll see later in this chapter and the next, aldehydes and ketones are involved in
many of the most used reactions in synthetic organic chemistry. Where do aldehydes and
ketones come from?
Many occur naturally. In terms of both variety and quantity, aldehydes and ketones
rank among the most common and familiar natural products. Several are shown in
Figure 17.3.
Many are made in the laboratory from alkenes, alkynes, arenes, and alcohols by
reactions that you already know about and are summarized in Table 17.1.
To the synthetic chemist, the most important of the reactions in Table 17.1 are the
last two: the oxidation of primary alcohols to aldehydes and secondary alcohols to
ketones. Indeed, when combined with reactions that yield alcohols, the oxidation meth-
ods are so versatile that it will not be necessary to introduce any new methods for prepar-
ing aldehydes and ketones in this chapter. A few examples will illustrate this point.
Let’s first consider how to prepare an aldehyde from a carboxylic acid. There are
no good methods for going from RCO
2
H to RCHO directly. Instead, we do it indirectly
by first reducing the carboxylic acid to the corresponding primary alcohol, then oxidiz-
ing the primary alcohol to the aldehyde.
COH
O
Benzoic acid
CH
2
OH
Benzyl alcohol (81%)
CH
O
Benzaldehyde (83%)
1. LiAlH
4
2. H
2
O
PDC
CH
2
Cl
2
RCO
2
H
Carboxylic acid
RCH
2
OH
Primary alcohol
RCH
O
Aldehyde
reduce oxidize
17.4 Sources of Aldehydes and Ketones 659
O
O
O
Undecanal
(sex pheromone of greater wax moth)
2-Heptanone
(component of alarm pheromone of bees)
O
trans-2-Hexenal
(alarm pheromone of myrmicine ant)
O
Citral
(present in lemon grass oil)
O
Civetone
(obtained from scent glands of
African civet cat)
Jasmone
(found in oil of jasmine)
H
H H
FIGURE 17.3 Some
naturally occurring alde-
hydes and ketones.
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TABLE 17.1 Summary of Reactions Discussed in Earlier Chapters That Yield Aldehydes and Ketones
Reaction (section) and comments
Ozonolysis of alkenes (Section 6.19) This
cleavage reaction is more often seen in
structural analysis than in synthesis. The
substitution pattern around a double
bond is revealed by identifying the
carbonyl-containing compounds that
make up the product. Hydrolysis of the
ozonide intermediate in the presence of
zinc (reductive workup) permits alde-
hyde products to be isolated without
further oxidation.
Friedel-Crafts acylation of aromatic
compounds (Section 12.7) Acyl chlorides
and carboxylic acid anhydrides acylate
aromatic rings in the presence of alumi-
num chloride. The reaction is electrophil-
ic aromatic substitution in which acylium
ions are generated and attack the ring.
Oxidation of primary alcohols to alde-
hydes (Section 15.10) Pyridinium dichro-
mate (PDC) or pyridinium chlorochro-
mate (PCC) in anhydrous media such as
dichloromethane oxidizes primary alco-
hols to aldehydes while avoiding overox-
idation to carboxylic acids.
Oxidation of secondary alcohols to
ketones (Section 15.10) Many oxidizing
agents are available for converting sec-
ondary alcohols to ketones. PDC or PCC
may be used, as well as other Cr(VI)-
based agents such as chromic acid or
potassium dichromate and sulfuric acid.
Hydration of alkynes (Section 9.12) Reac-
tion occurs by way of an enol intermedi-
ate formed by Markovnikov addition of
water to the triple bond.
General equation and specific example
Two carbonyl compounds
RCRH11032
O
X
RH11033CH
O
X
H11001
1. O
3
2. H
2
O, Zn
Alkene
C?C
±
±
±
±
RH
RH11032 RH11033
Acetone
CH
3
CCH
3
O
X
HCCH
2
CH
2
CHCH
2
CH
3
O
XW
CH
3
4-Methylhexanal (91%)
H11001
1. O
3
2. H
2
O, Zn
2,6-Dimethyl-2-octene
Alkyne
RCPCRH11032 H
2
OH11001
H
2
SO
4
HgSO
4
RCCH
2
RH11032
O
X
Ketone
ArH HCl orH11001H11001
AlCl
3
ArCR
O
X
RCCl
O
X
RCH
2
OH
Primary alcohol
PDC or PCC
CH
2
Cl
2
Aldehyde
RCH
O
X
RCHRH11032
W
OH
Secondary alcohol
Cr(VI)
Ketone
RCRH11032
O
X
C
6
H
5
CHCH
2
CH
2
CH
2
CH
3
W
OH
1-Phenyl-1-pentanol
CrO
3
acetic acid/
water
1-Phenyl-1-pentanone (93%)
C
6
H
5
CCH
2
CH
2
CH
2
CH
3
O
X
CH
3
(CH
2
)
8
CH
2
OH
1-Decanol
PDC
CH
2
Cl
2
Decanal (98%)
CH
3
(CH
2
)
8
CH
O
X
ArH RCO
2
HH11001H11001
AlCl
3
ArCR
O
X
RCOCR
O
X
O
X
1-Octyne
HCPC(CH
2
)
5
CH
3
H
2
OH11001
H
2
SO
4
HgSO
4
CH
3
C(CH
2
)
5
CH
3
O
X
2-Octanone (91%)
H11001
AlCl
3
CCH
3
O
X
CH
3
O
p-Methoxyacetophenone
(90–94%)
CH
3
COCCH
3
O
X
O
X
Acetic anhydride
CH
3
O
Anisole
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PROBLEM 17.3 Can catalytic hydrogenation be used to reduce a carboxylic acid
to a primary alcohol in the first step of this sequence?
It is often necessary to prepare ketones by processes involving carbon–carbon bond
formation. In such cases the standard method combines addition of a Grignard reagent
to an aldehyde with oxidation of the resulting secondary alcohol:
PROBLEM 17.4 Show how 2-butanone could be prepared by a procedure in
which all of the carbons originate in acetic acid (CH
3
CO
2
H).
Many low-molecular-weight aldehydes and ketones are important industrial chemi-
cals. Formaldehyde, a starting material for a number of plastics, is prepared by oxidation of
methanol over a silver or iron oxide/molybdenum oxide catalyst at elevated temperature.
Similar processes are used to convert ethanol to acetaldehyde and isopropyl alcohol to
acetone.
The “linear H9251-olefins” described in Section 14.15 are starting materials for the
preparation of a variety of aldehydes by reaction with carbon monoxide. The process is
called hydroformylation.
Excess hydrogen brings about the hydrogenation of the aldehyde and allows the process
to be adapted to the preparation of primary alcohols. Over 2 H11003 10
9
lb/year of a variety
of aldehydes and alcohols is prepared in the United States by hydroformylation.
A number of aldehydes and ketones are prepared both in industry and in the lab-
oratory by a reaction known as the aldol condensation, which will be discussed in detail
in Chapter 18.
17.5 REACTIONS OF ALDEHYDES AND KETONES: A REVIEW AND A
PREVIEW
Table 17.2 summarizes the reactions of aldehydes and ketones that you’ve seen in ear-
lier chapters. All are valuable tools to the synthetic chemist. Carbonyl groups provide
access to hydrocarbons by Clemmensen of Wolff–Kishner reduction (Section 12.8), to
H11001H11001 RCH
2
CH
2
CH
O
Aldehyde
Co
2
(CO)
8
Hydrogen
H
2
Carbon
monoxide
CO
Alkene
RCH CH
2
CH
3
OH
Methanol
H11001H11001HCH
O
Formaldehyde
H
2
O
Water
catalyst
500°C
Oxygen
O
2
1
2
RCH
O
Aldehyde
RCHRH11032
OH
Secondary alcohol
RCRH11032
O
Ketone
1. RH11032MgX, diethyl ether
2. H
3
O
H11001
oxidize
CH
3
CH
2
CH
O
Propanal
CH
3
CH
2
CH(CH
2
)
3
CH
3
OH
3-Heptanol
CH
3
CH
2
C(CH
2
)
3
CH
3
O
3-Heptanone
(57% from propanal)
1. CH
3
(CH
2
)
3
MgBr
diethyl ether
2. H
3
O
H11001
H
2
CrO
4
17.5 Reactions of Aldehydes and Ketones: A Review and a Preview 661
The name aldehyde was in-
vented to stand for alcohol
dehydrogenatum, indicating
that aldehydes are related to
alcohols by loss of hydrogen.
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alcohols by reduction (Section 15.2) or by reaction with Grignard or organolithium
reagents (Sections 14.6 and 14.7).
The most important chemical property of the carbonyl group is its tendency to
undergo nucleophilic addition reactions of the type represented in the general equation:
C O
H9254H11002
H9254H11001
Aldehyde
or ketone
H11001 XY
H9254H11001 H9254H11002
C
Y
OX
Product of
nucleophilic addition
662 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
TABLE 17.2 Summary of Reactions of Aldehydes and Ketones Discussed in Earlier Chapters
Reaction (section) and comments
Reduction to hydrocarbons (Section 12.8)
Two methods for converting carbonyl
groups to methylene units are the Clem-
mensen reduction (zinc amalgam and con-
centrated hydrochloric acid) and the
Wolff–Kishner reduction (heat with hydra-
zine and potassium hydroxide in a high-
boiling alcohol).
Addition of Grignard reagents and
organolithium compounds (Sections
14.6-14.7) Aldehydes are converted to
secondary alcohols and ketones to tertiary
alcohols.
Reduction to alcohols (Section 15.2) Alde-
hydes are reduced to primary alcohols, and
ketones are reduced to secondary alcohols
by a variety of reducing agents. Catalytic
hydrogenation over a metal catalyst and
reduction with sodium borohydride or
lithium aluminum hydride are general
methods.
General equation and specific example
NaBH
4
CH
3
OH
CH
O
X
CH
3
O
p-Methoxybenzaldehyde
CH
2
OHCH
3
O
p-Methoxybenzyl alcohol
(96%)
Hydrocarbon
RCH
2
RH11032RCRH11032
O
X
Aldehyde
or ketone
H
2
NNH
2
, KOH
diethylene
glycol, heat
Citronellal 2,6-Dimethyl-2-octene
(80%)
CH
O
X
RCHRH11032
OH
W
Alcohol
RCRH11032
O
X
Aldehyde
or ketone
RCRH11032
RH11033
O
H11002
M
H11001
W
W
RCRH11032
RH11033
OH
W
W
RCRH11032
O
X
RH11033MH11001
H
3
O
H11001
CH
3
CH
2
MgBr
Ethylmagnesium
bromide
Cyclohexanone
O
H11001
1. diethyl ether
2. H
3
O
H11001
1-Ethylcyclohexanol
(74%)
HO CH
2
CH
3
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A negatively polarized atom or group attacks the positively polarized carbon of the car-
bonyl group in the rate-determining step of these reactions. Grignard reagents, organo-
lithium reagents, lithium aluminum hydride, and sodium borohydride, for example, all
react with carbonyl compounds by nucleophilic addition.
The next section explores the mechanism of nucleophilic addition to aldehydes and
ketones. There we’ll discuss their hydration, a reaction in which water adds to the C?O
group. After we use this reaction to develop some general principles, we’ll then survey
a number of related reactions of synthetic, mechanistic, or biological interest.
