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Electrophilic Aromatic Substitution Reactions of Substituted Benzenes, Lecture notes of Organic Chemistry

Directing Effects of Substituents, Meta-Directing Groups and The Ortho, Para Directing Groups.

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762 CHAPTER 16 THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES
16.19 Show two different Friedel–Crafts acylation reactions that can be used to prepare the follow-
ing compound.
16.20 The following compound reacts with AlCl3followed by water to give a ketone Awith the for-
mula C10H10O. Give the structure of Aand a curved-arrow mechanism for its formation.
16.5 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS
OF SUBSTITUTED BENZENES
A. Directing Effects of Substituents
When a monosubstituted benzene undergoes an electrophilic aromatic substitution reaction,
three possible disubstitution products might be obtained. For example, nitration of bromoben-
zene could in principle give ortho-,meta-,or para-bromonitrobenzene. If substitution were
totally random, an ortho:meta:para product ratio of 2 : 2: 1 would be expected. (Why?) It is
found experimentally that this substitution is not random, but is regioselective.
Other electrophilic substitution reactions of bromobenzene also give mostly ortho and para
isomers. If a substituted benzene undergoes further substitution mostly at the ortho and para
positions, the original substituent is called an ortho, para-directing group. Thus, bromine is
an ortho, para-directing group, because all electrophilic substitution reactions of bromoben-
zene occur at the ortho and para positions.
In contrast, some substituted benzenes react in electrophilic aromatic substitution to give
mostly the meta disubstitution product. For example, the bromination of nitrobenzene gives only
the meta isomer.
Other electrophilic substitution reactions of nitrobenzene also give mostly the meta isomers.
If a substituted benzene undergoes further substitution mainly at the meta position, the origi-
(16.28)
NO2 NO2
M
i
"iBr
"
nitrobenzene m-bromonitrobenzene
(only product observed)
Br2
FeBr3
heat
(16.27)
i
Br
NO2
NO2
M
NO2
M
"i
Br
"
i
Br
"i
Br
"
"
o-bromonitrobenzene
(36%)
p-bromonitrobenzene
(62%)
m-bromonitrobenzene
(2%)
HNO3
acetic acid ++
bromobenzene
C
O
Cl
LLL S
L
H3C CH2CH2
LLL
S
O
C
CH3
CH3
CH3
cc
)
)
16_BRCLoudon_pgs4-3.qxd 11/26/08 9:07 AM Page 762
pf3
pf4
pf5
pf8
pf9
pfa
pfd
pfe
pff

Partial preview of the text

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762 CHAPTER 16 • THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES

16.19 Show two different Friedel–Crafts acylation reactions that can be used to prepare the follow-

ing compound.

16.20 The following compound reacts with AlCl

3

followed by water to give a ketone A with the for-

mula C

10

H

10

O. Give the structure of A and a curved-arrow mechanism for its formation.

ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS

OF SUBSTITUTED BENZENES

A. Directing Effects of Substituents

When a monosubstituted benzene undergoes an electrophilic aromatic substitution reaction,

three possible disubstitution products might be obtained. For example, nitration of bromoben-

zene could in principle give ortho - , meta - , or para -bromonitrobenzene. If substitution were

totally random, an ortho:meta:para product ratio of 2 : 2 :1 would be expected. (Why?) It is

found experimentally that this substitution is not random, but is regioselective.

Other electrophilic substitution reactions of bromobenzene also give mostly ortho and para

isomers. If a substituted benzene undergoes further substitution mostly at the ortho and para

positions, the original substituent is called an ortho, para-directing group. Thus, bromine is

an ortho, para-directing group, because all electrophilic substitution reactions of bromoben-

zene occur at the ortho and para positions.

In contrast, some substituted benzenes react in electrophilic aromatic substitution to give

mostly the meta disubstitution product. For example, the bromination of nitrobenzene gives only

the meta isomer.

Other electrophilic substitution reactions of nitrobenzene also give mostly the meta isomers.

