726 CHAPTER EIGHTEEN Enols and Enolates

Alkylation occurs by an SN2 mechanism in which the enolate ion acts as a nucleophile
toward the alkyl halide.
In practice, this reaction is difficult to carry out with simple aldehydes and ketones
because aldol condensation competes with alkylation. Furthermore, it is not always pos-
sible to limit the reaction to the introduction of a single alkyl group. The most success-
ful alkylation procedures use b-diketones as starting materials. Because they are rela-
tively acidic, b-diketones can be converted quantitatively to their enolate ions by weak
bases and do not self-condense. Ideally, the alkyl halide should be a methyl or primary
alkyl halide.
O O O O
K2CO3
CH3CCH2CCH3 1 CH3I CH3CCHCCH3
CH3
2,4-Pentanedione Iodomethane 3-Methyl-2,4-pentanedione
(7577%)

18.16 SUMMARY
Section 18.1 Greek letters are commonly used to identify various carbons in alde-
hydes and ketones. Using the carbonyl group as a reference, the adjacent
carbon is designated a, the next one b, and so on as one moves down
the chain. Attached groups take the same Greek letter as the carbon to
which they are connected.
Sections Because aldehydes and ketones exist in equilibrium with their corre-
18.218.15 sponding enol isomers, they can express a variety of different kinds of
chemical reactivity.

O OH
R2C CR9 R2C CR9
H
a proton is Carbonyl group is a carbon atom of
relatively acidic; electrophilic; enol is nucleophilic;
it can be removed nucleophilic reagents it attacks electrophilic
by strong bases. add to carbonyl carbon. reagents.

Reactions that proceed via enol or enolate intermediates are summarized

in Table 18.1.

PROBLEMS
18.18 (a) Write structural formulas or build molecular models for all the noncyclic aldehydes and
ketones of molecular formula C4H6O.
(b) Are any of these compounds stereoisomeric?
(c) Are any of these compounds chiral?
(d) Which of these are a,b-unsaturated aldehydes or a,b-unsaturated ketones?
(e) Which of these can be prepared by a simple (i.e., not mixed) aldol condensation?
18.19 The main flavor component of the hazelnut is (2E,5S)-5-methyl-2-hepten-4-one. Write a
structural formula or build a molecular model showing its stereochemistry.

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 Problems 727

TABLE 18.1 Reactions of Aldehydes and Ketones That Involve Enol or Enolate Ion Intermediates

Reaction (section) and comments General equation and typical example

a Halogenation (Sections 18.2 O O

and 18.3) Halogens react with X X
aldehydes and ketones by substi- R2CHCR9 1 X2 R2CCR9 1 HX
W
tution; an a hydrogen is replaced X
by a halogen. Reaction occurs by
electrophilic attack of the halo- Aldehyde Halogen a-Halo aldehyde Hydrogen
gen on the carboncarbon dou- or ketone or ketone halide
ble bond of the enol form of O O
acetic
the aldehyde or ketone. An acid X acid X
catalyst increases the rate of Br CCH3 1 Br2 Br CCH2Br 1 HBr
enolization, which is the rate-
determining step.
p-Bromoacetophenone Bromine p-Bromophenacyl Hydrogen
bromide (6972%) bromide
Enolization (Sections 18.4 O OH
through 18.6) Aldehydes and X W
ketones exist in equilibrium with R2CHCR9 R2CCR9
their enol forms. The rate at Aldehyde Enol
which equilibrium is achieved is or ketone
increased by acidic or basic cata-
lysts. The enol content of simple O K OH
aldehydes and ketones is quite K 5 1 3 1028
small; b-diketones, however, are
extensively enolized. Cyclopentanone Cyclopenten-1-ol
2
Enolate ion formation (Section O O
18.6) An a proton of an aldehyde X W
or a ketone is more acidic than R2CHCR9 1 HO2 R2CCR9 1 H2O
most other protons bound to car- Aldehyde Hydroxide Enolate Water
bon. Aldehydes and ketones are or ketone ion anion
weak acids, with Kas in the range 2
10216 to 10220 (pKa 1620). Their O O
enhanced acidity is due to the X W
electron-withdrawing effect of CH3CH2CCH2CH3 1 HO2 CH3CHCCH2CH3 1 H2O
the carbonyl group and the reso- 3-Pentanone Hydroxide ion Enolate anion Water
nance stabilization of the enolate of 3-pentanone
anion.
Haloform reaction (Section 18.7) O O
Methyl ketones are cleaved on X HO2 X
reaction with excess halogen in RCCH3 1 3X2 RCO2 1 HCX3
the presence of base. The prod- Methyl Halogen Carboxylate Trihalomethane
ucts are a trihalomethane (halo- ketone ion (haloform)
form) and a carboxylate salt.
O
X 1. Br2, NaOH
(CH3)3CCH2CCH3 2. H1
(CH3)3CCH2CO2H 1 CHBr3
4,4-Dimethyl-2-pentanone 3,3-Dimethylbutanoic Bromoform
acid (89%)

