09

Benzene and
Its Derivatives

Peppers of the capsicum family. Hot peppers contain significant amounts of the
chemical capsaicin, which is used for medicinal purposes as well as for tantalizing
taste buds (see Chemical Connections, “Capsaicin, for Those Who Like It Hot”).
Inset: A model of capsaicin. (Courtesy Douglas Brown)

KEY QUESTIONS

9.1 What Is the Structure of Benzene? HOW TO

9.2 What Is Aromaticity? 9.1 How to Determine Whether a Lone Pair
9.3 How Are Benzene Compounds Named, and What of Electrons Is or Is Not Part of an Aromatic
Are Their Physical Properties? Pi System

9.4 What Is the Benzylic Position, and How Does It 9.2 How to Determine Whether a
Contribute to Benzene Reactivity? Substituent on Benzene Is Electron
Withdrawing
9.5 What Is Electrophilic Aromatic Substitution?
9.6 What Is the Mechanism of Electrophilic Aromatic CHEMICAL CONNECTIONS
Substitution?
9A Carcinogenic Polynuclear Aromatics
9.7 How Do Existing Substituents on Benzene Affect and Cancer
Electrophilic Aromatic Substitution?
9B Capsaicin, for Those Who Like It Hot
9.8 What Are Phenols?

B EN Z EN E , A C O LORLESS LIQUID, was first isolated by Michael Faraday in 1825 from

the oily residue that collected in the illuminating gas lines of London. Benzene’s molecular
formula, C6H6 , suggests a high degree of unsaturation. For comparison, an alkane with six
carbons has a molecular formula of C6 H14 , and a cycloalkane with six carbons has a molecular
formula of C6H12 . Considering benzene’s high degree of unsaturation, it might be expected to

282
 9.1 What Is the Structure of Benzene? 283
show many of the reactions characteristic of alkenes. Yet, benzene is remarkably unreactive!
It does not undergo the addition, oxidation, and reduction reactions characteristic of alkenes.
For example, benzene does not react with bromine, hydrogen chloride, or other reagents that
usually add to carbon–carbon double bonds. Nor is benzene oxidized by peracids under con-
ditions that readily oxidize alkenes. When benzene reacts, it does so by substitution in which Aromatic compound A
term used to classify
a hydrogen atom is replaced by another atom or a group of atoms.
benzene and its derivatives.
The term aromatic was originally used to classify benzene and its derivatives because
many of them have distinctive odors. It became clear, however, that a sounder classification Arene An aromatic
hydrocarbon.
for these compounds would be one based on structure and chemical reactivity, not aroma.
As it is now used, the term aromatic refers instead to the fact that benzene and its derivatives Aryl group A group
derived from an aromatic
are highly unsaturated compounds that are unexpectedly stable toward reagents that react
compound (an arene) by the
with alkenes. removal of an H; given the
We use the term arene to describe aromatic hydrocarbons, by analogy with alkane and symbol Ar J .
alkene. Benzene is the parent arene. Just as we call a group derived by the removal of an H Ar J The symbol used for
from an alkane an alkyl group and give it the symbol R J , we call a group derived by the an aryl group, by analogy
removal of an H from an arene an aryl group and give it the symbol Ar J . with R J for an alkyl group.

9.1 What Is the Structure of Benzene?

Let us imagine ourselves in the mid-nineteenth century and examine the evidence on
which chemists attempted to build a model for the structure of benzene. First, because the
molecular formula of benzene is C6 H6 , it seemed clear that the molecule must be highly
unsaturated. Yet benzene does not show the chemical properties of alkenes, the only un-
saturated hydrocarbons known at that time. Benzene does undergo chemical reactions, but
its characteristic reaction is substitution rather than addition. When benzene is treated with
bromine in the presence of ferric chloride as a catalyst, for example, only one compound
with the molecular formula C6 H5 Br forms:
FeCl
3
C6H6  Br2  C6H5Br  HBr
Benzene Bromobenzene

Chemists concluded, therefore, that all six carbons and all six hydrogens of benzene must
be equivalent. When bromobenzene is treated with bromine in the presence of ferric chlo-
ride, three isomeric dibromobenzenes are formed:
FeCl
3
C6H5Br  Br2  C6H4Br2  HBr
Bromobenzene Dibromobenzene
(formed as a mixture of
three constitutional isomers)

For chemists in the mid-nineteenth century, the problem was to incorporate these
observations, along with the accepted tetravalence of carbon, into a structural formula for
benzene. Before we examine their proposals, we should note that the problem of the struc-
ture of benzene and other aromatic hydrocarbons has occupied the efforts of chemists for
over a century. It was not until the 1930s that chemists developed a general understanding
of the unique structure and chemical properties of benzene and its derivatives.

A. Kekulé’s Model of Benzene

The first structure for benzene, proposed by August Kekulé in 1872, consisted of a six-
membered ring with alternating single and double bonds and with one hydrogen bonded
to each carbon. Kekulé further proposed that the ring contains three double bonds that
shift back and forth so rapidly that the two forms cannot be separated. Each structure has
become known as a Kekulé structure.
284 CHAPTER 9 Benzene and Its Derivatives

Kekulé incorrectly believed that the double

bonds of benzene rapidly shift back and forth
H
H C H
C C
Δ
C C
H C H

H
A Kekulé structure, Kekulé structures
showing all atoms as line-angle formulas

Because all of the carbons and hydrogens of Kekulé’s structure are equivalent, sub-
stituting bromine for any one of the hydrogens gives the same compound. Thus, Kekulé’s
proposed structure was consistent with the fact that treating benzene with bromine in the
presence of ferric chloride gives only one compound with the molecular formula C6 H5 Br.
His proposal also accounted for the fact that the bromination of bromobenzene gives
three (and only three) isomeric dibromobenzenes:
Br Br Br Br
Br
FeCl3
+Br2 ¡ + + +HBr

Br

Br
The three isomeric dibromobenzenes

Although Kekulé’s proposal was consistent with many experimental observations, it

was contested for years. The major objection was that it did not account for the unusual
chemical behavior of benzene. If benzene contains three double bonds, why, his critics
asked, doesn’t it show the reactions typical of alkenes? Why doesn’t it add three moles of
bromine to form 1,2,3,4,5,6-hexabromocyclohexane? Why, instead, does benzene react by
substitution rather than addition?

B. The Orbital Overlap Model of Benzene

The concepts of the hybridization of atomic orbitals and the theory of resonance, devel-
oped by Linus Pauling in the 1930s, provided the first adequate description of the structure
of benzene. The carbon skeleton of benzene forms a regular hexagon with C J C J C and
H J C J C bond angles of 120°. For this type of bonding, carbon uses sp2 hybrid orbitals
(Section 1.6E). Each carbon forms sigma bonds to two adjacent carbons by the overlap of
sp2–sp2 hybrid orbitals and one sigma bond to hydrogen by the overlap of sp2–1s orbitals.
As determined experimentally, all carbon–carbon bonds in benzene are the same length,
1.39 Å, a value almost midway between the length of a single bond between sp3 hybridized
carbons (1.54 Å) and that of a double bond between sp2 hybridized carbons (1.33 Å):
H H
120°
sp 2 - sp 2
120° C C
H C 120° C H
C C
1.09 Å sp 2 -1s
H H
1.39 Å
Each carbon also has a single unhybridized 2p orbital that contains one electron.
These six 2p orbitals lie perpendicular to the plane of the ring and overlap to form a
continuous pi cloud encompassing all six carbons. The electron density of the pi system of
 9.1 What Is the Structure of Benzene? 285
a benzene ring lies in one torus (a doughnut-shaped region) above the plane
H   H
of the ring and a second torus below the plane (Figure 9.1).

 
C. The Resonance Model of Benzene
H H
One of the postulates of resonance theory is that, if we can represent a mol-  
ecule or ion by two or more contributing structures, then that molecule
cannot be adequately represented by any single contributing structure. We
H H
represent benzene as a hybrid of two equivalent contributing structures,
often referred to as Kekulé structures:
(a)

œ
H H

Benzene as a hybrid of two equivalent

contributing structures
H H
Each Kekulé structure makes an equal contribution to the hybrid; thus, the
C J C bonds are neither single nor double bonds, but something intermedi-
ate. We recognize that neither of these contributing structures exists (they are
merely alternative ways to pair 2p orbitals with no reason to prefer one over H H
the other) and that the actual structure is a superposition of both. Neverthe-
less, chemists continue to use a single contributing structure to represent this (b)
molecule because it is as close as we can come to an accurate structure within FIGURE 9.1
the limitations of classical Lewis structures and the tetravalence of carbon. Orbital overlap model of the
bonding in benzene. (a) The
carbon, hydrogen framework.
D. The Resonance Energy of Benzene The six 2p orbitals, each with
Resonance energy is the difference in energy between a resonance hybrid and its most sta- one electron, are shown
ble hypothetical contributing structure. One way to estimate the resonance energy of ben- uncombined. (b) The overlap
zene is to compare the heats of hydrogenation of cyclohexene and benzene (benzene can be of parallel 2p orbitals forms a
continuous pi cloud, shown
made to undergo hydrogenation under extreme conditions). In the presence of a transition
by one torus above the plane
metal catalyst, hydrogen readily reduces cyclohexene to cyclohexane (Section 5.6):
of the ring and a second
below the plane of the ring.
Ni $H 0  120 kJmol
H2 1–2 atm (28.6 kcalmol) Resonance energy The
difference in energy
between a resonance hybrid
By contrast, benzene is reduced only very slowly to cyclohexane under these conditions. and the most stable of its
It is reduced more rapidly when heated and under a pressure of several hundred atmo- hypothetical contributing
spheres of hydrogen: structures.
because benzene does not react readily with reagents
that add to alkenes, hydrogenation of benzene must be
performed at extremely high pressures

Ni $H 0   20 9 kJmol
+3 H2 200–300 atm (4 9 .8 kcalmol)

The catalytic reduction of an alkene is an exothermic reaction (Section 5.6B). The heat
of hydrogenation per double bond varies somewhat with the degree of substitution of the
double bond; for cyclohexene $H 0  120 kJ/mol (28.6 kcal/mol). If we imagine ben-
zene in which the 2p electrons do not overlap outside of their original C J C double bonds,
a hypothetical compound with alternating single and double bonds, we might expect its heat
of hydrogenation to be 3  120  359 kJ/mol (85.8 kcal/mol). Instead, the heat of hy-
drogenation of benzene is only 209 kJ/mol (49.8 kcal/mol). The difference of 150 kJ/mol
(35.8 kcal/mol) between the expected value and the experimentally observed value is the res-
onance energy of benzene. Figure 9.2 shows these experimental results in the form of a graph.
286 CHAPTER 9 Benzene and Its Derivatives

FIGURE 9.2
The resonance energy of
benzene, as determined Benzene with isolated
by a comparison of the double bonds
heats of hydrogenation of
(hypothetical)
cyclohexene, benzene, and Resonance
the hypothetical benzene. energy of
benzene + 3 H2
Benzene

150 kJ/mol compounds lower

+ 3 H2 on the energy scale
Energy
Cyclohexene (35.8 kcal/mol)
are more stable

+ H2
-359 kJ/mol Cyclohexane
-209 kJ/mol (-85.8 kcal/mol)
(-49.8 kcal/mol) calculated
-120 kJ/mol
(-28.6 kcal/mol)

For comparison, the strength of a carbon–carbon single bond is approximately

333–418 kJmol (80–100 kcalmol), and that of hydrogen bonding in water and low-
molecular-weight alcohols is approximately 8.4–21 kJmol (2–5 kcalmol). Thus, although
the resonance energy of benzene is less than the strength of a carbon–carbon single bond, it
is considerably greater than the strength of hydrogen bonding in water and alcohols. In Sec-
tion 8.1C, we saw that hydrogen bonding has a dramatic effect on the physical properties of
alcohols compared with those of alkanes. In this chapter, we see that the resonance energy of
benzene and other aromatic hydrocarbons has a dramatic effect on their chemical reactivity.
Following are resonance energies for benzene and several other aromatic
hydrocarbons:

Resonance energy Benzene Naphthalene Anthracene Phenanthrene

[kJ/mol (kcal/mol)] 150 (35.8) 255 (60.9) 347 (82.9) 381 (91.0)

9.2 What Is Aromaticity?

Many other types of molecules besides benzene and its derivatives show aromatic character;
that is, they contain high degrees of unsaturation, yet fail to undergo characteristic alkene
addition and oxidation–reduction reactions. What chemists had long sought to understand
were the principles underlying aromatic character. The German chemical physicist Erich
Hückel solved this problem in the 1930s.
this criterion is also called Hückel’s criteria are summarized as follows. To be aromatic, a ring must
the 4n  2 rule because
the allowable numbers 1. Have one 2p orbital on each of its atoms.
of pi electrons can be
determined when n is
2. Be planar or nearly planar, so that there is continuous overlap or nearly continuous
substituted by any integer, overlap of all 2p orbitals of the ring.
including zero 3. Have 2, 6, 10, 14, 18, and so forth pi electrons in the cyclic arrangement of 2p orbitals.
 9.2 What Is Aromaticity? 287
Benzene meets these criteria. It is cyclic, planar, has one 2p orbital on each carbon atom
of the ring, and has 6 pi electrons (an aromatic sextet) in the cyclic arrangement of its 2p
orbitals.
Let us apply these criteria to several heterocyclic compounds, all of which are aro- Heterocyclic compound
matic. Pyridine and pyrimidine are heterocyclic analogs of benzene. In pyridine, one CH An organic compound that
contains one or more atoms
group of benzene is replaced by a nitrogen atom, and in pyrimidine, two CH groups are
other than carbon in its ring.
replaced by nitrogen atoms:

N N
Pyridine Pyrimidine

Each molecule meets the Hückel criteria for aromaticity: Each is cyclic and planar, has
one 2p orbital on each atom of the ring, and has six electrons in the pi system. In pyri-
dine, nitrogen is sp 2 hybridized, and its unshared pair of electrons occupies an sp 2 orbital
perpendicular to the 2p orbitals of the pi system and thus is not a part of the pi system.
In pyrimidine, neither unshared pair of electrons of nitrogen is part of the pi system.
The resonance energy of pyridine is 134 kJ  mol (32.0 kcal  mol), slightly less than that of
benzene. The resonance energy of pyrimidine is 109 kJ  mol (26.0 kcal  mol).

this orbital is perpendicular to

the six 2p orbitals of the pi system
N
this electron pair is not a part
of the aromatic sextet

Pyridine

Determine Whether a Lone Pair of Electrons Is

w
or Is Not Part of an Aromatic Pi System
(a) First, determine whether the atom containing the lone pair of electrons is
part of a double bond. If it is part of a double bond, it is not possible for the
HOW TO 9.1

lone pair to be part of the aromatic pi system.

this lone pair of electrons cannot be part of the

aromatic pi system because the nitrogen is already
sharing two electrons through the pi bond with carbon

N N

(b) If the atom containing the lone pair of electrons is not part of a double
bond, it is possible for the lone pair of electrons to be part of the pi system.
288 CHAPTER 9 Benzene and Its Derivatives

Determine this by placing the atom in a hybridization state that places

the lone pair of electrons in a p orbital. If this increases the number of
aromatic pi electrons to either 2, 6, 10, 14, and so on, then the lone pair
of electrons is part of the pi aromatic system. If placing the lone pair of
electrons in the pi system changes the total number of pi electrons to any
other number (e.g., 3–5, 7–9, etc.), the lone pair is not part of the aromatic
pi system.

a nitrogen atom with three single bonds is normally sp3

hybridized. However, to determine if the lone pair of electrons
belongs in the pi system, we must change the hybridization of
nitrogen to sp2 so that the electrons can reside in a p orbital

this electron pair is in The lone pair on nitrogen gives the

a p orbital and is a part pi system six electrons. Therefore, the
of the aromatic sextet NH NH
nitrogen should be sp2 hybridized.