If a substituted benzene undergoes further substitution mainly at the meta position, the origi-

(16.28)

NO

2

NO

2

M

i

i

Br

nitrobenzene m -bromonitrobenzene

(only product observed)

Br 2

FeBr 3

heat

(16.27) i

Br

NO

2

NO

2

M

NO

2

M

i

Br

i

Br

i

Br

o -bromonitrobenzene

(36%)

p -bromonitrobenzene

(62%)

m -bromonitrobenzene

(2%)

HNO 3

acetic acid

bromobenzene

C

O

L L L Cl

S

H L

3

C CH

2

CH

2

L L L

S

O

C

CH

3

CH

3

CH

3

c c

)

)

16.5 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF SUBSTITUTED BENZENES 763

nal substituent group is called a meta-directing group. Thus, the nitro group is a meta-

directing group because all electrophilic substitution reactions of nitrobenzene occur at the

meta position.

A substituent group is either an ortho, para-directing group or a meta-directing group in

all electrophilic aromatic substitution reactions; that is, no substituent is ortho, para directing

in one reaction and meta directing in another. A summary of the directing effects of common

substituent groups is given in the third column of Table 16.2.

16.21 Using the information in Table 16.2, predict the product(s) of

(a) Friedel–Crafts acylation of anisole (methoxybenzene) with acetyl chloride (structure in

Eq. 16.23) in the presence of one equivalent of AlCl

3

followed by H

2

O.

(b) Friedel–Crafts alkylation of a large excess of ethylbenzene with chloromethane in the

presence of AlCl

3

.

PROBLEM

Summary of Directing and Activating or

Deactivating Effects of Some Common Functional Groups

(Groups are listed in decreasing order of activation.)

Activating or

Substituent group Name of group Directing effect deactivating

amino

hydroxy

alkoxy

acylamino

LR alkyl

acyloxy

phenyl

,

halogens

acyl

LSO

3

H sulfonic acid

LCN cyano

LNO

2

nitro

C

$

R

O

L

carboxy, carboxamido,

carboalkoxy

C ,

$

OH

O

L C ,

$

NH

2

O

L C

$

OR

O

L

F 3

1

1

L I 3

1

1

L Br 3

1

1

L Cl 3

1

1

L

, , ,

L

O C

$

R

O

L 2 L

2

NH C

$

R

O

L L 2

OR

L 2

2

L OH 2

2

NH

2

L , 2

NR

2

L 2

TABLE 16.

meta

directors

deactivating

substituents

ortho, para

directors

activating

substituents

16.5 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF SUBSTITUTED BENZENES 765

bons of the ring. When meta substitution occurs, the positive charge is not shared by the carbon

adjacent to the oxygen.

We now use the resonance structures in Eqs. 16.29 and 16.30 (as well as those you drew in

Problem 16.22) to assess relative rates. The logic to be used follows the general outline given

in Study Problem 15.3, page 715. A comparison of Eq. 16.29 and the structures you drew for

Problem 16.22 with Eq. 16.30 shows that the reaction of an electrophile at either the ortho or

para positions of anisole gives a carbocation with more resonance structures—that is, a more

stable carbocation. The rate-limiting step in many electrophilic aromatic substitution reactions

is formation of the carbocation intermediate. Hammond’s postulate (Sec. 4.8D) suggests that

the more stable carbocation should be formed more rapidly. Hence, the products derived from

the more rapidly formed carbocation—the more stable carbocation—are the ones observed.

Because the reaction of the electrophile at an ortho or para position of anisole gives a more sta-

ble carbocation than the reaction at a meta position, the products of ortho, para substitution are

formed more rapidly, and are thus the products observed (see Fig. 16.5). This is why the

LOCH

3

group is an ortho, para-directing group.

To summarize: Substituents containing atoms with unshared electron pairs adjacent to the

benzene ring are ortho, para directors in electrophilic aromatic substitution reactions because

their electron pairs can be involved in the resonance stabilization of the carbocation inter-

mediates.

Now imagine the reaction of an electrophile E

|

with an alkyl-substituted benzene such as

toluene. Alkyl groups such as a methyl group have no unshared electrons, but the explanation

reaction coordinates

CH

3

O 21

r

M

CH

3

O

+ E

|

D G 8

(para

substitution)

(a)

`

more stable

carbocation

intermediate

CH

3

O 21

`

!!

r

M

CH

3

O

+ E

|

D G 8

(meta

substitution)

(b)

M

CH

3

O 21

`

less stable

carbocation

intermediate

M

CH

3

O 21

`

H E

H E

!!

