KOT 222 ORGANIC CHEMISTRY II
CHAPTER 17
REACTIONS of
AROMATIC COMPOUNDS
1
Electrophilic Aromatic Substitution
¾ Substitution of an electrophile for a proton on the
aromatic ring.
¾ benzene’s pi electrons are available to attack a
strong electrophile to give a carbocation (sigma
complex).
Highly
endothermic
Loss of a proton to
regain aromaticity
2
Mechanism:
Step 1: Attack on the electrophile forms the sigma complex.
Regain the aromaticity
3
Bromination of Benzene
¾ Follows the mechanism for electrophilic aromatic
substitution.
¾ Requires a stronger electrophile than Br2.
¾ Use a strong Lewis acid catalyst, FeBr3.
Br Br
FeBr3
Br
H
Br
H
H
H
Br
FeBr
3
H
H
H
+
+
Br
-
H
H
Br
FeBr3
+
H
_
+ FeBr4
H
H
4
Energy Diagram for Bromination
¾ The first step is strongly endothermic.
¾ Second step is strongly exothermic.
¾ Overall reaction is exothermic by 45 kJ/mol.
5
Comparison with Alkenes
¾ Cyclohexene adds Br2, ΔH = -121 kJ/mol.
H
H
+ Br2
Br
Br
H
H
¾ Similar addition to benzene is endothermic, not
normally seen.
¾ Substitution of Br for H retains aromaticity, ΔH =
-45 kJ.
6
Chlorination and Iodination of Benzene
¾ Chlorination is similar to bromination. Use AlCl3
as the Lewis acid catalyst.
H
Cl
AlCl3
+ Cl2
+ HCl
¾ Iodination requires an acidic oxidizing agent,
like nitric acid, which oxidizes the iodine to an
iodonium ion.
H+
+
HNO3
+
1/2 I2
I+
+
NO2
+
H 2O
I
H
+ 1/2 I2 +
HNO3
+
NO2
+
H2 O
7
Nitration of Benzene
¾ Use sulfuric acid with nitric acid to form the
nitronium ion electrophile.
Protonation of -OH
Attack on the electrophile
Formation of nitronium ion
Loss of a proton gives nitrobenzene
H
H
H
O
N
H
H
O
H
8
Reduction of nitro group
HNO3
R
H2SO4
R
Zn, Sn, or Fe
R
NO2
NO2
R
NH2
aq HCl
The best way to add an amino group to an
aromatic ring.
9
Sulfonation of Benzene
¾ Electrophile = Sulfur trioxide, SO3, in fuming
sulfuric acid.
O
O
O
O
O
S
S
S
S
O
O
O
O
O
O
O
benzenesulfonic acid
10
Desulfonation
¾ Sulfonation is reversible.
¾ sulfonic acid group can be removed by heating
in dilute sulfuric acid.
¾ a proton adds to the ring (the electrophile) and
loss of sulfur trioxide gives back benzene.
SO3H
H+, heat
+
H 2O
H
+
H2SO4
11
Effects of Substituents
The slow step of an electrophilic aromatic substitution
reaction is the formation of the cation intermediate
Electron-donating substituents increase the rate of the
substitution reactions by stabilizing the carbocation
intermediate and the transition state leading to its
formation
Electron-donating groups are activating substituents
Electron-withdrawing groups are deactivating
substituents
12
Nitration of Toluene
¾ Toluene reacts 25 times faster than benzene.
The methyl group is an activating group.
¾ The product mix contains mostly ortho and para
substituted molecules.
ortho
meta
ortho
para
meta
Stability of the intermediate sigma complex determine
the substitution pattern.
13
Sigma Complex
Positive
charge is
delocalized
onto the 3o
carbon
atom
Positive
charge is
not
delocalized
onto the 3o
carbon
14
atom
Energy Diagram
Methyl group stabilize the sigma complex and the
transition state leading to them.
15
Activating, O-, PDirecting Substituents
¾ Alkyl groups stabilize the sigma complex
by induction, donating electron density
through the sigma bond.
¾ Substituents with a lone pair of electrons
stabilize the sigma complex by
resonance.
16
Substitution on Anisole
All atoms
(except H)
have complete
octets.
Resonance stabilization is provided by a pi bond between the -OCH3
substituent and the ring.
