17 - reactions of aromatic compounds - wade 7th
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Organic Chemistry, 7th Edition L. G. Wade, JrTRANSCRIPT
Chapter 17
Copyright © 2010 Pearson Education, Inc.
Organic Chemistry, 7th EditionL. G. Wade, Jr.
Reactions of Aromatic Compounds
Chapter 17 2
Electrophilic Aromatic Substitution
Although benzene’s pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation.
This resonance-stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond.
Aromaticity is regained by loss of a proton.
Chapter 17 3
Mechanism of Electrophilic Aromatic Substitution
Chapter 17 4
Bromination of Benzene
Chapter 17 5
Mechanism for the Bromination of Benzene: Step
1
Before the electrophilic aromatic substitution can take place, the electrophile must be activated.
A strong Lewis acid catalyst, such as FeBr3, should be used.
Br Br FeBr3 Br Br FeBr3+ -
(stronger electrophile than Br2)
Chapter 17 6
H
H
H
H
H
H
Br Br FeBr3
H
H
H
H
H
H
Br+ FeBr4
-
H
H
H
H
H
H
Br
FeBr4-
Br
H
H
H
H
H
+ FeBr3 + HBr
Step 2: Electrophilic attack and formation of the sigma complex.
Step 3: Loss of a proton to give the products.
Mechanism for the Bromination of Benzene: Steps
2 and 3
Chapter 17 7
Energy Diagram for Bromination
Chapter 17 8
Chlorination and Iodination
Chlorination is similar to bromination. AlCl3 is most often used as catalyst, but FeCl3 will also work.
Iodination requires an acidic oxidizing agent, like nitric acid, to produce iodide cation.
H+ + HNO3 + ½ I2 I+ + NO2 + H2O
Chapter 17 9
Predict the major product(s) of bromination of p-chloroacetanilide.
The amide group (–NHCOCH3) is a strong activating and directing group because the nitrogen atom with its nonbonding pair of electrons is bonded to the aromatic ring. The amide group is a stronger director than the chlorine atom, and substitution occurs mostly at the positions ortho to the amide. Like an alkoxyl group, the amide is a particularly strong activating group, and the reaction gives some of the dibrominated product.
Solved Problem 1
Solution
Chapter 17 10
Nitration of Benzene
Sulfuric acid acts as a catalyst, allowing the reaction to be faster and at lower temperatures.
HNO3 and H2SO4 react together to form the electrophile of the reaction: nitronium ion (NO2
+).
HNO3H2SO4
NO2
+ H2O
Chapter 17 11
Mechanism for the Nitration of Benzene
Chapter 17 12
Reduction of the Nitro Group
NO2
Zn, Sn, or Feaq. HCl
NH2
Treatment with zinc, tin, or iron in dilute acid will reduce the nitro to an amino group.
This is the best method for adding an amino group to the ring.
Chapter 17 13
Sulfonation of Benzene
Sulfur trioxide (SO3) is the electrophile in the reaction. A 7% mixture of SO3 and H2SO4 is commonly referred
to as “fuming sulfuric acid”. The —SO3H groups is called a sulfonic acid.
SO3H
+ SO3H2SO4
Chapter 17 14
Mechanism of Sulfonation
Benzene attacks sulfur trioxide, forming a sigma complex.
Loss of a proton on the tetrahedral carbon and reprotonation of oxygen gives benzenesulfonic acid.
Chapter 17 15
Desulfonation Reaction
Sulfonation is reversible. The sulfonic acid group may be removed from
an aromatic ring by heating in dilute sulfuric acid.
HSO3H
+ H2OH+, heat
+ H2SO4
Chapter 17 16
Mechanism of Desulfonation
In the desulfonation reaction, a proton adds to the ring (the electrophile) and loss of sulfur trioxide gives back benzene.
Chapter 17 17
Nitration of Toluene
Toluene reacts 25 times faster than benzene. The methyl group is an activator. The product mix contains mostly ortho and
para substituted molecules.
Chapter 17 18
Ortho and Para Substitution
Ortho and para attacks are preferred because their resonance structures include one tertiary carbocation.
Chapter 17 19
Energy Diagram
Chapter 17 20
Meta Substitution
When substitution occurs at the meta position, the positive charge is not delocalized onto the tertiary carbon, and the methyl groups has a smaller effect on the stability of the sigma complex.