The lone pair gives the pi system eight
  electrons. Therefore, the nitrogen
NH NH
should not be sp2 hybridized.


O
 

Furan this electron pair

is in an sp2 orbital
and is not a part of
The five-membered-ring compounds furan, pyrrole, and imidazole are also aromatic:
the aromatic sextet
N

this electron pair is in

O N N
a p orbital and is a part
of the aromatic sextet H H
 Furan Pyrrole Imidazole

  In these planar compounds, each heteroatom is sp 2 hybridized, and its unhybridized

H
2p orbital is part of a continuous cycle of five 2p orbitals. In furan, one unshared pair
N
  of electrons of the heteroatom lies in the unhybridized 2p orbital and is a part of the pi
system (Figure 9.3). The other unshared pair of electrons lies in an sp 2 hybrid orbital,
perpendicular to the 2p orbitals, and is not a part of the pi system. In pyrrole, the un-
shared pair of electrons on nitrogen is part of the aromatic sextet. In imidazole, the
Pyrrole unshared pair of electrons on one nitrogen is part of the aromatic sextet; the unshared
pair on the other nitrogen is not.
FIGURE 9.3
Nature abounds with compounds having a heterocyclic aromatic ring fused to one or
Origin of the six pi electrons
(the aromatic sextet) in
more other rings. Two such compounds especially important in the biological world are
furan and pyrrole. The indole and purine:
resonance energy of furan is
67 kJ/mol (16 kcal/mol); that NH2
of pyrrole is 88 kJ/mol NH2 N
HO N
(21 kcal/mol). N
N
N N N
N N
H H N
H H
Indole Serotonin Purine Adenine
(a neurotransmitter)
 9.3 How Are Benzene Compounds Named, and What Are Their Physical Properties? 289
Indole contains a pyrrole ring fused with a benzene ring. Compounds derived from in-
dole include the amino acid L-tryptophan (Section 18.2C) and the neurotransmitter
serotonin. Purine contains a six-membered pyrimidine ring fused with a five-membered
imidazole ring. Adenine is one of the building blocks of deoxyribonucleic acids (DNA)
and ribonucleic acids (RNA), as described in Chapter 20. It is also a component of the
biological oxidizing agent nicotinamide adenine dinucleotide, abbreviated NAD  (Sec-
tion 21.1B).

EXAMPLE 9.1
Which of the following compounds are aromatic? O Treat the molecule as planar for the pur-
(c) poses of determining aromaticity. Also,
O
N treat each carbon atom in the ring as
(a) (b) (c) containing a 2p orbital. That is, treat the
O
+ oxygen atom as sp2 hybridized, so that
one of its lone pairs of electrons will enter
the pi electron system (if we do not do
S T R AT E G Y
this, the molecule cannot be aromatic
Determine whether each atom of the ring contains a 2p because an oxygen atom with two lone
orbital and whether the molecule is planar. If these criteria pairs of electrons and two single bonds
are met, determine the number of pi electrons. Those having is normally sp3 hybridized). Despite these
2, 6, 10, 14, and so on electrons are aromatic. special considerations, the molecule ends
up with a total of eight pi electrons, so
SOLUTION the molecule is not aromatic. Because it
This molecule is planar, and each atom is not aromatic, the oxygen has no driving
N
(a) of the ring contains a 2p orbital. There is force to be sp2 hybridized and is, in fact,
O a total of 6 pi electrons. The molecule is sp3 hybridized. Also, the molecule has no
+
aromatic. driving force to be planar, and in fact, the
(b) This molecule is planar, and each atom of molecule is nonplanar.
the ring contains a 2p orbital. There is a
total of 4 pi electrons. The molecule is not
aromatic. See problem 9.11

PROBLEM 9.1
Which of the following compounds are aromatic?
H
¬

H
B
(a) +
O+
(b) (c)

9.3 How Are Benzene Compounds Named,

and What Are Their Physical Properties?

A. Monosubstituted Benzenes
Monosubstituted alkylbenzenes are named as derivatives of benzene; an example is ethyl-
benzene. The IUPAC system retains certain common names for several of the simpler
monosubstituted alkylbenzenes. Examples are toluene (rather than methylbenzene) and
290 CHAPTER 9 Benzene and Its Derivatives

styrene (rather than phenylethylene):

CH2CH3 CH3 CH “ CH2

Benzene Ethylbenzene Toluene Styrene

mp (
C) 5.5 -95 -93 -31

bp (
C) 80 136 110 145

The common names phenol, aniline, benzaldehyde, benzoic acid, and anisole are also re-
tained by the IUPAC system:

O H O OH
OH NH2 OCH3

Phenol Aniline Benzaldehyde Benzoic acid Anisole

mp (
C) 41 -6 -26 123 -37

bp (
C) 182 184 178 249 154

The physical properties of substituted benzenes vary depending on the nature of the sub-
stituent. Alkylbenzenes, like other hydrocarbons, are nonpolar and thus have lower boiling
points than benzenes with polar substituents such as phenol, aniline, and benzoic acid.
The melting points of substituted benzenes depend on whether or not their molecules
can be packed close together. Benzene, which has no substituents and is flat, can pack its
molecules very closely, giving it a considerably higher melting point than many substituted
benzenes.
As noted in the introduction to Chapter 5, the substituent group derived by the loss of
Phenyl group C6H5 J , an H from benzene is a phenyl group (Ph); that derived by the loss of an H from the methyl
the aryl group derived by group of toluene is a benzyl group (Bn):
removing a hydrogen from
benzene.
Benzyl group C6H5CH2 J , H CH3 CH2 ¬
the alkyl group derived by
removing a hydrogen from
the methyl group of toluene. Benzene Phenyl group (Ph) Toluene Benzyl group (Bn)

In molecules containing other functional groups, phenyl groups and benzyl groups are
often named as substituents:

CH 3 H


CC PhCH 2CH 2OH PhCH 2Cl


Ph CH 3
Ortho (o) Refers to groups
(Z )-2-Phenyl-2-butene 2-Phenylethanol Benzyl chloride
occupying positions 1 and 2
on a benzene ring.
Meta (m) Refers to groups B. Disubstituted Benzenes
occupying positions 1 and 3
on a benzene ring. When two substituents occur on a benzene ring, three constitutional isomers are possible.
Para (p) Refers to groups We locate substituents either by numbering the atoms of the ring or by using the locators
occupying positions 1 and 4 ortho, meta, and para. The numbers 1,2- are equivalent to ortho (Greek: straight); 1,3- to
on a benzene ring. meta (Greek: after); and 1,4- to para (Greek: beyond).
 9.3 How Are Benzene Compounds Named, and What Are Their Physical Properties? 291
When one of the two substituents on the ring imparts a special name to the com-
pound, as, for example, toluene, phenol, and aniline, then we name the compound as a
derivative of that parent molecule. In this case, the special substituent occupies ring posi-
tion number 1. The IUPAC system retains the common name xylene for the three isomeric
dimethylbenzenes. When neither group imparts a special name, we locate the two sub-
stituents and list them in alphabetical order before the ending -benzene. The carbon of the
benzene ring with the substituent of lower alphabetical ranking is numbered C-1.

CH3 NH2 CH3 CH2CH3

Cl CH3

Br Cl
4-Bromotoluene 3-Chloroaniline 1,3-Dimethylbenzene 1-Chloro-4-ethylbenzene
(p -Bromotoluene) (m -Chloroaniline) (m -Xylene) (p -Chloroethylbenzene)

C. Polysubstituted Benzenes
When three or more substituents are present on a ring, we specify their locations by num-
bers. If one of the substituents imparts a special name, then the molecule is named as a
derivative of that parent molecule. If none of the substituents imparts a special name, we
number them to give the smallest set of numbers and list them in alphabetical order before
the ending -benzene. In the following examples, the first compound is a derivative of tolu-
ene, and the second is a derivative of phenol. Because there is no special name for the third
compound, we list its three substituents in alphabetical order, followed by the word benzene:

CH3 OH NO2
1 1 4
2 NO2 Br 6 2 Br
6 5 3

5 3 5 3 6 2

4 4 1 Br
Cl Br CH2CH3
4-Chloro-2-nitrotoluene 2,4,6-Tribromophenol 2-Bromo-1-ethyl-4-
nitrobenzene

EXAMPLE 9.2
Write names for these compounds:
COOH Cl
CH3 I NO2
(a) (b) (c) (d)

Br Br
NO2

S T R AT E G Y
First, determine whether one of the substituents imparts a special name to the benzene compound (e.g., toluene, phenol,
aniline). Identify all substituents and list them in alphabetical order. Use numbers to indicate relative position. The locators
ortho, meta, or para can be used for disubstituted benzenes.
292 CHAPTER 9 Benzene and Its Derivatives

SOLUTION
(a) 3-Iodotoluene or m-iodotoluene (b) 3,5-Dibromobenzoic acid (c) 1-Chloro-2,4-dinitrobenzene (d) 3-Phenylpropene

See problems 9.13, 9.14

PROBLEM 9.2
Write names for these compounds:

COOH
OH

(a) (b) (c)

CH3

Polynuclear aromatic Polynuclear aromatic hydrocarbons (PAHs) contain two or more aromatic rings,
hydrocarbon A hydrocarbon each pair of which shares two ring carbon atoms. Naphthalene, anthracene, and phen-
containing two or more fused
anthrene, the most common PAHs, and substances derived from them are found in
aromatic rings.
coal tar and high-boiling petroleum residues. At one time, naphthalene was used as a
moth repellent and insecticide in protecting woolens and furs, but its use has decreased
due to the introduction of chlorinated hydrocarbons such as p-dichlorobenzene. Also
found in coal tar are lesser amounts of benzo[a]pyrene. This compound is found as
well in the exhausts of gasoline-powered internal combustion engines (for example,
automobile engines) and in cigarette smoke. Benzo[a]pyrene is a very potent carcino-
gen and mutagen.

Naphthalene Anthracene Phenanthrene Benzo[a]pyrene

9.4 What Is the Benzylic Position, and How Does

It Contribute to Benzene Reactivity?
As we have mentioned, benzene’s aromaticity causes it to resist many of the reactions that
alkenes typically undergo. However, chemists have been able to react benzene in other
ways. This is fortunate because benzene rings are abundant in many of the compounds that
society depends upon, including various medications, plastics, and preservatives for food.
Benzylic carbon An sp3 We begin our discussion of benzene reactions with processes that take place not on the ring
hybridized carbon bonded itself, but at the carbon immediately bonded to the benzene ring. This carbon is known as
to a benzene ring. a benzylic carbon.
 9.4 What Is the Benzylic Position, and How Does It Contribute to Benzene Reactivity? 293
Benzene is unaffected by strong oxidizing agents, such as H2 CrO4 and KMnO4 . When
we treat toluene with these oxidizing agents under vigorous conditions, the side-chain
methyl group is oxidized to a carboxyl group to give benzoic acid:

CH3 COOH

+H2CrO4 ¡ +Cr 3±

Toluene Benzoic acid

The fact that the side-chain methyl group is oxidized, but the aromatic ring is un-
changed, illustrates the remarkable chemical stability of the aromatic ring. Halogen and
nitro substituents on an aromatic ring are unaffected by these oxidations. For example,
chromic acid oxidizes 2-chloro-4-nitrotoluene to 2-chloro-4-nitrobenzoic acid. Notice that
in this oxidation, the nitro and chloro groups remain unaffected:

CH3 COOH
H2CrO4

O2N Cl O2N Cl

2-Chloro-4-nitrotoluene 2-Chloro-4-nitrobenzoic acid

Chemical
Ch i l
Co ect o s
Connections 9A
C A R CI N OG EN I C POLYNU C L E AR AR O MAT IC S AND C ANC E R
A carcinogen is a compound that causes cancer. The Benzo[a]pyrene causes cancer in the following
first carcinogens to be identified were a group of poly- way: Once it is absorbed or ingested, the body at-
nuclear aromatic hydrocarbons, all of which have at tempts to convert it into a more soluble compound
least four aromatic rings. Among them is benzo[a] that can be excreted easily. To this end, a series
pyrene, one of the most carcinogenic of the aromatic of enzyme-catalyzed reactions transforms benzo[a]
hydrocarbons. It forms whenever there is incomplete pyrene into a diol epoxide, a compound that can bind
combustion of organic compounds. Benzo[a]pyrene to DNA by reacting with one of its amino groups,
is found, for example, in cigarette smoke, automobile thereby altering the structure of DNA and producing a
exhaust, and charcoal-broiled meats. cancer-causing mutation:

enzyme-catalyzed O
oxidation

HO
OH
Benzo[a]pyrene A diol epoxide

Question
Show how the outer perimeter of benzo[a]pyrene perimeter of the highlighted portion of the diol epox-
satisfies Hückel’s criteria for aromaticity. Is the outer ide product of benzo[a]pyrene also aromatic?
294 CHAPTER 9 Benzene and Its Derivatives

Ethylbenzene and isopropylbenzene are also oxidized to benzoic acid under these condi-
tions. The side chain of tert-butylbenzene, which has no benzylic hydrogen, is not affected
by these oxidizing conditions.

benzylic carbons + H2CrO4

bonded to at least COOH
one hydrogen are
oxidized Ethylbenzene
+ Cr3+

Benzoic acid
+ H2CrO4

Isopropylbenzene
benzylic carbons not
bonded to hydrogen
are not oxidized
+ H2CrO4 No
reaction
tert-Butylbenzene

From these observations, we conclude that, if a benzylic hydrogen exists, then the
benzylic carbon (Section 9.3A) is oxidized to a carboxyl group and all other carbons of the
side chain are removed. If no benzylic hydrogen exists, as in the case of tert-butylbenzene,
then the side chain is not oxidized.
If more than one alkyl side chain exists, each is oxidized to J COOH. Oxidation
of m-xylene gives 1,3-benzenedicarboxylic acid, more commonly named isophthalic
acid:
CH3 COOH

H2CrO4

CH3 COOH
m -Xylene 1,3-Benzenedicarboxylic acid
(Isophthalic acid)

EXAMPLE 9.3
Predict the products resulting from vigorous oxidation of each compound by H2CrO4. The various by-products that are formed
from benzylic oxidation reactions are usually not specified.