H

E

H

E

STANDARD FREE ENERGY

d +

d +

d +

d +

d +

faster reaction slower reaction

Figure 16.5 Basis of the directing effect of the methoxy group in the electrophilic aromatic substitution

reactions of anisole. Substitution of anisole by an electrophile E

|

occurs more rapidly at (a) the para position than

at (b) the meta position because a more stable carbocation intermediate is involved in para substitution. The

dashed lines within the structures symbolize the delocalization of electrons.

766 CHAPTER 16 • THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES

for the directing effects of these groups is similar. Reaction of E

|

at a position that is ortho or

para to an alkyl group gives an ion that has one tertiary carbocation resonance structure (col-

ored structure in the following equation).

Reaction of the electrophile meta to the alkyl group also gives an ion with three resonance

structures, but all resonance forms are secondary carbocations.

Because reaction at the ortho or para position gives the more stable carbocation, alkyl groups

are ortho, para-directing groups.

Meta-Directing Groups The meta-directing groups in Table 16.2 are all polar groups

that do not have an unshared electron pair on an atom adjacent to the benzene ring. The di-

recting effect of these groups can be understood by considering as an example the reactions

of a general electrophile E

|

with nitrobenzene at the meta and para positions.

(16.34)

|

|

|

N

M

!!

para

H

E

i

M M

3 O 3

S

|

N

M M

3 O 3

S

|

|

N

M M

3 O 3

S

p q

H

E

M

M

H

E

M

M

H

E

M

M

|

|

N

M M

3 O 3

S

o

positive charges on

adjacent atoms

_

21 O

_

O

_

O

_

O

(16.33)

|

|

|

N

M

!!

meta

H

E

i

|

H

E

M

M

H

E

M

M

H

E

M M

M M

3 O 3

S

|

N

M M

3 O 3

S

|

N

M M

3 O 3

S

p q

| |

N

M M

3 O 3

S

d

_

O 21

_

O 21

_

O

_

O

(16.32)

|

|

CH

3

M

CH

3

M

CH

3

CH

3

M

!!

meta

H

H E

E

i s

|

|

M

H E

s

H E

e

(16.31)

|

|

CH

3

H

M

M

CH

3

M

!!

para

E

i s

|

CH

3

M

t

|

CH

3

M

p

tertiary carbocation

H

E

H

E

H

E

768 CHAPTER 16 • THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES

found that the para substitution product is the major one in the reaction mixture. In some cases

this result can be explained by the spatial demands of the electrophile. For example,

Friedel–Crafts acylation of toluene gives essentially all para substitution product and almost

no ortho product. The electrophile cannot react at the ortho position without developing van

der Waals repulsions with the methyl group that is already on the ring. Consequently, reaction

occurs at the para position, where such repulsions cannot occur.

Typically, para substitution predominates over ortho substitution, but not always. For ex-

ample, nitration of toluene gives twice as much o -nitrotoluene as p -nitrotoluene. This result

occurs because the nitration of toluene at either the ortho or para position is so fast that it oc-

curs on every encounter of the reagents; that is, the energy barrier for the reaction is insignif-

icant. Hence, the product distribution corresponds simply to the relative probability of the re-

actions. Because the ratio of ortho and para positions is 2 :1, the product distribution is 2 :1.

In fact, the ready availability of o- nitrotoluene makes it is a good starting material for certain

other ortho-substituted benzene derivatives.

In summary, the reasons for the ortho, para ratio vary from case to case, and in some cases

these reasons are not well understood.

Whatever the reasons for the ortho, para ratio, if an electrophilic aromatic substitution re-

action yields a mixture of ortho and para isomers, a problem of isomer separation arises that

must be solved if the reaction is to be useful. Usually, syntheses that give mixtures of isomers

are avoided because, in many cases, isomers are difficult to separate. However, the ortho and

para isomers obtained in many electrophilic aromatic substitution reactions have sufficiently

different physical properties that they are readily separated (Sec. 16.2). For example, the boil-

ing points of o - and p -nitrotoluene, 220°C and 238°C, respectively, are sufficiently different

that these isomers can be separated by careful fractional distillation. Thus, either isomer can

be obtained relatively pure from the nitration of toluene. The melting points of o - and p -

chloronitrobenzene, 34°C and 84°C, respectively, are so different that the para isomer can be

selectively crystallized. As you learned in Sec. 16.2, the para isomer of an ortho , para pair typ-

ically has the higher melting point, often considerably higher. Most aromatic substitution re-

actions are so simple and inexpensive to run that when the separation of isomeric products is

not difficult, these reactions are useful for organic synthesis despite the product mixtures ob-

tained. Thus, you may assume in working problems involving electrophilic aromatic substitu-

tion on compounds containing ortho, para-directing groups that the para isomer can be iso-

lated in useful amounts. For the reasons pointed out in the previous paragraph, o- nitrotoluene

is a relatively rare example of a readily obtained ortho - substituted benzene derivative.