Chapter 17 21
Alkyl Group StabilizationCH2CH3
Br2FeBr3
CH2CH3
Br
CH2CH3
Br
CH2CH3
Br
+ +
o-bromo(38%)
m-bromo(< 1%)
p-bromo(62%)
Alkyl groups are activating substituents and ortho, para-directors.
This effect is called the inductive effect because alkyl groups can donate electron density to the ring through the sigma bond, making them more active.
Chapter 17 22
Substituents with Nonbonding Electrons
Resonance stabilization is provided by a pi bond between the —OCH3 substituent and the ring.
Chapter 17 23
Meta Attack on Anisole
Resonance forms show that the methoxy group cannot stabilize the sigma complex in the meta substitution.
Chapter 17 24
Bromination of Anisole
A methoxy group is so strongly activating that anisole is quickly tribrominated without a catalyst.
Chapter 17 25
The Amino Group
Aniline reacts with bromine water (without a catalyst) to yield the tribromoaniline.
Sodium bicarbonate is added to neutralize the HBr that is also formed.
Chapter 17 26
Summary of Activators
Chapter 17 27
Activators and Deactivators
If the substituent on the ring is electron donating, the ortho and para positions will be activated.
If the group is electron withdrawing, the ortho and para positions will be deactivated.
Chapter 17 28
Nitration of Nitrobenzene
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.
Chapter 17 29
Ortho Substitution on Nitrobenzene
The nitro group is a strongly deactivating group when considering its resonance forms. The nitrogen always has a formal positive charge.
Ortho or para addition will create an especially unstable intermediate.
Chapter 17 30
Meta Substitution on Nitrobenzene
Meta substitution will not put the positive charge on the same carbon that bears the nitro group.
Chapter 17 31
Energy Diagram
Chapter 17 32
Deactivators and Meta- Directors
Most electron withdrawing groups are deactivators and meta-directors.
The atom attached to the aromatic ring has a positive or partial positive charge.
Electron density is withdrawn inductively along the sigma bond, so the ring has less electron density than benzene and thus, it will be slower to react.
Chapter 17 33
Ortho Attack of Acetophenone
In ortho and para substitution of acetophenone, one of the carbon atoms bearing the positive charge is the carbon attached to the partial positive carbonyl carbon.
Since like charges repel, this close proximity of the two positive charges is especially unstable.
Chapter 17 34
Meta Attack on Acetophenone
The meta attack on acetophenone avoids bearing the positive charge on the carbon attached to the partial positive carbonyl.
Chapter 17 35
Other Deactivators
Chapter 17 36
Nitration of Chlorobenzene
When chlorobenzene is nitrated the main substitution products are ortho and para. The meta substitution product is only obtained in 1% yield.
Chapter 17 37
Halogens Are Deactivators
X
Inductive Effect: Halogens are deactivating because they are electronegative and can withdraw electron density from the ring along the sigma bond.
Chapter 17 38
Halogens Are Ortho, Para-Directors
Resonance Effect: The lone pairs on the halogen can be used to stabilize the sigma complex by resonance.
Chapter 17 39
Energy Diagram
Chapter 17 40
Summary of Directing Effects
Chapter 17 41
Effect of Multiple Substituents
The directing effect of the two (or more) groups may reinforce each other.
Chapter 17 42
Effect of Multiple Substituents (Continued)
The position in between two groups in Positions 1 and 3 is hindered for substitution, and it is less reactive.
Chapter 17 43
Effect of Multiple Substituents (Continued)
OCH3
O2N
Br2FeBr3
OCH3
O2N
Br
OCH3
O2N
Br
If directing effects oppose each other, the most powerful activating group has the dominant influence.
major products obtained
Chapter 17 44
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.
Chapter 17 45
Mechanism of the Friedel–Crafts Reaction
Step 1
Step 2
Step 3
Chapter 17 46
Protonation of Alkenes
An alkene can be protonated by HF. This weak acid is preferred because the
fluoride ion is a weak nucleophile and will not attack the carbocation.
Chapter 17 47
Alcohols and Lewis Acids
Alcohols can be treated with BF3 to form the carbocation.
Chapter 17 48
Limitations of Friedel–Crafts
Reaction fails if benzene has a substituent that is more deactivating than halogens.
Rearrangements are possible. The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
Chapter 17 49
Rearrangements
Chapter 17 50
Devise a synthesis of p-nitro-t-butylbenzene from benzene.
