Download Chapter 17

Organic Chemistry
Chemistry, 7th Edition
L. G. Wade, Jr.
Chapter
p 17
Reactions of Aromatic Compounds
©2010, Prentice Hall
Electrophilic
p
Aromatic
Substitution
ƒ Alth
Although
h benzene’s
b
’ pii electrons
l t
are iin a stable
t bl aromatic
ti
system, they are available to attack a strong electrophile to give
a carbocation.
ƒ This resonance-stabilized carbocation is called a sigma
complex because the electrophile is joined to the benzene ring
by a new sigma bond.
ƒ Aromaticity is regained by loss of a proton.
Chapter 17
2
Mechanism of Electrophilic
p
Aromatic Substitution
Chapter 17
3
B
Bromination
i ti off Benzene
B
Chapter 17
4
Mechanism for the Bromination
of Benzene: Step 1
Br Br
FeBr3
Br
+
Br
FeBr3
(stronger electrophile than Br2)
ƒ Before the electrophilic
p
aromatic substitution can take
place, the electrophile must be activated.
ƒ A strong Lewis acid catalyst, such as FeBr3, should
be used.
Chapter 17
5
Mechanism for the Bromination
of Benzene: Steps 2 and 3
Step 2: Electrophilic attack and formation of the sigma complex.
H
H
H
H
Br
H
H
H
Br
Br
FeBr3
H
H
H
+ FeBr4-
H
H
Step 3: Loss of a proton to give the products.
H
H
H
Br
H
FeBr4H
Br
+ FeBr3 + HBr
H
H
H
H
H
H
Chapter 17
6
Energy Diagram for Bromination
Chapter 17
7
Chl i ti and
Chlorination
d IIodination
di ti
ƒ Chlorination is similar to bromination.
AlCl3 is most often used as catalyst, but
FeCl3 will also work.
ƒ Iodination requires an acidic oxidizing
agent like nitric acid
agent,
acid, to produce iodide
cation.
H+ + HNO3 + ½ I2
Chapter 17
I+ + NO2 + H2O
8
Solved Problem 1
Predict the major product(s) of bromination of p-chloroacetanilide.
Solution
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
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.
Chapter 17
9
Nit ti off B
Nitration
Benzene
NO2
HNO3
H2SO4
+
H 2O
ƒ Sulfuric acid acts as a catalyst, allowing the reaction
to be faster and at lower temperatures.
ƒ HNO3 and H2SO4 react together to form the
electrophile of the reaction: nitronium ion (NO2+).
Chapter 17
10
Mechanism for the Nitration of
Benzene
Chapter 17
11
R d ti off th
Reduction
the Nit
Nitro G
Group
NO2
NH2
Zn, Sn,
Zn
Sn or Fe
aq. HCl
ƒ T
Treatment
t
t with
ith zinc,
i
tin,
ti or iron
i
iin dil
dilute
t acid
id
will reduce the nitro to an amino group.
ƒ This is the best method for adding an amino
group to the ring.
Chapter 17
12
S lf
Sulfonation
ti off Benzene
B
+
SO3
H2SO4
SO3H
ƒ Sulfur trioxide (SO3) is the electrophile in the
reaction.
ƒ A 7% mixture of SO3 and H2SO4 is commonly
referred to as “fuming sulfuric acid”.
ƒ The —SO3H groups is called a sulfonic acid.
Chapter 17
13
M h i
Mechanism
off S
Sulfonation
lf
ti
ƒ Benzene attacks sulfur trioxide, forming a sigma
complex.
complex
ƒ Loss of a proton on the tetrahedral carbon and
reprotonation of oxygen gives benzenesulfonic acid
acid.
Chapter 17
14
D
Desulfonation
lf
ti R
Reaction
ti
SO3H
+
H , heat
H
+ H2 O
+ H2SO4
ƒ S
Sulfonation
lf
ti is
i reversible.
ibl
ƒ The sulfonic acid group may be removed
from an aromatic ring by heating in dilute
sulfuric acid.
Chapter 17
15
M h i
Mechanism
off D
Desulfonation
lf
ti
ƒ In the desulfonation reaction, a proton adds
to the ring (the electrophile) and loss of sulfur
trioxide gives back benzene.
Chapter 17
16
Nit ti off T
Nitration
Toluene
l
ƒ T
Toluene
l
reacts
t 25 ti
times ffaster
t than
th benzene.
b
ƒ The methyl group is an activator.
ƒ The product mix contains mostly ortho and
para substituted molecules.
p
Chapter 17
17
O th and
Ortho
d Para
P
Substitution
S b tit ti
ƒ Ortho and para attacks are preferred because their
resonance structures include one tertiary carbocation.
carbocation
Chapter 17
18
E
Energy
Di
Diagram
Chapter 17
19
M t S
Meta
Substitution
b tit ti
ƒ When substitution occurs at the meta position, the
positive charge
p
g is not delocalized onto the tertiary
y
carbon, and the methyl groups has a smaller effect
on the stability of the sigma complex.
Chapter 17
20
Alk l G
Alkyl
Group Stabilization
St bili ti
CH2CH3
CH2CH3
CH2CH3
CH2CH3
Br
Br2
FeBr3
+
+
Br
o-bromo
(38%)
m-bromo
(< 1%)
Br
p-bromo
(62%)
ƒ Alkyl groups are activating substituents and ortho,
para-directors.
