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540 CHAPTER TWELVE Reactions of Arenes: Electrophilic Aromatic Substitution

LEARNING BY MODELING
All of the following problems illustrate the use of molecular orbital calculations as an aid to under-
standing reactions. Instead of using resonance, substituent effects on rate and regioselectivity can be
explained on the basis of calculated energy differences between key species, all of which are included
in the Database. Energies are accessed by selecting Properties on the Display menu. These energies
compare a bonded species to the separated nuclei and electrons, and all are negative numbers. They
are cited in atomic units (au); 1 au  2627.2 kJ/mol  627.47 kcal/mol. The more negative the num-
ber, the more stable the species.
Spartan 12.1 This exercise concerns the low reactivity of benzene compared with alkenes toward attack
by electrophiles by comparing benzene with a noncyclic triene. The energy change for the following
hypothetical reaction is a measure of the relative tendency of a proton to bond to benzene versus a non-
cyclic triene.

H H
H H H H H
H H H 
H H
 C C  C C
H H H2C CH CH CH2 H H H2C CH CH CH2
H H
Benzene Vinyl(3-butenyl) cation Benzenium ion (Z )-1,3,5-hexatriene
(A noncyclic hexadienyl cation) Cyclohexadienyl cation

(a) Calculate the energy change for this reaction. Is the reaction exothermic or endothermic? Is
the calculated result consistent with the experimentally observed low reactivity of benzene?
(b) The hypothetical reaction is related to the first step in electrophilic aromatic substitution in
that benzene is converted to cyclohexadienyl cation. It is also an acidbase reaction. On
the basis of the calculations, which is a stronger base: benzene or (Z)-1,3,5-hexatriene?
What does this tell you about how strongly the  electrons are bound in each?

The next few exercises (Spartan 12.212.5) show how the effects of substituents can be derived
directly from calculations. As in Spartan 12.1, calculations are simplified by using protonation of the
ring to represent the rate-determining step in electrophilic aromatic substitution. In the case of regio-
selectivity we compare the stabilities (relative energies) of the cyclohexadienyl cations corresponding
to protonation at positions ortho, meta, and para to a substituent. For the effect of a substituent on rate,
we compare the energy change between benzene and its cyclohexadienyl cation to that of the substi-
tuted benzene and its cyclohexadienyl cation.

Spartan 12.2 Compare the energies of the cyclohexadienyl cations formed on protonation of toluene by
Retrieving the models in the Database.

CH3 CH3 CH3

H
H  H H H  H
H 
H
H H H H H
H
H H H H
ortho meta para

(a) Which cation is the most stable? Which is the least stable? Does the order of stability
support the interpretation that the ortho, para-directing properties of the methyl group are
governed by the stability of the cyclohexadienyl cation intermediate?
(b) Using the energy of toluene from the Database, calculate the energy difference between
toluene and each of the intermediates. How do these values compare with the values for
benzene and its protonated form in Spartan 12.1? Do they coincide with the experimental
fact that a methyl group activates all of the ring carbons toward electrophilic aromatic
substitution?
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Learning By Modeling 541

Spartan 12.3 Repeat the preceding exercise for fluorobenzene. What do the calculations tell us about
the effect of fluorine on the rate and regioselectivity of electrophilic aromatic substitution?
Spartan 12.4 Repeat the exercise for (trifluoromethyl)benzene.

Spartan 12.5 It is not always possible to tell by inspection if a particular substituent is activating or
deactivating, ortho, para-directing or meta-directing. Use the calculated values in the Database to ascer-
tain these properties for a methylsulfinyl group. Notice that the sulfur atom attached to the ring is
unusual in that it has both a positive charge and an unshared pair.

O

S CH3

Methyl phenyl sulfoxide

Spartan 12.6 Dimethylphenylsulfonium ion is isoelectronic with methyl phenyl sulfoxide.

CH3

S CH3

Dimethylphenylsulfonium ion

Using the models in the Database, compare the electrostatic potential maps of methyl phenyl sulfox-
ide and dimethylphenylsulfonium ion. Be sure to adjust the Property Range on the Properties menu
so that it is the same for both. A range of 66 to 140 is suggested. Which one should be more reac-
tive toward electrophilic aromatic substitution?
Spartan 12.7 The first step in the preparation of phenolformaldehyde resins such as Bakelite is the

acid-catalyzed reaction of phenol with the conjugate acid of formaldehyde (H2C OH). According to

the model in the Database, which atom of H2C OH bears the greatest share of positive charge?
Assume this is the atom that bonds to the para position of phenol in an electrophilic aromatic substi-
tution and write the structure of the product of this reaction.
Spartan 12.8 1-fluoro-2-nitrobenzene and 1-fluoro-4-nitrobenzene are more reactive than 1-fluoro-3-
nitrobenzene toward nucleophilic aromatic substitution. Make a molecular model of each compound
and replace it by the calculated model in the Database. Explain how the nodal properties of the respec-
tive LUMOs are consistent with the experimental observations.
Spartan 12.9 Seven chloro derivatives of quinoline are possible. Use the charge distribution in quino-
line from the Database to predict which of these chloro derivatives is the most reactive toward nucleo-
philic aromatic substitution by the additionelimination mechanism.

N
Quinoline

Spartan 12.10 C-2 has the greater positive charge, but C-4 is the site of nucleophilic aromatic substi-
tution in 2,4-dichloropyrimidine. Examine the LUMO of 2,4-dichloropyrimidine in the Database to see
why.

Cl OCH3

N NaOCH3 N

N Cl N Cl
2,4-Dichloropyrimidine 2-Chloro-4-methoxypyrimidine (72%)