Electrophilic Aromatic Substitution

1
Chapter 13

• Electrophilic Aromatic Substitution

2
The general reaction

• Start at paragraph 13.5! The first four
  paragraphs are not very important.
• In an electrophilic aromatic substitution
  reaction, a hydrogen atom is replaced by an
  electrophile.

3
The reaction mechanism
A

• Question write a detailed mechanism, including
  resonance structures of the intermediate cation
  A.
• Reminder draw the double bonds and not the
  circles......!
• Due to the stability of the aromatic ring, the
  electrophile must be very electrophilic!!
• What will be the slowest and the fastest step in
  this sequence?

4
Sulfonation of benzene

• Concentrated sulfonic acid always contains some
  SO3 (oleum), which is the electrophile in this
  reaction

5
Nitration of benzene

• The nitronium ion (NO2) is the reactive
  electrophile in this reaction
• The mechanism is analogous to the sulfonation
  mechanism

6
Halogenation of benzene

• Benzene does not react with Br2 or Cl2, unless
  there is some type of activation
• A Lewis acid (FeCl3) can be used to do so

7
Friedel-Crafts alkylation of benzene

• Alkyl halides can also be activated with strong
  Lewis acids such as AlBr3 or AlCl3 to give
  strongly electrophilic cations that can react
  with aromatic rings

8
Examples

• If a primary alkyl halide is used, mixtures of
  products arise. Why?

9
A hydride shift can occur

• The initially formed primary carbocation can via
  a hydride shift rearrange to the more stable
  secondary cation. This will then give the
  isopropyl-substituent

10
Friedel-Crafts acylation of benzene

• Treatment of an acid chloride (or acyl chloride)
  with a Lewis acid (AlCl3) will give the very
  electrophilic acylium ion

11
The substitution itself

• Attack of the aromatic ring onto the acylium ion,
  followed by rearomatization eventually gives the
  acylated benzene

12
Examples

• A big advantage of the acylation is that
  rearrangements such as hydride shifts do not
  occur. Therefore, if it would be possible to
  reduce the carbonyl to the CH2, this would give
  access to primary alkyl groups on the aromatic
  ring

13
Two reduction methods

• There is one acidic (Clemmensen) and one basic
  (Wolff-Kishner) reduction method both require
  quite harsh conditions

14
Summary
15
Problems

• Make problems 13.12 and 13.38a

16
Further chemistry

• While the nitro group is not particularly useful
  itself, reduction to the amine gives many
  opportunities for further reactions
• Reaction of the amine with NaNO2 (sodium nitrite)
  in the presence of HCl gives a (stable) diazonium
  salt

17
The mechanism
N?O

• The first step involves protonation of nitric
  acid and formation of the electrophile, NO
• Then, the amine attacks this electrophile and
  loses a proton

18
The mechanism (II)

• Via protonation/deprotonation and loss of water,
  the diazonium salt is formed

19
Reactions of the diazonium salt

• The N2 group can be readily displaced by
  different Cu-containing nucleophiles e.g. CuCN,
  CuBr and CuCl. These reactions are aka Sandmeyer
  reactions

20
Other reactions

• N2 can also be replaced by a hydride, hydroxide,
  iodide and fluoride virtually any heteroatom can
  be introduced in this way

21
EAS with a substituent present

• In other words, what is the effect of
  substituents on the aromatic ring in the
  electrophilic aromatic substitution

22
Activating/o,p-directing
23
Deactivating/m-directing
24
Question

• Explain for anisole why only the ortho and para
  products are formed and not the meta product.
  Hint draw the intermediate cations and their
  resonance forms

25
The energy picture

• In terms of energy because the inter-mediate
  cation for the ortho and para product are
  signi-ficantly lower in energy, the meta product
  will not be formed

26
Reactions of toluene

• The directing and activating effect of an alkyl
  group is less strong. Why?

27
Examples

• Indeed, trace amounts of the para-products are
  formed

28
Question

• Explain the meta-directing and the deactivating
  effect of the ammonium substituent. Again, draw
  all the resonance structures

29
Reactions of nitrobenzene

• A similar effect is encountered in case of a
  nitro substituent
• Why is the nitro group deactivating?

30
Ester-substituted aromates

• Also the ester group is a strong meta-director
• Again, why is the ester group deactivating?

31
Resonance/inductive effects

• So far, we have mainly looked at resonance
  effects and hardly at inductive effects
• What inductive effects are there?

32
What about aryl halides?

• In halide substituted aromatic systems, the
  inductive and resonance effects work
  counterproductive
• Inductively, the halide destabilizes the positive
  charge

33
O,p-directing, but deactivating

• But via a resonance effect, the cation is
  stabilized this effect is stronger than the
  inductive effect
• Both cause the o,p-directing and the deactivating
  properties

34
Problems

• Make problems 13.35, 13.38b-d, 13.39, 13.41,
  13.42

35
More than one substituent...

• In general, the outcome is quite logic...

36
A combined action
37
The influence of large groups

• The size of the substituents is also of
  influence, especially in the case of
  ortho-substitution

38
Other examples

• With strongly activating groups, multiple
  additions can occur

39
Changing the substituent

• While the amine is a strongly activating
  substituent, the acetylated amine (amide) is not.
  Now, mono-substitution will selectively take
  place.

40
The amount of the electrophile

• Under carefully controlled conditions,
  mono-bromination is possible with an excess of
  bromine complete bromination wilkl occur

41
Selective meta-bromination

• This is easy...... But how to make the
  para-isomer?

42
The solution......
43
Problems

• Make problems 13.30, 13.36,13.44 and 13.47