B. Activating and Deactivating Effects of Substituents

Different benzene derivatives have greatly different reactivities in electrophilic aromatic sub-

stitution reactions. If a substituted benzene derivative reacts more rapidly than benzene itself,

then the substituent group is said to be an activating group. The Friedel–Crafts acylation of

anisole (methoxybenzene), for example, is 300,000 times faster than the same reaction of ben-

zene under comparable conditions. Furthermore, anisole shows a similar enhanced reactivity

relative to benzene in all other electrophilic substitution reactions. Thus, the methoxy group is

an activating group.

On the other hand, if a substituted benzene derivative reacts more slowly than benzene it-

self, then the substituent is called a deactivating group. For example, the rate for the bromi-

nation of nitrobenzene is less than 10

_ 5

times the rate for the bromination of benzene; further-

more, nitrobenzene reacts much more slowly than benzene in all other electrophilic aromatic

substitution reactions. Thus, the nitro group is a deactivating group.

A given substituent group is either activating in all electrophilic aromatic substitution re-

actions or deactivating in all such reactions. Whether a substituent is activating or deactivat-

16.5 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF SUBSTITUTED BENZENES 769

ing is shown in the last column of Table 16.2, p. 763. In this table the most activating sub-

stituent groups are near the top of the table. Three generalizations emerge from examining this

table.

  1. All meta-directing groups are deactivating groups.
  2. All ortho, para-directing groups except for the halogens are activating groups.
  3. The halogens are deactivating groups.

Thus, except for the halogens, there appears to be a correlation between the activating and di-

recting effects of substituents.

In view of this correlation, it is not surprising that the explanation of activating and deacti-

vating effects is closely related to the explanation for directing effects. A key to understand-

ing these effects is the realization that directing effects are concerned with the relative rates of

substitution at different positions of the same compound, whereas activating or deactivating

effects are concerned with the relative rates of substitution of different compounds—a substi-

tuted benzene compared with benzene itself. As in the discussion of directing effects, we con-

sider the effect of the substituent on the stability of the intermediate carbocation, and we then

apply Hammond’s postulate by assuming that the stability of this carbocation is related to the

stability of the transition state for its formation.

Two properties of substituents must be considered to understand activating and deactivat-

ing effects. First is the resonance effect of the substituent. The resonance effect of a sub-

stituent group is the ability of the substituent to stabilize the carbocation intermediate in elec-

trophilic substitution by delocalization of electrons from the substituent into the ring. The

resonance effect is the same effect responsible for the ortho, para-directing effects of sub-

stituents with unshared electron pairs, such as LOCH 3

and halogen (colored structure in Eq.

16.29, p. 764). We can summarize this effect with the following two of the four resonance

structures for the carbocation intermediate in Eq. 16.29.

The second property is the polar effect of the substituent. The polar effect is the tendency

of the substituent group, by virtue of its electronegativity, to pull electrons away from the ring.

This is the same effect discussed in connection with substituent effects on acidity (Sec. 3.6C).

When a ring substituent is electronegative, it pulls the electrons of the ring toward itself and

creates an electron deficiency, or positive charge, in the ring. In the carbocation intermediate

of an electrophilic substitution reaction, the positive end of the bond dipole interacts repul-

sively with the positive charge in the ring, thus raising the energy of the ion:

|

OCH

3

E H

s

repulsive interaction

the polar effect of the

methoxy group destabilizes

the carbocation

d

d +

the resonance effect of the

methoxy group stabilizes

the carbocation

(two of the four important

resonance structures)

|

OCH

3

E H

e

S

|

OCH

3

s

E H

16.5 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF SUBSTITUTED BENZENES 771

reaction coordinates

r

D G 8

benzene

(a)

`

"

L

H

E

r

  • E

|

  • E

|

  • E

|

(b)

faster reaction

than benzene

slower reaction

than benzene

"

L

H

E

r

M

CH 3

O 21

M

CH 3

O 21

(c)