To make p-nitro-t-butylbenzene, we would first use a Friedel–Crafts reaction to make t-butylbenzene. Nitration gives the correct product. If we were to make nitrobenzene first, the Friedel–Crafts reaction to add the t-butyl group would fail.
Solved Problem 2
Solution
Chapter 17 51
Friedel–Crafts Acylation
Acyl chloride is used in place of alkyl chloride. The product is a phenyl ketone that is less
reactive than benzene.
Chapter 17 52
Mechanism of Acylation
Step 1: Formation of the acylium ion.
Step 2: Electrophilic attack to form the sigma complex.
Chapter 17 53
Clemmensen Reduction
The Clemmensen reduction is a way to convert acylbenzenes to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc.
Chapter 17 54
Nucleophilic Aromatic Substitution
A nucleophile replaces a leaving group on the aromatic ring.
This is an addition–elimination reaction. Electron-withdrawing substituents activate the
ring for nucleophilic substitution.
Chapter 17 55
Mechanism of Nucleophilic Aromatic Substitution
Step 1: Attack by hydroxide gives a resonance-stabilized complex.
Step 2: Loss of chloride gives the product. Step 3: Excess base deprotonates the product.
Chapter 17 56
Activated Positions
Nitro groups ortho and para to the halogen stabilize the intermediate (and the transition state leading to it).
Electron-withdrawing groups are essential for the reaction to occur.
Chapter 17 57
Benzyne Reaction: Elimination-Addition
Reactant is halobenzene with no electron-withdrawing groups on the ring.
Use a very strong base like NaNH2.
Chapter 17 58
Benzyne Mechanism
Sodium amide abstract a proton. The benzyne intermediate forms when the bromide is
expelled and the electrons on the sp2 orbital adjacent to it overlap with the empty sp2 orbital of the carbon that lost the bromide.
Benzynes are very reactive species due to the high strain of the triple bond.
Chapter 17 59
Nucleophilic Substitution on the Benzyne Intermediate
Chapter 17 60
Chlorination of Benzene
Addition to the benzene ring may occur with excess of chlorine under heat and pressure.
The first Cl2 addition is difficult, but the next two moles add rapidly. An insecticide
Chapter 17 61
Catalytic Hydrogenation
Elevated heat and pressure is required. Possible catalysts: Pt, Pd, Ni, Ru, Rh. Reduction cannot be stopped at an
intermediate stage.
CH 3
CH 3Ru, 100°C
1000 psi3 H 2,
CH 3
CH 3
Chapter 17 62
Birch Reduction
H
H
H
H
H
HNa or Li
NH3 (l), ROH
H
H
H
H
H
H
H
H
This reaction reduces the aromatic ring to a nonconjugated 1,4-cyclohexadiene.
The reducing agent is sodium or lithium in a mixture of liquid ammonia and alcohol.
Chapter 17 63
Mechanism of the Birch Reduction
Chapter 17 64
Limitations of the Birch Reduction
Chapter 17 65
Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic acid by heating in basic KMnO4 or heating in Na2Cr2O7/H2SO4.
The benzylic carbon will be oxidized to the carboxylic acid.
CH2CH3
(or Na2Cr2O7, H2SO4 , heat)
CO2HKMnO4, NaOHH2O, 100oC
Chapter 17 66
Side-Chain Halogenation
CH2CH3 Br2 or NBS
h
CHCH3
Br
The benzylic position is the most reactive. Br2 reacts only at the benzylic position.
Cl2 is not as selective as bromination, so results in mixtures.
Chapter 17 67
Mechanism of Side-Chain Halogenation
Chapter 17 68
SN1 Reactions
Benzylic carbocations are resonance-stabilized, easily formed.
Benzyl halides undergo SN1 reactions.
CH 2BrCH3CH2O H, heat
CH2O CH 2CH3
Chapter 17 69
SN2 Reactions
Benzylic halides are 100 times more reactive than primary halides via SN2.
The transition state is stabilized by a ring.
Chapter 17 70
Oxidation of Phenols
Na2Cr2O7 H2SO4
OH
Cl
O
Cl
O2-chloro-1,4-benzoquinone
Phenol will react with oxidizing agents to produce quinones.
Quinones are conjugated 1,4-diketones. This can also happen (slowly) in the presence of air.