(a) 1,4 -dimethylbenzene (p-xylene) (b)

S T R AT E G Y
Identify all the alkyl groups in the reactant. If a benzylic hydrogen exists on an alkyl group, chromic acid will oxidize it to a
J COOH group.
 9.5 What Is Electrophilic Aromatic Substitution? 295

SOLUTION

chromic acid oxidizes both alkyl groups to ¬COOH groups,

and the product is terephthalic acid, one of two compounds
required for the synthesis of Dacron polyester and Mylar
(Section 17.4B)

O O
H2CrO4 ‘ ‘
(a) CH3 CH3 HOC COH

1,4-Dimethylbenzene 1,4-Benzenedicarboxylic acid

(p-Xylene) (Terephthalic acid)

(b) H2CrO4

COOH
this alkyl group has no benzylic
hydrogens and is not oxidized

See problem 9.30

PROBLEM 9.3
Predict the products resulting from vigorous oxidation of each compound by H2 CrO4 :

(a) (b)
O2N

9.5 What Is Electrophilic Aromatic Substitution?

Although benzene is resistant to most of the reactions presented thus far for alkenes, it is
not completely unreactive. By far the most characteristic reaction of aromatic compounds
is substitution at a ring carbon. Some groups that can be introduced directly onto the
ring are the halogens, the nitro ( J NO2) group, the sulfonic acid ( J SO3 H) group, alkyl
( J R) groups, and acyl (RCO J ) groups.
Halogenation:

FeCl3
H+Cl2 Cl+HCl

Chlorobenzene

Nitration:

H2SO4
H+HNO3 NO2+H2O

Nitrobenzene
296 CHAPTER 9 Benzene and Its Derivatives

Sulfonation:

H+H2SO4 SO3H+H2O

Benzenesulfonic acid

Alkylation:
AlCl3
H+RX R+HX

An alkylbenzene

Acylation:
O O
‘ AlCl3 ‘
H+R ¬ C ¬ X CR+HX

An acyl An acylbenzene
halide

9.6 What Is the Mechanism of Electrophilic

Aromatic Substitution?
Electrophilic aromatic In this section, we study several types of electrophilic aromatic substitution reactions—that
substitution A reaction in is, reactions in which a hydrogen of an aromatic ring is replaced by an electrophile, E. The
which an electrophile, E, mechanisms of these reactions are actually very similar. In fact, they can be broken down
substitutes for a hydrogen
on an aromatic ring.
into three common steps:
Step 1: Generation of the electrophile. This is a reaction pattern specific to each particular
electrophilic aromatic substitution reaction.
Reagent(s)  E

Step 2: Reaction of a nucleophile and an electrophile to form a new covalent bond. At-
tack of the electrophile on the aromatic ring to give a resonance-stabilized cation
intermediate:
H H + H
H
E E E
+E±
slow
· ·
+ +

(the nucleophile) Resonance-stabilized cation intermediate

Step 3: Take a proton away. Proton transfer to a base to regenerate the aromatic ring:

H
E
E fast
+ Base +Base-H
+

The reactions we are about to study differ only in the way the electrophile is generated
and in the base that removes the proton to re-form the aromatic ring. You should keep this
principle in mind as we explore the details of each reaction.
 9.6 What Is the Mechanism of Electrophilic Aromatic Substitution? 297

A. Chlorination and Bromination

Chlorine alone does not react with benzene, in contrast to its instantaneous addition to
cyclohexene (Section 5.3C). However, in the presence of a Lewis acid catalyst, such as
ferric chloride or aluminum chloride, chlorine reacts to give chlorobenzene and HCl.
Chemists account for this type of electrophilic aromatic substitution by the following
three-step mechanism:

Mechanism
Electrophilic Aromatic Substitution—Chlorination
STEP 1: Formation of the Electrophile. Reaction between chlorine (a Lewis base) and FeCl3
(a Lewis acid) gives an ion pair containing a chloronium ion (an electrophile):

the electrophile
Cl Cl Cl

 




Cl  Cl
Fe  Cl  Cl  Cl  Fe Cl  Cl Cl  Fe Cl
  


Cl Cl Cl

A molecular complex with

Chlorine Ferric chloride An ion pair containing
a positive charge on chlorine
(a Lewis base) (a Lewis acid) a chloronium ion
and a negative charge on iron

STEP 2: Reaction of a nucleophile and an electrophile to form a new covalent bond.

Reaction of the Cl2 FeCl3 ion pair with the pi electron cloud of the aromatic ring
forms a resonance-stabilized cation intermediate, represented here as a hybrid of
three contributing structures:

+
slow. rate H H H
+ determining
+Cl · + ·
Cl Cl + Cl

(the nucleophile) Resonance-stabilized cation intermediate The positive charge on the

resonance-stabilized
STEP 3: Take a proton away. Proton transfer from the cation intermediate to FeCl4  forms intermediate is distributed
HCl, regenerates the Lewis acid catalyst, and gives chlorobenzene: approximately equally on the
carbon atoms 2, 4, and 6 of
+ Cl Cl the ring relative to the point
H ƒ – ƒ of substitution.
fast
+ Cl ¬ Fe ¬ Cl Cl +H ¬ Cl +Fe ¬ Cl
Cl ƒ ƒ
Cl Cl
Cation Chlorobenzene
intermediate

Treatment of benzene with bromine in the presence of ferric chloride or aluminum

chloride gives bromobenzene and HBr. The mechanism for this reaction is the same as that
for chlorination of benzene.
The major difference between the addition of halogen to an alkene and substi-
tution by halogen on an aromatic ring is the fate of the cation intermediate formed
after the halogen is added to the compound. Recall from Section 5.3C that the addi-
tion of chlorine to an alkene is a two-step process, the first and slower step of which
298 CHAPTER 9 Benzene and Its Derivatives

is the formation of a bridged chloronium ion intermediate. This intermediate then

reacts with chloride ion to complete the addition. With aromatic compounds, the
cation intermediate loses H  to regenerate the aromatic ring and regain its large
resonance stabilization. There is no such resonance stabilization to be regained in
the case of an alkene.

B. Nitration and Sulfonation

The sequence of steps for the nitration and sulfonation of benzene is similar to that for
chlorination and bromination. For nitration, the electrophile is the nitronium ion, NO2 ,
generated by the reaction of nitric acid with sulfuric acid. In the following equations nitric
acid is written HONO2 to show more clearly the origin of the nitronium ion.

Mechanism
Formation of the Nitronium Ion
STEP 1: Add a proton. Proton transfer from sulfuric acid to the OH group of nitric acid gives
the conjugate acid of nitric acid:

H

 
H  O  NO2  H  O  SO3H  H  O  NO2  HSO4


Nitric acid Conjugate acid
of nitric acid

STEP 2: Break a bond to form a stable ion or molecule. Loss of water from this conjugate
acid gives the nitronium ion, NO2 :

H H the electrophile
 


H  O  NO2  H  O  NO2 
The nitronium ion

Mechanism
Formation of the Sulfonium Ion
The sulfonation of benzene is carried out using hot, concentrated sulfuric acid. The electro-
phile under these conditions is either SO3 or HSO3 , depending on the experimental condi-
tions. The HSO3  electrophile is formed from sulfuric acid in the following way:

STEP 1: Add a proton. Proton transfer from one molecule of sulfuric acid to the OH
group of another molecule of sulfuric acid gives the conjugate acid of sulfuric
acid:

O O O H O
   
 

HO  S  OH
H  O  S  OH  HO  S  O
O  S  OH
    
O O H
O O
Sulfuric acid Sulfuric acid
 9.6 What Is the Mechanism of Electrophilic Aromatic Substitution? 299
STEP 2: Break a bond to form a more stable ion or molecule. Loss of water from this conju-
gate acid gives the sulfonium ion as the electrophile:

the electrophile
O O
 H  H
  
HO
S
O  HO
S   O
   
 H H
O O
The sulfonium ion

EXAMPLE 9.4
Write a stepwise mechanism for the nitration of benzene.

S T R AT E G Y
Keep in mind that the mechanisms of electrophilic aromatic substitution reactions are all very similar. After the formation of
the electrophile, attack of the electrophile on the aromatic ring occurs to give a resonance-stabilized cation intermediate. The
last step of the mechanism is proton transfer to a base to regenerate the aromatic ring. The base in nitration is water, which
was generated in the formation of the electrophile.

SOLUTION
STEP 1: Reaction of a nucleophile and an electrophile to form a new covalent bond. Reaction of the nitronium ion (an elec-
trophile) with the benzene ring (a nucleophile) gives a resonance-stabilized cation intermediate.

H NO2 H NO2 H NO2

+ +
+NO2± ¡ · ·

STEP 2: Take a proton away. Proton transfer from this intermediate to H2 O regenerates the aromatic ring and gives
nitrobenzene:
H NO2 NO2

+
H2O + ¡ +H3O±

Nitrobenzene

See problems 9.21, 9.22

PROBLEM 9.4
Write a stepwise mechanism for the sulfonation of benzene. Use HSO3  as the electrophile.

C. Friedel–Crafts Alkylation
Alkylation of aromatic hydrocarbons was discovered in 1877 by the French chemist
Charles Friedel and a visiting American chemist, James Crafts. They discovered that mix-
ing benzene, a haloalkane, and AlCl3 results in the formation of an alkylbenzene and
300 CHAPTER 9 Benzene and Its Derivatives

HX. Friedel–Crafts alkylation forms a new carbon–carbon bond between benzene and an
alkyl group, as illustrated by reaction of benzene with 2-chloropropane in the presence
of aluminum chloride:

AlCl3
+ Cl +HCl

Benzene 2-Chloropropane Isopropylbenzene

(Isopropyl chloride) (Cumene)

Friedel–Crafts alkylation is among the most important methods for forming new carbon–
carbon bonds to aromatic rings.

Mechanism
Friedel–Crafts Alkylation
STEP 1: Formation of an electrophile. Reaction of a haloalkane (a Lewis base) with alumi-
num chloride (a Lewis acid) gives a molecular complex in which aluminum has a
negative formal charge and the halogen of the haloalkane has a positive formal
charge. Redistribution of electrons in this complex then gives an alkyl carbocation
as part of an ion pair:

the electrophile

Cl Cl Cl
     



R
Cl  A l
Cl  R
Cl
A l
Cl  R Cl
A l
Cl
  


Cl Cl Cl
A molecular complex An ion pair
with a positive charge on containing
chlorine and a negative a carbocation
charge on aluminum

STEP 2: Reaction of a nucleophile and an electrophile to form a new covalent bond.

Reaction of the alkyl carbocation with the pi electrons of the aromatic ring gives a
resonance-stabilized cation intermediate:

+
H H H
+R± ¡ · + ·
R R R
+
The positive charge is delocalized onto
three atoms of the ring

STEP 3: Take a proton away. Proton transfer regenerates the aromatic character of the ring
and the Lewis acid catalyst:

+ Cl
H ƒ –
+ Cl ¬ Al ¬ Cl ¡ R+AlCl3+H ¬ Cl
R ƒ
Cl
 9.6 What Is the Mechanism of Electrophilic Aromatic Substitution? 301
There are two major limitations on Friedel–Crafts alkylations. The first is that it is
practical only with stable carbocations, such as 3° carbocations, resonance-stabilized car-
bocations, or 2° carbocations that cannot undergo rearrangement (Section 5.4). Primary
carbocations will undergo rearrangement, resulting in multiple products as well as bond-
ing of the benzene ring to unexpected carbons in the former haloalkane.
The second limitation on Friedel–Crafts alkylation is that it fails altogether on ben-
zene rings bearing one or more strongly electron-withdrawing groups. The following table
shows some of these groups:
Y

AlCl3
+RX No reaction

When Y Equals Any of These Groups, the Benzene Ring

Does Not Undergo Friedel–Crafts Alkylation
O O O O O
’ ’ ’ ’ ’
J CH J CR J COH J COR J CNH2
J SO3 H JCžN J NO2 J NR3 
J CF3 J CCl3

Determine Whether a Substituent

on Benzene Is Electron Withdrawing
Determine the charge or partial charge on the atom directly bonded to the ben-
zene ring. If it is positive or partially positive, the substituent can be considered
HOW TO 9.2

to be electron withdrawing. An atom will be partially positive if it is bonded to

an atom more electronegative than itself.

the atom directly bonded to the benzene ring is partially positive

in character due to inductive effects from electronegative
atoms. The substituent acts as an electron-withdrawing group

d±
O d– CH3
N
C d± d– C d–
d± N
OR d– CH3
d±

the atom (nitrogen)directly bonded to the benzene ring

is partially negative in character because it is bonded to
less electronegative atoms (carbons). The substituent
does not act as an electron-withdrawing group

A common characteristic of the groups listed in the preceding table is that each has
either a full or partial positive charge on the atom bonded to the benzene ring. For car-
bonyl-containing compounds, this partial positive charge arises because of the difference in
electronegativity between the carbonyl oxygen and carbon. For J CF3 and J CCl3 groups,
the partial positive charge on carbon arises because of the difference in electronegativity
302 CHAPTER 9 Benzene and Its Derivatives

between carbon and the halogens bonded to it. In both the nitro group and the trialkylam-
monium group, there is a positive charge on nitrogen:
recall that nitrogens with four
bonds have a formal charge of +1

d-
O d- F O CH3
F d- CH3
C d+ d+ C N+ -
N
CH3 F d- O + CH
3

The carbonyl A trifluoro- A trimethyl-

A nitro group
group of a ketone methyl group ammonium group
recall that oxygens with only one
bond and three lone pairs of electrons
have a formal charge of -1

D. Friedel–Crafts Acylation
Friedel and Crafts also discovered that treating an aromatic hydrocarbon with an acyl
Acyl halide A derivative of halide in the presence of aluminum chloride gives a ketone. An acyl halide is a derivative
a carboxylic acid in which of a carboxylic acid in which the J OH of the carboxyl group is replaced by a halogen,
the J OH of the carboxyl
group is replaced by a
most commonly chlorine. Acyl halides are also referred to as acid halides. An RCO J
halogen—most commonly, group is known as an acyl group; hence, the reaction of an acyl halide with an aromatic
chlorine. hydrocarbon is known as Friedel–Crafts acylation, as illustrated by the reaction of ben-
zene and acetyl chloride in the presence of aluminum chloride to give acetophenone:
O
O CCH3
‘ AlCl3
+ CH3CCl +HCl

Benzene Acetyl chloride Acetophenone

(an acyl halide) (a ketone)

In Friedel–Crafts acylations, the electrophile is an acylium ion, generated in the following way:

Mechanism
Friedel–Crafts Acylation—Generation of an Acylium Ion
STEP 1: Formation of an electrophile. Reaction between the halogen atom of the acyl chloride
(a Lewis base) and aluminum chloride (a Lewis acid) gives a molecular complex. The
redistribution of valence electrons in turn gives an ion pair containing an acylium ion:
the electrophile
O Cl O Cl O Cl
        
R
C
Cl  Al
Cl  R
C
Cl
Al
Cl  R
C Cl
Al
Cl
   
Cl Cl Cl
An acyl Aluminum A molecular complex
chloride chloride An ion pair
with a positive charge on
(a Lewis acid) (a Lewis acid) containing
chlorine and a negative
an acylium ion
charge on aluminum

Steps 2 and 3 are identical to steps 2 and 3 of Friedel–Crafts alkylation (Section 9.6C).
 9.6 What Is the Mechanism of Electrophilic Aromatic Substitution? 303

EXAMPLE 9.5
Write a structural formula for the product formed by Friedel–Crafts alkylation or acylation of benzene with

“
Cl
Cl Cl
(a) (b) (c)

S T R AT E G Y
Utilize the fact that the halogenated reagent in Friedel–Crafts reactions will normally form a bond with benzene at the carbon
bonded to the halogen (Br or Cl). Therefore, to predict the product of a Friedel–Crafts reaction, replace the halogen in the
haloalkane or acyl halide with the benzene ring. One thing to be wary of, however, is the possibility of rearrangement once
the carbocation is formed.

SOLUTION
(a) Treatment of benzyl chloride with aluminum chloride gives the resonance-stabilized benzyl cation. Reaction of this cation
(an electrophile) with benzene (a nucleophile), followed by loss of H, gives diphenylmethane:

CH2± + ¡ CH2 +H ±

Benzyl cation (a nucleophile) Diphenylmethane

(an electrophile)

(b) Treatment of benzoyl chloride with aluminum chloride gives an acyl cation. Reaction of this cation with benzene,
followed by loss of H, gives benzophenone:

O O
‘ ‘
C ±+ ¡ C +H ±

Benzoyl cation Benzophenone

(an electrophile)

(c) Treatment of 2-chloro-3-methylbutane with aluminum chloride gives a 2° carbocation. Because there is an adjacent
3° hydrogen, a 1,2-hydride shift can occur to form the more stable 3° carbon. It is this carbon that reacts with benzene,
followed by loss of H, to give 2-methyl-2-phenylbutane.

rearrangement produces a more stable cation

and occurs before benzene can attack

H 1,2-hydride H H
+ shift
H
+

A 2° carbocation A 3° carbocation 2-Methyl-2-phenylbutane

See problems 9.18, 9.19

304 CHAPTER 9 Benzene and Its Derivatives

PROBLEM 9.5
Write a structural formula for the product formed from Friedel–Crafts alkylation or acylation of benzene with

Cl
O
Cl
(a) Cl (b) (c)

E. Other Electrophilic Aromatic Alkylations

Once it was discovered that Friedel–Crafts alkylations and acylations involve cationic inter-
mediates, chemists realized that other combinations of reagents and catalysts could give
the same intermediates. We study two of these reactions in this section: the generation of
carbocations from alkenes and from alcohols.
As we saw in Section 5.3B, treatment of an alkene with a strong acid, most commonly
H2 SO4 or H3 PO4 , generates a carbocation. Isopropylbenzene is synthesized industrially by
reacting benzene with propene in the presence of an acid catalyst:

H3PO4
+CH3CH “ CH2

Benzene Propene Isopropylbenzene

(Cumene)
Carbocations are also generated by treating an alcohol with H2 SO4 or H3 PO4 (Section 8.2E):

H3PO4
+ HO + H2 O

Benzene 2-Methyl-2-
phenylpropane
(tert -Butylbenzene)

EXAMPLE 9.6
Write a mechanism for the formation of isopropylbenzene from benzene and propene in the presence of phosphoric acid.