17.6 PRINCIPLES OF NUCLEOPHILIC ADDITION: HYDRATION OF
ALDEHYDES AND KETONES
Effects of Structure on Equilibrium: Aldehydes and ketones react with water in a
rapid equilibrium:
Overall, the reaction is classified as an addition. The elements of water add to the car-
bonyl group. Hydrogen becomes bonded to the negatively polarized carbonyl oxygen,
hydroxyl to the positively polarized carbon.
Table 17.3 compares the equilibrium constants K
hydr
for hydration of some simple
aldehydes and ketones. The position of equilibrium depends on what groups are attached
to C?O and how they affect its steric and electronic environment. Both effects con-
tribute, but the electronic effect controls K
hydr
more than the steric effect.
RCRH11032
O
Aldehyde
or ketone
H11001 H
2
O
Water
RCRH11032
OH
OH
Geminal diol
(hydrate)
fast
K
hydr
H11005
[hydrate]
[carbonyl compound][water]
17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones 663
TABLE 17.3
Equilibrium Constants (K
hydr
) for Hydration of Some
Aldehydes and Ketones
Hydrate
CH
2
(OH)
2
CH
3
CH(OH)
2
(CH
3
)
3
CCH(OH)
2
(CH
3
)
2
C(OH)
2
K
hydr
*
41
1.8 H11003 10
H110022
4.1 H11003 10
H110023
2.5 H11003 10
H110025
Percent conversion
to hydrate
?
99.96
50
19
0.14
Carbonyl
compound
HCH
O
X
CH
3
CH
O
X
(CH
3
)
3
CCH
O
X
CH
3
CCH
3
O
X
?
Total concentration (hydrate plus carbonyl compound) assumed to be 1 M. Water concentration is 55.5 M.
*K
hydr
H11005 . Units of K
hydr
are M
H110021
.
[hydrate]
[carbonyl compound][water]
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Consider first the electronic effect of alkyl groups versus hydrogen atoms attached
to C?O. Recall from Section 17.2 that alkyl substituents stabilize C?O, making a
ketone carbonyl more stable than an aldehyde carbonyl. As with all equilibria, factors
that stabilize the reactants decrease the equilibrium constant. Thus, the extent of hydra-
tion decreases as the number of alkyl groups on the carbonyl increase.
A striking example of an electronic effect on carbonyl group stability and its relation
to the equilibrium constant for hydration is seen in the case of hexafluoroacetone. In con-
trast to the almost negligible hydration of acetone, hexafluoroacetone is completely hydrated.
Instead of stabilizing the carbonyl group by electron donation as alkyl substituents do,
trifluoromethyl groups destabilize it by withdrawing electrons. A less stabilized carbonyl
group is associated with a greater equilibrium constant for addition.
PROBLEM 17.5 Chloral is one of the common names for trichloroethanal. A
solution of chloral in water is called chloral hydrate; this material has featured
prominently in countless detective stories as the notorious “Mickey Finn” knock-
out drops. Write a structural formula for chloral hydrate.
Now let’s turn our attention to steric effects by looking at how the size of the
groups that were attached to C?O affect K
hydr
. The bond angles at carbon shrink from
H11015120° to H11015109.5° as the hybridization changes from sp
2
in the reactant (aldehyde or
ketone) to sp
3
in the product (hydrate). The increased crowding this produces in the
hydrate is better tolerated, and K
hydr
is greater when the groups are small (hydrogen)
than when they are large (alkyl).
Increasing crowding in hydrate;
decreasing K for formation
C
H
H
HO
OH
Hydrate of formaldehyde
C
H
3
C
H
HO
OH
Hydrate of acetaldehyde
C
H
3
C
CH
3
HO
OH
Hydrate of acetone
CF
3
CCF
3
O
Hexafluoroacetone
H11001 H
2
O
Water
CF
3
CCF
3
OH
OH
1,1,1,3,3,3-Hexafluoro-
2,2-propanediol
K
hydr
H11005 22,000
Increasing stabilization of carbonyl group;
decreasing K for hydration
HCH
O
X
Formaldehyde
(almost completely
hydrated in water)
CH
3
CH
O
X
Acetaldehyde
(comparable amounts of
aldehyde and hydrate present in water)
CH
3
CCH
3
O
X
Acetone
(hardly any hydrate
present in water)
664 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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Electronic and steric effects operate in the same direction. Both cause the equilibrium
constants for hydration of aldehydes to be greater than those of ketones.
Mechanism of Hydration: Hydration of aldehydes and ketones is a rapid reaction,
quickly reaching equilibrium, but faster in acid or base than in neutral solution. Thus
instead of a single mechanism for hydration, we’ll look at two mechanisms, one for basic
and the other for acidic solution.
The base-catalyzed mechanism (Figure 17.4) is a two-step process in which the
first step is rate-determining. In it, the nucleophile, a hydroxide ion, attacks the carbon
of the carbonyl group and bonds to it. The product of this step is an alkoxide ion, which
abstracts a proton from water in the second step, yielding the geminal diol. The second
step, like all the other proton transfers between oxygens that we have seen, is fast.
The role of the basic catalyst (HO
H11002
) is to increase the rate of the nucleophilic addi-
tion step. Hydroxide ion, the nucleophile in the base-catalyzed reaction, is much more
reactive than a water molecule, the nucleophile in neutral media.
Aldehydes react faster than ketones for almost the same reasons that their equi-
librium constants for hydration are more favorable. The sp
2
→ sp
3
hybridization change
that the carbonyl carbon undergoes on hydration is partially developed in the transition
state for the rate-determining nucleophilic addition step (Figure 17.5). Alkyl groups at
the reaction site increase the activation energy by simultaneously lowering the energy of
the starting state (ketones have a more stabilized carbonyl group than aldehydes) and
raising the energy of the transition state (a steric crowding effect).
Three steps are involved in the acid-catalyzed hydration reaction, as shown in Figure
17.6. The first and last are rapid proton-transfer processes. The second is the nucleophilic
addition step. The acid catalyst activates the carbonyl group toward attack by a weakly
nucleophilic water molecule. Protonation of oxygen makes the carbonyl carbon of an alde-
hyde or a ketone much more electrophilic. Expressed in resonance terms, the protonated
carbonyl has a greater degree of carbocation character than an unprotonated carbonyl.
C
H11001
O
H
C
H
O
H11001
17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones 665
Step 1: Nucleophilic addition of hydroxide ion to the carbonyl group
Step 2: Proton transfer from water to the intermediate formed in the first step
RH11032
HO CO
H11002
H11002H11002
H11002slow
R
Hydroxide Aldehyde
or ketone
H11001
HO
CO
RH11032 R
HO
C
RH11032 R
O HOH
fast
H11001 CO
RH11032 R
H H11001 OH
Water Geminal diol Hydroxide ion
HO
FIGURE 17.4 The mechanism of hydration of an aldehyde or ketone in basic solution. Hydrox-
ide ion is a catalyst; it is consumed in the first step, and regenerated in the second.
Learning By Modeling in-
cludes models of formaldehyde
(H
2
C?O) and its protonated
form (H
2
C?OH
H11001
). Compare the
two with respect to their elec-
trostatic potential maps and the
degree of positive charge at
carbon.
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666
, H
2
O
δ –
Potential energy
R
R'
R
R'
R
R
C
C
C
C
HO
HO
HO
RR'
sp
3
sp
3
sp
2
HO
OHO
O
O
–
H
2
O
RCR', H
2
O, HO
–
OH,
–
OH
H
E
act
O
δ – δ –
δ –
H11001
Step 1: Protonation of the carbonyl oxgyen
C
H11001
RH11032
R
O HO
fast
H11001 O
H
Hydronium
ion
Conjugate acid of
carbonyl compound
Water
H
Aldehyde
or ketone
C
RH11032
R
H11001
H
HOH
Step 2: Nucleophilic addition to the protonated aldehyde or ketone
O H11001H
H
Water
O
Conjugate acid of
carbonyl compound
C
RH11032
R
H11001
H
slow
C O
RH11032 R
HOH
H
H11001
Conjugate acid of
geminal diol
Step 3: Proton transfer from the conjugate acid of the geminal diol to a water molecule
CO
RH11032 R
HOH
H
H11001
Conjugate acid of
geminal diol
H11001 H
2
O
fast
CO
RH11032 R
HOH
Geminal diol
H11001 H
3
O
H11001
Hydronium
ion
Water
FIGURE 17.5 Potential
energy diagram for base-
catalyzed hydration of an
aldehyde or ketone.
FIGURE 17.6 The mecha-
nism of hydration of an
aldehyde or ketone in acidic
solution. Hydronium ion is a
catalyst; it is consumed in
the first step, and regener-
ated in the third.
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Steric and electronic effects influence the rate of nucleophilic addition to a proton-
ated carbonyl group in much the same way as they do for the case of a neutral one, and
protonated aldehydes react faster than protonated ketones.
With this as background, let us now examine how the principles of nucleophilic
addition apply to the characteristic reactions of aldehydes and ketones. We’ll begin with
the addition of hydrogen cyanide.
17.7 CYANOHYDRIN FORMATION
The product of addition of hydrogen cyanide to an aldehyde or a ketone contains both
a hydroxyl group and a cyano group bonded to the same carbon. Compounds of this type
are called cyanohydrins.
The mechanism of this reaction is outlined in Figure 17.7. It is analogous to the mech-
anism of base-catalyzed hydration in that the nucleophile (cyanide ion) attacks the car-
bonyl carbon in the first step of the reaction, followed by proton transfer to the carbonyl
oxygen in the second step.
The addition of hydrogen cyanide is catalyzed by cyanide ion, but HCN is too weak
an acid to provide enough for the reaction to proceed at a reasonable rate.
Cyanohydrins are therefore normally prepared by adding an acid to a solution containing
the carbonyl compound and sodium or potassium cyanide. This procedure ensures that free
cyanide ion is always present in amounts sufficient to increase the rate of the reaction.
Cyanohydrin formation is reversible, and the position of equilibrium depends on
the steric and electronic factors governing nucleophilic addition to carbonyl groups
described in the preceding section. Aldehydes and unhindered ketones give good yields
of cyanohydrins.
Converting aldehydes and ketones to cyanohydrins is of synthetic value for two rea-
sons: (1) a new carbon–carbon bond is formed, and (2) the cyano group in the product can
be converted to a carboxylic acid function (CO
2
H) by hydrolysis (to be discussed in Section
19.12) or to an amine of the type CH
2
NH
2
by reduction (to be discussed in Section 22.10).
NaCN, ether–water
then HCl
Cl CH
Cl
O
2,4-Dichlorobenzaldehyde
Cl CHC
Cl
OH
N
2,4-Dichlorobenzaldehyde
cyanohydrin (100%)
NaCN, H
2
O
then H
2
SO
4
CH
3
CCH
3
O
Acetone
OH
CH
3
CCH
3
C N
Acetone
cyanohydrin (77–78%)
C
H11002
N
RCRH11032
O
Aldehyde
or ketone
H11001
Hydrogen
cyanide
HC N
Cyanohydrin
RCRH11032
OH
C N
17.7 Cyanohydrin Formation 667
In substitutive IUPAC nomen-
clature, cyanohydrins are
named as hydroxy deriva-
tives of nitriles. Since nitrile
nomenclature will not be dis-
cussed until Section 20.1, we
will refer to cyanohydrins as
derivatives of the parent
aldehyde or ketone as shown
in the examples. This con-
forms to the practice of most
chemists.
