Effect on Rate
Rate and Regioselectivity in
Electrophilic Aromatic Substitution
A substituent already present on the ring
affects both the rate and regioselectivity
of electrophilic aromatic substitution.
Activating substituents increase the rate
compared to that of benzene.
Deactivating substituents decrease
the rate compared to benzene.
Methyl Group
CH3
Trifluoromethyl Group
Toluene undergoes nitration
20-25 times faster than
benzene.
CF3
A methyl group is an
activating substituent.
substituent.
A trifluoromethyl group is a
deactivating substituent.
substituent.
Nitration of Toluene
Effect on Regioselectivity
CH3
CH3
Ortho-para directors direct an incoming
electrophile to positions ortho and/or
para to themselves.
Meta directors direct an incoming
electrophile to positions meta to
themselves.
(Trifluoromethyl)benzene
Trifluoromethyl)benzene
undergoes nitration 40,000
times more slowly than benzene .
CH3
CH3
NO2
HNO3
+
acetic
anhydride
+
NO2
NO2
63%
3%
34%
o - and p -nitrotoluene together comprise 97%
of the product
a methyl group is an ortho-para director
Nitration of (Trifluoromethyl
)benzene
(Trifluoromethyl)benzene
CF3
CF3
CF3
CF3
NO2
HNO3
+
H2 SO4
+
NO2
NO2
6%
91%
Substituent Effects in Electrophilic
Aromatic Substitution:
Activating Substituents
3%
m -nitro(trifluoromethyl)benzene comprises
91% of the product
a trifluoromethyl group is a meta director
Table
Classification of Substituents in Electrophilic
Aromatic Substitution Reactions
Very strongly activating
Strongly activating
Activating
Standard of comparison is H
Deactivating
Strongly deactivating
Very strongly deactivating
Generalizations
1. All activating substituents are
ortho-para directors.
Electron-Releasing Groups (ERGs)
are ortho-para directing and activating
ERG
2. Halogen substituents are slightly
deactivating but ortho-para directing.
3. Strongly deactivating substituents are
meta directors.
ERGs include —R, —Ar, and —C=C
Electron-Releasing Groups (ERGs)
Nitration of Phenol
occurs about 1000 times faster than nitration
of benzene
are ortho-para directing and strongly activating
ERG
OH
OH
HNO3
+
NO2
ERGs such as —OH, and —OR are
strongly activating
44%
Bromination of Anisole
OCH3
Br2
acetic
acid
••
•• OCH3
H
H
+
H
Br
90%
Electron-Releasing Groups (ERGs)
or Electron “Donors”
Donors”
•• ERG
ERGs with a lone pair on the atom directly
attached to the ring are ortho-para directing
and strongly activating
56%
Oxygen Lone Pair Stabilizes Intermediate
FeBr3 catalyst is not necessary
OCH3
OH
NO2
Br
••
•• OCH3
H
H
H
H
+
H
Br
••
+ OCH3
H
H
H
H
H
H
H
Br
all atoms
have octets
A substituent can donate electrons into the ring by
delocalizing its lone-pair electrons (resonance):
Examples
Lone Pair Stabilizes Intermediates for
ortho and para Substitution
O
•• ERG =
••
••
•• OH
•• OR
••
+ ERG
•• OCR
O
•• NH
2
•• NHR
•• NHCR
•• NR
2
+ ERG
H
H
H
H
X
H
H
H
H
H
All of these are ortho-para directing
and strongly to very strongly activating
X
H
comparable stabilization not possible for intermediate
leading to meta substitution
ERGs Stabilize Intermediates for
ortho and para Substitution
•• ERG
Substituent Effects in Electrophilic
Aromatic Substitution:
Strongly Deactivating Substituents
H
•• ERG
X
+
H
H
H
H
H
EWG
X
+
H
H
H
H
H
+
H
H
H
H
X
—CF3 is a powerful EWG. It is strongly
deactivating and meta directing
X
Many EWGs Have a Carbonyl Group
Attached Directly to the Ring
—EWG =
EWG
H
H
H
Electron-withdrawing Groups (EWGs
(EWGs)) Destabilize
Intermediates for ortho and para Substitution
H
+
H
O
O
—CH
—CR
O
O
—COH
—COR
O
—CCl
All of these are meta directing and strongly deactivating
Nitration of Benzaldehyde
O2 N
O
HNO3
CH
O
O
CH
CCl
H2 SO4
Cl
O
Cl2
CCl
FeCl3
75-84%
62%
Other EWGs Include:
Electron withdrawing by resonance:
—EWG =
—NO2
—SO3 H
—C
N
All of these are meta directing and strongly deactivating
Disulfonation of Benzene
C=O, CN, and NO2 also withdraw
electrons by resonance
Bromination of Nitrobenzene
Br
HO3S
SO3
SO3H
H2 SO4
90%
NO2
Br2
Fe
NO2
60-75%
Nitration of Chlorobenzene
Cl
Cl
Substituent Effects in Electrophilic
Aromatic Substitution:
Halogens
Cl
Cl
NO2
HNO3
+
+
H2 SO4
NO2
NO2
F, Cl, Br, and I are ortho-para directing,
but deactivating
30%
1%
69%
The rate of nitration of chlorobenzene is about
30 times slower than that of benzene.