M

CH 3

O 21

`

less stable

carbocation

intermediate

more stable

carbocation

intermediate

carbocation

intermediate

H E

$)

CH

3

O 21

`

M

D G 8

anisole

(para)

D G 8

anisole

(meta)

STANDARD FREE ENERGY

Figure 16.6 Basis of the activating effect of the methoxy group on electrophilic aromatic substitution in

anisole. (a) The energy barrier for substitution of benzene by an electrophile E

|

. (b) The energy barrier for substi-

tution of anisole by E

|

at the para position. (c) The energy barrier for substitution of anisole by E

|

at the meta po-

sition. (Notice that the diagrams for parts (b) and (c) are the same as parts (a) and (b) of Fig. 16.5, p. 765.) The sub-

stitution of anisole at the para position is faster than the substitution of benzene; the substitution of anisole at

the meta position is slower than the substitution of benzene.The methoxy group is an activating group because

the observed reaction of anisole—substitution at the para position—is faster than the substitution of benzene.

Cl C O C

CH

3

overlap of carbon 2 p

and chlorine 3 p orbitals

(b)

overlap of carbon and oxygen 2 p orbitals

(a)

Figure 16.7 The overlap of carbon and oxygen 2 p orbitals, which is shown in part (a), is more effective than the

overlap of carbon 2 p and chlorine 3 p orbitals, shown in part (b), because orbitals with different quantum numbers

have different sizes and different numbers of nodes.The blue and green parts of the orbitals represent wave peaks

and wave troughs, respectively. Bonding overlap occurs only when peaks overlap with peaks and troughs overlap

with troughs.

772 CHAPTER 16 • THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES

that alkyl groups activate substitution at all ring positions, but they are ortho, para directors be-

cause they activate ortho, para substitution more than they activate meta substitution (Eqs.

16.31 and 16.32, p. 766).

Finally, consider the deactivating effects of meta-directing groups such as the nitro group.

Because a nitro group has no electron-donating resonance effect, the polar effect of this elec-

tronegative group destabilizes the carbocation intermediate and retards electrophilic substitu-

tion at all positions of the ring. The nitro group is a meta-directing group because substitution

is retarded more at the ortho and para positions than at the meta positions (Eqs. 16.33 and

16.34, p. 766). In other words, the meta-directing effect of the nitro group is not due to selec-

tive activation of the meta positions, but rather to greater deactivation of the ortho and para po-

sitions. For this reason, the nitro group and the other meta-directing groups might be called

meta-allowing groups.

PROBLEMS

16.25 Draw reaction-free energy profiles analogous to that in Fig. 16.6 in which substitution on

benzene by a general electrophile E

|

is compared with substitution at the para and meta po-

sitions of (a) chlorobenzene; (b) nitrobenzene.

16.26 Explain why the nitration of anisole is much faster than the nitration of thioanisole under the

same conditions.

16.27 Which should be faster: bromination of benzene or bromination of N , N -dimethylaniline?

Explain your answer carefully.

C. Use of Electrophilic Aromatic Substitution in Organic Synthesis

Both activating/deactivating and directing effects of substituents can come into play in plan-

ning an organic synthesis that involves electrophilic substitution reactions. The importance of

directing effects is illustrated in Study Problem 16.2.

Study Problem 16.

Outline a synthesis of p -bromonitrobenzene from benzene.

Solution The key to this problem is whether the bromine or the nitro group should be the first

ring substituent introduced. Introduction of the bromine first takes advantage of its directing effect

in the subsequent nitration reaction:

(16.35)

Br 2

c

Br

L

bromobenzene

NO 2

c

Br

L L

p -bromonitrobenzene

HNO 3

H 2

SO 4

c Fe

benzene

c

N(CH

3

)

2

L 2

N , N -dimethylaniline

c

SCH 3

L 2

2

thioanisole

c

OCH 3

L 2

2

anisole

774 CHAPTER 16 • THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES

After the first bromination, the LOH and LBr groups direct subsequent brominations to dif-

ferent positions. The strong activating and directing effect of the LOH group at the ortho and

para positions overrides the weaker directing effect of the LBr group.

In other cases, mixtures of isomers are typically obtained.