(Continued)

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 728 CHAPTER EIGHTEEN Enols and Enolates

Reactions of Aldehydes and Ketones That Involve Enol or Enolate Ion Intermediates
TABLE 18.1 (Continued)

Reaction (section) and comments General equation and typical example

Aldol condensation (Section 18.9) O O

A reaction of great synthetic val- X HO2 X
ue for carboncarbon bond for- 2RCH2CR9 RCH2CCCR9 1 H2O
W W
mation. Nucleophilic addition of R9 R
an enolate ion to a carbonyl
group, followed by dehydration Aldehyde a,b-Unsaturated Water
of the b-hydroxy aldehyde, yields aldehyde
an a,b-unsaturated aldehyde. O
X NaOCH2CH3
CH3(CH2)6CH CH3CH2OH
CH3(CH2)6CHC(CH2)5CH3
W
HCO
Octanal 2-Hexyl-2-decenal (79%)
Claisen-Schmidt reaction (Section O O O
18.10) A mixed aldol condensa- X X HO2 X
tion in which an aromatic alde- ArCH 1 RCH2CR9 ArCHCCR9 1 H2O
W
hyde reacts with an enolizable R
aldehyde or ketone.
Aromatic Aldehyde a,b-Unsaturated Water
aldehyde or ketone carbonyl compound
O O O
X X NaOH X
C6H5CH 1 (CH3)3CCCH3 ethanol
C6H5CHCHCC(CH3)3
Benzaldehyde 3,3-Dimethyl-2- water 4,4-Dimethyl-1-phenyl-
butanone 1-penten-3-one (8893%)
Conjugate addition to a,b-unsat- O O
urated carbonyl compounds (Sec- X X
tions 18.11 through 18.14) The b- R2CCHCR9 1 HY R2CCH2CR9
W
carbon atom of an a,b-unsaturat- Y
ed carbonyl compound is electro-
philic; nucleophiles, especially a,b-Unsaturated Nucleophile Product of conjugate
weakly basic ones, yield the prod- aldehyde or ketone addition
ucts of conjugate addition to a,b- O O
unsaturated aldehydes and X NH3 X
ketones. (CH3)2CCHCCH3 H2O
(CH3)2CCH2CCH3
W
NH2
4-Methyl-3-penten-2-one 4-Amino-4-methyl-2-
(mesityl oxide) pentanone (6370%)
Robinson annulation (Section O CH3
18.13) A combination of conju- CH3 1. NaOCH2CH3,
X CH3CH2OH
gate addition of an enolate anion 1 CH2CHCCH3 2. KOH, heat
to an a,b-unsaturated ketone
O O
with subsequent intramolecular
aldol condensation. 2-Methylcyclohexanone Methyl vinyl 6-Methylbicyclo[4.4.0]-
ketone 1-decen-3-one (46%)

