Electrophilic Aromatic Substitution

1
Electrophilic Aromatic Substitution

• Activating and Directing effects of substituents
  already on the ring

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Products of Nitration
1 hr
48 hr
0.0003 hr
3
Mechanism of Electrophilic Aromatic Substitution
With a substituent group G
Depending on the nature of the substituent, the
substituent G may stabilize the carbocation
intermediate and therefore speed the reaction, or
it may raise the energy of the carbocation and
slow the reaction. Substituents that make the
ring react faster (than benzene) with
electrophiles are called activators those that
make the ring react slower (than benzene) are
called deactivators.
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Substituent effects

• All activators also direct incoming electrophiles
  to the ortho- and the para-positions.
• Most deactivators direct incoming electrophiles
  to the meta position. The exceptions are the
  halogens, which are weakly deactivating yet
  ortho-para directing.

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Classification of Substituents
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Product Distribution in Nitration

• (Percent )
  (Percent )
• X ortho meta para X
  ortho meta para
• (meta-directing Deactivators)
  (ortho- and para-directing Deactivators)
• -N(CH3)3 2 89 11 -F 13 1
  86
• -NO2 7 91 2 -Cl 35 1 64
• -CO2H 22 77 2 -Br 43 1 56
• -CN 17 81 2 -I 45 1 54
• -CO2CH2CH3 28 72 2 (ortho- and
  para-directing Activators)
• -COCH3 26 72 2 -CH3 63 3 34
• -CHO 19 72 9 -OH 50 0 50

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o,p-Activators (alkyl aryl groups)
3º, especially stable
3º, especially stable
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o,p-Activators with a lp of electrons
o-
4 resonance forms
m-
p-
4 resonance forms
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o,p-Deactivators (Halogens)
o-
4 resonance forms
m-
p-
4 resonance forms
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meta-directing Deactivators
o-
Especially UNSTABLE
m-
p-
Especially UNSTABLE
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Explanation of meta- deactivators

• Meta directors slow the reaction by raising the
  energy of the carbocation intermediate
  because they have (in one resonance form, shown
  below) a positively charged atom attached to the
  ring. Two positively charged atoms so close
  together is very high in energy (especially
  unstable).

nitro group sulfonic acid
ketone nitrile
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Summary of Substituent Effects

• When the substituent is R (alkyl) or Ar (aryl),
  the resonance hybrid cation intermediate has
  three resonance forms. For attack of the
  electrophile at the ortho or para positions, one
  of these is a 3º carbocation, which is especially
  stable. This lowers the energy of the
  intermediate, thus facilitates (speeds) the
  substitution reaction at the o- and p- positions.
• When the substituent has a lone pair of
  electrons, such as the halogens, oxygen or
  nitrogen, the resonance hybrid for attack of the
  electrophile at the ortho and para positions has
  four resonance forms. This lowers the energy of
  the those intermediates, thus facilitates
  (speeds) the substitution reaction at the o- and
  p- positions.

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Summary of Substituent Effects

• When the substituent has a multiple bond
  conjugated with the ring, and the second atom
  from the ring is more electronegative than the
  first, the substituent deactivates the ring and
  directs incoming electrophiles meta. It does
  this by raising the energy of the carbocation
  intermediates from ortho and para attack by an
  electrophile even more than it raises the energy
  of the intermediate resulting from meta attack.

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Summary
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Additivity of substituent effects in
disubstituted aromatic rings

• Rule 1 If the directing effects of two
  substituents reinforce each other, the predicted
  product predominates.

(o,p)
(m)
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Additivity of substituent effects

• Rule 2 If the directing effects of two
  substituents oppose each other, the more
  activating group dominates, but mixtures often
  result.

(o,p STRONG activator)
(o,p weak activator)
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Additivity of substituent effects

• Rule 3 Substitution almost never occurs between
  two substituents meta to each other.

(o,p)
X (too crowded)
(o,p)
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Additivity of substituent effects

• Rule 4 With a bulky o,p- director and/or a
  bulky electrophile, para substitution
  predominates.

(o,p BULKY)
(HSO3 is a BULKY electrophile)