Chapter 17 Reactions of Aromatic Compounds
Electrophilic Aromatic Substitution
Electrophile substitutes for a hydrogen on the benzene ring.
Chapter 17: Aromatics 2-Reactions Slide 17-2
1 Mechanism
Step 1: Attack on the electrophile forms the sigma complex.
Step 2: Loss of a proton gives the substitution product.
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Chapter 17: Aromatics 2-Reactions Slide 17-3
Bromination of Benzene
• Requires a stronger electrophile than Br2.
• Use a strong Lewis acid catalyst, FeBr3.
Br Br + - FeBr3 Br Br FeBr3 H H H H H H + - Br _ Br Br FeBr3 + + FeBr4 H H H H H H
Br + HBr =>
Chapter 17: Aromatics 2-Reactions Slide 17-4
2 Comparison with Alkenes
• Cyclohexene adds Br2, ΔH = -121 kJ • Addition to benzene is endothermic, not normally seen. • Substitution of Br for H retains aromaticity, ΔH = -45 kJ. • Formation of sigma complex is rate-limiting. =>
Chapter 17: Aromatics 2-Reactions Slide 17-5
Energy Diagram for Bromination
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Chapter 17: Aromatics 2-Reactions Slide 17-6
3 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.
+ + H + HNO3 + 1/2 I2 I + NO2 + H2O
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Chapter 17: Aromatics 2-Reactions Slide 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: Aromatics 2-Reactions Slide 17-8
4 Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric acid is the electrophile. _ O O O O S S + S + S + _ _ O O O O O O O O
Chapter 17: Aromatics 2-Reactions Slide 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.
H D H H large excess D D D2SO4/D2O
H H D D H D Benzene-d6 Chapter 17: Aromatics 2-Reactions Slide 17-10
5 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: Aromatics 2-Reactions Slide 17-11
Sigma Complex
Intermediate is more stable if nitration occurs at the ortho or para position.
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Chapter 17: Aromatics 2-Reactions Slide 17-12
6 Energy Diagram
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Chapter 17: Aromatics 2-Reactions Slide 17-13
Activating, O-, P- Directing 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.
+ OCH3 OCH3 + NO NO2 2 => H H
Chapter 17: Aromatics 2-Reactions Slide 17-14
7 Substitution on Anisole
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Chapter 17: Aromatics 2-Reactions Slide 17-15
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: Aromatics 2-Reactions Slide 17-16
8 Summary of Activators
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Chapter 17: Aromatics 2-Reactions Slide 17-17
Deactivating Meta- Directing 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. =>
Chapter 17: Aromatics 2-Reactions Slide 17-18
9 Ortho Substitution on Nitrobenzene
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Chapter 17: Aromatics 2-Reactions Slide 17-19
Para Substitution on Nitrobenzene
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Chapter 17: Aromatics 2-Reactions Slide 17-20
10 Meta Substitution on Nitrobenzene
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Chapter 17: Aromatics 2-Reactions Slide 17-21
Energy Diagram
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Chapter 17: Aromatics 2-Reactions Slide 17-22
11 Structure of Meta-Directing 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: Aromatics 2-Reactions Slide 17-23
Summary of Deactivators
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Chapter 17: Aromatics 2-Reactions Slide 17-24
12 More Deactivators
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Chapter 17: Aromatics 2-Reactions Slide 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. =>
Chapter 17: Aromatics 2-Reactions Slide 17-26
13 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: Aromatics 2-Reactions Slide 17-27
Energy Diagram
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Chapter 17: Aromatics 2-Reactions Slide 17-28
14 Summary of Directing Effects
=> Chapter 17: Aromatics 2-Reactions Slide 17-29
Multiple Substituents
The most strongly activating substituent will determine the position of the next substitution. May have mixtures.
OCH3 OCH3 OCH3 SO H SO 3 3 + H2SO4 O2N O2N O2N
SO3H =>
Chapter 17: Aromatics 2-Reactions Slide 17-30
15 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. =>
Chapter 17: Aromatics 2-Reactions Slide 17-31
Examples of Carbocation Formation
Cl CH3 + _ C Cl AlCl CH3 CH CH3 + AlCl3 3 H3C H
_ F HF + H2C CH CH3 H3C CH CH3
+ BF3 OH H O BF + _ 3 + H3C CH CH3 H3C CH CH3 H3C CH CH3 HOBF3 =>
Chapter 17: Aromatics 2-Reactions Slide 17-32
16 Formation of Alkyl Benzene
CH3 H
+C H CH(CH3)2 + CH3 H
F - CH H F B OH 3 HF CH + + CH(CH ) F F 3 2 CH B OH 3 F H =>
Chapter 17: Aromatics 2-Reactions Slide 17-33
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: Aromatics 2-Reactions Slide 17-34
17 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: Aromatics 2-Reactions Slide 17-35
Mechanism of Acylation
O O O HCl C R _ C R + C + Cl AlCl3 H AlCl3 R + H => Chapter 17: Aromatics 2-Reactions Slide 17-36
18 Clemmensen Reduction
Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc. Works for non- aromatic ketones as well; rearrangements can occur.
