182

CHAPTER 5 |

Aromatic Compounds
5.24 How would you synthesize the following compound starting from benzene?
More than one step is needed.

5.25 The following compound cant be synthesized using the methods discussed
in this chapter. Why not?

Additional Problems
N AMING A ROMATIC
C OMPOUNDS

5.26 Give IUPAC names for the following compounds:

(a)

CH3

CH3

(b)

(c)

CO2H

Br

CHCH2CH2CHCH3

H3C

Br
(d)

(e)

Br

(f)

NH2

NO2

CH2CH2CH3

NO2

Cl

CH3

| Exercises

183

5.27 Draw structures corresponding to the following names:

(a) m-Bromophenol
(b) Benzene-1,3,5-triol
(c) p-Iodonitrobenzene
(d) 2,4,6-Trinitrotoluene (TNT)
(e) o-Aminobenzoic acid
(f ) 3-Methyl-2-phenylhexane
5.28 Draw and name all aromatic compounds with the formula C7H7Cl.
5.29 Draw and name all isomeric bromodimethylbenzenes.
R EACTIONS AND
S UBSTITUENT E FFECTS

5.30 Propose structures for aromatic hydrocarbons meeting the following

descriptions:
(a) C9H12; can give only one product on aromatic bromination
(b) C8H10; can give three products on aromatic chlorination
(c) C10H14; can give two products on aromatic nitration
5.31 Formulate the reaction of benzene with 2-chloro-2-methylpropane in the
presence of AlCl3 catalyst to give tert-butylbenzene.
5.32 Identify each of the following groups as an activator or deactivator and as
an o,p-director or m-director:
(a)

N(CH3)2

(b)

(c)

OCH2CH3

(d)

5.33 Predict the major product(s) of the following reactions:

(a)

Cl

(b)
CH3CH2Cl
AlCl3

(c)

CH3CH2COCl

CO2H

AlCl3

(d)
HNO3
H2SO4

N(CH2CH3)2
SO3
H2SO4

5.34 Predict the major product(s) of mononitration of the following substances:

(a) Bromobenzene
(b) Benzonitrile (cyanobenzene)
(c) Benzoic acid
(d) Nitrobenzene
(e) Phenol
(f ) Benzaldehyde
5.35 Which of the substances listed in Problem 5.34 react faster than benzene
and which react slower?

184

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Aromatic Compounds
5.36 Rank the compounds in each group according to their reactivity toward
electrophilic substitution:
(a) Chlorobenzene, o-dichlorobenzene, benzene
(b) p-Bromonitrobenzene, nitrobenzene, phenol
(c) Fluorobenzene, benzaldehyde, o-dimethylbenzene
5.37 The orientation of electrophilic aromatic substitution on a disubstituted
benzene ring is usually controlled by whichever of the two groups already
on the ring is the more powerful activator. Name and draw the structure(s)
of the major product(s) of electrophilic chlorination of the following
substances:
(a) m-Nitrophenol
(b) o-Methylphenol
(c) p-Chloronitrobenzene
5.38 Predict the major product(s) you would expect to obtain from sulfonation of
the following substances (see Problem 5.37):
(a) o-Chlorotoluene
(b) m-Bromophenol
(c) p-Nitrotoluene
5.39 Rank the following aromatic compounds in the expected order of their reactivity toward FriedelCrafts acylation. Which compounds are unreactive?
(a) Bromobenzene
(b) Toluene
(c) Anisole (C6H5OCH3)
(d) Nitrobenzene
(e) p-Bromotoluene
5.40 In some cases, the FriedelCrafts acylation reaction can occur intramolecularly, that is, within the same molecule. Predict the product of the following
reaction:
O
Cl

AlCl3

5.41 What is the structure of the compound with formula C8H9Br that gives
p-bromobenzoic acid on oxidation with KMnO4?
5.42 Draw the three additional resonance structures of anthracene.