S T R AT E G Y
Draw the mechanism for the formation of the carbocation. This step constitutes the generation of the electrophile. The remain-
ing steps in the mechanism are the usual: attack of the electrophile on benzene and proton transfer to rearomatize the ring.

SOLUTION
STEP 1: Add a proton. Proton transfer from phosphoric acid to propene gives the isopropyl cation:
O  fast and O
 


reversible

CH3CH  CH2
H  O  P  O  H  CH3CHCH3
O  P O H
 
OH OH
STEP 2: Reaction of a nucleophile and an electrophile to form a new covalent bond. Reaction of the isopropyl cation with
benzene gives a resonance-stabilized carbocation intermediate:
H
slow, rate ±
limiting CH(CH3)2
+ ± CH(CH3)2
H
 9.7 How Do Existing Substituents on Benzene Affect Electrophilic Aromatic Substitution? 305

STEP 3: Take a proton away. Proton transfer from this intermediate to dihydrogen phosphate ion gives isopropylbenzene:

H
± O O
CH(CH3)2 ‘ ‘
- fast
+ O¬P¬O¬H ¡ CH(CH3)2+H ¬ O ¬ P ¬ O ¬ H
H ƒ ƒ
OH OH
Isopropylbenzene

See problems 9.18, 9.19, 9.33, 9.34

PROBLEM 9.6
Write a mechanism for the formation of tert-butylbenzene from benzene and tert-butyl alcohol in the presence of
phosphoric acid.

F. Comparison of Alkene Addition and Electrophilic Aromatic

Substitution (EAS)
Electrophilic aromatic substitution represents the second instance in which we have
encountered a C  C double bond attacking an electrophile. The first instance was
in our discussion of alkene addition reactions in Section 5.3. Notice the similarities
in the first step where a C  C double bond attacks an electrophilic atom (H or
E ). In Step 2, however, alkene addition results in the attack of a nucleophile on the
carbocation, while EAS results in abstraction of a hydrogen by base. In one reaction,
the C  C double bond is destroyed, while in the other, the C  C double bond is
regenerated.

Addition to an Alkene
H H
H @+ @-
H¬X H - H
+ X
step 1 + step 2
X
H H
H

Electrophilic Aromatic Substitution

H
H E
E+ E
+ Base
step 1 + step 2

H H H

9.7 How Do Existing Substituents on Benzene Affect

Electrophilic Aromatic Substitution?

A. Effects of a Substituent Group on Further Substitution

In the electrophilic aromatic substitution of a monosubstituted benzene, three isomeric
products are possible: The new group may be oriented ortho, meta, or para to the exist-
ing group. On the basis of a wealth of experimental observations, chemists have made the
306 CHAPTER 9 Benzene and Its Derivatives

following generalizations about the manner in which an existing substituent influences

further electrophilic aromatic substitution:
1. Substituents affect the orientation of new groups. Certain substituents direct a second sub-
stituent preferentially to the ortho and para positions; other substituents direct it pref-
erentially to a meta position. In other words, we can classify substituents on a benzene
Ortho–para director Any ring as ortho–para directing or meta directing.
substituent on a benzene
ring that directs electrophilic
2. Substituents affect the rate of further substitution. Certain substituents cause the rate of a
aromatic substitution second substitution to be greater than that of benzene itself, whereas other substituents
preferentially to ortho and cause the rate of a second substitution to be lower than that of benzene. In other words,
para positions. we can classify groups on a benzene ring as activating or deactivating toward further
Meta director Any substitution.
substituent on a benzene
ring that directs electrophilic To see the operation of these directing and activating–deactivating effects, compare,
aromatic substitution for example, the products and rates of bromination of anisole and nitrobenzene. Bromina-
preferentially to a meta tion of anisole proceeds at a rate 1.8  109 greater than that of bromination of benzene
position. (the methoxy group is activating), and the product is a mixture of o-bromoanisole and
Activating group Any p-bromoanisole (the methoxy group is ortho–para directing):
substituent on a benzene
ring that causes the rate
of electrophilic aromatic the bromination of anisole proceeds many times faster
substitution to be greater than the bromination of benzene. In fact, –OCH3 is so
than that for benzene. activating that no catalyst is necessary in this reaction

Deactivating group Any OCH3 OCH3 OCH3

substituent on a benzene
ring that causes the rate Br
of electrophilic aromatic
substitution to be lower +Br2 CH3COOH
+ +HBr
than that for benzene.

Br
Anisole o -Bromoanisole (4%) p -Bromoanisole (96%)

We see quite another situation in the nitration of nitrobenzene, which proceeds

10,000 times slower than the nitration of benzene itself. (A nitro group is strongly
deactivating.) Also, the product consists of approximately 93% of the meta isomer
and less than 7% of the ortho and para isomers combined (the nitro group is meta
directing):

the nitration of nitrobenzene proceeds many

times slower than the nitration of benzene

NO2 NO2 NO2 NO2

NO2
H2SO4
+HNO3 100
C
+ + +H2O
NO2
NO2
Nitrobenzene m -Dinitrobenzene o -Dinitrobenzene p -Dinitrobenzene
(93%)
Less than 7% combined

Table 9.1 lists the directing and activating–deactivating effects for the major func-
tional groups with which we are concerned in this text.
 9.7 How Do Existing Substituents on Benzene Affect Electrophilic Aromatic Substitution? 307

T A B L E 9 . 1 Effects of Substituents on Further Electrophilic Aromatic Substitution

strongly
activating JN
 H2 JN
 HR JN
 R2 JO
H JO
R

increasing reactivity
relative to benzene
Relative importance in directing further substitution
Ortho–Para Directing

moderately O O O O
activating ‘ ‘ ‘ ‘
¬ NHCR ¬ NHCAr ¬ O CR ¬ OCAr

weakly
activating JR

weakly

decreasing reactivity
deactivating JF
 J Cl
 J Br
  J I 

relative to benzene
moderately O O O O O O
Meta Directing

deactivating ’ ’ ’ ’ ’ ’
J CH J CR J COH J COR J CNH2 J SOH
’
O
strongly
deactivating J NO2 J NH3  J CF3 J CCl3

If we compare these ortho–para and meta directors for structural similarities and
differences, we can make the following generalizations:
1. Alkyl groups, phenyl groups, and substituents in which the atom bonded to the ring has
an unshared pair of electrons are ortho–para directing. All other substituents are meta
directing.
2. Except for the halogens, all ortho–para directing groups are activating toward further
substitution. The halogens are weakly deactivating.
3. All meta directing groups carry either a partial or full positive charge on the atom
bonded to the ring.
We can illustrate the usefulness of these generalizations by considering the syn-
thesis of two different disubstituted derivatives of benzene. Suppose we wish to prepare
m-bromonitrobenzene from benzene. This conversion can be carried out in two steps:
nitration and bromination. If the steps are carried out in just that order, the major
product is indeed m-bromonitrobenzene. The nitro group is a meta director and di-
rects bromination to a meta position:

¬NO2 is a meta director

NO2 NO2

H2SO4 Br2
HNO3 FeCl3

Br
Nitrobenzene m-Bromonitrobenzene

If, however, we reverse the order of the steps and first form bromobenzene, we now
have an ortho–para directing group on the ring. Nitration of bromobenzene then
308 CHAPTER 9 Benzene and Its Derivatives

takes place preferentially at the ortho and para positions, with the para product
predominating:

—Br is an ortho–para director

Br Br Br
NO2
Br2 H2SO4
FeCl3 HNO3 +

NO2
Bromobenzene o -Bromonitrobenzene p -Bromonitrobenzene

As another example of the importance of order in electrophilic aromatic substitu-

tions, consider the conversion of toluene to nitrobenzoic acid. The nitro group can be
introduced with a nitrating mixture of nitric and sulfuric acids. The carboxyl group can be
produced by oxidation of the methyl group (Section 9.4).
CH3 COOH

¬CH3 is an ortho–para
H2SO4 K2Cr2O7
director
HNO3 H2SO4

CH3
NO2 NO2
4 -Nitrotoluene 4 -Nitrobenzoic acid

COOH COOH
Toluene
K2Cr2O7 H2SO4
H2SO4 HNO3

NO2
¬COOH is a meta director Benzoic acid 3-Nitrobenzoic acid

Nitration of toluene yields a product with the two substituents para to each other,
whereas nitration of benzoic acid yields a product with the substituents meta to each other.
Again, we see that the order in which the reactions are performed is critical.
Note that, in this last example, we show nitration of toluene producing only the para
isomer. In practice, because methyl is an ortho–para directing group, both ortho and para
isomers are formed. In problems in which we ask you to prepare one or the other of these
isomers, we assume that both form and that there are physical methods by which you can
separate them and obtain the desired isomer.

EXAMPLE 9.7
Complete the following electrophilic aromatic substitution reactions. Where you predict meta substitution, show only the
meta product. Where you predict ortho–para substitution, show both products:
OCH3 SO3H
Cl
AlCl3
(a) + (b) + HNO3 H2SO4
 9.7 How Do Existing Substituents on Benzene Affect Electrophilic Aromatic Substitution? 309

S T R AT E G Y
Determine whether the existing substituent is ortho–para or meta directing prior to completing the reaction.

SOLUTION
The methoxyl group in (a) is ortho–para directing and strongly activating. The sulfonic acid group in (b) is meta directing and
moderately deactivating.

¬OCH3 is an ortho–para director

OCH3 OCH3 OCH3

Cl
AlCl3
(a) + +

2-Isopropylanisole 4-Isopropylanisole
(ortho-isopropylanisole) (para-isopropylanisole)

¬SO3H is a meta director

SO3H SO3H

H2SO4
(b) + HNO3

NO2

3-Nitrobenzenesulfonic acid
(meta-nitrobenzenesulfonic acid)

See problems 9.24–9.26, 9.31, 9.32, 9.42–9.44, 9.46, 9.47

PROBLEM 9.7
Complete the following electrophilic aromatic substitution reactions. Where you predict meta substitution, show only the
meta product. Where you predict ortho–para substitution, show both products:

O
O H2SO4 H2SO4
(a) +HNO3 (b) +HNO3
O

B. Theory of Directing Effects

As we have just seen, a group on an aromatic ring exerts a major effect on the patterns of
further substitution. We can make these three generalizations:
1. If there is a lone pair of electrons on the atom bonded to the ring, the group is an
ortho–para director.
2. If there is a full or partial positive charge on the atom bonded to the ring, the group is
a meta director.
3. Alkyl groups are ortho–para directors.
310 CHAPTER 9 Benzene and Its Derivatives

We account for these patterns by means of the general mechanism for electrophilic
aromatic substitution first presented in Section 9.5. Let us extend that mechanism to con-
sider how a group already present on the ring might affect the relative stabilities of cation
intermediates formed during a second substitution reaction.
We begin with the fact that the rate of electrophilic aromatic substitution is determined
by the slowest step in the mechanism, which, in almost every reaction of an electrophile
with the aromatic ring, is attack of the electrophile on the ring to give a resonance-stabilized
cation intermediate. Thus, we must determine which of the alternative carbocation inter-
mediates (that for ortho–para substitution or that for meta substitution) is the more stable.
That is, we need to show which of the alternative cationic intermediates has the lower acti-
vation energy for its formation.

Nitration of Anisole
The rate-determining step in nitration is reaction of the nitronium ion with the aromatic
ring to produce a resonance-stabilized cation intermediate. Figure 9.4 shows the cation
intermediate formed by reaction meta to the methoxy group. The figure also shows the
cationic intermediate formed by reaction para to the methoxy group. The intermediate
formed by reaction at a meta position is a hybrid of three major contributing structures:
(a), (b), and (c). These three are the only important contributing structures we can draw
for reaction at a meta position.
The cationic intermediate formed by reaction at the para position is a hybrid of four
major contributing structures: (d), (e), (f), and (g). What is important about structure
(f) is that all atoms in it have complete octets, which means that this structure contributes
more to the hybrid than structures (d), (e), or (g). Because the cation formed by reaction
at an ortho or para position on anisole has a greater resonance stabilization and, hence, a
lower activation energy for its formation, nitration of anisole occurs preferentially in the
ortho and para positions.

Nitration of Nitrobenzene
Figure 9.5 shows the resonance-stabilized cation intermediates formed by reaction of the
nitronium ion meta to the nitro group and also para to it.
Each cation in the figure is a hybrid of three contributing structures; no additional
ones can be drawn. Now we must compare the relative resonance stabilizations of each

meta attack
OCH3 OCH3 OCH3 OCH3 OCH3

+ +
slow fast
+ NO2+ H H H H±

NO2 NO2 + NO2 NO2

(a) (b) (c)

the most important

contributing structure
para attack
.. .. + .. ..
..

..

..