17
The Amino Group
¾ Nitrogen atom with a pair of nonbonding electron
serves as powerful activating group.
¾ Aniline reacts with bromine water (without a
catalyst) to yield the tribromide. Sodium
bicarbonate is added to neutralize the HBr that’s
also formed.
18
Summary of Activators
19
Deactivating, MetaDirecting Substituents
¾ Substituent on a benzene ring has its greatest
effect on the ortho and para positions.
¾ Nitrobenzene is about 100,000 less reactive than
benzene in electrophilic substitution reactions.
¾ The product mix contains mostly the meta isomer,
only small amounts of the ortho and para isomers.
20
Nitro group on benzene
¾ The nitrogen always has a formal positive charge.
¾ The positively charged nitrogen inductively
withdraws elecron density from the ring.
¾ The benzene ring is deactivated toward reaction
with electrophiles.
21
Sigma Complex
22
Energy Diagram
23
Effect of carbonyl group - Meta director
24
Summary of Deactivators
¾ The atom attached to the aromatic ring will have
a positive / partial positive charge.
25
Halobenzenes
¾ 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.
26
Sigma Complex for Bromobenzene
Ortho and para attacks produce a bromonium ion which
provide extra resonance stability and other resonance
structures.
No bromonium ion
possible with meta
attack.
27
Energy Diagram
28
Effects of Multiple Substituents
¾ If the groups reinforce each other, the result is
easy to predict.
29
A strongly activating substituent will win out over a
weakly activating substituent or a deactivating
substituent.
30
If the two substituents have similar activating
properties, neither will dominate.
31
Friedel-Crafts Alkylation
¾ Synthesis of alkyl benzenes from alkyl halides
and a Lewis acid, usually AlCl3.
¾ Lewis acid is used as a catalyst to generate the
carbocation from the alkyl halide (2° or 3°) or to
activate the alkyl halide (1° or methyl halide)
toward nucleophilic attack.
¾ Other sources of carbocations:
alkenes + HF, or alcohols + BF3.
32
With 2o and 3o alkyl halides
Step 1: Formation of carbocation
Step 2: Electrophilic attack
Step 3: Loss of proton
33
With 1o alkyl halides
34
Protonation of Alkenes for Friedel-Crafts Alkylation
35
Alcohols with BF3 for Friedel-Crafts Alkylation
F
(+)
H
(+)
H
F
H
B
OH
F
H
+
H
HF
F
F
B
OH
The reaction is promoted by BF3
36
Limitations of Friedel-Crafts
1. Reaction fails if benzene has a substituent that
is more deactivating than halogen.
C(CH3)3
C(CH3)3
C(CH3)3
(CH3)3C-Cl
HNO3
AlCl3
H2SO4
?
NO2
NO2
HNO3
H2SO4
NO2
(CH3)3C-Cl
AlCl3
Reaction
fails
37
2. Carbocations rearrange. Reaction of benzene
with n-propyl chloride and AlCl3 produces
isopropylbenzene.
No or low yield of n-propylbenzene
38
3. The alkylbenzene product is more reactive
than benzene, so multiple alkylation occurs.
¾ To overcome carbocation rearrangement and
polyalkylation, Friedel-Crafts acylation is used.
39
Friedel-Crafts Acylation
¾ Acyl chloride is used in place of alkyl chloride.
benzoyl chloride
¾ The product is a phenyl ketone that is less
reactive than benzene.
40
Mechanism of Acylation
Step 1: formation of an acylium ion (the
electrophilic species) by reaction of the
acyl chloride with the catalyst.
The acylium ion intermediate is resonance
stabilized and does not rearrange like a
carbocation.
41
Step 2: benzene attacks the acylium ion to form the sigma
complex.
Step 3: Loss of proton regenerates the aromatic system
Step 4: Complexation of the product
H2O
42
Carbonyl group deactivate
the benzene ring toward
further substitution.
When the aromatic substrate has an ortho, paradirecting group, para substitution will prevail.
O
CH3CH2
+ H3 C
C
Cl
1. AlCl3
2. H2O
O
CH3CH2
C
CH3
43
Gatterman-Koch Formylation
¾ Formyl chloride is unstable, cannot be used in
acylation.
¾ Use a high pressure mixture of CO, HCl, and
catalyst.