Anthracene

M ECHANISMS

5.43 Show the steps involved in the FriedelCrafts reaction of benzene with
CH3Cl.
5.44 Propose a mechanism to explain the fact that deuterium (D, 2H) slowly
replaces hydrogen (1H) in the aromatic ring when benzene is treated with
D2SO4.

| Exercises

185

5.45 Use resonance structures of the possible carbocation intermediates to

explain why bromination of biphenyl occurs at the ortho and para positions
rather than at the meta positions.

Biphenyl

5.46 In light of your answer to Problem 5.45, at what position and on which ring
would you expect nitration of 4-bromobiphenyl to occur?
Br

S YNTHESIS

4-Bromobiphenyl

5.47 Starting with benzene, how would you synthesize the following substances?
Assume that you can separate ortho and para isomers if necessary.
(a) m-Bromobenzenesulfonic acid
(b) o-Chlorobenzenesulfonic acid
(c) p-Chlorotoluene
5.48 Starting from any aromatic hydrocarbon of your choice, how would you
synthesize the following substances? Ortho and para isomers can be separated if necessary.
(a) o-Nitrobenzoic acid
(b) p-tert-Butylbenzoic acid
5.49 Explain by drawing resonance structures of the intermediate carbocations
why naphthalene undergoes electrophilic aromatic substitution at C1
rather than at C2.
Br
1
2

G ENERAL P ROBLEMS

Br2

5.50 We said in Section 4.9 that an allylic carbocation is stabilized by resonance.

Draw resonance structures to account for the similar stabilization of a
benzylic carbocation.
+
CH2
A benzylic carbocation

5.51 Addition of HBr to 1-phenylpropene yields (1-bromopropyl)benzene as the

only product. Propose a mechanism for the reaction, and explain why none
of the other regioisomer is produced (see Problem 5.50).
Br

HBr

186

CHAPTER 5 |

Aromatic Compounds
5.52 The following syntheses have flaws in them. What is wrong with each?
(a)

CH3

CO2H
1. Cl2, FeCl3
2. KMnO4

Cl
(b) Cl

Cl
1. (CH3)3CCl, AlCl3
2. KMnO4, H2O

CO2H

5.53 Indole is an aromatic compound that has a benzene ring fused to a pyrrole
ring. Look at the electronic structure of pyrrole in Figure 5.9c, and then
draw an orbital picture of indole.
(a) How many electrons does indole have?
(b) What is the electronic relationship of indole to naphthalene?
Indole
N
H

5.54 Would you expect the trimethylammonium group to be an activating or

deactivating substituent? Explain.
+
N(CH3)3 Br
Phenyltrimethylammonium bromide

5.55 Starting with toluene, how would you synthesize the three nitrobenzoic
acids?
5.56 Carbocations generated by reaction of an alkene with a strong acid catalyst can react with aromatic rings in a FriedelCrafts reaction. Propose a
mechanism to account for the industrial synthesis of the food preservative
BHT from p-cresol and 2-methylpropene:
OH
H3C
H3C

CH2

H3PO4

H3C

CH3

OH

H3C
CH3
p-Cresol

CH3
BHT

CH3
CH3
C
CH3

| Exercises

187

5.57 You know the mechanism of HBr addition to alkenes, and you know the
effects of various substituent groups on aromatic substitution. Use this
knowledge to predict which of the following two alkenes reacts faster with
HBr. Explain your answer by drawing resonance structures of the carbocation intermediates.
CH

CH

CH2

CH2

and
CH3O

O2N

5.58 Identify the reagents represented by the letters a through d in the following scheme:
CH2CH3
a

CH2CH3
b

Br
CO2H

HO3S

CO2H

Br

Br

5.59 Benzene can be hydroxylated by reaction with H2O2 in the presence of

an acid catalyst. What is the likely structure of the reactive electrophile?
Propose a mechanism for the reaction.
OH
H2O2
CF3SO3H catalyst