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PROBLEM 17.6 The hydroxyl group of a cyanohydrin is also a potentially reac-
tive site. Methacrylonitrile is an industrial chemical used in the production of plas-
tics and fibers. One method for its preparation is the acid-catalyzed dehydration
of acetone cyanohydrin. Deduce the structure of methacrylonitrile.
A few cyanohydrins and ethers of cyanohydrins occur naturally. One species of
millipede stores benzaldehyde cyanohydrin, along with an enzyme that catalyzes its
cleavage to benzaldehyde and hydrogen cyanide, in separate compartments above its
legs. When attacked, the insect ejects a mixture of the cyanohydrin and the enzyme,
repelling the invader by spraying it with hydrogen cyanide.
17.8 ACETAL FORMATION
Many of the most interesting and useful reactions of aldehydes and ketones involve trans-
formation of the initial product of nucleophilic addition to some other substance under
the reaction conditions. An example is the reaction of aldehydes with alcohols under con-
668 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
Step 1: Nucleophilic attack by the negatively charged carbon of cyanide ion at the
carbonyl carbon of the aldehyde or ketone. Hydrogen cyanide itself is not very
nucleophilic and does not ionize to form cyanide ion to a significant extent.
Thus, a source of cyanide ion such as NaCN or KCN is used.
RH11032
R
CO H11001
Aldehyde or ketone Hydrogen cyanide Cyanohydrin
CHN N C OHC
R
RH11032
The overall reaction:
H11001
Cyanide ion
O
Aldehyde or
ketone
C
RH11032
R
ONC
H11002
Conjugate base of cyanohydrin
N C C
R
RH11032
H11002
Step 2: The alkoxide ion formed in the first step abstracts a proton from hydrogen
cyanide. This step yields the cyanohydrin product and regenerates cyanide ion.
O
Conjugate base of
cyanohydrin
N C C
R
RH11032
H11002
H11001
Hydrogen
cyanide
CHN N C OHC
R
RH11032
Cyanohydrin
C N
H11002
H11001
Cyanide ion
FIGURE 17.7 The mecha-
nism of cyanohydrin forma-
tion from an aldehyde or a
ketone. Cyanide ion is a cat-
alyst; it is consumed in the
first step, and regenerated
in the second.
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ditions of acid catalysis. The expected product of nucleophilic addition of the alcohol to
the carbonyl group is called a hemiacetal. The product actually isolated, however, cor-
responds to reaction of one mole of the aldehyde with two moles of alcohol to give gem-
inal diethers known as acetals:
The overall reaction proceeds in two stages. The hemiacetal is formed in the first
stage by nucleophilic addition of the alcohol to the carbonyl group. The mechanism of
hemiacetal formation is exactly analogous to that of acid-catalyzed hydration of alde-
hydes and ketones (Section 17.6):
Under the acidic conditions of its formation, the hemiacetal is converted to an acetal by
way of a carbocation intermediate:
This carbocation is stabilized by electron release from its oxygen substituent:
H11001
RH
C
ORH11032
RH
C
H11001
ORH11032
A particularly stable
resonance form; both
carbon and oxygen have
octets of electrons.
H
H11001
, fast slow
H11001
HH
RCH
O
ORH11032ORH11032
RCH
OH
Hemiacetal
H11001
RH
C
ORH11032
Carbocation
H11001
Water
H
2
O
RCH
O
Aldehyde
H
H11001
H11002H
H11001
RH11032OH
RCH
H11001
OH
H11001
O
HRH11032
RCH
OH
ORH11032
RCH
OH
Hemiacetal
RCH
O
Aldehyde
RH11032OH, H
H11001
RH11032OH, H
H11001
RCH
OH
ORH11032
Hemiacetal
RCH
ORH11032
ORH11032
Acetal
H11001 H
2
O
Water
CH
O
Benzaldehyde
H11001 2CH
3
CH
2
OH
Ethanol
HCl
CH(OCH
2
CH
3
)
2
Benzaldehyde
diethyl acetal (66%)
17.8 Acetal Formation 669
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Nucleophilic capture of the carbocation intermediate by an alcohol molecule leads to an
acetal:
PROBLEM 17.7 Write a stepwise mechanism for the formation of benzaldehyde
diethyl acetal from benzaldehyde and ethanol under conditions of acid catalysis.
Acetal formation is reversible in acid. An equilibrium is established between the reac-
tants, that is, the carbonyl compound and the alcohol, and the acetal product. The position
of equilibrium is favorable for acetal formation from most aldehydes, especially when excess
alcohol is present as the reaction solvent. For most ketones the position of equilibrium is
unfavorable, and other methods must be used for the preparation of acetals from ketones.
Diols that bear two hydroxyl groups in a 1,2 or 1,3 relationship to each other yield
cyclic acetals on reaction with either aldehydes or ketones. The five-membered cyclic
acetals derived from ethylene glycol are the most commonly encountered examples.
Often the position of equilibrium is made more favorable by removing the water formed
in the reaction by azeotropic distillation with benzene or toluene:
PROBLEM 17.8 Write the structures of the cyclic acetals derived from each of
the following.
(a) Cyclohexanone and ethylene glycol
(b) Benzaldehyde and 1,3-propanediol
(c) Isobutyl methyl ketone and ethylene glycol
(d) Isobutyl methyl ketone and 2,2-dimethyl-1,3-propanediol
SAMPLE SOLUTION (a) The cyclic acetals derived from ethylene glycol contain
a five-membered 1,3-dioxolane ring.
CH
3
(CH
2
)
5
CH
O
Heptanal
H11001 HOCH
2
CH
2
OH
Ethylene glycol
(1,2-ethanediol)
p-toluenesulfonic
acid
benzene
OO
H (CH
2
)
5
CH
3
2-Hexyl-1,3-dioxolane
(81%)
p-toluenesulfonic
acid
benzene
C
6
H
5
CH
2
CCH
3
O
Benzyl methyl
ketone
H11001 HOCH
2
CH
2
OH
Ethylene glycol
(1,2-ethanediol)
2-Benzyl-2-methyl-1,3-dioxolane
(78%)
C
6
H
5
CH
2
CH
3
OO
H11001
RH11032
H
O
Alcohol
H11001
HRH11032
RCH
O
ORH11032
H11002
H
H11001
, fast
ORH11032
RCH
ORH11032
Acetal
fast
RH
C
H11001
ORH11032
670 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
At one time it was customary
to designate the products of
addition of alcohols to ke-
tones as ketals. This term has
been dropped from the
IUPAC system of nomencla-
ture, and the term acetal is
now applied to the adducts
of both aldehydes and
ketones.
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Acetals are susceptible to hydrolysis in aqueous acid:
This reaction is simply the reverse of the reaction by which acetals are formed—acetal
formation is favored by excess alcohol, acetal hydrolysis by excess water. Acetal for-
mation and acetal hydrolysis share the same mechanistic pathway but travel along that
pathway in opposite directions. In the following section you’ll see a clever way in which
acetal formation and hydrolysis have been applied to synthetic organic chemistry.
PROBLEM 17.9 Problem 17.7 asked you to write a mechanism describing for-
mation of benzaldehyde diethyl acetal from benzaldehyde and ethanol. Write a
stepwise mechanism for the acid hydrolysis of this acetal.
17.9 ACETALS AS PROTECTING GROUPS
In an organic synthesis, it sometimes happens that one of the reactants contains a func-
tional group that is incompatible with the reaction conditions. Consider, for example, the
conversion
It looks as though all that is needed is to prepare the acetylenic anion, then alkylate it
with methyl iodide (Section 9.6). There is a complication, however. The carbonyl group
in the starting alkyne will neither tolerate the strongly basic conditions required for anion
formation nor survive in a solution containing carbanions. Acetylide ions add to carbonyl
groups (Section 14.8). Thus, the necessary anion
is inaccessible.
The strategy that is routinely followed is to protect the carbonyl group during the
reactions with which it is incompatible and then to remove the protecting group in a sub-
sequent step. Acetals, especially those derived from ethylene glycol, are among the most
CH
3
CCH
2
CH
2
C
O
C
H11002
5-Hexyn-2-one
CH
3
CCH
2
CH
2
C
O
CH
5-Heptyn-2-one
CH
3
CCH
2
CH
2
C
O
CCH
3
RCRH11032
O
Aldehyde
or ketone
RCRH11032
ORH11033
ORH11033
Acetal
H11001 H
2
O H11001 2RH11033OH
Alcohol
H
H11001
O
Cyclohexanone
H11001 HOCH
2
CH
2
OH
Ethylene glycol
O
O
Acetal of cyclohexanone
and ethylene glycol
H
H11001
17.9 Acetals As Protecting Groups 671
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useful groups for carbonyl protection, because they can be introduced and removed read-
ily. A key fact is that acetals resemble ethers in being inert to many of the reagents, such
as hydride reducing agents and organometallic compounds, that react readily with car-
bonyl groups. The following sequence is the one that was actually used to bring about
the desired transformation.
(a) Protection of carbonyl group
(b) Alkylation of alkyne
(c) Unmasking of the carbonyl group by hydrolysis
Although protecting and unmasking the carbonyl group add two steps to the synthetic pro-
cedure, both steps are essential to its success. The tactic of functional group protection is
frequently encountered in preparative organic chemistry, and considerable attention has
been paid to the design of effective protecting groups for a variety of functionalities.
PROBLEM 17.10 Acetal formation is a characteristic reaction of aldehydes and
ketones, but not of carboxylic acids. Show how you could advantageously use a
cyclic acetal protecting group in the following synthesis:
17.10 REACTION WITH PRIMARY AMINES: IMINES
A second two-stage reaction that begins with nucleophilic addition to aldehydes and
ketones is their reaction with primary amines, compounds of the type RNH
2
or ArNH
2
.
In the first stage of the reaction the amine adds to the carbonyl group to give a species
known as a carbinolamine. Once formed, the carbinolamine undergoes dehydration to
yield the product of the reaction, an N-alkyl- or N-aryl-substituted imine:
Convert CH
3
C COH
O O
CH
3
CCH
2
OH
O
to
H
2
O
HCl
CH
2
CH
2
C CCH
3
OO
H
3
C
5-Heptyn-2-one (96%)
CH
3
CCH
2
CH
2
C
O
CCH
3
1. NaNH
2
, NH
3
2. CH
3
I
CH
2
CH
2
C CCH
3
OO
H
3
C
Acetal of product
CH
2
CH
2
C CH
OO
H
3
C
CH
3
CCH
2
CH
2
C
O
CH
5-Hexyn-2-one
HOCH
2
CH
2
OH
p-toluenesulfonic
acid, benzene
CH
2
CH
2
C CH
OO
H
3
C
Acetal of reactant
672 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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Both the addition and the elimination phase of the reaction are accelerated by acid
catalysis. Careful control of pH is essential, since sufficient acid must be present to give
a reasonable equilibrium concentration of the protonated form of the aldehyde or ketone.
Too acidic a reaction medium, however, converts the amine to its protonated form, a
form that is not nucleophilic, and retards reaction.