OCH3 OCH3 OCH3 OCH3 OCH3 OCH3

+
slow fast
+ NO2+
+ H±
+

ortho attack would H NO2 H NO2 H NO2 H NO2 NO2

similarly yield 4 (d) (e) (f) (g)
contributing structures
FIGURE 9.4
Nitration of anisole. Reaction of the electrophile meta and para to a methoxy group. Regeneration
of the aromatic ring is shown from the rightmost contributing structure in each case.
 9.7 How Do Existing Substituents on Benzene Affect Electrophilic Aromatic Substitution? 311

meta attack
NO2 NO2 NO2 NO2 NO2

+ +
slow fast
+ NO2+ H H H
H±

NO2 NO2 + NO2 NO2

(a) (b) (c)

the most disfavored

para attack contributing structure
NO2 NO2 NO2 NO2 NO2
+
slow fast
+ NO2+
H±
+ +

H NO2 H NO2 H NO2 NO2

(d) (e) (f) ortho attack would similarly
FIGURE 9.5
yield 3 contributing structures,
Nitration of nitrobenzene. Reaction of the electrophile meta and para to a nitro group. Regeneration one with the positive charge
of the aromatic ring is shown from the rightmost contributing structure in each case. adjacent to –NO2

hybrid. If we draw a Lewis structure for the nitro group showing the positive formal charge
on nitrogen, we see that contributing structure (e) places positive charges on adjacent
atoms:
–
O ± O
N
positive charges
±
on adjacent atoms
destabilize the
intermediate

H NO2
(e)

Because of the electrostatic repulsion thus generated, structure (e) makes only a negli-
gible contribution to the hybrid. None of the contributing structures for reaction at a
meta position places positive charges on adjacent atoms. As a consequence, resonance
stabilization of the cation formed by reaction at a meta position is greater than that for
the cation formed by reaction at a para (or ortho) position. Stated alternatively, the
activation energy for reaction at a meta position is less than that for reaction at a para
position.
A comparison of the entries in Table 9.1 shows that almost all ortho–para directing
groups have an unshared pair of electrons on the atom bonded to the aromatic ring. Thus,
the directing effect of most of these groups is due primarily to the ability of the atom
bonded to the ring to delocalize further the positive charge on the cation intermediate.
The fact that alkyl groups are also ortho–para directing indicates that they, too, help
to stabilize the cation intermediate. In Section 5.3A, we saw that alkyl groups stabilize car-
bocation intermediates and that the order of stability of carbocations is 3°  2°  1° 
methyl. Just as alkyl groups stabilize the cation intermediates formed in reactions of al-
kenes, they also stabilize the carbocation intermediates formed in electrophilic aromatic
substitutions.
To summarize, any substituent on an aromatic ring that further stabilizes the cation
intermediate directs ortho–para, and any group that destabilizes the cation intermediate
directs meta.
312 CHAPTER 9 Benzene and Its Derivatives

EXAMPLE 9.8
Draw contributing structures formed during the para SOLUTION
nitration of chlorobenzene, and show how chlorine par- Contributing structures (a), (b), and (d) place the positive
ticipates in directing the incoming nitronium ion to ortho– charge on atoms of the ring, while contributing structure (c)
para positions. places it on chlorine and thus creates additional resonance
stabilization for the cation intermediate:
S T R AT E G Y
±
Draw the intermediate that is formed initially from para Cl Cl Cl Cl
attack of the electrophile. Then draw a contributing struc-
ture by moving electrons from the pi bond adjacent to the ±
positive charge. Repeat for all contributing structures until · · ·
all resonance possibilities have been exhausted. Note: ± ±
Be sure to look for resonance possibilities outside of the
benzene ring. H NO2 H NO2 H NO2 H NO2
(a) (b) (c) (d)

See problem 9.29

PROBLEM 9.8
Because the electronegativity of oxygen is greater than that d–
O
of carbon, the carbon of a carbonyl group bears a partial
positive charge, and its oxygen bears a partial negative C d±
charge. Using this information, show that a carbonyl group CH3
is meta directing:

C. Theory of Activating–Deactivating Effects

We account for the activating–deactivating effects of substituent groups by a combination
of resonance and inductive effects:
1. Any resonance effect, such as that of J NH2 , J OH, and J OR, which delocalizes the
positive charge of the cation intermediate lowers the activation energy for its forma-
tion and is activating toward further electrophilic aromatic substitution. That is, these
groups increase the rate of electrophilic aromatic substitution, compared with the rate
at which benzene itself reacts.
2. Any resonance or inductive effect, such as that of J NO2 , J C  O, J SO3 H, J NR3 ,
J CCl3 , and J CF3 , which decreases electron density on the ring, deactivates the ring
to further substitution. That is, these groups decrease the rate of further electrophilic
aromatic substitution, compared with the rate at which benzene itself reacts.
3. Any inductive effect (such as that of J CH3 or another alkyl group), which releases
electron density toward the ring, activates the ring toward further substitution.
In the case of the halogens, the resonance and inductive effects operate in opposite
directions. As Table 9.1 shows, the halogens are ortho–para directing, but, unlike other
ortho–para directors listed in the table, the halogens are weakly deactivating. These obser-
vations can be accounted for in the following way.
1. The inductive effect of halogens. The halogens are more electronegative than carbon and
have an electron-withdrawing inductive effect. Aryl halides, therefore, react more slowly
in electrophilic aromatic substitution than benzene does.
 9.7 How Do Existing Substituents on Benzene Affect Electrophilic Aromatic Substitution? 313
2. The resonance effect of halogens. A halogen ortho or para to the site of electrophilic attack
stabilizes the cation intermediate by delocalization of the positive charge:

H ± H
Cl +E± ¡ Cl ± · Cl
E E

EXAMPLE 9.9
Predict the product of each electrophilic aromatic substitution.

OH COOH

FeCl3 H2SO4
(a) +Br2 (b) +HNO3

NO2

CH3

S T R AT E G Y
Determine the activating and deactivating effect of each group. The key to predicting the orientation of further substitution on
a disubstituted arene is that ortho–para directing groups are always better at activating the ring toward further substitution
than meta directing groups (Table 9.1). This means that, when there is competition between ortho–para directing and meta
directing groups, the ortho–para group wins.

SOLUTION
(a) The ortho–para directing and activating J OH group determines the position of bromination. Bromination
between the J OH and J NO2 groups is only a minor product because of steric hindrance to attack of bromine at
this position:

this ortho position is too sterically

hindered for attack by the electrophile

OH OH OH

Br
FeCl3
+ Br2 + + HBr

NO2 NO2 NO2

Br

(b) The ortho–para directing and activating methyl group determines the position of nitration:

COOH COOH

H2SO4
+HNO3 +H2O

NO2

CH3 CH3

See problems 9.24–9.26, 9.31, 9.32, 9.42–9.44, 9.46, 9.47

314 CHAPTER 9 Benzene and Its Derivatives

PROBLEM 9.9
Predict the product of treating each compound with HNO3 H2 SO4 :

CH3 COOH

(a) (b)

NO2
Cl

9.8 What Are Phenols?

A. Structure and Nomenclature

Phenol A compound that The functional group of a phenol is a hydroxyl group bonded to a benzene ring. We name
contains an J OH group substituted phenols either as derivatives of phenol or by common names:
bonded to a benzene ring.
OH OH OH OH OH
OH

CH3 OH
OH
Eriko Koga/Digital Vision/Getty Images, Inc

Phenol 3-Methylphenol 1,2-Benzenediol 1,3-Benzenediol 1,4-Benzenediol

(m -Cresol) (Catechol) (Resorcinol) (Hydroquinone)

Phenols are widely distributed in nature. Phenol itself and the isomeric cresols (o-,
m-, and p-cresol) are found in coal tar. Thymol and vanillin are important constituents of
thyme and vanilla beans, respectively:

OH CHO

Thymol is a constituent OCH3

of garden thyme, Thymus
OH
vulgaris.
2-Isopropyl-5-methylphenol 4-Hydroxy-3-methoxy-
(Thymol) benzaldehyde
(Vanillin)

Phenol, or carbolic acid, as it was once called, is a low-melting solid that is only slightly
soluble in water. In sufficiently high concentrations, it is corrosive to all kinds of cells. In di-
Charles D. Winters

lute solutions, phenol has some antiseptic properties and was introduced into the practice
of surgery by Joseph Lister, who demonstrated his technique of aseptic surgery in the surgi-
cal theater of the University of Glasgow School of Medicine in 1865. Nowadays, phenol has
been replaced by antiseptics that are both more powerful and have fewer undesirable side
effects. Among these is hexylresorcinol, which is widely used in nonprescription prepara-
Poison ivy. tions as a mild antiseptic and disinfectant.
 9.8 What Are Phenols? 315

OH OH
OCH3 OH

OH OH

Hexylresorcinol Eugenol Urushiol

Eugenol, which can be isolated from the flower buds (cloves) of Eugenia aromatica, is used
as a dental antiseptic and analgesic. Urushiol is the main component in the irritating oil
of poison ivy.

B. Acidity of Phenols
Phenols and alcohols both contain an J OH group. We group phenols as a separate class
of compounds, however, because their chemical properties are quite different from those
of alcohols. One of the most important of these differences is that phenols are significantly
more acidic than are alcohols. Indeed, the acid ionization constant for phenol is 106 times
larger than that of ethanol!

–
OH+H2O Δ O + H3O± Ka  1.1  10 10 pKa  9.95

Phenol Phenoxide ion


 H  H2 N CH3CH2 O
CH3CH2O   H3O Ka  1.3  10 16 pKa  15.9
Ethanol Ethoxide ion

Another way to compare the relative acid strengths of ethanol and phenol is to
look at the hydrogen ion concentration and pH of a 0.1-M aqueous solution of each
(Table 9.2). For comparison, the hydrogen ion concentration and pH of 0.1 M HCl are
also included.
In aqueous solution, alcohols are neutral substances, and the hydrogen ion concen-
tration of 0.1 M ethanol is the same as that of pure water. A 0.1-M solution of phenol is
slightly acidic and has a pH of 5.4. By contrast, 0.1 M HCl, a strong acid (completely ionized
in aqueous solution), has a pH of 1.0.
The greater acidity of phenols compared with alcohols results from the greater sta-
bility of the phenoxide ion compared with an alkoxide ion. The negative charge on the
phenoxide ion is delocalized by resonance. The two contributing structures on the left
for the phenoxide ion place the negative charge on oxygen, while the three on the right
place the negative charge on the ortho and para positions of the ring. Thus, in the reso-
nance hybrid, the negative charge of the phenoxide ion is delocalized over four atoms,

T A B L E 9 . 2 Relative Acidities of 0.1-M Solutions of Ethanol, Phenol, and HCl

Acid Ionization Equation [H] pH

CH3CH2OH  H2 O N CH3CH2O   H3O 1  10 7 7.0

C6H5OH  H2O N C6 H5O  H3O  3.3  10 6 5.4

  0.1 1.0
HCl  H2O N Cl  H3O
316 CHAPTER 9 Benzene and Its Derivatives

which stabilizes the phenoxide ion realtive to an alkoxide ion, for which no delocaliza-
tion is possible:

– –
O O O O O

H – – H
· · · ·

–
H

These two Kekulé structures These three contributing structures delocalize

are equivalent the negative charge onto carbon atoms of the ring

Note that, although the resonance model gives us a way of understanding why phe-
nol is a stronger acid than ethanol, it does not provide us with any quantitative means
of predicting just how much stronger an acid it might be. To find out how much stron-
ger one acid is than another, we must determine their pK a values experimentally and
compare them.
Ring substituents, particularly halogen and nitro groups, have marked effects on
the acidities of phenols through a combination of inductive and resonance effects. Be-
cause the halogens are more electronegative than carbon, they withdraw electron den-
sity from the negatively charged oxygen in the conjugate base, stabilizing the phenoxide
ion. Nitro groups have greater electron-withdrawing ability than halogens and thus have a
greater stabilizing effect on the phenoxide ion, making nitrophenol even more acidic than
chlorophenol.

Increasing acid strength

OH Cl OH O2N OH

Phenol 4-Chlorophenol 4-Nitrophenol

pKa 9.95 pKa 9.18 pKa 7.15
Δ

- - -
O Cl O O2N O

electron-withdrawing groups withdraw electron density

from the negatively charged oxygen of the conjugate base,
delocalizing the charge, and thus stabilizing the ion

EXAMPLE 9.10
Arrange these compounds in order of increasing acidity: 2,4-dinitrophenol, phenol, and benzyl alcohol.

S T R AT E G Y
Draw each conjugate base. Then determine which conjugate base is more stable using the principles of resonance and induc-
tive effects. The more stable the conjugate base, the more acidic the acid from which it was generated.
 9.8 What Are Phenols? 317

SOLUTION
Benzyl alcohol, a primary alcohol, has a pK a of approximately 16–18 (Section 8.2A). The pK a of phenol is 9.95. Nitro groups are
electron withdrawing and increase the acidity of the phenolic J OH group. In order of increasing acidity, these compounds are:
NO2

CH2OH OH O2N OH

Benzyl alcohol Phenol 2,4-Dinitrophenol

pK a 16–18 pK a 9.95 pK a 3.96

See problems 9.36–9.38

PROBLEM 9.10
Arrange these compounds in order of increasing acidity: 2,4-dichlorophenol, phenol, cyclohexanol.

C. Acid–Base Reactions of Phenols

Phenols are weak acids and react with strong bases, such as NaOH, to form water-soluble
salts:

OH+NaOH ¡ O–Na±+H2O

Phenol Sodium Sodium Water

pK a 9.95 hydroxide phenoxide pK a 15.7
(stronger acid) (stronger base) (weaker base) (weaker acid)

Most phenols do not react with weaker bases, such as sodium bicarbonate, and do not dis-
solve in aqueous sodium bicarbonate. Carbonic acid is a stronger acid than most phenols,
and, consequently, the equilibrium for their reaction with bicarbonate ion lies far to the
left (see Section 2.4):

OH+NaHCO3 O– Na±+H2CO3

Phenol Sodium Sodium Carbonic acid

pK a 9.95 bicarbonate phenoxide pK a 6.36
(weaker acid) (weaker base) (stronger base) (stronger acid)

The fact that phenols are weakly acidic, whereas alcohols are neutral, provides a con-
venient way to separate phenols from water-insoluble alcohols. Suppose that we want to sep-
arate 4-methylphenol from cyclohexanol. Each is only slightly soluble in water; therefore,
they cannot be separated on the basis of their water solubility. They can be separated, how-
ever, on the basis of their difference in acidity. First, the mixture of the two is dissolved in
diethyl ether or some other water-immiscible solvent. Next, the ether solution is placed in a
separatory funnel and shaken with dilute aqueous NaOH. Under these conditions, 4-meth-
ylphenol reacts with NaOH to give sodium 4-methylphenoxide, a water-soluble salt. The
upper layer in the separatory funnel is now diethyl ether (density 0.74 gcm3), containing
only dissolved cyclohexanol. The lower aqueous layer contains dissolved sodium 4-meth-
ylphenoxide. The layers are separated, and distillation of the ether (bp 35°C) leaves pure
cyclohexanol (bp 161°C). Acidification of the aqueous phase with 0.1 M HCl or another
318 CHAPTER 9 Benzene and Its Derivatives

strong acid converts sodium 4-methylphenoxide to 4-methylphenol, which is insoluble in

water and can be extracted with ether and recovered in pure form. The following flowchart
summarizes these experimental steps:

OH + CH3 OH

Cyclohexanol 4-Methylphenol

dissolve in diethyl ether

mix with 0.1 M NaOH

Ether layer Aqueous layer

containing containing the
cyclohexanol sodium 4-methylphenoxide

distill ether acidify with 0.1 M HCl

OH CH3 OH

Cyclohexanol 4-Methylphenol

Chemical
Ch i l
Co ect o s
Connections 9B
C A P S A IC I N , FOR T H OSE W H O L IKE IT H OT
Capsaicin, the pungent principle from the fruit of vari- Ironically, capsaicin is able to cause pain and
ous peppers (Capsicum and Solanaceae), was isolated relieve it as well. Currently, two capsaicin-containing
in 1876, and its structure was determined in 1919: creams, Mioton and Zostrix®, are prescribed to treat the
burning pain associated with postherpetic neuralgia, a
O complication of shingles. They are also prescribed for
CH3O diabetics, to relieve persistent foot and leg pain.
N The mechanism by which capsaicin relieves pain
is not fully understood. It has been suggested that, af-
H ter it is applied, the nerve endings in the area respon-
HO sible for the transmission of pain remain temporarily
Capsaicin numb. Capsaicin remains bound to specific receptor
(from various types of peppers) sites on these pain-transmitting neurons, blocking
them from further action. Eventually, capsaicin is re-
The inflammatory properties of capsaicin are well
moved from the receptor sites, but in the meantime,
known; the human tongue can detect as little as one
its presence provides needed relief from pain.
drop of it in 5 L of water. Many of us are familiar with
the burning sensation in the mouth and sudden tear-
ing in the eyes caused by a good dose of hot chili pep- Questions
pers. Capsaicin-containing extracts from these flam- Would you predict capsaicin to be more soluble in
ing foods are also used in sprays to ward off dogs or water or more soluble in 1-octanol?
other animals that might nip at your heels while you Would your prediction remain the same if capsaicin
are running or cycling. were first treated with a molar equivalent of NaOH?
 9.8 What Are Phenols? 319

D. Phenols as Antioxidants
An important reaction in living systems, foods, and other materials that contain carbon–
carbon double bonds is autoxidation—that is, oxidation requiring oxygen and no other
reactant. If you open a bottle of cooking oil that has stood for a long time, you will notice
a hiss of air entering the bottle. This sound occurs because the consumption of oxygen by
autoxidation of the oil creates a negative pressure inside the bottle.
Cooking oils contain esters of polyunsaturated fatty acids. You need not worry now
about what esters are; we will discuss them in Chapter 14. The important point here is that
all vegetable oils contain fatty acids with long hydrocarbon chains, many of which have one
or more carbon–carbon double bonds. (See Problem 4.44 for the structures of three of
these fatty acids.) Autoxidation takes place at a carbon adjacent to a double bond—that is,
at an allylic carbon.
Autoxidation is a radical chain process that converts an R J H group into an
R J O J O J H group, called a hydroperoxide. The process begins when energy in the form
of heat or light causes a molecule with a weak bond to form two radicals, atoms, or mol-
ecules with an unpaired electron. This step is known as chain initiation. In the laboratory,
small amounts of compounds such as peroxides, ROOR, are used as initiators because they
are easily converted to RO radicals by light or heat. Scientists are still unsure precisely
what compounds act as initiators in nature. Once a radical is generated, it reacts with a
molecule by removing the hydrogen atom together with one of its electrons (H) from an
allylic carbon. The carbon losing the H now has only seven electrons in its valence shell,
one of which is unpaired.