IN

THE

M EDICINE
C ABINET

5.60 Ribavirin, an antiviral agent used against hepatitis C and viral pneumonia, contains a 1,2,4-triazole ring. Look at the electronic structure of imidazole in Figure 5.9d, and then explain why the ring is aromatic.
1,2,4-Triazole
ring

O
C

N
HOCH2

N
O

OH

OH

NH2
N

Ribavirin

188

CHAPTER 5 |

IN

THE

Aromatic Compounds
F IELD

5.61 The herbicide metolachlor is broadly used in the United States to control
weeds but is being phased out in Europe because of possible environmental
risks. Usually marketed under the name Dual, approximately 50 million
pounds of metolachlor are applied on crops each year in the United States.
The preparation of metolachlor begins with the conversion of acetanilide to
2-ethyl-6-methylacetanilide. How would you accomplish this conversion?
O
H

C
N

H
CH3

C
N

CH3

C
CH3

H3C

Acetanilide

O
ClCH2

CH2CH3

2-Ethyl-6-methylacetanilide

CHCH2OCH3

H3C

CH2CH3

Metolachlor

5.62 Synthesis of the herbicide 2,4-D begins with chlorination of phenol

followed by reaction of the product with NaOH and chloroacetic acid.
Name the chlorinated intermediate, and use resonance structures to
explain the pattern of chlorination in the first step.
OH

OH

OCH2CO2H
Cl

Cl2

Cl

1. ClCH2CO2H,
NaOH
2. H O+
3

Cl
Phenol

Cl
2,4-D

216

CHAPTER 6 |

Stereochemistry at Tetrahedral Centers

Additional Problems
I DENTIFYING C HIRALITY
C ENTERS

6.26 Which of the following objects are chiral?

(a) A basketball
(b) A fork
(d) A golf club
(e) A monkey wrench

(c) A wine glass

(f) A snowake

6.27 Which of the following compounds are chiral?

(a) 2,4-Dimethylheptane
(b) 5-Ethyl-3,3-dimethylheptane
(c) cis-1,3-Dimethylcyclohexane
(d) 4,5-Dimethylocta-2,6-diene
6.28 Draw chiral molecules that meet the following descriptions:
(b) An alcohol, C6H14O
(a) A chloroalkane, C5H11Cl
(c) An alkene, C6H12
(d) An alkane, C8H18
6.29 Which of the following compounds are chiral? Label all chirality centers.
(a)

H3C CH3

(b) H C
3

(c)

CH3CH2CHCCH2CH3
H3C

CH3
(e)

(d)

CH3
H

(f)

H
O

H3C

H
H

H3C

BrCH2CHCHCH2Br

CH3

6.30 There are eight alcohols with the formula C5H12O. Draw them, and tell
which are chiral.
6.31 Propose structures for compounds that meet the following descriptions:
(a) A chiral alcohol with four carbons
(b) A chiral carboxylic acid
(c) A compound with two chirality centers
6.32 Erythronolide B, the biological precursor of the broad-spectrum antibiotic
erythromycin, has ten chirality centers. Identify them with asterisks.
O
H3C

CH3
OH

H3C

CH3

OH

H3C

Erythronolide B

H3C
O

OH
OH

O
CH3

| Exercises
O PTICAL A CTIVITY

217

6.33 Cholic acid, the major steroid found in bile, was found to have a rotation
of 2.22 when a 3.00 g sample was dissolved in 5.00 mL of alcohol in a
sample tube with a 1.00 cm pathlength. Calculate []D for cholic acid.
6.34 Polarimeters are so sensitive that they can measure rotations to the thousandth of a degree, an important advantage when only small amounts of
a sample are available. For example, when 7.00 mg of ecdysone, an insect
hormone that controls molting in the silkworm moth, was dissolved in
1.00 mL of chloroform in a cell with a 2.00 cm pathlength, an observed rotation of 0.087 was found. Calculate []D for ecdysone.
6.35 Naturally occurring (S)-serine has []D 6.83. What specic rotation do
you expect for (R)-serine?