PROBLEM 17.11 Write the structure of the carbinolamine intermediate and the
imine product formed in the reaction of each of the following:
(a) Acetaldehyde and benzylamine, C
6
H
5
CH
2
NH
2
(b) Benzaldehyde and butylamine, CH
3
CH
2
CH
2
CH
2
NH
2
(c) Cyclohexanone and tert-butylamine, (CH
3
)
3
CNH
2
(d) Acetophenone and cyclohexylamine,
SAMPLE SOLUTION The carbinolamine is formed by nucleophilic addition of the
amine to the carbonyl group. Its dehydration gives the imine product.
A number of compounds of the general type H
2
NZ react with aldehydes and
ketones in a manner analogous to that of primary amines. The carbonyl group (C?O)
is converted to C?NZ, and a molecule of water is formed. Table 17.4 presents exam-
ples of some of these reactions. The mechanism by which each proceeds is similar to
the nucleophilic addition–elimination mechanism described for the reaction of primary
amines with aldehydes and ketones.
The reactions listed in Table 17.4 are reversible and have been extensively stud-
ied from a mechanistic perspective because of their relevance to biological processes.
NH
2
O
Cyclohexanone
H11001 (CH
3
)
2
CHCH
2
NH
2
Isobutylamine
NCH
2
CH(CH
3
)
2
N-Cyclohexylideneisobutylamine (79%)
CH
O
Benzaldehyde
H11001 CH
3
NH
2
Methylamine
NCH
3
CH
N-Benzylidenemethylamine (70%)
H
2
O
Water
O
RCRH11032
Aldehyde
or ketone
H11001 RH11033NH
2
Primary
amine
addition elimination
OH
RCRH11032
HNRH11033
Carbinolamine
RCRH11032
NRH11033
N-substituted
imine
H11001
17.10 Reaction with Primary Amines: Imines 673
N-substituted imines are
sometimes called Schiff’s
bases, after Hugo Schiff, a
German chemist who de-
scribed their formation in
1864.
CH
3
CH
O
Acetaldehyde
C
6
H
5
CH
2
NH
2
Benzylamine
H11001
H11002H
2
O
Carbinolamine
intermediate
CH
3
CH NCH
2
C
6
H
5
OH
H
Imine product
(N-ethylidenebenzylamine)
CH
3
CH NCH
2
C
6
H
5
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Many biological reactions involve initial binding of a carbonyl compound to an enzyme
or coenzyme via imine formation. The boxed essay “Imines in Biological Chemistry”
gives some important examples.
17.11 REACTION WITH SECONDARY AMINES: ENAMINES
Secondary amines are compounds of the type R
2
NH. They add to aldehydes and ketones
to form carbinolamines, but their carbinolamine intermediates can dehydrate to a stable
product only in the direction that leads to a carbon–carbon double bond:
The product of this dehydration is an alkenyl-substituted amine, or enamine.
H11001
benzene
heat
O
Cyclopentanone
N
H
Pyrrolidine N-(1-Cyclopentenyl)-
pyrrolidine (80–90%)
N
H11001 H
2
O
Water
O
RCH
2
CRH11032
Aldehyde
or ketone
H11001 RH11033
2
NH
Secondary
amine
H11002H
2
O
OH
RH11032RCH
2
C
NRH11033
2
Carbinolamine Enamine
CRH11032RCH
NRH11033
2
674 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
TABLE 17.4
Reaction of Aldehydes and
Ketones with Derivatives of Ammonia:
Name of reagent
Hydroxylamine
Phenylhydrazine
Semicarbazide
Type of product
Oxime
Phenylhydrazone
Semicarbazone
H
2
NOH
H
2
NNHC
6
H
5
*
Reagent (H
2
NZ)
H
2
NNHCNH
2
O
X
*Compounds related to phenylhydrazine react in an analogous way. p-Nitrophenylhydrazine yields p-nitrophenylhydrazones; 2,4-dinitro-
phenylhydrazine yields 2,4-dinitrophenylhydrazones.
H11001H11001RCRH11032
O
X
RCRH11032
X
NZ
H
2
NZ H
2
O
Example
Heptanal
CH
3
(CH
2
)
5
CH
O
X
Heptanal oxime (81–93%)
CH
3
(CH
2
)
5
CH
X
NOH
H
2
NOH
2-Dodecanone
CH
3
C(CH
2
)
9
CH
3
O
X
2-Dodecanone
semicarbazone (93%)
CH
3
C(CH
2
)
9
CH
3
X
NNHCNH
2
O
X
H
2
NNHCNH
2
O
X
CCH
3
O
X
Acetophenone
CCH
3
X
NNHC
6
H
5
Acetophenone
phenylhydrazone (87–91%)
H
2
NNHC
6
H
5
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PROBLEM 17.12 Write the structure of the carbinolamine intermediate and the
enamine product formed in the reaction of each of the following:
(a) Propanal and dimethylamine, CH
3
NHCH
3
(b) 3-Pentanone and pyrrolidine
(c)
SAMPLE SOLUTION (a) Nucleophilic addition of dimethylamine to the carbonyl
group of propanal produces a carbinolamine:
Propanal
CH
3
CH
2
CH
O
H11001 CH
3
NCH
3
H
Dimethylamine
CH
3
CH
2
CH
CH
3
OH
CH
3
N
Carbinolamine intermediate
Acetophenone and HN
17.11 Reaction with Secondary Amines: Enamines 675
IMINES IN BIOLOGICAL CHEMISTRY
M
any biological processes involve an “associa-
tion” between two species in a step prior to
some subsequent transformation. This asso-
ciation can take many forms. It can be a weak associ-
ation of the attractive van der Waals type, or a
stronger interaction such as a hydrogen bond. It can
be an electrostatic attraction between a positively
charged atom of one molecule and a negatively
charged atom of another. Covalent bond formation
between two species of complementary chemical re-
activity represents an extreme kind of “association.”
It often occurs in biological processes in which alde-
hydes or ketones react with amines via imine inter-
mediates.
An example of a biologically important alde-
hyde is pyridoxal phosphate. Pyridoxal phosphate is
the active form of vitamin B
6
and is a coenzyme for
many of the reactions of H9251-amino acids. In these reac-
tions the amino acid binds to the coenzyme by react-
ing with it to form an imine of the kind shown in the
equation. Reactions then take place at the amino
acid portion of the imine, modifying the amino acid.
In the last step, enzyme-catalyzed hydrolysis cleaves
the imine to pyridoxal and the modified amino acid.
A key step in the chemistry of vision is binding
of an aldehyde to an enzyme via an imine. An out-
line of the steps involved is presented in Figure 17.8.
It starts with H9252-carotene, a pigment that occurs natu-
rally in several fruits and vegetables, including car-
rots. H9252-Carotene undergoes oxidative cleavage in the
liver to give an alcohol known as retinol or vitamin
A. Oxidation of vitamin A, followed by isomerization
of one of its double bonds, gives the aldehyde 11-cis-
retinal. In the eye, the aldehyde function of 11-cis-
retinal combines with an amino group of the protein
opsin to form an imine called rhodopsin. When
rhodopsin absorbs a photon of visible light, the cis
double bond of the retinal unit undergoes a photo-
chemical cis-to-trans isomerization, which is at-
tended by a dramatic change in its shape and a
change in the conformation of rhodopsin. This con-
formational change is translated into a nerve im-
pulse perceived by the brain as a visual image.
Enzyme-promoted hydrolysis of the photochemically
isomerized rhodopsin regenerates opsin and a mole-
cule of all-trans-retinal. Once all-trans-retinal has
been enzymatically converted to its 11-cis isomer, it
and opsin reenter the cycle.
CH
CH
2
OPO
3
2H11002
N
CH
3
OH
O
Pyridoxal phosphate
H11001 H
2
NCHCO
2
H11002
R
H9251-Amino acid
CH
CH
2
OPO
3
2H11002
N
CH
3
OH
NCHCO
2
H11002
R
Imine
H11001 H
2
O
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676 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
OH
H
OH
H
2
N-protein
H
hv
N-protein
N-protein
H
O
H
2
O
H
O H11001 H
2
N-protein
H9252-Carotene obtained from the
diet is cleaved at its central
carbon-carbon bond to give
vitamin A (retinol)
Oxidation of retinol converts it to
the corresponding aldehyde, retinal.
The double bond at C-11 is isomerized
from the trans to the cis configuration
11-cis-Retinal is the biologically
active stereoisomer and reacts
with the protein opsin to form
an imine. The covalently bound
complex between 11-cis-retinal
and ospin is called rhodopsin.
Rhodopsin absorbs a photon of
light, causing the cis double-bond at
C-11 to undergo a photochemical
transformation to trans, which
triggers a nerve impulse detected
by the brain as a visual image.
Hydrolysis of the isomerized (inactive)
form of rhodopsin liberates opsin and
the all-trans isomer of retinal.
FIGURE 17.8 Imine formation between the aldehyde function of 11-cis-retinal and an amino group of a protein (opsin)
is involved in the chemistry of vision. The numbering scheme used in retinal is based on one specifically developed for
carotenes and compounds derived from them.
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Dehydration of this carbinolamine yields the enamine:
Enamines are used as reagents in synthetic organic chemistry and are involved in cer-
tain biochemical transformations.
17.12 THE WITTIG REACTION
The Wittig reaction uses phosphorus ylides (called Wittig reagents) to convert alde-
hydes and ketones to alkenes.
Wittig reactions may be carried out in a number of different solvents; normally
tetrahydrofuran (THF) or dimethyl sulfoxide (DMSO) is used.
The most attractive feature of the Wittig reaction is its regiospecificity. The loca-
tion of the double bond is never in doubt. The double bond connects the carbon of the
original C?O group of the aldehyde or ketone and the negatively charged carbon of the
ylide.
PROBLEM 17.13 Identify the alkene product in each of the following Wittig
reactions:
(a)
(b)
(c)
SAMPLE SOLUTION (a) In a Wittig reaction the negatively charged substituent
attached to phosphorus is transferred to the aldehyde or ketone, replacing the
carbonyl oxygen. The reaction shown has been used to prepare the indicated
alkene in 65% yield.
Cyclohexyl methyl ketone H11001 (C
6
H
5
)
3
PCH
2
H11002
H11001
Butanal H11001 (C
6
H
5
)
3
P CHCH
H11001
H11002
CH
2
Benzaldehyde H11001 (C
6
H
5
)
3
P
H11001
H11002
O
Cyclohexanone
CH
2
Methylenecyclohexane
(86%)
H11001 (C
6
H
5
)
3
P
H11001
H11002
CH
2
Methylenetriphenyl-
phosphorane
DMSO
H11001 (C
6
H
5
)
3
P
H11001
O
H11002
Triphenylphosphine
oxide
H11001
R
RH11032
C O
Aldehyde or
ketone
H11001 (C
6
H
5
)
3
P
A
B
H11001
H11002
C
Triphenylphosphonium
ylide
(C
6
H
5
)
3
P
H11001
O
H11002
Triphenylphosphine
oxide
R
RH11032
C
A
B
C
Alkene
CH
3
CH
2
CH
CH
3
OH
CH
3
N
Carbinolamine intermediate
H11002H
2
O
N-(1-Propenyl)dimethylamine
CH
3
CH
3
NCH
3
CH CH
17.12 The Wittig Reaction 677
The reaction is named after
Georg Wittig, a German
chemist who shared the 1979
Nobel Prize in chemistry for
demonstrating its synthetic
potential.