Nitration of Toluene
Effect on Regioselectivity
CH3
CH3
Ortho-para directors direct an incoming
electrophile to positions ortho and/or
para to themselves.
CH3
NO2
HNO3
+
acetic
anhydride
Meta directors direct an incoming
electrophile to positions meta to
themselves.
CH3
+
NO2
NO2
63%
3%
34%
o - and p -nitrotoluene together comprise 97%
of the product
a methyl group is an ortho-para director
Nitration of (Trifluoromethyl
)benzene
(Trifluoromethyl)benzene
CF3
CF3
CF3
NO2
HNO3
+
H2 SO4
Question
CF3
• Arrange the compounds below in order
of decreasing rate of chlorination.
+
NO2
NO2
6%
91%
m -nitro(trifluoromethyl
)benzene comprises
-nitro(trifluoromethyl)benzene
91% of the product
a trifluoromethyl group is a meta director
3%
•
•
•
•
A)
B)
C)
D)
1>2>3
2>3>1
3>2>1
1>3>2
Question
• Which compound will add a nitro group
to the meta position?
• A)
B)
• C)
D)
Rate and Regioselectivity
in the
Nitration of Toluene
Carbocation Stability Controls Regioselectivity
CH3
H
NO2
+
H
H
H
CH3
H
H
+
H
H
gives ortho
CH3
H
H
H
H
CH3
H
H
H
NO2
H
+
NO2
gives para
Carbocation Stability Controls Regioselectivity
H
gives meta
NO2
H
+
H
CH3
H
+
H
H
H
gives ortho
NO2
gives para
more stable
CH3
H
H
H
H
H
+
H
H
NO2
gives meta
less stable
Nitration of Toluene: Interpretation
Nitration of Toluene: Partial Rate Factors
• The rate-determining intermediates for ortho and para
nitration each have a resonance form that is a tertiary
carbocation.
carbocation. All of the resonance forms for the ratedetermining intermediate in meta nitration are
secondary carbocations.
carbocations.
• Tertiary carbocations,
carbocations, being more stable, are formed
faster than secondary ones. Therefore, the
intermediates for attack at the ortho and para
positions are formed faster than the intermediate for
attack at the meta position. This explains why the
major products are o- and p-nitrotoluene.
-nitrotoluene.
• The experimentally determined reaction rate can be
combined with the ortho/meta/para distribution to give
partial rate factors for substitution at the various ring
positions.
• Expressed as a numerical value, a partial rate factor
tells you by how much the rate of substitution at a
particular position is faster (or slower) than at a single
position of benzene.
Nitration of Toluene: Partial Rate Factors
Nitration of Toluene vs.
vs. tert-Butylbenzene
CH3
CH3
1
1
1
42
42
1
1
2.5
2.5
1
CH3
58
All of the available ring positions in toluene are more
reactive than a single position of benzene.
A methyl group activates all of the ring positions but
the effect is greatest at the ortho and para positons.
positons.
Steric hindrance by the methyl group makes each
ortho position slightly less reactive than para.
para.
Nitration of Toluene vs.
vs. Chlorobenzene
CH3
H3 C
42
42
4.5
2.5
2.5
3
CH3
4.5
3
75
58
tert-Butyl
tert-Butyl is activating and orthoortho- para directing
tert-Butyl
tert-Butyl crowds the ortho positions and decreases
the rate of attack at those positions.
Nitration of (Trifluoromethyl
)benzene:
(Trifluoromethyl)benzene:
Partial Rate Factors
CF3
Cl
42
42
0.029
0.029
2.5
2.5
0.009
0.009
58
C
0.137
Question
• Which is the most likely candidate for
substituent X based on the partial rate
factors for nitration given beside the
structural formula?
•
A) -OCH3
•
B) -CH=O
•
C) -SO3H
•
D) -Br
4.5 x 10-6
67 x 10-6
4.5 x 10-6
67 x 10-6
4.5 x
10-6
All of the available ring positions in
(trifluoromethyl)benzene
trifluoromethyl)benzene are much less reactive than
a single position of benzene.
A CF3 group deactivates all of the ring positions but
the degree of deactivation is greatest at the ortho and
para positons.
positons.
Question
• Which reactants combine to
•
give the species shown at
•
the right as a reactive
•
intermediate?
•
•
A)
Benzene, isopropyl bromide, and HBr
•
B)
Bromobenzene, isopropyl chloride, and
AlCl3
•
C)
Isopropylbenzene, Br2, FeBr3
•
D)
Isopropylbenzene, light, and heat
Question
• Which of the following statements is false?
•
A)
All activating groups are ortho, para
directors.
•
B)
Halogen substituents are slightly
deactivating, but are ortho, para directing.
•
C)
Strongly activating substances are
meta directors.
•
D)
Some of the most powerful activating
substances are those with an oxygen
directly attached to the ring.
Question
• Which step is incorrect in respect to its
major organic product? Give the letter
•
corresponding to the first incorrect step.
•
•
A)
C)
Step A
Step C
B)
D)
Step B
Step D