Transcript Reactions of Aromatic Compounds

Organic Chemistry, 6th Edition
L. G. Wade, Jr.
Chapter 17
Reactions of
Aromatic Compounds
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2006, Prentice Hall
Electrophilic
Aromatic Substitution
Electrophile substitutes for a hydrogen on
the benzene ring.
=>
Chapter 17
2
Mechanism
Step 1: Attack on the electrophile forms the sigma complex.
Step 2: Loss of a proton gives the substitution product.
=>
Chapter 17
3
Bromination of Benzene
• Requires a stronger electrophile than Br2.
• Use a strong Lewis acid catalyst, FeBr3.
Br Br
FeBr3
Br
H
+
Br
H
Br
FeBr3
H
H
H
+
H
Br
-
H
H
Br
FeBr3
+
H
_
+ FeBr4
H
H
H
Br
+
Chapter 17
HBr
=>
4
Comparison with Alkenes
• Cyclohexene adds Br2, H = -121 kJ
• Addition to benzene is endothermic, not
normally seen.
• Substitution of Br for H retains
aromaticity, H = -45 kJ.
• Formation of sigma complex is ratelimiting.
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Chapter 17
5
Energy Diagram
for Bromination
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Chapter 17
6
Chlorination
and Iodination
• Chlorination is similar to bromination.
Use AlCl3 as the Lewis acid catalyst.
• Iodination requires an acidic oxidizing
agent, like nitric acid, which oxidizes
the iodine to an iodonium ion.
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Chapter 17
7
Nitration of Benzene
Use sulfuric acid with nitric acid to form
the nitronium ion electrophile.
NO2+ then forms a
sigma complex with
benzene, loses H+ to
form nitrobenzene. =>
Chapter 17
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Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric
acid is the electrophile.
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Chapter 17
9
Desulfonation
• All steps are reversible, so sulfonic
acid group can be removed by heating
in dilute sulfuric acid.
• This process is used to place deuterium
in place of hydrogen on benzene ring.
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Chapter 17
Benzene-d6
10
Nitration of Toluene
• Toluene reacts 25 times faster than benzene.
The methyl group is an activating group.
• The product mix contains mostly ortho and
para substituted molecules.
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Chapter 17
11
Sigma Complex
Intermediate
is more
stable if
nitration
occurs at
the ortho
or para
position.
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Chapter 17
12
Energy Diagram
Chapter 17
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13
Activating, O-, PDirecting Substituents
• Alkyl groups stabilize the sigma complex
by induction, donating electron density
through the sigma bond.
• Substituents with a lone pair of electrons
stabilize the sigma complex by resonance.
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Chapter 17
14
Substitution on Anisole
Chapter 17
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15
The Amino Group
Aniline, like anisole, reacts with bromine
water (without a catalyst) to yield the
tribromide. Sodium bicarbonate is added
to neutralize the HBr that’s also formed.
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Chapter 17
16
Summary of
Activators
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Chapter 17
17
Deactivating MetaDirecting Substituents
• Electrophilic substitution reactions for
nitrobenzene are 100,000 times slower
than for benzene.
• The product mix contains mostly the
meta isomer, only small amounts of the
ortho and para isomers.
• Meta-directors deactivate all positions
on the ring, but the meta position is less
deactivated.
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Chapter 17
18
Ortho Substitution
on Nitrobenzene
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Chapter 17
19
Para Substitution
on Nitrobenzene
=>
Chapter 17
20
Meta Substitution
on Nitrobenzene
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Chapter 17
21
Energy Diagram
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22
Structure of MetaDirecting Deactivators
• The atom attached to the aromatic ring
will have a partial positive charge.
• Electron density is withdrawn inductively
along the sigma bond, so the ring is less
electron-rich than benzene.
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Chapter 17
23
Summary of Deactivators
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Chapter 17
24
More Deactivators
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Chapter 17
25
Halobenzenes
• Halogens are deactivating toward
electrophilic substitution, but are ortho,
para-directing!
• Since halogens are very electronegative,
they withdraw electron density from the
ring inductively along the sigma bond.
• But halogens have lone pairs of electrons
that can stabilize the sigma complex by
resonance.
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Chapter 17
26
Sigma Complex
for Bromobenzene
Ortho and para attacks produce a bromonium ion
and other resonance structures.