(Continued)

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 Problems 729

Reactions of Aldehydes and Ketones That Involve Enol or Enolate Ion Intermediates
TABLE 18.1 (Continued)

Reaction (section) and comments General equation and typical example

Conjugate addition of organocop- O 1. diethyl O

per compounds (Section 18.14) X ether X
The principal synthetic application R2CCHCR9 1 R02CuLi 2. H2O
R2CCH2CR9
W
of lithium dialkylcuprate reagents R0
is their reaction with a,b-
unsaturated carbonyl compounds. a,b-Unsaturated Lithium b-Alkyl
Alkyl-ation of the b carbon aldehyde or ketone dialkylcuprate aldehyde or ketone
occurs. O O

1. LiCu(CH3)2
2. H2O
CH3 CH3 CH3
6-Methylcyclohept- 3,6-Dimethylcycloheptanone (85%)
2-enone
a Alkylation of aldehydes and O O O O
ketones (Section 18.15) Alkylation X X R9CH2X, HO2 X X
of simple aldehydes and ketones RCCH2CR RCCHCR
W
via their enolates is difficult. b- CH2R9
Diketones can be converted quan-
titatively to their enolate anions, b-Diketone a-Alkyl-b-diketone
which react efficiently with pri- O O
mary alkyl halides.
CH2C6H5 CH2C6H5
KOCH2CH3
1 C6H5CH2Cl ethanol
H CH2C6H5
O O
2-Benzyl-1,3- Benzyl 2,2-Dibenzyl-1,3-
cyclohexanedione chloride cyclohexanedione (69%)

18.20 The simplest a,b-unsaturated aldehyde acrolein is prepared by heating glycerol with an acid
catalyst. Suggest a mechanism for this reaction.

O
KHSO4
HOCH2CHCH2OH heat
CH2 CHCH 1 H2O

OH

18.21 In each of the following pairs of compounds, choose the one that has the greater enol con-
tent, and write the structure of its enol form:
O O

(a) (CH3)3CCH or (CH3)2CHCH

O O

(b) C6H5CC6H5 or C6H5CH2CCH2C6H5

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 730 CHAPTER EIGHTEEN Enols and Enolates

O O O
(c) C6H5CCH2CC6H5 or C6H5CH2CCH2C6H5

(d) O or O

(e) O or O

O O

(f) or
O
O
18.22 Give the structure of the expected organic product in the reaction of 3-phenylpropanal with
each of the following:
(a) Chlorine in acetic acid
(b) Sodium hydroxide in ethanol, 10C
(c) Sodium hydroxide in ethanol, 70C
(d) Product of part (c) with lithium aluminum hydride; then H2O
(e) Product of part (c) with sodium cyanide in acidic ethanol
18.23 Each of the following reactions has been reported in the chemical literature. Write the struc-
ture of the product(s) formed in each case.

O
Cl2
(a) CCH2CH3 CH2Cl2

Cl

O
C6H5CH2SH
(b) CH3 C(CH3)2 NaOH, H2O

O
C6H5
Br2
(c)
C6H5 diethyl ether

O
O C6H5
KOH
(d) Cl CH 1 C6H5 ethanol

O O
NaOH
(e) O CH 1 CH3CCH3 water

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 Problems 731

O
CH3
1. diethyl ether
(f) 1 LiCu(CH3)2 2. H2O

H3C CH3

O
O
NaOH
(g) 1 C6H5CH ethanolwater

KOH
(h) 1 CH2 CHCH2Br

18.24 Show how each of the following compounds could be prepared from 3-pentanone. In most
cases more than one synthetic transformation will be necessary.
(a) 2-Bromo-3-pentanone (d) 3-Hexanone
(b) 1-Penten-3-one (e) 2-Methyl-1-phenyl-1-penten-3-one
(c) 1-Penten-3-ol
18.25 (a) A synthesis that begins with 3,3-dimethyl-2-butanone gives the epoxide shown. Suggest
reagents appropriate for each step in the synthesis.