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FIGURE 17.9 An elec-
trostatic potential map of
the ylide . The re-
gion of greatest negative
charge is concentrated at
carbon.
H
3
P±CH
2
H11545
In order to understand the mechanism of the Wittig reaction, we need to examine
the structure and properties of ylides. Ylides are neutral molecules that have two oppo-
sitely charged atoms, each with an octet of electrons, directly bonded to each other. In
an ylide such as , phosphorus has eight electrons and is positively
charged; its attached carbon has eight electrons and is negatively charged.
PROBLEM 17.14 Can you write a resonance structure for in
which neither phosphorus nor carbon has a formal charge? (Hint: Remember phos-
phorus can have more than eight electrons in its valence shell.)
We can focus on the charge distribution in an ylide by replacing the phenyl groups
in by hydrogens. Figure 17.9 shows the electrostatic potential map of
, where it can be seen that the electron distribution is highly polarized in the
direction that makes carbon electron-rich. The carbon has much of the character of a car-
banion and can act as a nucleophile toward C?O.
Figure 17.10 outlines a mechanism for the Wittig reaction. The first stage is a
cycloaddition in which the ylide reacts with the carbonyl group to give an intermediate
containing a four-membered ring called an oxaphosphetane. This oxaphosphetane then
dissociates to give an alkene and triphenylphosphine oxide. Presumably the direction of
dissociation of the oxaphosphetane is dictated by the strong phosphorus–oxygen bond
that results. The P±O bond strength in triphenylphosphine oxide has been estimated to
be greater than 540 kJ/mol (130 kcal/mol).
17.13 PLANNING AN ALKENE SYNTHESIS VIA THE WITTIG REACTION
In order to identify the carbonyl compound and the ylide required to produce a given
alkene, mentally disconnect the double bond so that one of its carbons is derived from
a carbonyl group and the other is derived from an ylide. Taking styrene as a represen-
tative example, we see that two such disconnections are possible; either benzaldehyde
or formaldehyde is an appropriate precursor.
H
3
P
H11001
H11002
CH
2
(C
6
H
5
)
3
P
H11001
H11002
CH
2
(C
6
H
5
)
3
PCH
2
H11001
H11002
(C
6
H
5
)
3
P
H11001
H11002
CH
2
CH
O
Benzaldehyde
H11001 (C
6
H
5
)
3
P
H11001
H11002
Cyclopentylidenetriphenyl-
phosphorane
CH
Benzylidenecyclopentane (65%)
678 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
The Wittig reaction is one
that is still undergoing mech-
anistic investigation. An-
other possibility is that the
oxaphosphetane intermedi-
ate is formed by a two-step
process, rather than the one-
step process shown in Figure
17.10.
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Either route is a feasible one, and indeed styrene has been prepared from both combina-
tions of reactants. Typically there will be two Wittig routes to an alkene, and any choice
between them is made on the basis of availability of the particular starting materials.
PROBLEM 17.15 What combinations of carbonyl compound and ylide could you
use to prepare each of the following alkenes?
(a) (b) CH
3
CH
2
CH
2
CH?CH
2
SAMPLE SOLUTION (a) Two Wittig reaction routes lead to the target molecule.
and
CH
3
CH
2
CH
2
CH
CH
3
CCH
2
CH
3
3-Methyl-3-heptene
CH
3
CH
2
CH
2
CH
O
Butanal
H11001
CH
3
(C
6
H
5
)
3
P CCH
2
CH
3
H11001
H11002
1-Methylpropylidenetriphenyl-
phosphorane
CH
3
CH
2
CH
2
CH
CH
3
CCH
2
CH
3
C
6
H
5
CH CH
2
Styrene
O
C
6
H
5
CH
Benzaldehyde
H11001 (C
6
H
5
)
3
P
H11001
H11002
CH
2
Methylenetriphenylphosphorane
C
6
H
5
CH CH
2
Styrene
(C
6
H
5
)
3
P
H11001
H11002
CHC
6
H
5
Benzylidenetriphenylphosphorane
H11001 HCH
O
Formaldehyde
17.13 Planning an Alkene Synthesis via the Wittig Reaction 679
C
O
RRH11032
Aldehyde
or ketone
C
P(C
6
H
5
)
3
AB
Triphenylphosphonium
ylide
H11001
H11002
RH11032
RC
O
C B
P(C
6
H
5
)
3
Oxaphosphetane
A
Step 1: The ylide and the aldehyde or ketone combine to form an oxaphosphetane.
Step 2: The oxaphosphetane dissociates to an alkene and triphenylphosphine oxide.
RH11032
RC
O
C B
P(C
6
H
5
)
3
Oxaphosphetane
A
R
RH11032
B
A
CC
Alkene
O P(C
6
H
5
)
3
H11001
H11001H11002
Triphenylphosphine
oxide
FIGURE 17.10 The mecha-
nism of the Wittig reaction.
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Phosphorus ylides are prepared from alkyl halides by a two-step sequence. The
first step is a nucleophilic substitution of the S
N
2 type by triphenylphosphine on an alkyl
halide to give an alkyltriphenylphosphonium salt:
Triphenylphosphine is a very powerful nucleophile, yet is not strongly basic. Methyl,
primary, and secondary alkyl halides are all suitable substrates.
The alkyltriphenylphosphonium salt products are ionic and crystallize in high yield
from the nonpolar solvents in which they are prepared. After isolation, the alkyltriphe-
nylphosphonium halide is converted to the desired ylide by deprotonation with a strong base:
Suitable strong bases include the sodium salt of dimethyl sulfoxide (in dimethyl sulfox-
ide as the solvent) and organolithium reagents (in diethyl ether or tetrahydrofuran).
PROBLEM 17.16 The sample solution to Problem 17.15(a) showed the prepara-
tion of 3-methyl-3-heptene by a Wittig reaction involving the ylide shown. Write
equations showing the formation of this ylide beginning with 2-bromobutane.
CH
3
(C
6
H
5
)
3
P CCH
2
CH
3
H11001
H11002
C
A
B
H
(C
6
H
5
)
3
P
H11001
Alkyltriphenylphosphonium salt
H11001 Y
H11002
Base
B
A
(C
6
H
5
)
3
P
H11001
H11002
C
Triphenylphosphonium ylide
H11001
Conjugate acid
of base used
HY
(C
6
H
5
)
3
P
Triphenylphosphine
CH
3
Br
Bromomethane
H11001 Br
H11002
CH
3
(C
6
H
5
)
3
P
H11001
Methyltriphenylphosphonium
bromide (99%)
benzene
(C
6
H
5
)
3
P
Triphenylphosphine
B
A
CH X
Alkyl halide
X
H11002
CH
A
B(C
6
H
5
)
3
P
H11001
Alkyltriphenylphosphonium
halide
CH
3
CH
2
CH
2
CH
CH
3
CCH
2
CH
3
3-Methyl-3-heptene
CH
3
CCH
2
CH
3
O
2-Butanone
H11001P(C
6
H
5
)
3
H11001
CH
3
CH
2
CH
2
CH
H11002
Butylidenetriphenylphosphorane
680 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
H11001H11001H11001Br
H11002
CH
3
(C
6
H
5
)
3
P
H11001
Methyltriphenylphos-
phonium bromide
O
NaCH
2
SCH
3
Sodiomethyl
methyl sulfoxide
O
CH
3
SCH
3
Dimethyl
sulfoxide
NaBr
Sodium
bromide
DMSO
(C
6
H
5
)
3
P
H11001
H11002
CH
2
Methylenetri-
phenylphos-
phorane
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Normally the ylides are not isolated. Instead, the appropriate aldehyde or ketone
is added directly to the solution in which the ylide was generated.
17.14 STEREOSELECTIVE ADDITION TO CARBONYL GROUPS
Nucleophilic addition to carbonyl groups sometimes leads to a mixture of stereoisomeric
products. The direction of attack is often controlled by steric factors, with the nucle-
ophile approaching the carbonyl group at its less hindered face. Sodium borohydride
reduction of 7,7-dimethylbicyclo[2.2.1]heptan-2-one illustrates this point:
Approach of borohydride to the top face of the carbonyl group is sterically hindered by
one of the methyl groups. The bottom face of the carbonyl group is less congested, and
the major product is formed by hydride transfer from this direction.
The reduction is stereoselective. A single starting material can form two stereoisomers
of the product but yields one of them preferentially.
It is possible to predict the preferred stereochemical path of nucleophilic addition
if one face of a carbonyl group is significantly more hindered to the approach of the
reagent than the other. When no clear distinction between the two faces is evident, other,
more subtle effects, which are still incompletely understood, come into play.
Enzyme-catalyzed reductions of carbonyl groups are, more often than not, com-
pletely stereoselective. Pyruvic acid is converted exclusively to (S)-(H11001)-lactic acid by the
lactate dehydrogenase-NADH system (Section 15.11). The enantiomer (R)-(H11002)-lactic
acid is not formed.
CH
3
CCOH
OO
Pyruvic
acid
H11001 NADH
Reduced
form of
coenzyme
H11001 H
H11001
lactate
dehydrogenase
C
HO
COH
OH
H
3
C
(S)-(H11001)-Lactic
acid
H11001 NAD
H11001
Oxidized
form of
coenzyme
O
CH
3
H
3
C
Preferred direction of approach of
borohydride is to less hindered face
of carbonyl group.
Approach of nucleophile from this
direction is hindered by methyl
group.
H
3
B H
H11002
17.14 Stereoselective Addition to Carbonyl Groups 681
O
CH
3
H
3
C
7,7-Dimethylbicyclo[2.2.1]-
heptan-2-one
H
OH
CH
3
H
3
C
exo-7,7-Dimethylbicyclo[2.2.1]-
heptan-2-ol (80%)
H11001
OH
H
CH
3
H
3
C
endo-7,7-Dimethylbicyclo[2.2.1]-
heptan-2-ol (20%)
NaBH
4
isopropyl
alcohol,
0°C
You may find it helpful to
make molecular models of the
reactant and products in the re-
action shown.
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Here the enzyme, a chiral molecule, binds the coenzyme and substrate in such a way
that hydrogen is transferred exclusively to the face of the carbonyl group that leads to
(S)-(H11001)-lactic acid (Figure 17.11).
The stereochemical outcome of enzyme-mediated reactions depends heavily on the
way the protein chain is folded. Aspects of protein conformation will be discussed in
Chapter 27.
17.15 OXIDATION OF ALDEHYDES
Aldehydes are readily oxidized to carboxylic acids by a number of reagents, including
those based on Cr(VI) in aqueous media.
Mechanistically, these reactions probably proceed through the hydrate of the aldehyde
and follow a course similar to that of alcohol oxidation.
RCH
O
Aldehyde
H11001 H
2
O RCOH
O
Carboxylic
acid
RCH
OH
OH
Geminal diol
(hydrate)
oxidize
oxidize
RCH
O
Aldehyde
RCOH
O
Carboxylic acid
K
2
Cr
2
O
7
H
2
SO
4
, H
2
O
O
CH
O
Furfural
O
CO
2
H
Furoic acid (75%)
682 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
NADH-binding
site of enzyme
Carbo
xylate-binding
site of enzyme
N
A
D H
C
CH
3
OH
H
H11002
O
2
C
Carbon
yl-binding
site of enzyme
C
C
O
H
3
C O
O
H11002
FIGURE 17.11 Enzyme-catalyzed reduction of pyruvate to (S)-(H11001)-lactate. A preferred orienta-
tion of binding of pyruvate to the enzyme, coupled with a prescribed location of the reducing
agent, the coenzyme NADH, leads to hydrogen transfer exclusively to a single face of the car-
bonyl group.