O
AlCl3 / CuCl
CO + HCl
H
C
Cl
formyl chloride
(unstable)
H
C
O
AlCl4
formyl cation
O
+
H
C
O
C
H
+
HCl
benzaldehyde
44
Clemmensen Reduction
¾ Acylbenzenes can be converted to
alkylbenzenes by treatment with aqueous HCl
and amalgamated zinc.
45
Nucleophilic Aromatic Substitution
¾ Aryl halide normally do not reacts with
nucleophiles at standard condition.
¾ Electron-withdrawing groups (at ortho or para to
the halide) activate the ring for nucleophilic
substitution.
46
Nucleophilic aromatic substitution may
involves either of the two mechanisms:
1. Addition-Elimination Mechanism
2.Birch Mechanism (Elimination-addition)
47
Addition-Elimination Mechanism
Electron-withdrawing group at ortho or para-position stabilize
the negatively charge sigma complex
48
Benzyne Mechanism
¾ Nucleophilic aromatic substitution without
electron-withdrawing substituents.
¾ Require a strong base or high temperature.
49
Amide attacks at
either end of the
benzyne triple bond`
50
Chlorination of Benzene
¾ Addition of chlorine (excess) to the benzene ring
may occur with high heat and pressure (or light).
H
H
H
H
heat, pressure
+ 3 Cl2
H
H
H
or hv
H
Cl
H
Cl
Cl
H
H
Cl
H
Cl
Cl
¾ First addition is difficult as it destroy the ring’s
aromaticity.
¾ Next two mole of Cl2 add very rapidly.
51
Catalytic Hydrogenation
¾ Transformation of benzene to cyclohexane.
¾ Take places at elevated temperature and
pressure.
¾ Possible catalysts: Pt, Pd, Ni, Ru, Rh.
H
H
H
H
H
H
H
H
H
H
3 H2, 1000 psi
H
H
Pt
H
H
H
H
H
H
52
Birch Reduction
¾ Transformation of benzene to 1,4-cyclohexane.
¾ Involves twice adding a solvated electron,
followed by a proton.
53
Mechanism:
54
Side-Chain Oxidation
¾ Alkylbenzenes are oxidized to benzoic acid by
hot KMnO4 or Na2Cr2O7/H2SO4
55
Side-Chain Halogenation
¾ Free-radical halogenation is much more easily to
happen at the benzylic position.
56
¾ Chlorination is not as selective as bromination,
results in mixtures.
¾ Br2 reacts only at the benzylic position.
β
α
CH2CH3
Cl
H
β
C
CH3
α
H
α
H
β
C
CH2Cl
Cl2
+ dichlorinated
products
+
hv
56%
α
44%
H
β
CH2CH3
Br
α
C
β
CH3
Br
α
Br
C
β
CH3
Br2 or NBS
hv
+
trace
57
Nucleophilic Substitution at the
Benzylic Position
SN1 Reactions
¾ Benzylic carbocations are resonance-stabilized,
easily formed.
¾ Benzyl halides undergo SN1 reactions
CH2Br
CH3CH2OH, heat
CH2OCH2CH3
58
SN2 Reactions
¾ Benzylic halides are 100 times more reactive
than primary halides via SN2.
¾ Transition state is stabilized by conjugation with
the pi electrons in the ring.
59
Reactions of Phenols
¾ Some reactions like aliphatic alcohols:
™phenol + carboxylic acid → ester
™phenol + aq. NaOH → phenoxide ion
¾ Reactions that are peculiar to phenols are:
™Oxidation of phenols to quinones
™Electrophilic aromatic substitution of phenols
60
Oxidation of Phenols
¾ Phenols oxidized to quinones: 1,4-diketones.
O
OH
Na2Cr2O7, H2SO4
CH3
CH3
O
¾ Hydroquinone is used as a developer for film. It
reacts with light-sensitized AgBr grains,
converting it to black Ag.
O
OH
+ 2 AgBr *
OH
+
O
2 Ag
+
2 HBr
61
Electrophilic Aromatic
Substitution of Phenols
¾ Phenols and phenoxides are highly reactive.
¾ Only a weak catalyst (HF) required for FriedelCrafts reaction.
¾ Tribromination occurs without catalyst.
¾ Even reacts with CO2, a weak electrophile .
O
_
_
O
-
CO2, OH
O
C
OH
O
_
+
O
C
H
OH
salicylic acid
62
63