Chapter 17
Aromatic Substitution
Reactions
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17.1 Mechanism for Electricphilic Aromatic
Substitution
Arenium ion
resonance stabilization
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Example 1.
Example 2.
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Example 2. Mechanism of the nitration of benzene
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Addition reaction vs.
Electrophilic aromatic substitution
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<
Stability
<
E
H
E
Ga < Gs
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Bezene is very stable so it is very diificult to
break the resonance stabilization
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Is the addition reaction possible for a benzene ?
Very difficult because of the stability of the product
E
resonance
stabilization
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17.2 Effect of Substituent
17 times faster than the substitution of benzene
Why ?
Resonance stabilization
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Ortho attack
Meta attack
Para attack
Meta and para attack is favored
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CH3 is an ortho/para directing group
Nitration of anisole (methoxy benzene)
10,000 times faster than the substitution of benzene
Why ? Resonance stabilization
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The effect of methoxy group
1.Inductive effect,
then as the oxygen is electronegative Methoxy is deactivating
group not true
2. Resonance effect explanation is possible
This is what scientists are doing, you also should have this
attitude, then find reasons. Otherwise no result at all.
Therefore, any group that has an unshared pair of
electrons is the ortho/para director
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Nitration of nitrobenzene
1. 1017 times slower than the substitution of
benzene
2. meta director
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Until now,
Activating group (elecron donating group): ortho/para director
Deactivationg group (elecron withdrawing group): meta
dircectot
Exception: Halogens,
ortho/para derector + deactivating group
1. 17 times slower than the substitution of benzene
2. ortho/para director
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F is highly electronegative, therefore
F inductive withdrawing effect is stronger
than the resonance effect
Cl, Br, I
Cl, Br, and I are not very electronegative,
while the resonance effect is not strong
enough as the methoxy
Because the overlapping netween 2p AO
of carbon and 3p(Cl), 4p(Br), 5p(I) AOs
are not good. (2p AO for oxygen)
Still halogens are ortho/para director because
there is the resonance effect although it is much
weaker.
Nose ring theory !
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Accurate experiment results are most important !
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@
Two ortho positions and one para
position, therefore statistically the ratio or
ortho to para products should be 2 to 1,
Which is generally true! (nitration of
toluene)
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See P 680
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17.3 Effect of Multiple Substituent
Methyl group controls the regiochemistry, because methyl
group is a strong activating group
Rule: Groups that are closer to the top of Table 17.1
controls the regiochemistry!
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17.4 Nitration
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Preparation of NO2+
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A problem occurs with amino substitution
N with unpaired electrons looks like a activating group and o/p
director. But under acidic condition it can be protonated, then
deactivating group and m director. Although the amine (strong
activating group) conc. is very low, 18% is para product!
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Amide group: much less basis, still activator and o/p director
Example,
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17.5 Halogenation
Mechanism
Same as the nitration
Cl
Resonance stabiliztion,
Activating group faciliate the reaction
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+ AlCl3 + HCl
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17.6 Sulfonation
Fuming sulfuric acid
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Mechanism
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17.7 Friedel-Craft Alkylation
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Mechanism of the Friedel-Craft Alkylation
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Drawbacks
1. The alkyl groups that is added to the ring is an
activated group: a large amount of products w/ two
or more alkyl groups
2. Aromatic compound w/ strongly deactivating
groups cannot be alkylated.
3. Rearrangement
CH3CH2CH2CH2Cl + AlCl 3
CH3CH2CH2CH2 AlCl 4
Because
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CH3CH2CHCH3
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Other ways to generate carbocations
Strong acid, TsOH, can eliminate water,
then CH3-ph-CH2+ can be generated
Other examples
Lewis acid is used
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Synthetic detergents
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BHT and BHA are anti oxidant added to food prepared
by Friedel-Crafts alkylation reactions
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17.8 Friedel-Craft Acylation
Generation of acyl cation
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Drawback: like the alkylation, this reaction does not work
with strongly deactivated substrates (m directors)
Examples
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Examples
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17.9 Electrophilic Substitution of
Polycyclic Aromatic Compounds
Why the 1 position is preferred?
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Containing
stable benzene
ring
Containing
stable
benzene ring
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17.10 Nucleophilic Aromatic
Substitution; Diazonium ion
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Examples
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17.11 Nucleophilic Aromatic
Substitution; Addition-Elimination
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Mechanism
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Not SN2 but Addition-Elimination
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The order of leaving group ability
Examples
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17.12 Nucleophilic Aromati Substitution;
Elimination-Addition
When there is no electron withdrawing group at o/p
position, then elimination-addition occurs with very
strong base (amide anion) or with weak base at high
temperature
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Mechanism
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Benzyne
The existence of benzyne
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17.13 Some Additional Useful Reactions
Reduction of nitro group to amine using hydrogen and a catalyst
or by using acid and a metal (Fe, Sn, or SnCl2)
O
H3CH2COC
NH2
Cl
Application
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Reduction of carbonyl group (aldehyde or ketone) to
a methylene group
1. Clemmenson
reduction
2. Wolff-Kishner
reduction
3. Catalytic
hydrogenation
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H2/Pt reduction vs Wolff-Kishner and Clemmenson
reduction
-H2/Pt works for the carbonyl attached to the aromatic ring
-Wolff-Kishner and Clemmenson reduction do not have this restriction
Oxidation of alkyl groups bonded to the aromatic ring
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If the carbon bonded to the ring is not tertiary
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17.14 Synthesis of Aromatic Compound
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Preparation of m-chlorobenzene and p-chlorobenzene
Preparation of o-bromophenol
HO
HO
HO
+
Br2
Br
+
Mixuture
Br
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Preparation of m-bromochlorobenzene
Problem: both chloro and bromo groups are o/p directors
Solution: use NO2, a m director
Preparation of m-bromotoluene
Problem: methyl group is an o/p director
Solution: use NO2, the m director
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Preparation of m-butylbenzenesulfonic acid
Benzene sulfonic acid cannot be alkylated because the FriedelCraft alkyl- or acylation does not work with deactivating group
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Preparation of
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