12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution

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12.9Rate and Regioselectivity in Electrophilic
Aromatic Substitution

• A substituent already present on the ring can
  affect both the rate and regioselectivityof
  electrophilic aromatic substitution.

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Effect on Rate

• Activating substituents increase the rate of
  EAS compared to that of benzene.
• Deactivating substituents decrease the rate of
  EAS compared to benzene.

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Methyl Group

• Toluene undergoes nitration 20-25 times faster
  than benzene.
• A methyl group is an activating substituent.

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Trifluoromethyl Group

• (Trifluoromethyl)benzene undergoes nitration
  40,000 times more slowly than benzene .
• A trifluoromethyl group is adeactivating
  substituent.

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Effect on Regioselectivity

• 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.

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Nitration of Toluene


34
3
63

• o- and p-nitrotoluene together comprise 97 of
  the product
• a methyl group is an ortho-para director

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Nitration of (Trifluoromethyl)benzene


3
91
6

• m-nitro(trifluoromethyl)benzene comprises 91 of
  the product
• a trifluoromethyl group is a meta director

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12.10Rate and Regioselectivityin theNitration
of Toluene
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Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
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Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
more stable
less stable
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ortho Nitration of Toluene
CH3
NO2
H
H
H
H
H
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ortho Nitration of Toluene
CH3
CH3
NO2
NO2
H
H
H
H

H
H
H
H
H
H
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ortho Nitration of Toluene
CH3
CH3
CH3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• this resonance form is a tertiary carbocation

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ortho Nitration of Toluene
CH3
CH3
CH3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• the rate-determining intermediate in the
  orthonitration of toluene has tertiary
  carbocation character

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para Nitration of Toluene
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para Nitration of Toluene

• this resonance form is a tertiary carbocation

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para Nitration of Toluene

• this resonance form is a tertiary carbocation

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para Nitration of Toluene

• the rate-determining intermediate in the
  paranitration of toluene has tertiary
  carbocation character

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meta Nitration of Toluene
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meta Nitration of Toluene

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meta Nitration of Toluene

• all the resonance forms of the rate-determining
  intermediate in the meta nitration of toluene
  have their positive charge on a secondary carbon

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Nitration of Toluene Interpretation

• The rate-determining intermediates for ortho and
  para nitration each have a resonance form that is
  a tertiary carbocation. All of the resonance
  forms for the rate-determining intermediate in
  meta nitration are secondary carbocations.
• Tertiary 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.

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Nitration of Toluene Partial Rate Factors

• 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.

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Nitration of Toluene Partial Rate Factors
1
42
42
1
1
2.5
2.5
1
1
1
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.
• Steric hindrance by the methyl group makes each
  ortho position slightly less reactive than para.

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Nitration of Toluene vs. tert-Butylbenzene

• tert-Butyl is activating and ortho-para
  directing
• tert-Butyl crowds the ortho positions and
  decreases the rate of attack at those positions.

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Generalization

• all alkyl groups are activating and ortho-para
  directing

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Theory of Directing Effects
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12.11Rate and Regioselectivityin theNitration
of (Trifluoromethyl)benzene
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A Key Point

• A methyl group is electron-donating and
  stabilizes a carbocation.
• Because F is so electronegative, a CF3 group
  destabilizes a carbocation.

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Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
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Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
less stable
more stable
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ortho Nitration of (Trifluoromethyl)benzene
CF3
NO2
H
H
H
H
H
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ortho Nitration of (Trifluoromethyl)benzene
CF3
CF3
NO2
NO2
H
H
H
H

H
H
H
H
H
H
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ortho Nitration of (Trifluoromethyl)benzene
CF3
CF3
CF3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• this resonance form is destabilized

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ortho Nitration of (Trifluoromethyl)benzene
CF3
CF3
CF3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• one of the resonance forms of the
  rate-determining intermediate in the
  orthonitration of (trifluoromethyl)benzene is
  strongly destabilized

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para Nitration of (Trifluoromethyl)benzene
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para Nitration of (Trifluoromethyl)benzene

• this resonance form is destabilized

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para Nitration of (Trifluoromethyl)benzene

• this resonance form is destabilized

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para Nitration of (Trifluoromethyl)benzene

• one of the resonance forms of the
  rate-determining intermediate in the
  paranitration of (trifluoromethyl)benzene is
  strongly destabilized

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meta Nitration of (Trifluoromethyl)benzene
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meta Nitration of (Trifluoromethyl)benzene

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meta Nitration of (Trifluoromethyl)benzene

• none of the resonance forms of the
  rate-determining intermediate in the meta
  nitration of (trifluoromethyl)benzene have their
  positive charge on the carbon that bears the CF3
  group

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Nitration of (Trifluoromethyl)benzene
Interpretation

• The rate-determining intermediates for ortho and
  para nitration each have a resonance form in
  which the positive charge is on a carbon that
  bears a CF3 group. Such a resonance structure is
  strongly destabilized. The intermediate in meta
  nitration avoids such a structure. It is the
  least unstable of three unstable intermediates
  and is the one from which most of the product is
  formed.

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Nitration of (Trifluoromethyl)benzenePartial
Rate Factors

• All of the available ring positions in
  (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.

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Theory of Directing Effects
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12.12Substituent Effects in ElectrophilicAromati
c SubstitutionActivating Substituents
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Table 12.2
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

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Generalizations

• 1. All activating substituents are ortho-para
  directors.
• 2. Halogen substituents are slightly
  deactivating but ortho-para directing.
• 3. Strongly deactivating substituents are meta
  directors.

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Electron-Releasing Groups (ERGs)

• are ortho-para directing and activating

ERG
ERGs include R, Ar, and CC
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Electron-Releasing Groups (ERGs)

• are ortho-para directing and strongly activating

ERG
ERGs such as OH, and OR arestrongly activating
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Nitration of Phenol

• occurs about 1000 times faster than nitration of
  benzene

HNO3

44
56
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Bromination of Anisole

• FeBr3 catalyst not necessary

Br2
aceticacid
90
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Oxygen Lone Pair Stabilizes Intermediate

H
H
H
H
Br
H

• all atomshave octets

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Electron-Releasing Groups (ERGs)
ERG

• ERGs with a lone pair on the atom
  directlyattached to the ring are ortho-para
  directingand strongly activating

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Examples

• All of these are ortho-para directingand
  strongly to very strongly activating

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Lone Pair Stabilizes Intermediates forortho and
para Substitution

• comparable stabilization not possible for
  intermediate leading to meta substitution

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