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17.16 BAEYER–VILLIGER OXIDATION OF KETONES
The reaction of ketones with peroxy acids is both novel and synthetically useful. An oxy-
gen from the peroxy acid is inserted between the carbonyl group and one of the attached
carbons of the ketone to give an ester. Reactions of this type were first described by Adolf
von Baeyer and Victor Villiger in 1899 and are known as Baeyer–Villiger oxidations.
Methyl ketones give esters of acetic acid; that is, oxygen insertion occurs between
the carbonyl carbon and the larger of the two groups attached to it.
The mechanism of the Baeyer–Villiger oxidation is shown in Figure 17.12. It
begins with nucleophilic addition of the peroxy acid to the carbonyl group of the ketone,
which is followed by migration of an alkyl group from the carbonyl group to oxygen.
C
6
H
5
CO
2
OH
CHCl
3
CCH
3
O
Cyclohexyl methyl ketone
O
OCCH
3
Cyclohexyl acetate (67%)
RCRH11032
O
Ketone
RCORH11032
O
Ester
RH11033COOH
O
Peroxy acid
RH11033COH
O
Carboxylic acid
H11001H11001
17.16 Baeyer–Villiger Oxidation of Ketones 683
Peroxy acids have been seen
before as reagents for the
epoxidation of alkenes (Sec-
tion 6.18).
The overall reaction:
O
RCRH11032
Ketone
H11001 RH11033COOH
O
Peroxy acid
ROCRH11032
O
Ester
H11001 RH11033COH
O
Carboxylic acid
Step 1: The peroxy acid adds to the carbonyl group of the ketone. This step is a
nucleophilic addition analogous to gem-diol and hemiacetal formation.
O
RCRH11032
Ketone
H11001 RH11033COOH
O
Peroxy acid
O
RCRH11032
H
HOCRH11033
(Peroxy monoester of gem-diol)
Step 2: The intermediate from step 1 undergoes rearrangement. Cleavage of the
weak O—O bond of the peroxy ester is assisted by migration of one of the
substituents from the carbonyl group to oxygen. The group R migrates with
its pair of electrons in much the same way as alkyl groups migrate in
carbocation rearrangements.
OOCRH11033
O
H11001
O
OCRH11033
O
O
R
C
O
RH11032
Ester Carboxylic acid
O
C
R
RH11032
O
H
FIGURE 17.12 Mechanism
of the Baeyer–Villiger oxida-
tion of a ketone.
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In general, it is the more substituted group that migrates. The migratory aptitude of the
various alkyl groups is:
Tertiary alkyl H11022 secondary alkyl H11022 primary alkyl H11022 methyl
PROBLEM 17.17 Using Figure 17.12 as a guide, write a mechanism for the
Baeyer–Villiger oxidation of cyclohexyl methyl ketone by peroxybenzoic acid.
PROBLEM 17.18 Baeyer–Villiger oxidation of aldehydes yields carboxylic acids
(e.g., m-nitrobenzaldehyde yields m-nitrobenzoic acid). What group migrates to
oxygen?
The reaction is stereospecific; the alkyl group migrates with retention of configu-
ration.
In the companion experiment carried out on the trans stereoisomer of the ketone, only
the trans acetate was formed.
As unusual as the Baeyer–Villiger reaction may seem, what is even more remark-
able is that an analogous reaction occurs in living systems. Certain bacteria, including
those of the Pseudomonas and Acinetobacter type, can use a variety of organic com-
pounds, even hydrocarbons, as a carbon source. With cyclohexane, for example, the early
stages proceed by oxidation to cyclohexanone, which then undergoes the “biological
Baeyer–Villiger reaction.”
The product (6-hexanolide) is a cyclic ester or lactone (Section 19.15). Like the
Baeyer–Villiger oxidation, an oxygen atom is inserted between the carbonyl group and
the carbon attached to it. But peroxy acids are not involved in any way; the oxidation
of cyclohexanone is catalyzed by an enzyme called cyclohexanone monooxygenase with
the aid of certain coenzymes.
17.17 SPECTROSCOPIC ANALYSIS OF ALDEHYDES AND KETONES
Infrared: Carbonyl groups are among the easiest functional groups to detect by infrared
spectroscopy. The C?O stretching vibration of aldehydes and ketones gives rise to
strong absorption in the region 1710–1750 cm
H110021
as illustrated for butanal in Figure
17.13. In addition to a peak for C?O stretching, the CH?O group of an aldehyde
exhibits two weak bands for C±H stretching near 2720 and 2820 cm
H110021
.
1
H NMR: Aldehydes are readily identified by the presence of a signal for the hydro-
gen of CH?O at H9254 9–10 ppm. This is a region where very few other protons ever appear.
Figure 17.14 shows the
1
H NMR spectrum of 2-methylpropanal [(CH
3
)
2
CHCH?O)],
oxidation
in Pseudomonas
O
2
,
cyclohexanone monooxygenase,
and coenzymes
Cyclohexane
O
Cyclohexanone 6-Hexanolide
O
O
C
6
H
5
CO
2
OH
CHCl
3
CCH
3
O
CH
3
HH
cis-1-Acetyl-2-methylcyclopentane
OCCH
3
O
CH
3
HH
cis-2-Methylcyclopentyl acetate
(only product; 66% yield)
684 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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17.17 Spectroscopic Analysis of Aldehydes and Ketones 685
Wave number, cm
H110021
Transmittance (%)
H±C
O
X
CH
3
CH
2
CH
2
CH
C?O
O
X
H±C±C±CH
3
Chemical shift (δ, ppm)
9.609.70
(ppm)
2.8 2.6
(ppm)
2.4 2.2
(ppm)
1.4 1.2 1.0 0.8
9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0
CH
3
W
W
H
O
O
CHCl
3
FIGURE 17.13 Infrared spectrum of butanal showing peaks characteristic of the CH?O
unit at 2720 and 2820 cm
H110021
(C±H) and at 1720 cm
H110021
(C?O).
FIGURE 17.14 The 200-MHz
1
H NMR spectrum of 2-
methylpropanal, showing
the aldehyde proton as a
doublet at low field strength
(9.7 ppm).
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where the large chemical shift difference between the aldehyde proton and the other pro-
tons in the molecule is clearly evident. As seen in the expanded-scale inset, the aldehyde
proton is a doublet, split by the proton as C-2. Coupling between the protons in
HC±CH?O is much smaller than typical vicinal couplings, making the multiplicity of
the aldehyde peak difficult to see without expanding the scale.
Methyl ketones, such as 2-butanone in Figure 17.15, are characterized by sharp
singlets near H9254 2 ppm for the protons of CH
3
C?O. Similarly, the deshielding effect of
the carbonyl causes the protons of CH
2
C?O to appear at lower field (H9254 2.4 ppm) than
in a CH
2
group of an alkane.
13
C NMR: The signal for the carbon of C?O in aldehydes and ketones appears at
very low field, some 190–220 ppm downfield from tetramethylsilane. Figure 17.16 illus-
trates this for 3-heptanone, in which separate signals appear for each of the seven car-
bons. The six sp
3
-hybridized carbons appear in the range H9254 8–42 ppm, while the carbon
of the C?O group is at H9254 210 ppm. Note, too, that the intensity of the peak for the
C?O carbon is much less than all the others, even though each peak corresponds to a
single carbon. This decreased intensity is a characteristic of Fourier transform (FT) spec-
tra for carbons that don’t have attached hydrogens.
UV-VIS: Aldehydes and ketones have two absorption bands in the ultraviolet region.
Both involve excitation of an electron to an antibonding H9266*. In one, called a H9266→H9266*
686 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
7.0 6.08.09.010.0
1.10 1.00
5.0 4.0 3.0 2.0 1.0 0.0
Chemical shift (δ, ppm)
(ppm)
2.50 2.40
(ppm)
FIGURE 17.15 The 200-MHz
1
H NMR spectrum of 2-butanone. The triplet–quartet pattern of the ethyl
group is more clearly seen in the scale-expanded insets.
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transition, the electron is one of the H9266 electrons of the C?O group. In the other, called
an n→H9266* transition, it is one of the oxygen lone-pair electrons. Since the H9266 electrons
are more strongly held than the lone-pair electrons, the H9266→H9266* transition is of higher
energy and shorter wavelength than the n→H9266* transition. For simple aldehydes and
ketones, the H9266→H9266* transition is below 200 nm and of little use in structure determina-
tion. The n→H9266* transition, although weak, is of more diagnostic value.
Mass Spectrometry: Aldehydes and ketones typically give a prominent molecular ion
peak in their mass spectra. Aldehydes also exhibit an M-1 peak. A major fragmentation
pathway for both aldehydes and ketones leads to formation of acyl cations (acylium ions)
by cleavage of an alkyl group from the carbonyl. The most intense peak in the mass
spectrum of diethyl ketone, for example, is m/z 57, corresponding to loss of ethyl radi-
cal from the molecular ion.
H11001
m/z 86
CH
3
CH
2
CCH
2
CH
3
O
H11001
m/z 57
CH
3
CH
2
C O
H11001
CH
2
CH
3
Acetone
H
3
C
H
3
C
C O
H9266 → H9266* H9261
max
187 nm
n → H9266* H9261
max
270 nm
17.17 Spectroscopic Analysis of Aldehydes and Ketones 687
120 100 80 60 40 20 0200 180 160 140
Chemical shift (δ, ppm)
O
X
C
O
X
CH
3
CH
2
CCH
2
CH
2
CH
2
CH
3
CH
3
CH
3CH
2
CH
2
CH
2
CH
2
FIGURE 17.16 The
13
C NMR spectrum of 3-heptanone. Each signal corresponds to a single car-
bon. The carbonyl carbon is the least shielded and appears at H9254 210 ppm.
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17.18 SUMMARY
The chemistry of the carbonyl group is probably the single most important aspect of
organic chemical reactivity. Classes of compounds that contain the carbonyl group
include many derived from carboxylic acids (acyl chlorides, acid anhydrides, esters, and
amides) as well as the two related classes discussed in this chapter—aldehydes and
ketones.
Section 17.1 The substitutive IUPAC names of aldehydes and ketones are developed
by identifying the longest continuous chain that contains the carbonyl
group and replacing the final -e of the corresponding alkane by -al for
aldehydes and -one for ketones. The chain is numbered in the direction
that gives the lowest locant to the carbon of the carbonyl group.
Ketones are named using functional class IUPAC nomenclature by citing
the two groups attached to the carbonyl in alphabetical order followed by
the word “ketone.” Thus, 3-methyl-2-butanone (substitutive) becomes
isopropyl methyl ketone (functional class).
Section 17.2 The carbonyl carbon is sp
2
-hybridized, and it and the atoms attached to
it are coplanar (Section 17.2).
Section 17.3 Aldehydes and ketones are polar molecules. Nucleophiles attack C?O
at carbon (positively polarized) and electrophiles, especially protons,
attack oxygen (negatively polarized).