Mechanism
Autoxidation
STEP 1: Chain Initiation—Formation of a Radical from a Nonradical Compound. The
radical generated from the exposure of the initiator to light or heat causes the
removal of a hydrogen atom (H) adjacent to a C  C double bond to give an
allylic radical:

section of a fatty acid

hydrocarbon chain

H
ƒ
light ¬CH2CH“CH¬CH¬
RO¬OR or heat
2 RO ¬CH2CH“CH¬CH¬ + ROH
Radical Radical An allylic radical
initiator

STEP 2a: Chain Propagation—Reaction of a Radical and Oxygen to Form a New Radical.
The allylic radical reacts with oxygen, itself a diradical, to form a hydroper-
oxy radical. The new covalent bond of the hydroperoxy radical forms by the
combination of one electron from the allylic radical and one electron from the
oxygen diradical:

O¬O
ƒ
¬ CH2CH “ CH ¬ CH ¬ + O ¬ O ¡ ¬ CH2CH “ CH ¬ CH ¬
Oxygen is a A hydroperoxy radical
diradical

STEP 2b: Chain Propagation—Reaction of a Radical and a Molecule to Form a New Radical.
The hydroperoxy radical removes an allylic hydrogen atom (H) from a new fatty
320 CHAPTER 9 Benzene and Its Derivatives

O“O O¬O acid hydrocarbon chain to complete the formation of a hydroperoxide and, at the
same time, produce a new allylic radical:
(a) (b)
Although we represent O¬O H
molecular oxygen with
ƒ ƒ
¬ CH2CH “ CH ¬ CH ¬ + ¬ CH2CH “ CH ¬ CH ¬ ¡
the Lewis structure shown
in (a), oxygen has long Section of a new fatty
acid hydrocarbon chain
been known to exist and
behave as a diradical, as O¬O¬H
shown in (b). ƒ
¬ CH2CH “ CH ¬ CH ¬ CH2 ¬ + ¬ CH2CH “ CH ¬ CH ¬
A hydroperoxide A new allylic radical

The most important point about the pair of chain propagation steps is that they form
a continuous cycle of reactions. The new radical formed in Step 2b next reacts with another
molecule of O 2 in Step 2a to give a new hydroperoxy radical, which then reacts with a new
hydrocarbon chain to repeat Step 2b, and so forth. This cycle of propagation steps repeats
over and over in a chain reaction. Thus, once a radical is generated in Step 1, the cycle of
propagation steps may repeat many thousands of times, generating thousands and thou-
sands of hydroperoxide molecules. The number of times the cycle of chain propagation
Charles D. Winters

steps repeats is called the chain length.

Hydroperoxides themselves are unstable and, under biological conditions, degrade to
short-chain aldehydes and carboxylic acids with unpleasant “rancid” smells. These odors may be
familiar to you if you have ever smelled old cooking oil or aged foods that contain polyunsatu-
rated fats or oils. A similar formation of hydroperoxides in the low-density lipoproteins deposited
Butylated hydroxytoluene on the walls of arteries leads to cardiovascular disease in humans. In addition, many effects of ag-
(BHT) is often used as an ing are thought to be the result of the formation and subsequent degradation of hydroperoxides.
antioxidant in baked goods Fortunately, nature has developed a series of defenses, including the phenol vitamin E,
to “retard spoilage.”
ascorbic acid (vitamin C), and glutathione, against the formation of destructive hydroperox-
ides. The compounds that defend against hydroperoxides are “nature’s scavengers.” Vitamin E,
for example, inserts itself into either Step 2a or 2b, donates an H from its phenolic J OH
group to the allylic radical, and converts the radical to its original hydrocarbon chain. Be-
cause the vitamin E radical is stable, it breaks the cycle of chain propagation steps, thereby
preventing the further formation of destructive hydroperoxides. While some hydroperox-
ides may form, their numbers are very small and they are easily decomposed to harmless
materials by one of several enzyme-catalyzed reactions.
Unfortunately, vitamin E is removed in the processing of many foods and food prod-
ucts. To make up for this loss, phenols such as BHT and BHA are added to foods to “retard
[their] spoilage” (as they say on the packages) by autoxidation:
OH OH
O ( )3 H

HO

OCH3
Vitamin E Butylated hydroxy- Butylated hydroxy-
toluene anisole
(BHT) (BHA)
Similar compounds are added to other materials, such as plastics and rubber, to protect
them against autoxidation. The protective properties of phenols may explain why the health ben-
efits of foods such as green tea, wine, and blueberries (each of which contains large amounts of
phenolic compounds) have been lauded by nutritionists and others in the medical community.
 Summary of Key Questions 321

S U M M A RY O F K E Y Q U E ST I O N S

9.1 What Is the Structure of Benzene?

s Benzene is a molecule with a high degree of unsaturation ring and overlap to form a continuous pi cloud encom-
possessing the molecular formula C6H6. Each carbon has a passing all six carbons.
single unhybridized 2p orbital that contains one electron. s Benzene and its alkyl derivatives are classified as aromatic
These six 2p orbitals lie perpendicular to the plane of the hydrocarbons, or arenes.

9.2 What Is Aromaticity?

s According to the Hückel criteria for aromaticity, a cyclic and so on, pi electrons in the overlapping system of p orbit-
compound is aromatic if it (1) has one 2p orbital on each als (i.e., it has 4n  2 P electrons).
atom of the ring, (2) is planar so that overlap of all p orbitals s A heterocyclic aromatic compound contains one or more
of the ring is continuous or nearly so, and (3) has 2, 6, 10, 14, atoms other than carbon in an aromatic ring.

9.3 How Are Benzene Compounds Named, and What Are Their Physical Properties?
s Aromatic compounds are named by the IUPAC system. s To locate two substituents on a benzene ring, either num-
The common names toluene, xylene, styrene, phenol, ber the atoms of the ring or use the locators ortho (o),
aniline, benzaldehyde, and benzoic acid are retained. meta (m), and para (p).
s The C6H5 J group is named phenyl, and the C6H5CH2 J s Polynuclear aromatic hydrocarbons contain two or more
group is named benzyl. fused benzene rings.

9.4 What Is the Benzylic Position, and How Does It Contribute to Benzene Reactivity?
s The benzylic position is the carbon of an alkyl substituent s The benzylic position of a benzene ring can be oxidized by
immediately bonded to the benzene ring. chromic acid without affecting any of the benzene ring atoms.

9.5 What Is Electrophilic Aromatic Substitution?

s A characteristic reaction of aromatic compounds is elec- s The five types of electrophilic aromatic substitution dis-
trophilic aromatic substitution, which involves the sub- cussed here are nitration, halogenation, sulfonation,
stitution of one of the ring hydrogens of benzene for an Friedel–Crafts alkylation, and Friedel–Crafts acylation.
electrophilic reagent.

9.6 What Is the Mechanism of Electrophilic Aromatic Substitution?

s The mechanism of electrophilic aromatic substitution can s The five electrophilic aromatic substitution reactions
be broken down into three common steps: (1) generation of studied here differ in their mechanism of formation of
the electrophile, (2) attack of the electrophile on the aromatic the electrophile (Step 1) and the specific base used to
ring to give a resonance-stabilized cation intermediate, and effect the proton transfer to regenerate the aromatic
(3) proton transfer to a base to regenerate the aromatic ring. ring (Step 3).

9.7 How Do Existing Substituents on Benzene Affect Electrophilic Aromatic Substitution?

s Substituents on an aromatic ring influence both the rate s A mechanistic rationale for directing effects is based on
and site of further substitution. the degree of resonance stabilization of the possible cat-
s Substituent groups that direct an incoming group prefer- ion intermediates formed upon reaction of the aromatic
entially to the ortho and para positions are called ortho– ring and the electrophile.
para directors. Those that direct an incoming group pref- s Groups that stabilize the cation intermediate are ortho–
erentially to the meta positions are called meta directors. para directors; groups that destabilize it are deactivators
s Activating groups cause the rate of further substitution to and meta directors.
be faster than that for benzene; deactivating groups cause
it to be slower than that for benzene.
322 CHAPTER 9 Benzene and Its Derivatives

9.8 What Are Phenols?

s The functional group of a phenol is an J OH group bonded s Various phenols are used to prevent autoxidation, a
to a benzene ring. radical chain process that converts an R J H group into an
s Phenol and its derivatives are weak acids, with pKa R J O J O J H (hydroperoxide) group and causes spoil-
approximately 10.0, but are considerably stronger acids age in foods.
than alcohols, with pKa 16–18.

QUICK QUIZ
Answer true or false to the following questions to assess your general knowledge of the concepts in this chapter. If
you have difficulty with any of them, you should review the appropriate section in the chapter (shown in parenthe-
ses) before attempting the more challenging end-of-chapter problems.

1. The mechanism of electrophilic aromatic substitution benzene and the carbon that was bonded to the
involves three steps: generation of the electrophile, halogen. (9.5)
attack of the electrophile on the benzene ring, and pro- 13. Resonance energy is the energy a ring contains due to
ton transfer to regenerate the ring. (9.6) the stability afforded it by its contributing structures. (9.1)
2. The C J C double bonds in benzene do not undergo the 14. A phenol will react quantitatively with NaOH. (9.8)
same addition reactions that the C J C double bonds in 15. The use of a haloalkane and AlCl3 is the only way to
alkenes undergo. (9.1) synthesize an alkylbenzene. (9.6)
3. Friedel–Crafts acylation is not subject to rearrange- 16. Phenols are more acidic than alcohols. (9.8)
ments. (9.5) 17. Substituents of polysubstituted benzene rings can be
4. An aromatic compound is planar, possesses a 2p orbital numbered according to their distance from the substitu-
on every atom of the ring, and contains either 4, 8, 12, ent that imparts a special name to the compound. (9.3)
16, and so on, pi electrons. (9.2) 18. If a benzene ring contains both a weakly activating group
5. When naming disubstituted benzenes, the locators and a strongly deactivating group, the strongly deactivat-
para, meta, and ortho refer to substituents that are 1,2, ing group will direct the attack of an electrophile. (9.7)
1,3, and 1,4, respectively. (9.3) 19. Oxygen, O2, can be considered a diradical. (9.8)
6. The electrophile in the chlorination or bromination of 20. The contributing structures for the attack of an electro-
benzene is an ion pair containing a chloronium or bro- phile to the ortho position of aniline are more stable
monium ion. (9.6) than those for the attack at the meta position. (9.7)
7. An ammonium group ( J NH3 ) on a benzene ring will 21. A deactivating group will cause its benzene ring to react
direct an attacking electrophile to a meta position. (9.7) slower than benzene itself. (9.7)
8. Reaction of chromic acid, H2CrO4, with a substituted 22. Friedel–Crafts alkylation is promoted by the presence of
benzene always oxidizes every alkyl group at the ben- electron-withdrawing groups. (9.5)
zylic position to a carboxyl group. (9.4) 23. Autoxidation takes place at allylic carbons. (9.8)
9. Benzene consists of two contributing structures that 24. The contributing structures for the attack of an electrophile
rapidly interconvert between each other. (9.1) to the meta position of nitrobenzene are more stable than
10. The electrophile in the nitration of benzene is the nitrate those for the attack at the ortho or para position. (9.7)
ion. (9.6) (23) T (24) T
(12) F (13) F (14) T (15) F (16) T (17) T (18) F (19) T (20) T (21) T (22) F
11. A benzene ring with an J OH bonded to it is referred to Answers: (1) T (2) T (3) T (4) F (5) F (6) T (7) T (8) F (9) F (10) F (11) F
as “phenyl.” (9.3)
12. Friedel–Crafts alkylation of a primary haloalkane with accompanying Solutions Manual.
Detailed explanations for many of these answers can be found in the
benzene will always result in a new bond between

K E Y R E AC T I O N S

1. Oxidation at a Benzylic Position (Section 9.4)

K2Cr2O7
A benzylic carbon bonded to at least one hydrogen is CH3 CH(CH3)2 H2SO4
oxidized to a carboxyl group:

HOOC COOH
 Key Reactions 323
2. Chlorination and Bromination (Section 9.6A) OH
 
The electrophile is a halonium ion, Cl or Br , formed by
CH3
treating Cl2 or Br2 with AlCl3 or FeCl3 : ƒ H3PO4
+2 CH3C “ CH2
AlCl3
+Cl2 Cl+HCl
CH3
OH
3. Nitration (Section 9.6B)
(CH3)3C C(CH3)3
The electrophile is the nitronium ion, NO2 , formed by
treating nitric acid with sulfuric acid:
Br

CH3
H2SO4
+HNO3
8. Alkylation Using an Alcohol (Section 9.6E)
The electrophile is a carbocation formed by treating an
Br Br
alcohol with H2 SO4 or H3 PO4 :
NO2
H3PO4
+ +H2O +(CH3)3COH C(CH3)3+H2O

9. Acidity of Phenols (Section 9.8B)

NO2
Phenols are weak acids:

4. Sulfonation (Section 9.6B)

OH+H2O Δ
The electrophile is HSO3 :

Phenol
+H2SO4 SO3H+H2O

5. Friedel–Crafts Alkylation (Section 9.6C) O–+H3O± K a=1.1*10–10

The electrophile is an alkyl carbocation formed by treat- pK a=9.95
ing an alkyl halide with a Lewis acid:
Phenoxide ion
AlCl3 Substitution by electron-withdrawing groups, such as
+(CH3)2CHCl
the halogens and the nitro group, increases the acidity
of phenols.
10. Reaction of Phenols with Strong Bases (Section 9.8C)
Water-insoluble phenols react quantitatively with strong
bases to form water-soluble salts:
CH(CH3)2+HCl

OH+NaOH ¡
6. Friedel–Crafts Acylation (Section 9.6D)
The electrophile is an acyl cation formed by treating an Phenol Sodium
acyl halide with a Lewis acid: pK a 9.95 hydroxide
(stronger acid) (stronger base)
O O
‘ AlCl3 ‘
+CH3CCl CCH3+HCl
O–Na±+H2O

7. Alkylation Using an Alkene (Section 9.6E)

Sodium Water
The electrophile is a carbocation formed by treating an phenoxide pK a 15.7
alkene with H2 SO4 or H3 PO4 : (weaker base) (weaker acid)
324 CHAPTER 9 Benzene and Its Derivatives

PROBLEMS
A problem marked with an asterisk indicates an applied “real-world” problem. Answers to problems whose
numbers are printed in blue are given in Appendix D.

Section 9.2 Aromaticity

9.11 Which of the following compounds or chemical enti- -2
ties are aromatic? (See Example 9.1)
O
(i) (j)

(a) (b)

-
H-
--
B
NH -H
(k) N N
H

-
(l)
B-
--H
B
H-
+ CH3 B N
O

-
H
(c) (d)

9.12 Explain why cyclopentadiene (pKa16) is many

orders of magnitude more acidic than cyclopentane
+ O (pKa  50). (Hint: Draw the structural formula for the
O
anion formed by removing one of the protons on the
(e) (f) J CH2 J group, and then apply the Hückel criteria
HN for aromaticity.)