O O 1) C CH2CH3 CH2CH2CH3 AlCl3 Zn(Hg) + CH3CH2C Cl 2) H2O aq. HCl
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Chapter 17: Aromatics 2-Reactions Slide 17-37
Wolff-Kishner Reduction
Acylbenzenes can be also converted to alkylbenzenes by treatment with aqueous NH2NH2 and hydroxide (mechanism next chapter). Works for non-aromatic ketones as well.
O H H
NH2NH2 KOH aq. ethylene glycol
Chapter 17: Aromatics 2-Reactions Slide 17-38
19 Gatterman-Koch Formylation
• Formyl chloride is unstable. Use a high pressure mixture of CO, HCl, and catalyst. • Product is benzaldehyde.
O + _ AlCl3/CuCl CO + HCl H C Cl H C O AlCl4 O O C + C H + + HCl H
Chapter 17: Aromatics 2-Reactions Slide 17-39
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: Aromatics 2-Reactions Slide 17-40
20 Examples of Nucleophilic Substitution
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Chapter 17: Aromatics 2-Reactions Slide 17-41
Addition-Elimination Mechanism
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Chapter 17: Aromatics 2-Reactions Slide 17-42
21 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: Aromatics 2-Reactions Slide 17-43
Benzyne Intermediate
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Chapter 17: Aromatics 2-Reactions Slide 17-44
22 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: Aromatics 2-Reactions Slide 17-45
Catalytic Hydrogenation
• Elevated heat and pressure is required. • Possible catalysts: Pt, Pd, Ni, Ru, Rh. • Reduction cannot be stopped at an intermediate stage.
CH3 CH3
3H2, 1000 psi Ru, 100°C => CH3 CH3
Chapter 17: Aromatics 2-Reactions Slide 17-46
23 Birch Reduction: Regiospecific
• A carbon bearing an e--withdrawing group is reduced. O O C _ C O OH Na, NH3 H CH3CH2OH • A carbon bearing an e--releasing group is not reduced.
OCH OCH3 3 Li, NH3
(CH3)3COH, THF =>
Chapter 17: Aromatics 2-Reactions Slide 17-47
Birch Mechanism
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Chapter 17: Aromatics 2-Reactions Slide 17-48
24 Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic acid by hot KMnO4 or Na2Cr2O7/H2SO4.
_ CH(CH3)2 COO KMnO , OH- 4 _ H2O, heat COO CH CH2
Chapter 17: Aromatics 2-Reactions Slide 17-49
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.
Br CH CH CH 2 2 3 CHCH2CH3 Br2, h!
Chapter 17: Aromatics 2-Reactions Slide 17-50
25 SN1 Reactions
• Benzylic carbocations are resonance-stabilized, easily formed.
• Benzyl halides (even primary!) undergo SN1 reactions.
CH3CH2OH, heat CH2Br CH2OCH2CH3
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Chapter 17: Aromatics 2-Reactions Slide 17-51
SN2 Reactions
• Benzylic halides are 100 times more reactive than primary
halides via SN2. • Transition state is stabilized by ring.
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Chapter 17: Aromatics 2-Reactions Slide 17-52
26 Reactions of Phenols
• Some reactions like aliphatic alcohols: phenol + carboxylic acid → ester phenol + aq. NaOH → phenoxide ion • Oxidation to quinones: 1,4-diketones.
O OH
Na2Cr2O7, H2SO4
CH CH3 3 => O
Chapter 17: Aromatics 2-Reactions Slide 17-53
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. =>
OH O
+ 2 AgBr + 2 Ag + 2 HBr
OH O
Chapter 17: Aromatics 2-Reactions Slide 17-54
27 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.
_ _ O O O OH O C _ C - + CO2, OH O H OH => salicylic acid
Chapter 17: Aromatics 2-Reactions Slide 17-55
End of Chapter 17
Homework: 44, 46, 47, 49, 52, 53, 56, 57, 61, 63, 64, 67
Chapter 17: Aromatics 2-Reactions Slide 17-56
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