Section 17.4 The numerous reactions that yield aldehydes and ketones discussed in
earlier chapters and reviewed in Table 17.1 are sufficient for most syn-
theses.
Sections The characteristic reactions of aldehydes and ketones involve nucle-
17.5–17.13 ophilic addition to the carbonyl group and are summarized in Table 17.5.
Reagents of the type HY react according to the general equation
Aldehydes undergo nucleophilic addition more readily and have more
favorable equilibrium constants for addition than do ketones.
The step in which the nucleophile attacks the carbonyl carbon is
C O
H9254H11002H9254H11001
Aldehyde
or ketone
H11001 HY
H9254H11001 H9254H11002
Product of nucleophilic
addition to carbonyl group
YCO H
C
R
RH11032
O
H9254H11001 H9254H11002
O
H
3-Methylbutanal
O
3-Methyl-2-butanone
688 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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17.18 Summary 689
TABLE 17.5 Nucleophilic Addition to Aldehydes and Ketones
Reaction (section) and comments
Hydration (Section 17.6) Can be either
acid- or base-catalyzed. Equilibrium con-
stant is normally unfavorable for hydra-
tion of ketones unless R, RH11032, or both are
strongly electron-withdrawing.
Acetal formation (Sections 17.8-17.9)
Reaction is acid-catalyzed. Equilibrium
constant normally favorable for alde-
hydes, unfavorable for ketones. Cyclic
acetals from vicinal diols form readily.
Reaction with primary amines (Section
17.10) Isolated product is an imine
(Schiff’s base). A carbinolamine inter-
mediate is formed, which undergoes
dehydration to an imine.
Cyanohydrin formation (Section 17.7)
Reaction is catalyzed by cyanide ion.
Cyanohydrins are useful synthetic inter-
mediates; cyano group can be hydro-
lyzed to ±CO
2
H or reduced to
±CH
2
NH
2
.
General equation and typical example
Aldehyde or ketone
RCRH11032
O
X
H
2
O
Water
H11001 RCRH11032
W
W
OH
OH
Geminal diol
Aldehyde
or ketone
RCRH11032
O
X
HCN
Hydrogen
cyanide
H11001 RCRH11032
W
W
OH
CN
Cyanohydrin
Chloroacetone
(90% at equilibrium)
ClCH
2
CCH
3
O
X
ClCH
2
CCH
3
W
W
OH
OH
Chloroacetone hydrate
(10% at equilibrium)
H
2
O
3-Pentanone
CH
3
CH
2
CCH
2
CH
3
O
X
CH
3
CH
2
CCH
2
CH
3
W
W
OH
CN
3-Pentanone cyanohydrin (75%)
KCN
H
H11001
2-Methylpropanal
(CH
3
)
2
CHCH
O
X
tert-Butylamine
(CH
3
)
3
CNH
2
H11001 (CH
3
)
2
CHCH?NC(CH
3
)
3
N-(2-Methyl-1-propylidene)-
tert-butylamine (50%)
Aldehyde
or ketone
RCRH11032
O
X
2RH11033OH
Alcohol
H
2
O
Water
H11001H11001RCRH11032
W
W
ORH11033
ORH11033
Acetal
H
H11001
H11001
HCl
NO
2
CH
O
X
m-Nitrobenzaldehyde
NO
2
CH(OCH
3
)
2
m-Nitrobenzaldehyde dimethyl
acetal (76–85%)
CH
3
OH
Methanol
Aldehyde or ketone
RCRH11032
O
X
RH11033NH
2
Primary amine
H
2
O
Water
H11001H11001RCRH11032
X
NRH11033
Imine
(Continued)
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rate-determining in both base-catalyzed and acid-catalyzed nucleophilic
addition. In the base-catalyzed mechanism this is the first step.
Under conditions of acid catalysis, the nucleophilic addition step follows
protonation of the carbonyl oxygen. Protonation increases the carboca-
tion character of a carbonyl group and makes it more electrophilic.
H11002
Y
Nucleophile
H11001 C O
Aldehyde
or ketone
YCO
H11002slow
fast
YCO
H11002
H11001 H Y YCOH
Product of
nucleophilic
addition
H11001
H11002
Y
690 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
TABLE 17.5 Nucleophilic Addition to Aldehydes and Ketones (Continued)
Reaction (section) and comments
Reaction with secondary amines (Sec-
tion 17.11) Isolated product is an en-
amine. Carbinolamine intermediate can-
not dehydrate to a stable imine.
The Wittig reaction (Sections
17.12-17.13) Reaction of a phosphorus
ylide with aldehydes and ketones leads
to the formation of an alkene. A versa-
tile method for the preparation of
alkenes.
General equation and typical example
Aldehyde
or ketone
RCCH
2
RH11032
O
X
RH11033
2
NH
Secondary
amine
H11001 H
2
O
Water
H11001RC?CHRH11032
W
RH11033NRH11033
Enamine
H11001
benzene
heat
O
Cyclohexanone
OHN
Morpholine
ON
1-Morpholinocyclohexene
(85%)
Aldehyde
or ketone
RCRH11032
O
X
H11001H11001(C
6
H
5
)
3
P±C
A
B
±
±
H11001
H11002
Wittig
reagent (an ylide)
(C
6
H
5
)
3
P±O
H11002
H11001
Triphenylphosphine
oxide
C?C
A
B
R
RH11032
±
±
±
±
Alkene
Acetone
CH
3
CCH
3
O
X
H11001
DMSO
(C
6
H
5
)
3
P±CHCH
2
CH
2
CH
2
CH
3
H11001
H11002
1-Pentylidenetriphenylphosphorane
2-Methyl-2-heptene
(56%)
(CH
3
)
2
C?CHCH
2
CH
2
CH
2
CH
3
H11001 (C
6
H
5
)
3
P±O
H11002
H11001
Triphenylphosphine
oxide
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Often the product of nucleophilic addition is not isolated but is an inter-
mediate leading to the ultimate product. Most of the reactions in Table
17.5 are of this type.
Section 17.14 Nucleophilic addition to the carbonyl group is stereoselective. When one
direction of approach to the carbonyl group is less hindered than the
other, the nucleophile normally attacks at the less hindered face.
Section 17.15 Aldehydes are easily oxidized to carboxylic acids.
Section 17.16 The oxidation of ketones with peroxy acids is called the Baeyer–Villiger
oxidation and is a useful method for preparing esters.
Section 17.17 A strong peak near 1700 cm
H110021
in the infrared is characteristic of com-
pounds that bear a C?O group. The
1
H and
13
C NMR spectra of alde-
hydes and ketones are affected by the deshielding of a C?O group. The
proton of an H±C?O group appears in the H9254 8–10 ppm range. The car-
bon of a C?O group is at H9254 190–210 ppm.
PROBLEMS
17.19 (a) Write structural formulas and provide IUPAC names for all the isomeric aldehydes and
ketones that have the molecular formula C
5
H
10
O. Include stereoisomers.
(b) Which of the isomers in part (a) yield chiral alcohols on reaction with sodium borohydride?
(c) Which of the isomers in part (a) yield chiral alcohols on reaction with methylmagne-
sium iodide?
RH11033COOH
O
X
RCRH11032
O
Ketone
RCORH11032
O
Ester
Cr(VI)
H
2
O
RCH
O
Aldehyde
RCOH
O
Carboxylic acid
H11001C O
Aldehyde
or ketone
fast
H Y
Resonance forms of protonated
aldehyde or ketone
C OH
H11001
C
H11001
OH
slow H11002H
H11001
H11001HY HY
H11001
C OH YCOH
Product of
nucleophilic
addition
C OH
H11001
Problems 691
3,3,5-Trimethylcyclohexanone
CH
3
O
H
3
C
H
3
C
trans-3,3,5-Trimethylcyclohexanol
(83%)
H
OHCH
3
H
3
C
H
3
C
OH
HCH
3
H
3
C
H
3
C
cis-3,3,5-Trimethylcyclohexanol
(17%)
1. LiAlH
4
diethyl ether
2. H
2
O
H11001
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17.20 Each of the following aldehydes or ketones is known by a common name. Its substitutive
IUPAC name is provided in parentheses. Write a structural formula for each one.
(a) Chloral (2,2,2-trichloroethanal)
(b) Pivaldehyde (2,2-dimethylpropanal)
(c) Acrolein (2-propenal)
(d) Crotonaldehyde [(E)-2-butenal]
(e) Citral [(E)-3,7-dimethyl-2,6-octadienal]
(f) Diacetone alcohol (4-hydroxy-4-methyl-2-pentanone)
(g) Carvone (5-isopropenyl-2-methyl-2-cyclohexenone)
(h) Biacetyl (2,3-butanedione)
17.21 Predict the product of the reaction of propanal with each of the following:
(a) Lithium aluminum hydride
(b) Sodium borohydride
(c) Hydrogen (nickel catalyst)
(d) Methylmagnesium iodide, followed by dilute acid
(e) Sodium acetylide, followed by dilute acid
(f) Phenyllithium, followed by dilute acid
(g) Methanol containing dissolved hydrogen chloride
(h) Ethylene glycol, p-toluenesulfonic acid, benzene
(i) Aniline (C
6
H
5
NH
2
)
(j) Dimethylamine, p-toluenesulfonic acid, benzene
(k) Hydroxylamine
(l) Hydrazine
(m) Product of part (l) heated in triethylene glycol with sodium hydroxide
(n) p-Nitrophenylhydrazine
(o) Semicarbazide
(p) Ethylidenetriphenylphosphorane
(q) Sodium cyanide with addition of sulfuric acid
(r) Chromic acid
17.22 Repeat the preceding problem for cyclopentanone instead of propanal.
17.23 Hydride reduction (with LiAlH
4
or NaBH
4
) of each of the following ketones has been
reported in the chemical literature and gives a mixture of two diastereomeric alcohols in each case.
Give the structures or build molecular models of both alcohol products for each ketone.
(a) (S)-3-Phenyl-2-butanone
(d)
(b) 4-tert-Butylcyclohexanone
(c)
O
O
[(C
6
H
5
)
3
P
H11001
H11002
CHCH
3
]
692 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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17.24 Choose which member in each of the following pairs reacts faster or has the more favor-
able equilibrium constant for reaction with the indicated reagent. Explain your reasoning.
(a) (rate of reduction with sodium borohydride)
(b) (equilibrium constant for hydration)
(c) Acetone or 3,3-dimethyl-2-butanone (equilibrium constant for cyanohydrin formation)
(d) Acetone or 3,3-dimethyl-2-butanone (rate of reduction with sodium borohydride)
(e) CH
2
(OCH
2
CH
3
)
2
or (CH
3
)
2
C(OCH
2
CH
3
)
2
(rate of acid-catalyzed hydrolysis)
17.25 Equilibrium constants for the dissociation (K
diss
) of cyanohydrins according to the equation
have been measured for a number of cyanohydrins. Which cyanohydrin in each of the following
pairs has the greater dissociation constant?
(a)
(b)
17.26 Each of the following reactions has been reported in the chemical literature and gives a sin-
gle organic product in good yield. What is the principal product in each reaction?