TO

A SSIGNING R,S
C ONFIGURATION
C HIRALITY C ENTERS

6.36 Rank the substituents in each of the following sets:

(a) H, OH, OCH3, CH3
(b) Br, CH3, CH2Br, Cl
(c) CHPCH2, CH(CH3)2, C(CH3)3, CH2CH3
(d) CO2CH3, COCH3, CH2OCH3, OCH3
6.37 Rank the substituents in each of the following sets:
(a)

CH3

CH3

CH2CCH3

CH2CH2CH2CH2CH3

CH2CHCH2CH3

CH3
(b)

SH

NH2

SO3H

OCH2CH2OH

6.38 One enantiomer of lactic acid is shown below. Is it R or S? Draw its mirror
image in the standard tetrahedral representation.
CO2H
H

OH
CH3

6.39 Draw tetrahedral representations of both enantiomers of the amino acid

serine. Tell which of your structures is S and which is R.
O
HOCH2CHCOH

Serine

NH2

6.40 Assign R or S conguration to the chirality centers in the following

molecules:
(a)

H
NC

C
CH3

(b)
OH

OCH2CH3
C

H
Cl

CH3

(c)

OH
C

H3C
H

CH2OH

218

CHAPTER 6 |

Stereochemistry at Tetrahedral Centers

6.41 Assign R or S conguration to the chirality centers in the following
molecules:
(a) H

OH

Cl

(b)

(c)

OCH3

HOCH2

CO2H

6.42 Assign R or S conguration to each chirality center in the following biological molecules:
(a)

(b)

OH
H

CH3

(c) HO
H3C

CH3CH2

OH
CH3

Cl
H

S TEREOCHEMICAL
R ELATIONSHIPS

6.43 What is the relationship between the specic rotations of (2R,3R)-pentane2,3-diol and (2S,3S)-pentane-2,3-diol? Between (2R,3S)-pentane-2,3-diol
and (2R,3R)-pentane-2,3-diol?
6.44 What is the stereochemical conguration of the enantiomer of
(2S,4R)-dibromooctane?
6.45 What are the stereochemical congurations of the two diastereomers of
(2S,4R)-dibromooctane?
6.46 Draw examples of the following:
(a) A meso compound with the formula C8H18
(b) A compound with two chirality centers, one R and the other S
6.47 Tell whether the following Newman projection of 2-chlorobutane is R or S.
(You might want to review Section 2.5.)
Cl
CH3

H3C
H

6.48 Draw a Newman projection that is enantiomeric with the one shown in
Problem 6.47.
6.49 Draw a Newman projection of meso-tartaric acid.
6.50 Draw Newman projections of (2R,3R)- and (2S,3S)-tartaric acid, and compare them to the projection you drew in Problem 6.49 for the meso form.
G ENERAL P ROBLEMS

6.51 -Glucose has the following structure. Identify the chirality centers in
-glucose, and tell how many stereoisomers of glucose are possible.
HO
HO

CH2OH
O
OH
OH

-Glucose

| Exercises

219

6.52 Draw a tetrahedral representation of (R)-3-chloropent-1-ene.

6.53 Draw the two cistrans stereoisomers of 1,2-dimethylcyclopentane, assign
R,S congurations to the chirality centers, and indicate whether the
stereoisomers are chiral or meso.
6.54 Draw the meso form of each of the following molecules, and indicate the
plane of symmetry in each:
(a)

OH

OH

(b)

(c) H3C

CH3

OH

CH3CHCH2CH2CHCH3
H3C
CH3

6.55 Assign R or S conguration to the chirality centers in ascorbic acid

(vitamin C).
OH

HO

OH
CH2OH

Ascorbic acid

O H
O

6.56 We saw in Section 4.6 that alkenes undergo reaction with peroxycarboxylic
acids to give epoxides. For example, cis-but-2-ene gives 2,3-epoxybutane:
CH3