O O OH O
58% 54% 68%
(CH3)3CCCH3 (CH3)3CCCH2Br (CH3)3CCHCH2Br (CH3)3CC CH2
H

(b) The yield for each step as actually carried out in the laboratory is given above each
arrow. What is the overall yield for the three-step sequence?
18.26 Using benzene, acetic anhydride, and 1-propanethiol as the source of all the carbon atoms,
along with any necessary inorganic reagents, outline a synthesis of the compound shown.

O
CCH2SCH2CH2CH3

18.27 Show how you could prepare each of the following compounds from cyclopentanone, D2O,
and any necessary organic or inorganic reagents.

H OH
D D D D
(a) (c)
D D D H

H
D D D D
(b) (d)
D D D

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 732 CHAPTER EIGHTEEN Enols and Enolates

18.28 (a) At present, butanal is prepared industrially by hydroformylation of propene (Section

17.4). Write a chemical equation for this industrial synthesis.
(b) Before about 1970, the principal industrial preparation of butanal was from acetalde-
hyde. Outline a practical synthesis of butanal from acetaldehyde.
18.29 Identify the reagents appropriate for each step in the following syntheses:

O O O
CH CH CH
(a) Br

O
OH O O
CH
(b) HCCH2CH2CH2CH2CH
OH

CH3 O
O O
(CH3)2CH CCH3
(c) CH3CCH2CH2CHCH2CH

CH(CH3)2
CH(CH3)2
O O

(d) (CH3)2C CHCH2CH2CCH3 (CH3)2CHCHCH2CH2CCH3

OH

O
O O
(CH3)2CHCCH2CH2CCH3

(CH3)2CH

18.30 Give the structure of the product derived by intramolecular aldol condensation of the keto
aldehyde shown:

O CH3
KOH, H2O
CH3CCH2CCHO C7H10O

CH3

18.31 Prepare each of the following compounds from the starting materials given and any neces-
sary organic or inorganic reagents:

CH3
(a) (CH3)2CHCHCCH2OH from (CH3)2CHCH2OH

HO CH3

(b) C6H5CH CCH2OH from benzyl alcohol and 1-propanol

CH3

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 Problems 733

CH3

(c) from acetophenone,

4-methylbenzyl alcohol,
and 1,3-butadiene
CC6H5
O

18.32 Terreic acid is a naturally occurring antibiotic substance. Its actual structure is an enol iso-
mer of the structure shown. Write the two most stable enol forms of terreic acid, and choose which
of those two is more stable.

O
O
O CH3
H
O

18.33 In each of the following, the indicated observations were made before any of the starting
material was transformed to aldol addition or condensation products:
(a) In aqueous acid, only 17% of (C6H5)2CHCHO is present as the aldehyde; 2% of the
enol is present. Some other species accounts for 81% of the material. What is it?
(b) In aqueous base, 97% of (C6H5)2CHCHO is present as a species different from any
of those in part (a). What is this species?
18.34 (a) For a long time attempts to prepare compound A were thwarted by its ready isomer-
ization to compound B. The isomerization is efficiently catalyzed by traces of base.
Write a reasonable mechanism for this isomerization.

O O
HO2
C6H5CHCH H2O
C6H5CCH2OH

OH
Compound A Compound B

(b) Another attempt to prepare compound A by hydrolysis of its diethyl acetal gave only
the 1,4-dioxane derivative C. How was compound C formed?