S
+
(g) (h)
Cyclopentadiene Cyclopentane

Section 9.3 Nomenclature and Structural Formulas

9.13 Name these compounds: (See Example 9.2)

NO2 CH3 OH
Br
OH
(a) (b) (c) (d)

Cl
COOH CH3
OH
Cl
C6H5
(e) (f) (g) C6H5 (h)
C6H5
NO2

Br Cl
Cl

(i) (j) (k) CH3CH2 NH2 (l) CH3O

Cl
F
 Problems 325
9.14 Draw structural formulas for these compounds: (See (m) 4-Bromo-1,2-dichlorobenzene
Example 9.2) (n) 5-Fluoro-2-methylphenol
(a) 1-Bromo-2-chloro-4-ethylbenzene (o) 1-Cyclohexyl-3-ethylbenzene
(b) 4-Iodo-1,2-dimethylbenzene (p) m-Phenylaniline
(c) 2,4,6-Trinitrotoluene (TNT) (q) 3-Methyl-2-vinylbenzoic acid
(d) 4-Phenyl-2-pentanol (r) 2,5-Dimethylanisole
(e) p-Cresol 9.15 Show that pyridine can be represented as a hybrid of
(f) 2,4-Dichlorophenol two equivalent contributing structures.
(g) 1-Phenylcyclopropanol
(h) Styrene (phenylethylene) 9.16 Show that naphthalene can be represented as a
(i) m-Bromophenol hybrid of three contributing structures. Show also,
(j) 2,4-Dibromoaniline by the use of curved arrows, how one contributing
(k) Isobutylbenzene structure is converted to the next.
(l) m-Xylene 9.17 Draw four contributing structures for anthracene.

Section 9.5 Electrophilic Aromatic Substitution: Monosubstitution

9.18 Draw a structural formula for the compound formed Cl
by treating benzene with each of the following com- 
binations of reagents: (See Examples 9.5, 9.6) AlCl3
(a)

(a) CH3 CH2 ClAlCl3 (b) CH2  CH2 H2 SO4
(c) CH3 CH2 OHH2 SO4 (d) CH3OCH3/H2SO4

9.19 Show three different combinations of reagents you

might use to convert benzene to isopropylbenzene.
(See Examples 9.5, 9.6)

9.20 How many monochlorination products are possible
HCl

when naphthalene is treated with Cl2 AlCl3 ?
9.21 Write a stepwise mechanism for the following reac-
tion, using curved arrows to show the flow of elec-
trons in each step: (See Example 9.4)

H2SO4
(b)

AlCl3
+ Cl + HCl

9.22 Write a stepwise mechanism for the preparation of

diphenylmethane by treating benzene with dichlo-
romethane in the presence of an aluminum chloride
HCl
catalyst. (See Example 9.4)
9.23 The following alkylation reactions do not yield the
compounds shown as the major product. Predict
the major product for each reaction and provide a
mechanism for their formation.

+ HCl
FeCl3
(c) + Cl

CH3
an important precursor in O “
the synthesis of ibuprofen,
which unfortunately cannot
be made using these reagents
OH
Ibuprofen
326 CHAPTER 9 Benzene and Its Derivatives

Section 9.7 Electrophilic Aromatic Substitution: Substitution Effects

9.24 When treated with Cl2 AlCl3 , 1,2-dimethylbenzene 9.29 Account for the observation that the trifluoromethyl
(o-xylene) gives a mixture of two products. Draw group is meta directing, as shown in the following
structural formulas for these products. (See Examples example: (See Example 9.8)
9.7, 9.9) CF3 CF3
9.25 How many monosubstitution products are possible
when 1,4-dimethylbenzene (p-xylene) is treated with H2SO4
Cl2 AlCl3 ? When m-xylene is treated with Cl2 AlCl3 ? +HNO3 +H2O
(See Examples 9.7, 9.9)
NO2
9.26 Draw the structural formula for the major product
formed upon treating each compound with Cl2 AlCl3 : 9.30 Show how to convert toluene to these carboxylic
(See Examples 9.7, 9.9) acids: (See Example 9.3)

(a) Toluene (b) Nitrobenzene (a) 4-Chlorobenzoic acid (b) 3-Chlorobenzoic acid
(c) Chlorobenzene (d) tert-Butylbenzene 9.31 Show reagents and conditions that can be used to
O O bring about these conversions: (See Examples 9.7, 9.9)
‘ ‘
(e) CCH3 (f) OCCH3 CH3 CH3

O O
‘ ‘ (a) ¡
(g) COCH3 (h) CH3¬ CCH3

O C
‘ O CH2CH3
(i) OCCH3 (j) Cl CH3
¬

NO2
OH OH
9.27 Which compound, chlorobenzene or toluene, undergoes
O2N
electrophilic aromatic substitution more rapidly when
treated with Cl2 AlCl3 ? Explain and draw structural (b) ¡
formulas for the major product(s) from each reaction.
9.28 Arrange the compounds in each set in order of
NO2
decreasing reactivity (fastest to slowest) toward elec-
trophilic aromatic substitution:
O O OCH3 OCH3
‘ ‘
(a) OCCH3 COCH3

(A) (B) (C) (c) ¡

(b) NO2 COOH CCH3

O
(A) (B) (C)
O O O O
‘ ‘
(c) NH2 NHCCH3 CNHCH3 ‘ ‘
O O
(A) (B) (C)
Cl

(d) ¡
(d) CH3 OCH3

(A) (B) (C) NO2

 Problems 327
9.32 Propose a synthesis of triphenylmethane from ben- OH
zene as the only source of aromatic rings. Use any
other necessary reagents. (See Examples 9.7, 9.9)
H3PO4
+ 2
*9.33 Reaction of phenol with acetone in the presence of
an acid catalyst gives bisphenol A, a compound used
in the production of polycarbonate and epoxy resins
(Sections 16.4C and 16.4E): (See Example 9.6)
4-Methylphenol 2-Methylpropene
O
‘ OH
H3PO4
2 OH+CH3CCH3

Acetone

CH3

HO C OH+H2O 2,6-Di-tert-butyl-4-methylphenol
(Butylated hydroxytoluene, BHT)
CH3
Propose a mechanism for this reaction.
Bisphenol A
*9.35 The first herbicide widely used for controlling
Propose a mechanism for the formation of bisphe- weeds was 2,4-dichlorophenoxyacetic acid (2,4-D).
nol A. (Hint: The first step is a proton transfer from Show how this compound might be synthesized
phosphoric acid to the oxygen of the carbonyl group from 2,4-dichlorophenol and chloroacetic acid,
of acetone.) ClCH2 COOH:

*9.34 2,6-Di-tert-butyl-4-methylphenol, more commonly O

‘
known as butylated hydroxytoluene, or BHT, is used Cl OH ¡ Cl OCH2COH
as an antioxidant in foods to “retard spoilage.”
BHT is synthesized industrially from 4-methylphenol
(p-cresol) by reaction with 2-methylpropene in the Cl Cl
presence of phosphoric acid: (See Example 9.6) 2,4-Dichlorophenol 2,4-Dichlorophenoxyacetic acid
(2,4-D)

Section 9.8 Acidity of Phenols

9.36 Use resonance theory to account for the fact that 9.38 From each pair, select the stronger base: (See
phenol (pKa 9.95) is a stronger acid than cyclohexanol Example 9.10)
(pKa 18). (See Example 9.10)
9.37 Arrange the compounds in each set in order of (a) O– or OH–
increasing acidity (from least acidic to most acidic):
(See Example 9.10)

(a) OH OH CH3COOH
(b) O– or O–

(b) OH NaHCO3 H2O

(c) O– or HCO3–
OH OH CH2OH

(c)

(d) O– or CH3COO–

NO2
328 CHAPTER 9 Benzene and Its Derivatives

9.39 Account for the fact that water-insoluble carboxylic 9.40 Describe a procedure for separating a mixture of
acids (pKa 45) dissolve in 10% sodium bicarbonate 1-hexanol and 2-methylphenol (o-cresol) and recov-
with the evolution of a gas, but water-insoluble phenols ering each in pure form. Each is insoluble in water,
(pKa 9.510.5) do not show this chemical behavior. but soluble in diethyl ether.

Syntheses
9.41 Using styrene, C6 H5 CH  CH2 , as the only aromatic *9.44 The following ketone, isolated from the roots of sev-
starting material, show how to synthesize these com- eral members of the iris family, has an odor like that
pounds. In addition to styrene, use any other neces- of violets and is used as a fragrance in perfumes.
sary organic or inorganic chemicals. Any compound Describe the synthesis of this ketone from benzene.
synthesized in one part of this problem may be used (See Examples 9.7, 9.9)
to make any other compound in the problem: O
O Br
‘ ƒ
(a) COH (b) CHCH3 4-Isopropylacetophenone

OH O
ƒ ‘
(c) CHCH3 (d) CCH3
*9.45 The bombardier beetle generates p-quinone, an
OH irritating chemical, by the enzyme-catalyzed oxida-
ƒ tion of hydroquinone, using hydrogen peroxide as
(e) CH2CH3 (f) CHCH2OH the oxidizing agent. Heat generated in this oxidation
produces superheated steam, which is ejected, along
9.42 Show how to synthesize these compounds, starting with p-quinone, with explosive force.
with benzene, toluene, or phenol as the only sources of OH O
aromatic rings. Assume that, in all syntheses, you can
separate mixtures of ortho–para products to give the enzyme
catalyst
desired isomer in pure form: (See Examples 9.7, 9.9) +H2O2 +H2O+heat
(a) m-Bromonitrobenzene
(b) 1-Bromo-4-nitrobenzene
(c) 2,4,6-Trinitrotoluene (TNT) OH O
(d) m-Bromobenzoic acid Hydroquinone p - Quinone
(e) p-Bromobenzoic acid
(a) Balance the equation.
(f) p-Dichlorobenzene
(b) Show that this reaction of hydroquinone is an
(g) m-Nitrobenzenesulfonic acid
oxidation.
(h) 1-Chloro-3-nitrobenzene
*9.46 Following is a structural formula for musk ambrette,
9.43 Show how to synthesize these aromatic ketones,
a synthetic musk used in perfumes to enhance and
starting with benzene or toluene as the only sources
retain fragrance: (See Examples 9.7, 9.9)
of aromatic rings. Assume that, in all syntheses,
mixtures of ortho–para products can be sepa- CH3 CH3
rated to give the desired isomer in pure form: (See
Examples 9.7, 9.9) O2N NO2
?
O O
OH OCH3
(a) (b)

Br m -Cresol Musk ambrette

O O Propose a synthesis for musk ambrette from m-cresol.

Br *9.47 (3-Chlorophenyl)propanone is a building block in

(c) (d) OH the synthesis of bupropion, the hydrochloride salt
of which is the antidepressant Wellbutrin. During
Cl clinical trials, researchers discovered that smokers
 Chemical Transformations 329
reported a diminished craving for tobacco after one ing cessation. Propose a synthesis for this building
to two weeks on the drug. Further clinical trials con- block from benzene. (We will see in Section 12.8
firmed this finding, and the drug is also marketed how to complete the synthesis of bupropion.) (See
under the trade name Zyban® as an aid in smok- Examples 9.7, 9.9)

O O H
Cl Cl N
?

Benzene (3-Chlorophenyl)-1-propanone Bupropion (Wellbutrin, Zyban)

C H E M I C A L T R A N S F O R M AT I O N S

9.48 Test your cumulative knowledge of the reactions +

NH3 Br-
learned thus far by completing the following chemi-
cal transformations. Note: Some will require more (h)
than one step.
OH
(a) NH2
(i)

CH3O CH3O O O

“
(j)
(b)
HO OH

COOH Cl
Cl

(c) (k)

+
NH2 NH3 Cl - OH

Cl NH2 Br
(l) NH
(d)

COOH
Cl NO2
Cl
NO2 (m)

(e)

Cl NO2
OH O
(f) OH Br O “O
(n)
H
Cl Cl
(g)

Cl
330 CHAPTER 9 Benzene and Its Derivatives

LOOKING AHEAD

9.49 Which of the following compounds can be made 9.52 Predict the product of the following acid–base
directly by using an electrophilic aromatic substitu- reaction:
tion reaction?
N
+H3O± ¡
(a) (b) N
H
OH NH2
9.53 Which haloalkane reacts faster in an SN1 reaction?
(c) (d)
Cl Cl

9.50 Which compound is a better nucleophile?

NH2 NH2 or
or
9.54 Which of the following compounds is more basic?
Aniline Cyclohexanamine
O O
9.51 Suggest a reason that the following arenes do not
undergo electrophilic aromatic substitution when
AlCl3 is used in the reaction: Furan or Tetrahydrofuran
OH

SH
(a) (b)

NH2

(c)

G R O U P L E A R N I N G AC T I V I T I E S

9.55 Following are benzene compounds with substituents 9.56 The following structures represent a play on words
we have yet to encounter. As a group, decide whether when named. Can you name them? Can you come
each ring will be activated or deactivated. Then deter- up with other funny names?
mine whether each substituent is ortho–para or meta
(a) phys (b)
directing by analyzing their intermediates in an
electrophilic aromatic substitution reaction. M.D.

(a) O± (b)
‰
C Si(CH3)3 ical M.D.
 10 Amines

Chlorphenamine, an organic amine, is an antihistamine used to prevent some of

the symptoms of allergies. Inset: A model of chlorphenamine. (© mandygodbehear/
iStockphoto)

KEY QUESTIONS

10.1 What Are Amines? HOW TO

10.2 How Are Amines Named? 10.1 How to Predict the Relative Basicity of Amines
10.3 What Are the Characteristic Physical Properties
of Amines?
CHEMICAL CONNECTIONS
10.4 What Are the Acid–Base Properties of Amines?
10A Morphine as a Clue in the Design and Discovery
10.5 What Are the Reactions of Amines with Acids? of Drugs
10.6 How Are Arylamines Synthesized? 10B The Poison Dart Frogs of South America: Lethal
10.7 How Do Amines Act as Nucleophiles? Amines

C AR B ON, HY D RO G EN , and oxygen are the three most common elements in organic
compounds. Because of the wide distribution of amines in the biological world, nitrogen
is the fourth most common element in organic compounds. The most important chemical
properties of amines are their basicity and their nucleophilicity.

331
332 C H A P T E R 10 Amines

Chemical
Connections 10A
M O R P HI N E A S A C LU E I N T H E D E SIGN AND
D I S C OVERY OF D R U G S
The analgesic, soporific, and euphoriant properties of system. Large doses of morphine (or heroin) can
the dried juice obtained from unripe seed pods of the lead to death by respiratory failure. One strategy
opium poppy Papaver somniferum have been known in the ongoing research to produce painkillers has
for centuries. By the beginning of the nineteenth been to synthesize compounds related in structure
century, the active principal, morphine, had been to morphine, in the hope that they would be equally
isolated and its structure determined: effective analgesics, but with diminished side effects.
Following are structural formulas for two such com-
CH3
pounds that have proven to be clinically useful:
N
CH3
H N

O
HO OH

Morphine
CH3O
Also occurring in the opium poppy is codeine, a mo- (–)-enantiomer = Levomethorphan
nomethyl ether of morphine: (+)-enantiomer = Dextromethorphan
CH3
CH3
N
N CH3
H
N

redraw

O O OCH2CH3
CH3O OH
O O
Codeine
Meperidine
Heroin is synthesized by treating morphine with two (Demerol)
moles of acetic anhydride:
Levomethorphan is a potent analgesic. Interest-
CH3 ingly, its dextrorotatory enantiomer, dextromethorphan,
N has no analgesic activity. It does, however, show
approximately the same cough-suppressing activ-
ity as morphine and is used extensively in cough
H
remedies.
It has been discovered that there can be even
further simplification in the structure of morphine-
like analgesics. One such simplification is represented
CH3 O by meperidine, the hydrochloride salt of which is the
CH3
O O widely used analgesic Demerol®.
It was hoped that meperidine and related
O O synthetic drugs would be free of many of the
Heroin morphine-like undesirable side effects. It is now clear,
however, that they are not. Meperidine, for example,
Even though morphine is one of modern is definitely addictive. In spite of much determined
medicine’s most effective painkillers, it has two research, there are as yet no agents as effective
serious side effects: It is addictive, and it depresses as morphine for the relief of severe pain that are
the respiratory control center of the central nervous absolutely free of the risk of addiction.
 10 . 1 What Are Amines? 333

How and in what regions of the brain does structure consisting of a sequence of five amino acids
morphine act? In 1979, scientists discovered that there (Section 18.4). Scientists have yet to understand the
are specific receptor sites for morphine and other opi- role of these natural brain opiates. Perhaps when we
ates and that these sites are clustered in the brain’s do understand their biochemistry, we may discover
limbic system, the area involved in emotion and the clues that will lead to the design and synthesis of
perception of pain. Scientists then asked, “Why does more potent, but less addictive, analgesics.
the human brain have receptor sites specific for mor-
phine?” Could it be that the brain produces its own
opiates? In 1974, scientists discovered that opiate-like Question
compounds are indeed present in the brain; in 1975, Identify the functional groups in morphine and
they isolated a brain opiate that was named enkepha- meperidine. Classify the amino group in these opiates
lin, meaning “in the brain.” Unlike morphine and its according to type (that is, primary, secondary, tertiary,
derivatives, enkephalin possesses an entirely different heterocyclic, aliphatic, or aromatic).