(a)
(b)
(c)
(d)
H
2
O, HCl
heat
CH
3
CH
3
CHCH
2
CH
2
O
O
CH
3
CH
2
CH
O
H11001 (CH
3
)
2
NNH
2
OCH
3
CH
O
HO
H11001 CH
3
ONH
2
HOCH
2
CH
2
CH
2
OH
CH
3
O
CH
Br
CH
3
O
CH
3
O
O
H11001
p-toluenesulfonic acid
benzene, heat
C
6
H
5
CHCN
W
OH
C
6
H
5
CCN
W
W
OH
CH
3
or
CH
3
CH
2
CHCN
W
OH
(CH
3
)
2
CCN
W
OH
or
RCRH11032
W
W
OH
CN
Cyanohydrin
RCRH11032
O
X
Aldehyde
or ketone
HCN
Hydrogen
cyanide
H11001
K
diss
Cl
3
CCH or CH
3
CH
O
X
O
X
C
6
H
5
CH or C
6
H
5
CCH
3
O
X
O
X
Problems 693
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(e)
(f)
(g)
17.27 Wolff–Kishner reduction (hydrazine, KOH, ethylene glycol, 130°C) of the compound shown
gave compound A. Treatment of compound A with m-chloroperoxybenzoic acid gave compound
B, which on reduction with lithium aluminum hydride gave compound C. Oxidation of compound
C with chromic acid gave compound D (C
9
H
14
O). Identify compounds A through D in this
sequence.
17.28 On standing in
17
O-labeled water, both formaldehyde and its hydrate are found to have
incorporated the
17
O isotope of oxygen. Suggest a reasonable explanation for this observation.
17.29 Reaction of benzaldehyde with 1,2-octanediol in benzene containing a small amount of
p-toluenesulfonic acid yields almost equal quantities of two products in a combined yield of 94%.
Both products have the molecular formula C
15
H
22
O
2
. Suggest reasonable structures for these prod-
ucts.
17.30 Compounds that contain both carbonyl and alcohol functional groups are often more stable
as cyclic hemiacetals or cyclic acetals than as open-chain compounds. Examples of several of these
are shown. Deduce the structure of the open-chain form of each.
(a) (c)
(b) (d)
17.31 Compounds that contain a carbon–nitrogen double bond are capable of stereoisomerism
much like that seen in alkenes. The structures
Talaromycin A (a toxic
substance produced by a
fungus that grows on
poultry house litter)
O
O
OH
CH
2
CH
3
HOCH
2
HO
O
CH
3
O
O
CH
3
CH
2
Brevicomin (sex attractant of
Western pine beetle)
OHO
O
CHCl
3
CCH
3
O
CH
3
CH
2
CH
3
H11001
O
C
6
H
5
COOH
p-toluenesulfonic acid
benzene, heat
C
6
H
5
CCH
3
O
H11001 OHN
NaCN
HCl
C
6
H
5
CCH
3
O
694 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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are stereoisomeric. Specifying stereochemistry in these systems is best done by using E–Z descrip-
tors and considering the nitrogen lone pair to be the lowest priority group. Write the structures or
build molecular models, clearly showing stereochemistry, of the following:
(a) (Z)-CH
3
CH?NCH
3
(c) (Z)-2-Butanone hydrazone
(b) (E)-Acetaldehyde oxime (d) (E)-Acetophenone semicarbazone
17.32 Compounds known as lactones, which are cyclic esters, are formed on Baeyer–Villiger oxi-
dation of cyclic ketones. Suggest a mechanism for the Baeyer–Villiger oxidation shown.
17.33 Organic chemists often use enantiomerically homogeneous starting materials for the synthe-
sis of complex molecules (see Chiral Drugs, p. 273). A novel preparation of the S enantiomer of
compound B has been described using a bacterial cyclohexanone monooxygenase enzyme system.
(a) What is compound A?
(b) How would the product obtained by treatment of compound A with peroxyacetic acid
differ from that shown in the equation?
17.34 Suggest reasonable mechanism for each of the following reactions:
(a)
(b)
17.35 Amygdalin, a substance present in peach, plum, and almond pits, is a derivative of the R
enantiomer of benzaldehyde cyanohydrin. Give the structure of (R)-benzaldehyde cyanohydrin.
17.36 Using ethanol as the source of all the carbon atoms, describe efficient syntheses of each of
the following, using any necessary organic or inorganic reagents:
(a) CH
3
CH(OCH
2
CH
3
)
2
(b)
O O
H CH
3
NaOCH
3
CH
3
OH
(CH
3
)
3
CCHCH
O
Cl
(CH
3
)
3
CCHCH(OCH
3
)
2
OH
(72%)
(CH
3
)
3
CCCH
2
OCH
3
O
(88%)
NaOCH
3
CH
3
OH
C
(CH
3
)
3
C
Cl
O
CH
2
O
2
,
cyclohexanone monooxygenase,
and coenzymes
Compound A
O
H
3
C
O
Compound B
O
Cyclopentanone
O
O
5-Pentanolide (78%)
C
6
H
5
CO
2
OH
C
RH11032
R
X
N and C
RH11032
R X
N
Problems 695
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(c) (e)
(d) (f) CH
3
CH
2
CH
2
CH
2
OH
17.37 Describe reasonable syntheses of benzophenone, , from each of the following
starting materials and any necessary inorganic reagents.
(a) Benzoyl chloride and benzene
(b) Benzyl alcohol and bromobenzene
(c) Bromodiphenylmethane, (C
6
H
5
)
2
CHBr
(d) Dimethoxydiphenylmethane, (C
6
H
5
)
2
C(OCH
3
)
2
(e) 1,1,2,2-Tetraphenylethene, (C
6
H
5
)
2
C?C(C
6
H
5
)
2
17.38 The sex attractant of the female winter moth has been identified as the tetraene
CH
3
(CH
2
)
8
CH?CHCH
2
CH?CHCH
2
CH?CHCH?CH
2
. Devise a synthesis of this material
from 3,6-hexadecadien-1-ol and allyl alcohol.
17.39 Hydrolysis of a compound A in dilute aqueous hydrochloric acid gave (along with methanol)
a compound B, mp 164–165°C. Compound B had the molecular formula C
16
H
16
O
4
; it exhibited
hydroxyl absorption in its infrared spectrum at 3550 cm
H110021
but had no peaks in the carbonyl region.
What is a reasonable structure for compound B?
17.40 Syntheses of each of the following compounds have been reported in the chemical litera-
ture. Using the indicated starting material and any necessary organic or inorganic reagents, describe
short sequences of reactions that would be appropriate for each transformation.
(a) 1,1,5-Trimethylcyclononane from 5,5-dimethylcyclononanone
(b)
(c)
(d)
(e) CH
2
OCH
3
CH
3
Cl
from 3-chloro-2-methylbenzaldehyde
CH
3
CCH
2
CH
2
C(CH
2
)
5
CH
3
OO
from CCH
2
CH
2
CH
2
OHHC
from o-bromotoluene and 5-hexenal
CCH
2
CH
2
CH
2
CH
CH
3
CH
2
CH
2
C
6
H
5
H
3
C
from C
6
H
5
C
O
CHCH(OCH
3
)
2
OH
Compound A
C
6
H
5
CC
6
H
5
O
X
CH
3
CHC
OH
CH
HCCH
2
C
O
CHO O
696 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
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17.41 The following five-step synthesis has been reported in the chemical literature. Suggest
reagents appropriate for each step.
17.42 Increased “single-bond character” in a carbonyl group is associated with a decreased car-
bon–oxygen stretching frequency. Among the three compounds benzaldehyde, 2,4,6-trimethoxy-
benzaldehyde, and 2,4,6-trinitrobenzaldehyde, which one will have the lowest frequency carbonyl
absorption? Which one will have the highest?
17.43 A compound has the molecular formula C
4
H
8
O and contains a carbonyl group. Identify the
compound on the basis of its
1
H NMR spectrum shown in Figure 17.17.
COCH
3
O
O
O
O
COCH
3
O
O
O
CH
2
OH
O
O
CH
O
O
O
CH
3
O
CH
3
Problems 697
C
4
H
8
O 1.0
1.601.70
2.302.402.50
1
2 2
3
9.6
6 5 4 3 2 1 07891011
Chemical shift (δ, ppm)
FIGURE 17.17 The 200-MHz
1
H NMR spectrum of a compound (C
4
H
8
O) (Problem 17.43).
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17.44 A compound (C
7
H
14
O) has a strong peak in its infrared spectrum at 1710 cm
H110021
. Its
1
H NMR
spectrum consists of three singlets in the ratio 9:3:2 at H9254 1.0, 2.1, and 2.3 ppm, respectively. Iden-
tify the compound.
17.45 Compounds A and B are isomeric diketones of molecular formula C
6
H
10
O
2
. The
1
H NMR
spectrum of compound A contains two signals, both singlets, at H9254 2.2 (6 protons) and 2.8 ppm
(4 protons). The
1
H NMR spectrum of compound B contains two signals, one at H9254 1.3 ppm (triplet,
6 protons) and the other at H9254 2.8 ppm (quartet, 4 protons). What are the structures of compounds
A and B?
17.46 A compound (C
11
H
14
O) has a strong peak in its infrared spectrum near 1700 cm
H110021
. Its 200-
MHz
1
H NMR spectrum is shown in Figure 17.18. What is the structure of the compound?
17.47 A compound is a ketone of molecular formula C
7
H
14
O. Its
13
C NMR spectrum is shown in
Figure 17.19. What is the structure of the compound?
698 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
6.0
2.42.83.2 1.6 1.2 .82.0
5.0 4.0 3.0 2.0 1.0 0.07.08.09.010.0
Chemical shift (δ, ppm)
(ppm)
C
11
H
14
O
2
2
2
2
3
3
FIGURE 17.18 The 200-MHz
1
H NMR spectrum of a compound (C
11
H
14
O) (Problem 17.46).
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17.48 Compound A and compound B are isomers having the molecular formula C
10
H
12
O. The mass
spectrum of each compound contains an abundant peak at m/z 105. The
13
C NMR spectra of com-
pound A (Figure 17.20) and compound B (Figure 17.21) are shown. Identify these two isomers.
Problems 699
100 80 60 40 20 0120140160180200
C
7
H
14
O
Chemical shift (δ, ppm)
120 100 80 60 40 20 0140160180200
Compound A
C
10
H
12
O
C
C
CH
CH CH
CH
2
CH
2
CH
3
Chemical shift (δ, ppm)
FIGURE 17.19 The
13
C NMR
spectrum of an unknown
compound (C
7
H
14
O) (Prob-
lem 17.47).
FIGURE 17.20 The
13
C NMR
spectrum of compound A
(C
10
H
12
O) (Problem 17.48).
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17.49 The most stable conformation of acetone has one of the hydrogens of each methyl group
eclipsed with the carbonyl oxygen. Construct a model of this conformation.
17.50 Construct a molecular model of cyclohexanone. Do either of the hydrogens of C-2 eclipse
the carbonyl oxygen?
700 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
FIGURE 17.21 The
13
C NMR
spectrum of compound B
(C
10
H
12
O) (Problem 17.48).
100 80 60 40 20 0120140160180200
Compound B
C
10
H
12
O
CH
3
CH
CH
CH
CH
C
C
Chemical shift (δ, ppm)
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| 课件名称： | 有机化学（英文原版） |
| 课件分类： | 化学 |
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