You’ve just learned that the activating and directing effects of substituents must be taken

into account in developing the strategy for an organic synthesis that involves a substitution re-

action on an already-substituted benzene ring. The activating or deactivating effects of sub-

stituents in an aromatic compound also determine the conditions that must be used in an elec-

trophilic substitution reaction. The bromination of nitrobenzene, for example (Eq. 16.28,

p. 762), requires relatively harsh conditions of heat and a Lewis acid catalyst because the nitro

group deactivates the ring toward electrophilic substitution. The conditions in Eq. 16.28 are

more severe than the conditions required for the bromination of benzene itself, because ben-

zene is the more reactive compound. An even more dramatic example in the other direction is

provided by the bromination of mesitylene (1,3,5-trimethylbenzene), Mesitylene can be

brominated under very mild conditions, because the ring is activated by three methyl groups;

a Lewis acid catalyst is not even necessary.

(16.41)

  • Br

2

CH

3

CH

3

H

3

C

i

M M

mesitylene

  • HBr

CH

3

CH

3

H

3

C

i

M M

Br

(80% yield)

0–10 °C

CCl 4

16.28 Predict the predominant product(s) from:

(a) monosulfonation of m -bromotoluene (b) mononitration of m -bromoiodobenzene

PROBLEM

(16.40)

4-chloro-3-nitrotoluene

(42%)

NO

2

CH

3

Cl

i

M

4-chloro-2-nitrotoluene

(58%)

NO

2

CH

3

Cl

i

M

HONO 2

4-chlorotoluene

Cl

CH

3

Cl directs ortho

CH

3

directs ortho

i

3 Br (16.39)

2

OH

i

phenol

    • 3 HBr

OH

i

M M

Br

Br

Br

2,4,6-tribromophenol

quantitative;

virtually instantaneous

H

2

O

STUDY GUIDE LINK 16.

Reaction Conditions

and Reaction Rate

16.5 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF SUBSTITUTED BENZENES 775

A similar contrast is apparent in the conditions required to sulfonate benzene and toluene. Sul-

fonation of benzene requires fuming sulfuric acid (Eq. 16.12, p. 755). However, because

toluene is more reactive than benzene, toluene can be sulfonated with concentrated sulfuric

acid, a milder reagent than fuming sulfuric acid.

Another very important consequence of activating and deactivating effects is that when a

deactivating group—for example, a nitro group—is being introduced by an electrophilic sub-

stitution reaction, it is easy to introduce one group at a time, because the products are less re-

active than the reactants. Thus, toluene can be nitrated only once because the nitro group that

is introduced retards a second nitration on the same ring. The following three equations show

the conditions required for successive nitrations. Notice that each additional nitration requires

harsher conditions.

Fuming nitric acid (Eq. 16.43c) is an especially concentrated form of nitric acid. Ordinary nitric acid

contains 68% by weight of nitric acid; fuming nitric acid is 95% by weight nitric acid. It owes its

name to the layer of colored fumes usually present in the bottle of the commercial product. Fuming

nitric acid is a much harsher (that is, more reactive) nitrating reagent than nitric acid itself.

In contrast, when an activating group is introduced by electrophilic substitution, the prod-

ucts are more reactive than the reactants; consequently, additional substitutions can occur eas-

ily under the conditions of the first substitution and, as a result, mixtures of products are ob-

tained. This is the situation in Friedel–Crafts alkylation. As noted in the discussion of Eq.

16.19 (p. 758), one way to avoid multiple substitution in such cases is to use a large excess of

O Lv L (16.43c)

2

N

NO

2

NO

2

CH

3

2,4,6-trinitrotoluene

“TNT”

(90% yield)

O L v L

2

N CH

3

NO

2

2,4-dinitrotoluene

50 g

170 g fuming HNO

3

H

2

SO

4

(680 g)

120 °C, 5 h

(16.43b)

O Lv L

2

N

NO

2

CH

3

2,4-dinitrotoluene

(90% yield)

O L v L

2

N CH

3

4-nitrotoluene

50 g

HNO 3

(30 g)

H 2

SO 4

(200 g)

70 °C, 30 min

(16.43a)

c

CH

3

L

toluene

50 g

ortho isomer

c

CH

3

L L

O

2

N

4-nitrotoluene

HNO 3

(30 g)

H

2

SO

4

(30 g)

50 °C, 1 h

(16.42) H

2

SO

4

c H

3

C

L

+ SO

3

H

cL H

3

C

L

H

2

+ O

toluene

p -toluenesulfonic acid