No bromonium ion
possible with meta attack.
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Chapter 17
27
Energy Diagram
=>
Chapter 17
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Summary of
Directing Effects
Chapter 17
29
=>
Multiple Substituents
The most strongly activating substituent
will determine the position of the next
substitution. May have mixtures.
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Chapter 17
30
Friedel-Crafts Alkylation
• Synthesis of alkyl benzenes from alkyl
halides and a Lewis acid, usually AlCl3.
• Reactions of alkyl halide with Lewis acid
produces a carbocation which is the
electrophile.
• Other sources of carbocations:
alkenes + HF, or alcohols + BF3.
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Chapter 17
31
Examples of
Carbocation Formation
Chapter 17
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32
Formation of
Alkyl Benzene
+
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33
Limitations of
Friedel-Crafts
• Reaction fails if benzene has a substituent
that is more deactivating than halogen.
• Carbocations rearrange. Reaction of
benzene with n-propyl chloride and AlCl3
produces isopropylbenzene.
• The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
=>
Chapter 17
34
Friedel-Crafts
Acylation
• Acyl chloride is used in place of alkyl
chloride.
• The acylium ion intermediate is
resonance stabilized and does not
rearrange like a carbocation.
• The product is a phenyl ketone that is
less reactive than benzene.
=>
Chapter 17
35
Mechanism of Acylation
Chapter 17
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36
Clemmensen Reduction
Acylbenzenes can be converted to
alkylbenzenes by treatment with
aqueous HCl and amalgamated zinc.
=>
Chapter 17
37
Gatterman-Koch
Formylation
• Formyl chloride is unstable. Use a high
pressure mixture of CO, HCl, and catalyst.
• Product is benzaldehyde.
Chapter 17
38
=>
Nucleophilic
Aromatic Substitution
• A nucleophile replaces a leaving group
on the aromatic ring.
• Electron-withdrawing substituents
activate the ring for nucleophilic
substitution.
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Chapter 17
39
Examples of
Nucleophilic Substitution
Chapter 17
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40
Addition-Elimination
Mechanism
Chapter 17
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41
Benzyne Mechanism
• Reactant is halobenzene with no
electron-withdrawing groups on the ring.
• Use a very strong base like NaNH2.
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Chapter 17
42
Benzyne Intermediate
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Chapter 17
43
Chlorination of Benzene
• Addition to the benzene ring may
occur with high heat and pressure
(or light).
• The first Cl2 addition is difficult, but the
next 2 moles add rapidly.
• The product, benzene hexachloride, is an
insecticide.
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Chapter 17
44
Catalytic Hydrogenation
• Elevated heat and pressure is required.
• Possible catalysts: Pt, Pd, Ni, Ru, Rh.
• Reduction cannot be stopped at an
intermediate stage.
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Chapter 17
45
Birch Reduction:
Regiospecific
• A carbon bearing an e--withdrawing group
is reduced.
• A carbon bearing an e--releasing group
is not reduced.
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Chapter 17
46
Birch Mechanism
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Chapter 17
47
Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic
acid by hot KMnO4 or Na2Cr2O7/H2SO4.
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48
Side-Chain Halogenation
• Benzylic position is the most reactive.
• Chlorination is not as selective as
bromination, results in mixtures.
• Br2 reacts only at the benzylic position.
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49
SN1 Reactions
• Benzylic carbocations are resonancestabilized, easily formed.
• Benzyl halides undergo SN1 reactions.
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Chapter 17
50
SN2 Reactions
• Benzylic halides are 100 times more
reactive than primary halides via SN2.
• Transition state is stabilized by ring.
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51
Reactions of Phenols
• Some reactions like aliphatic alcohols:
phenol + carboxylic acid  ester
phenol + aq. NaOH  phenoxide ion
• Oxidation to quinones: 1,4-diketones.
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52
Quinones
• Hydroquinone is used as a developer
for film. It reacts with light-sensitized
AgBr grains, converting it to black Ag.
• Coenzyme Q is an oxidizing agent
found in the mitochondria of cells.
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53
Electrophilic
Substitution of Phenols
• Phenols and phenoxides are highly reactive.
• Only a weak catalyst (HF) required for
Friedel-Crafts reaction.
• Tribromination occurs without catalyst.
• Even reacts with CO2.
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54
End of Chapter 17
Chapter 17
55