H3C
C
H

RCO3H

O
CH3CH CHCH3
2,3-Epoxybutane

Assuming that both C O bonds form from the same side of the double
bond (syn stereochemistry; Section 4.5), show the stereochemistry of the
product. Is the epoxide chiral? Is it optically active?
6.57 Ribose, an essential part of ribonucleic acid (RNA), has the following
structure:
H H

H OH
CHO

HO

Ribose

HO H HO H

How many chirality centers does ribose have? Identify them with asterisks. How many stereoisomers of ribose are there?
6.58 Draw the structure of the enantiomer of ribose (Problem 6.57).
6.59 Draw the structure of a diastereomer of ribose (Problem 6.57).

220

CHAPTER 6 |

Stereochemistry at Tetrahedral Centers

6.60 On catalytic hydrogenation over a platinum catalyst, ribose (Problem 6.57)
is converted into ribitol. Is ribitol optically active or inactive? Explain.
H H

H OH
CH2OH

HO

Ribitol

HO H HO H

6.61 Draw the structure of (R)-2-methylcyclohexanone.

6.62 Compound A, C7H14, is optically active. On catalytic reduction over a palladium catalyst, 1 equivalent of H2 is absorbed, yielding compound B,
C7H16. On cleavage of A with acidic KMnO4, two fragments are obtained.
One fragment is acetic acid, CH3CO2H, and the other fragment, C, is an
optically active carboxylic acid. Show the reactions, and propose structures
for A, B, and C.
6.63 Allenes are compounds with adjacent CC bonds. Even though they dont
contain chirality centers, many allenes are chiral. For example, mycomycin,
an antibiotic isolated from the bacterium Nocardia acidophilus, is chiral
and has []D 130. Can you explain why mycomycin is chiral? Making
a molecular model should be helpful.
HC

CH

CH

CH

CH

CH

CH

CH2CO2H

Mycomycin

6.64 One of the steps in fatty-acid biosynthesis is the dehydration of

(R)-3-hydroxybutyryl ACP to give trans-crotonyl ACP. The reaction occurs
with anti stereochemistry, meaning that the OH and H groups lost during
the reaction depart from opposite sides of the molecule. Which hydrogen
is lost, Ha or Hb?
O

HO H
C
H3C

C
C

C
SACP

H3C

Ha Hb

THE

M EDICINE C ABINET

C
C

SACP

H2O

(R)-3-Hydroxybutyryl ACP

IN

trans-Crotonyl ACP

6.65 Compound A is a precursor used for synthesizing dopa, whose S isomer is

used in treating Parkinsons disease.
CH3O

CO2H
NHCOCH3

CH3CO2
A

HO

CO2H
H

HO

NH2

Dopa

(a) The rst step in the synthesis is catalytic hydrogenation of

the carboncarbon double bond in A to yield two enantiomeric
hydrogenation products. Draw them, and assign R,S conguration to
each.

| Exercises

221

(b) Following hydrogenation, several additional transformations are

carried out to yield dopa. Do you expect the enantiomers of dopa to
have similar physical properties?
(c) Do you expect the enantiomers of dopa to perform equally well as
drugs?
(d) The Monsanto process, commercialized in 1974, carries out the
double-bond hydrogenation using a chiral catalyst that produces only
a single enantiomer, which is subsequently converted into (S)-dopa.
Show the stereochemistry of (S)-dopa, and explain how a chiral
hydrogenation catalyst can produce a single enantiomer as product.
IN

THE

F IELD

6.66 Metolachlor, a herbicide previously encountered in Problems 2.74 and

5.61, kills weeds by inhibiting the enzyme fatty-acid elongase, which is
needed to make a waxy coating on plant leaves. With the enzyme activity
inhibited, the wax is not produced and the weed dies.
O

CH3

C
ClCH2
H3C

CHCH2OCH3
CH2CH3

Metolachlor

(a) Only the S enantiomer of metolachlor inhibits fatty-acid elongase.

Draw it.
(b) Why do the R and S enantiomers have different activities?