chapter 17 reactions of aromatic compounds jo blackburn richland college, dallas, tx dallas county...
TRANSCRIPT
Chapter 17Reactions of
Aromatic Compounds
Jo BlackburnRichland College, Dallas, TX
Dallas County Community College District2003,Prentice Hall
Organic Chemistry, 5th EditionL. G. Wade, Jr.
Chapter 17 2
Electrophilic Aromatic Substitution
Electrophile substitutes for a hydrogen on the benzene ring.
=>
Chapter 17 3
Mechanism
=>
Chapter 17 4
Bromination of Benzene• Requires a stronger electrophile than Br2.
• Use a strong Lewis acid catalyst, FeBr3.
Br Br FeBr3 Br Br FeBr3 Animation
Br Br FeBr3
H
H
H
H
H
H
H
H
H
H
HH
Br+ + FeBr4
_
Animation
AnimationBr
HBr+ =>
Chapter 17 5
Energy Diagramfor Bromination
=>
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.
H+ HNO3 I21/2 I
+ NO2 H2O+ ++ +
=>
Chapter 17 7
Nitration of BenzeneUse sulfuric acid with nitric acid to form
the nitronium ion electrophile.
H O N
O
O
H O S O H
O
O
+ HSO4
_H O N
OH
O+
H O N
OH
O+
H2O + N
O
O
+NO2
+ then forms asigma complex withbenzene, loses H+ toform nitrobenzene. =>
Chapter 17 8
SulfonationSulfur trioxide, SO3, in fuming sulfuric acid
is the electrophile.
S
O
O OS
O
O OS
O
O OS
O
O O
+ + +
_
_ _
S
O
OO
H
S
O
O
OH
+
_S
HOO
O
benzenesulfonic acid
=>
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.
Benzene-d6
=>
D
D
D
D
D
DD2SO4/D2Olarge excess
H
H
H
H
H
H
Chapter 17 10
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 11
Sigma Complex
Intermediate is more stable if nitration occurs at the ortho or para position.
=>
Chapter 17 12
Energy Diagram
=>
Chapter 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
H
NO2
+
OCH3
H
NO2
+
=>
Chapter 17 14
Nitration of Anisole
Ortho attack
Meta attack
Para attack
=>
Chapter 17 15
The Amino Group
Aniline reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed.
NH2
Br23
H2O, NaHCO3
NH2
Br
Br
Br
=>
Chapter 17 16
Summary ofActivators
=>
Chapter 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 18
Ortho Substitutionon Nitrobenzene
=>
Chapter 17 19
Para Substitution on Nitrobenzene
=>
Chapter 17 20
Meta Substitutionon Nitrobenzene
=>
Chapter 17 21
Energy Diagram
=>
Chapter 17 22
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.
=>
Chapter 17 23
Summary of Deactivators
=>
Chapter 17 24
More Deactivators
=>
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. =>
Chapter 17 26
Sigma Complexfor Bromobenzene
Br
E+
BrH
E
(+)
(+)(+)
Ortho attack
+ Br
E+
Br
H E
+
(+)
(+)(+)
Para attack
Ortho and para attacks produce a bromonium ionand other resonance structures.
=>
Meta attack
Br
E+
Br
H
H
E
+
(+)
(+)No bromonium ion possible with meta attack.
Chapter 17 27
Energy Diagram
=>
Chapter 17 28
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.
OCH3
O2N
SO3
H2SO4
OCH3
O2N
SO3H
OCH3
O2N
SO3H
+
=>
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.
=>
Chapter 17 31
Examples ofCarbocation Formation
CH3 CH CH3
Cl
+ AlCl3
CH3C
H3C H
Cl AlCl3+ _
H2C CH CH3
HFH3C CH CH3
F+
_
H3C CH CH3
OHBF3
H3C CH CH3
OH BF3+
H3C CH CH3+
+ HOBF3
_
=>
Chapter 17 32
Formation of Alkyl Benzene
C
CH3
CH3
H+
H
H
CH(CH3)2+
H
H
CH(CH3)2
B
F
F
F
OHCH
CH3
CH3
+
HF
BF
OHF
=>
+
-
Chapter 17 33
Limitations ofFriedel-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-CraftsAcylation
• 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
R C
O
Cl AlCl3 R C
O
AlCl3Cl+ _
R C
O
AlCl3Cl+ _
AlCl4 +_ +
R C O R C O+
C
O
R
+
H
C
H
O
R
+
Cl AlCl3
_C
O
R +
HCl
AlCl3
=>
Chapter 17 36
Clemmensen Reduction
Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc.
+ CH3CH2C
O
Cl1) AlCl3
2) H2O
C
O
CH2CH3Zn(Hg)
aq. HCl
CH2CH2CH3
=>
Chapter 17 37
Gatterman-KochFormylation
• Formyl chloride is unstable. Use a high pressure mixture of CO, HCl, and catalyst.
• Product is benzaldehyde.
CO + HCl H C
O
ClAlCl3/CuCl
H C O+
AlCl4
_
C
O
H
+ C
O
H+ HCl+
=>
Chapter 17 38
NucleophilicAromatic Substitution
• A nucleophile replaces a leaving group on the aromatic ring.
• Electron-withdrawing substituents activate the ring for nucleophilic substitution.
=>
Chapter 17 39
Examples ofNucleophilic Substitution
=>
Chapter 17 40
Addition-EliminationMechanism
=>
Chapter 17 41
Benzyne Mechanism
• Reactant is halobenzene with no electron-withdrawing groups on the ring.
• Use a very strong base like NaNH2.
=>
Chapter 17 42
Benzyne Intermediate
CH3
HH
H NH2
CH3
HH
H NH2
_
or
CH3
HH
H
NH2
CH3
HH
H
NH2_
meta-toluidine para-toluidine =>
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.
=>
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.
=>
CH3
CH3Ru, 100°C
1000 psi3H2,
CH3
CH3
Chapter 17 45
Birch Reduction: Regiospecific
• A carbon with an e--withdrawing groupis reduced.
• A carbon with an e--releasing groupis not reduced.
C
O
OH Na, NH3
CH3CH2OH
C
O
OH
_
OCH3 Li, NH3
(CH3)3COH, THF
OCH3
=>
Chapter 17 46
Birch Mechanism
=>
Chapter 17 47
Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic acid by hot KMnO4 or Na2Cr2O7/H2SO4.
CH(CH3)2
CH CH2
KMnO4, OH-
H2O, heat
COO
COO_
_
=>
Chapter 17 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.
=>
CHCH2CH3
Br
hBr2, CH2CH2CH3
Chapter 17 49
SN1 Reactions
• Benzylic carbocations are resonance-stabilized, easily formed.
• Benzyl halides undergo SN1 reactions.
CH2BrCH3CH2OH, heat
CH2OCH2CH3
=>
Chapter 17 50
SN2 Reactions
• Benzylic halides are 100 times more reactive than primary halides via SN2.
• Transition state is stabilized by ring.
=>
Chapter 17 51
Reactions of Phenols
• Some reactions like aliphatic alcohols:phenol + carboxylic acid esterphenol + aq. NaOH phenoxide ion
• Oxidation to quinones: 1,4-diketones.
OH
CH3
Na2Cr2O7, H2SO4
CH3
O
O
=>
Chapter 17 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.
=>
Chapter 17 53
ElectrophilicSubstitution 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
_
CO2, OH-
O
C
O
O_
_
H+
OH
C
O
OH
salicylic acid=>
Chapter 17 54
End of Chapter 17