C6H5 O OH
H2O
C6H5CHCH(OCH2CH3)2 H1
OH HO O C6H5

Compound C

18.35 Consider the ketones piperitone, menthone, and isomenthone.

CH3 CH3 CH3

O O O
CH(CH3)2 CH(CH3)2 CH(CH3)2
(2)-Piperitone Menthone Isomenthone

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 734 CHAPTER EIGHTEEN Enols and Enolates

Suggest reasonable explanations for each of the following observations:

(a) Optically active piperitone (aD232) is converted to racemic piperitone on standing in
a solution of sodium ethoxide in ethanol.
(b) Menthone is converted to a mixture of menthone and isomenthone on treatment with
90% sulfuric acid.
18.36 Many nitrogen-containing compounds engage in a proton-transfer equilibrium that is anal-
ogous to ketoenol tautomerism:

HXNZ BA XNZH

Each of the following compounds is the less stable partner of such a tautomeric pair. Write the
structure of the more stable partner for each one.
NH
(a) CH3CH2NO
NH
(d)
(b) (CH3)2CCHNHCH3 N
O2 OH
1
(c) CH3CH N (e) HN C
OH NH2

18.37 Outline reasonable mechanisms for each of the following reactions:

O O
CH2CH2CH2CH2Br
KOC(CH3)3
(a)
benzene

(76%)

O O O
HO2
(b) (CH3)2C CHCH2CH2C CHCH heat
(CH3)2C CHCH2CH2CCH3 1 CH3CH
CH3 (96%)

O O CH3
KOH
(c) HCCH2CH2CHCCH3
H2O, CH3OH
CH3 O
(40%)

H CH3 H CH3
heat
(d) CH3 or CH3
base
H H
O O

C6H5 C6H5
OO O
KOH
(e) C6H5CCC6H5 1 C6H5CH2CCH2C6H5 ethanol C6H5 C6H5
O

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 Problems 735

C6H5
O O C6H5
NaOCH3
(f) C6H5CH2CCH2CH3 1 CH2 CCC6H5 CH OH
3

C6H5 C6H5 CH3

O

18.38 Suggest reasonable explanations for each of the following observations:

(a) The CO stretching frequency of a,b-unsaturated ketones (about 1675 cm21) is less
than that of typical dialkyl ketones (17101750 cm21).
(b) The CO stretching frequency of cyclopropenone (1640 cm21) is lower than that of
typical a,b-unsaturated ketones (1675 cm21).
(c) The dipole moment of diphenylcyclopropenone (m 5 5.1 D) is substantially larger than
that of benzophenone (m 5 3.0 D)
(d) The b carbon of an a,b-unsaturated ketone is less shielded than the corresponding car-
bon of an alkene. Typical 13C NMR chemical shift values are

O
CH2 CHCR CH2 CHCH2R
(d < 129 ppm) (d < 114 ppm)

18.39 Bromination of 3-methyl-2-butanone yielded two compounds, each having the molecular
formula C5H9BrO, in a 95:5 ratio. The 1H NMR spectrum of the major isomer A was character-
ized by a doublet at d 1.2 ppm (6 protons), a septet at d 3.0 ppm (1 proton), and a singlet at d
4.1 ppm (2 protons). The 1H NMR spectrum of the minor isomer B exhibited two singlets, one at
d 1.9 ppm and the other at d 2.5 ppm. The lower field singlet had half the area of the higher field
one. Suggest reasonable structures for these two compounds.
18.40 Treatment of 2-butanone (1 mol) with Br2 (2 mol) in aqueous HBr gave C4H6Br2O. The 1H
NMR spectrum of the product was characterized by signals at d 1.9 ppm (doublet, 3 protons), 4.6
ppm (singlet, 2 protons), and 5.2 ppm (quartet, 1 proton). Identify this compound.
18.41 2-Phenylpropanedial [C6H5CH(CHO)2] exists in the solid state as an enol in which the con-
figuration of the double bond is E. In solution (CDCl3), an enol form again predominates but this
time the configuration is Z. Make molecular models of these two enols, and suggest an explana-
tion for the predominance of the Z enol in solution. (Hint: Think about intermolecular versus
intramolecular hydrogen bonding.)

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