10.1 What Are Amines?

Amines are derivatives of ammonia (NH3) in which one or more hydrogens are replaced by
alkyl or aryl groups. Amines are classified as primary (1°), secondary (2°), or tertiary (3°),
depending on the number of hydrogen atoms of ammonia that are replaced by alkyl or aryl
groups (Section 1.7B). As we saw with ammonia, the three atoms or groups bonded to the
nitrogen in amines assume a trigonal pyramidal geometry:

NH 3 CH 3 JNH
 2 CH 3 JNH
 CH 3 J N
 J CH 3
… …
CH3 CH3
Ammonia Methylamine Dimethylamine Trimethylamine
(a 1° amine) (a 2° amine) (a 3° amine)

Amines are further divided into aliphatic amines and aromatic amines. In an
aliphatic amine, all the carbons bonded directly to nitrogen are derived from alkyl Aliphatic amine An amine
groups; in an aromatic amine, one or more of the groups bonded directly to nitrogen are in which nitrogen is bonded
only to alkyl groups.
aryl groups:
Aromatic amine An amine
CH3 CH3 in which nitrogen is bonded
ƒ ƒ to one or more aryl groups.
NH2 N¬H CH2 ¬ N ¬ CH3

Aniline N -Methylaniline Benzyldimethylamine

(a 1° aromatic amine) (a 2° aromatic amine) (a 3° aliphatic amine)

An amine in which the nitrogen atom is part of a ring is classified as a heterocyclic Heterocyclic amine An
amine. When the nitrogen is part of an aromatic ring (Section 9.2), the amine is classified amine in which nitrogen is
one of the atoms of a ring.
as a heterocyclic aromatic amine. Following are structural formulas for two heterocyclic
aliphatic amines and two heterocyclic aromatic amines: Heterocyclic aromatic
amine An amine in which
nitrogen is one of the atoms
of an aromatic ring.

N N N N
H H H

Pyrrolidine Piperidine Pyrrole Pyridine

(heterocyclic aliphatic amines) (heterocyclic aromatic amines)
334 C H A P T E R 10 Amines

EXAMPLE 10.1
Alkaloids are basic nitrogen-containing compounds of plant origin, many of which have physiological activity when admin-
istered to humans. The ingestion of coniine, present in water hemlock, can cause weakness, labored respiration, paralysis,
and, eventually, death. Coniine was the toxic substance in “poison hemlock” that caused the death of Socrates. In small
doses, nicotine is an addictive stimulant. In larger doses, it causes depression, nausea, and vomiting. In still larger doses,
it is a deadly poison. Solutions of nicotine in water are used as insecticides. Cocaine is a central nervous system stimulant
obtained from the leaves of the coca plant. Classify each amino group in these alkaloids according to type (that is, primary,
secondary, tertiary, heterocyclic, aliphatic, or aromatic):

CH3
O CH3
N
O
H
H
(a) (b) (c)
N H
N
CH3 O
H N
H O
(S )-Coniine (S )-Nicotine
Cocaine

S T R AT E G Y
Locate each nitrogen in each compound. If a nitrogen is part of a ring, the amine is heterocyclic. If that ring is aromatic, it is
classified as a heterocyclic aromatic amine (1°, 2°, or 3° does not apply). If the ring is not aromatic, it is a heterocyclic aliphatic
amine that should also be classified as 1°, 2°, or 3°. Note: The presence of more than one nitrogen can result in multiple
classifications for the molecule, depending on the part of the compound being referred to.

SOLUTION
(a) A secondary (2°) heterocyclic aliphatic amine.
(b) One tertiary (3°) heterocyclic aliphatic amine and one heterocyclic aromatic amine.
(c) A tertiary (3°) heterocyclic aliphatic amine.

See problems 10.13–10.16

PROBLEM 10.1
Identify all carbon stereocenters in coniine, nicotine, and cocaine.

10.2 How Are Amines Named?

A. Systematic Names
Systematic names for aliphatic amines are derived just as they are for alcohols. The suf-
fix -e of the parent alkane is dropped and is replaced by -amine; that is, they are named
alkanamines:
NH2

NH2
H2N(CH2)6NH2

2-Butanamine (S )-1-Phenylethanamine 1,6-Hexanediamine

 10 . 2 How Are Amines Named? 335

EXAMPLE 10.2
Write the IUPAC name or provide the structural formula for each amine:
NH2
(a) NH2 (b) 2-Methyl-1-propanamine (c) H2N

(d) trans-4-Methylcyclohexanamine (e)

NH2

S T R AT E G Y
When naming, look for the longest chain of carbons that contains the amino group. This will allow you to determine the
root name. Then identify and name the substituents, the atoms or groups of atoms that are not part of that chain of carbons.
To translate a name to a structure, identify the carbon chain from the root name and add the substituents to the correct
position on the chain.

SOLUTION

(a) 1-Hexanamine (b) (c) 1,4-Butanediamine (d) NH2

NH2
(e) The systematic name of this compound is (S)-1-phenyl-2-propanamine. Its common name is amphetamine. The dextroro-
tatory isomer of amphetamine (shown here) is a central nervous system stimulant and is manufactured and sold under
several trade names. The salt with sulfuric acid is marketed as Dexedrine sulfate.
longest carbon chain that
contains the amino group the commercial drug that
results from reaction with H2SO4
1 3
substituent = phenyl
2

NH2 NH3+ HSO4-

(S)-1-Phenyl-2-propanamine Dexedrine sulfate

See problems 10.11, 10.12, 10.16

PROBLEM 10.2
Write a structural formula for each amine:

(a) 2-Methyl-1-propanamine (b) Cyclohexanamine (c) (R )-2-Butanamine

IUPAC nomenclature retains the common name aniline for C6H5NH2 , the simplest
aromatic amine. Its simple derivatives are named with the prefixes o-, m-, and p-, or numbers
to locate substituents. Several derivatives of aniline have common names that are still widely
used. Among these are toluidine, for a methyl-substituted aniline, and anisidine, for a
methoxy-substituted aniline:
NH2 NH2 NH2 NH2

OCH3

NO2 CH3

Aniline 4-Nitroaniline 4-Methylaniline 3-Methoxyaniline

(p -Nitroaniline) (p -Toluidine) (m -Anisidine)
336 C H A P T E R 10 Amines

Secondary and tertiary amines are commonly named as N-substituted primary amines.
For unsymmetrical amines, the largest group is taken as the parent amine; then the smaller
group or groups bonded to nitrogen are named, and their location is indicated by the
prefix N (indicating that they are bonded to nitrogen):

CH3
NHCH3 N
CH3
N -Methylaniline N,N -Dimethyl-
cyclopentanamine

Following are names and structural formulas for four heterocyclic aromatic amines, the
common names of which have been retained by the IUPAC:

N
N

N N N
N N
H H
Indole Purine Quinoline Isoquinoline

Among the various functional groups discussed in this text, the J NH 2 group has
one of the lowest priorities. The following compounds each contain a functional group of
higher precedence than the amino group, and, accordingly, the amino group is indicated
by the prefix amino -:
COOH
OH
H2N
NH2

2-Aminoethanol 2-Aminobenzoic acid

(Ethanolamine) (Anthranilic acid)

B. Common Names
Common names for most aliphatic amines are derived by listing the alkyl groups bonded
to nitrogen in alphabetical order in one word ending in the suffix -amine ; that is, they are
named as alkylamines:
H
CH3NH2 NH2 N
N

Methylamine tert -Butylamine Dicyclopentylamine Triethylamine

EXAMPLE 10.3
Write the IUPAC name or provide the structural formula for each amine:

N
(a) H (b) Cyclohexylmethylamine (c) (d) Benzylamine
N
 10 . 3 What Are the Characteristic Physical Properties of Amines? 337

S T R AT E G Y
When naming, look for the longest chain of carbons that contains the amino group. This will allow you to determine the root
name. If the longest chain of carbons is a benzene ring, the amine may be named as an aniline derivative. When identifying
the substituents, remember that substitutents bonded to a nitrogen are preceded by “N-.”
To translate a name to a structure, identify the carbon chain from the root name and add the substituents to the correct
position on the molecule.

SOLUTION
H
N NH2
(a) N-ethyl-2-methyl-1-propanamine (b) (c) N-ethyl-N-methylaniline (d)

See problems 10.11, 10.12, 10.16

PROBLEM 10.3
Write a structural formula for each amine:

(a) Isobutylamine (b) Triphenylamine (c) Diisopropylamine

When four atoms or groups of atoms are bonded to a nitrogen atom, we name the
compound as a salt of the corresponding amine. We replace the ending -amine (or ani-
line, pyridine, or the like) by -ammonium (or anilinium, pyridinium, or the like) and add
the name of the anion (chloride, acetate, and so on). Compounds containing such ions
have properties characteristic of salts, such as increased water solubility, high melting
points, and high boiling points. Following are three examples (cetylpyridinium chloride is
used as a topical antiseptic and disinfectant):
Cl- OH - Charles D. Winters
± ±
(CH3)4 N± Cl- NCH2(CH2)14CH3 CH2N(CH3)3

Tetramethylammonium Hexadecylpyridinium chloride Benzyltrimethylammonium

chloride (Cetylpyridinium chloride) hydroxide Several over-the-counter
mouthwashes contain
N-alkylatedpyridinium
chlorides as an antibacterial
10.3 What Are the Characteristic Physical agent.
Properties of Amines?
Amines are polar compounds, and both primary and secondary amines form intermolecu-
lar hydrogen bonds (Figure 10.1).

hydrogen bonding

+
...
..

H R

–
+
– R
N ........... H N
R
...
..

R
FIGURE 10.1
Intermolecular association of 1˚ and 2˚ amines by hydrogen bonding. Nitrogen is approximately
tetrahedral in shape, with the axis of the hydrogen bond along the fourth position of the
tetrahedron.
338 C H A P T E R 10 Amines

Chemical
Ch i l
Co ect o s
Connections 10B
THE POISON DART FROGS OF SOUTH AMERICA: LETHAL AMINES
The Noanamá and Embrá peoples of the jungles of
western Colombia have used poison blow darts for cen-
turies, perhaps millennia.The poisons are obtained from

© Alfredo Maiquez/iStockphoto
the skin secretions of several highly colored frogs of the
genus Phyllobates (neará and kokoi in the language of
the native peoples). A single frog contains enough poi-
son for up to 20 darts. For the most poisonous species
(Phyllobates terribilis), just rubbing a dart over the frog’s
back suffices to charge the dart with poison.
Scientists at the National Institutes of Health be-
came interested in studying these poisons when it was
discovered that they act on cellular ion channels, which
would make them useful tools in basic research on mech-
anisms of ion transport. A field station was established in Poison dart frog, Phyllobates terribilis.
western Colombia to collect the relatively common poi- The batrachotoxin story illustrates several
son dart frogs. From 5,000 frogs, 11 mg of batrachotoxin common themes in the discovery of new drugs. First,
and batrachotoxinin A were isolated. These names are information about the kinds of biologically active
derived from batrachos, the Greek word for frog. compounds and their sources are often obtained
Batrachotoxin and batrachotoxinin A are among from the native peoples of a region. Second, tropical
the most lethal poisons ever discovered: rain forests are a rich source of structurally com-
plex, biologically active substances. Third, an entire
ecosystem, not only the plants, is a potential source
of fascinating organic molecules.
CH3
H O O CH3
CH3
CH2 C H
HO OH
CH2
CH3 HO
N
CH3 CH3
O O NCH3 H

HO O O NCH3
H
HO
Batrachotoxin H
Batrachotoxinin A

It is estimated that as little as 200 mg of batrachotoxin Questions

is sufficient to induce irreversible cardiac arrest in a Would you expect batrachotoxin or batrachotoxinin A
human being. It has been determined that they act to be more soluble in water? Why?
by causing voltage-gated Na channels in nerve and Predict the product formed from the reaction of
muscle cells to be blocked in the open position, which batrachotoxin with one equivalent of a weak acid such
leads to a huge influx of Na ions into the affected cell. as acetic acid, CH3COOH.

An N J H  N hydrogen bond is weaker than an O J H  O hydrogen

bond, because the difference in electronegativity between nitrogen and hydrogen
(3.0  2.1  0.9 ) is less than that between oxygen and hydrogen (3.5  2.1  1.4 ). We
can illustrate the effect of intermolecular hydrogen bonding by comparing the boiling
points of methylamine and methanol:

CH3NH2 CH3OH
molecular weight (gmol) 31.1 32.0
boiling point (C)  6.3 65.0
 10 . 3 What Are the Characteristic Physical Properties of Amines? 339

T A B L E 1 0 . 1 Physical Properties of Selected Amines

Melting Boiling
Structural Point Point Solubility
Name Formula (°C) (°C) in Water

Ammonia NH3 78 33 very soluble

Primary Amines
methylamine CH3NH2 95 6 very soluble
ethylamine CH3CH2NH2 81 17 very soluble
propylamine CH3CH2CH2NH2 83 48 very soluble
butylamine CH3(CH2)3NH2 49 78 very soluble
benzylamine C6H5CH2NH2 10 185 very soluble
cyclohexylamine C6H11NH2 17 135 slightly soluble
Secondary Amines
dimethylamine (CH3)2NH 93 7 very soluble
diethylamine (CH3CH2)2NH 48 56 very soluble
Tertiary Amines
trimethylamine (CH3)3N 117 3 very soluble
triethylamine (CH3CH2)3N 114 89 slightly soluble
Aromatic Amines
aniline C6H5NH2 6 184 slightly soluble
Heterocyclic Aromatic Amines
pyridine C5H5N 42 116 very soluble

Both compounds have polar molecules and interact in the pure liquid by hydrogen
bonding. Methanol has the higher boiling point because hydrogen bonding between its
molecules is stronger than that between molecules of methylamine.
All classes of amines form hydrogen bonds with water and are more soluble in water
than are hydrocarbons of comparable molecular weight. Most low-molecular-weight amines
are completely soluble in water (Table 10.1). Higher-molecular-weight amines are only
moderately soluble or insoluble.

EXAMPLE 10.4
Account for the fact that butylamine has a higher boiling point than t-butylamine.

NH2 NH2

Butylamine t-Butylamine
bp 78
C bp 46
C

S T R AT E G Y
Identify structural differences that might affect the intermolecular attractions between the molecules of each compound.

SOLUTION
Both molecules can participate in hydrogen bonding. However, the t-butyl group is larger and bulkier, making it more difficult
for the molecules of t-butylamine to hydrogen bond to each other.

See problems 10.18–10.20