ƒ This effect is called the inductive effect because
alkyl groups can donate electron density to the ring
through the sigma bond,
bond making them more active.
active
Chapter 17
21
Substituents with Nonbonding
g
Electrons
Resonance stabilization is provided by a pi bond between
th —OCH
the
OCH3 substituent
b tit
t and
d th
the ring.
i
Chapter 17
22
M t Att
Meta
Attackk on Anisole
A i l
ƒ Resonance forms show that the methoxy
group cannott stabilize
t bili th
the sigma
i
complex
l iin
the meta substitution.
Chapter 17
23
B
Bromination
i ti off Anisole
A i l
ƒ A methoxy group is so strongly activating that
anisole is quickly tribrominated without a
catalyst.
Chapter 17
24
Th A
The
Amino
i G
Group
ƒ Aniline reacts with bromine water (without a
catalyst)
y ) to yyield the tribromoaniline.
ƒ Sodium bicarbonate is added to neutralize
the HBr that is also formed.
Chapter 17
25
S
Summary
off Activators
A ti t
Chapter 17
26
A ti t
Activators
and
dD
Deactivators
ti t
ƒ If the substituent on the ring is electron donating, the
para p
positions will be activated.
ortho and p
ƒ If the group is electron withdrawing, the ortho and
para positions will be deactivated.
Chapter 17
27
Nit ti off Nit
Nitration
Nitrobenzene
b
ƒ Electrophilic substitution reactions for nitrobenzene
are 100,000
,
times slower than for benzene.
ƒ The product mix contains mostly the meta isomer,
only small amounts of the ortho and para isomers.
Chapter 17
28
Ortho Substitution on
Nitrobenzene
ƒ The nitro group is a strongly deactivating group when
considering its resonance forms. The nitrogen
always has a formal positive charge
charge.
ƒ Ortho or para addition will create an especially
unstable intermediate.
Chapter 17
29
Meta Substitution on
Nitrobenzene
ƒ Meta substitution will not put the positive
charge on the same carbon that bears the
nitro group.
Chapter 17
30
Energy Diagram
Chapter 17
31
Deactivators and MetaDirectors
ƒ Most electron withdrawing groups are
deactivators and meta-directors.
ƒ The atom attached to the aromatic ring has a
positive or partial positive charge.
ƒ Electron
El t
density
d
it is
i withdrawn
ithd
iinductively
d ti l
along the sigma bond, so the ring has less
electron
l t
d
density
it th
than b
benzene and
d th
thus, it will
ill
be slower to react.
Chapter 17
32
O th Attack
Ortho
Att k off Acetophenone
A t h
ƒ In ortho and para substitution of acetophenone,
acetophenone one
of the carbon atoms bearing the positive charge is
the carbon attached to the partial positive carbonyl
carbon.
carbon
ƒ Since like charges repel, this close proximity of the
two positive charges is especially unstable.
Chapter 17
33
M t Attack
Meta
Att k on Acetophenone
A t h
ƒ The meta attack on acetophenone avoids
bearing the positive charge on the carbon
attached to the partial positive carbonyl.
Chapter 17
34
Other Deactivators
Chapter 17
35
Nit ti off Chlorobenzene
Nitration
Chl b
ƒ Wh
When chlorobenzene
hl b
iis nitrated
it t d th
the main
i substitution
b tit ti
products are ortho and para. The meta substitution
product is only obtained in 1% yield
yield.
Chapter 17
36
H l
Halogens
A
Are D
Deactivators
ti t
X
ƒ IInductive
d ti Effect:
Eff t Halogens
H l
are d
deactivating
ti ti
because they are electronegative and can
withdraw
ithd
electron
l t
d
density
it ffrom th
the ring
i along
l
the sigma bond.
Chapter 17
37
Halogens
g
Are Ortho,, ParaDirectors
ƒ Resonance Effect: The lone pairs on the
halogen can be used to stabilize the sigma
complex by resonance
resonance.
Chapter 17
38
E
Energy
Di
Diagram
Chapter 17
39
S
Summary
off Directing
Di ti Eff
Effects
t
Chapter 17
40
Eff t off Multiple
Effect
M lti l Substituents
S b tit
t
ƒ The directing effect of the two (or more)
groups may reinforce each other.
Chapter 17
41
Effect of Multiple
p Substituents
(Continued)
ƒ The position in between two groups in
Positions 1 and 3 is hindered for substitution,
and it is less reactive.
Chapter 17
42
Effect of Multiple
p Substituents
(Continued)
OCH3
OCH3
OCH3
Br
Br2
FeBr3
O2N
O2N
O2N
Br
major
j products
p
obtained
ƒ If directing effects oppose each other, the
most powerful activating group has the
dominant influence.
Chapter 17
43
F i d l C ft Alkylation
Friedel–Crafts
Alk l ti
ƒ Synthesis of alkyl benzenes from alkyl halides
and a Lewis acid, usually AlCl3.
ƒ Reactions of alkyl halide with Lewis acid
produces a carbocation, which is the
electrophile
electrophile.
Chapter 17
44
Mechanism of the Friedel–Crafts
Reaction
Step 1
Step 2
Step 3
Chapter 17
45
P t
Protonation
ti off Alkenes
Alk
ƒ An alkene can be protonated by HF.
ƒ This weak acid is preferred because the
fluoride ion is a weak nucleophile and will not
attack the carbocation
carbocation.
Chapter 17
46
Al h l and
Alcohols
dL
Lewis
i A
Acids
id
ƒ Alcohols can be treated with BF3 to form the
carbocation.
Chapter 17
47
Limitations of Friedel–Crafts
ƒ Reaction fails if benzene has a substituent
that is more deactivating than halogens.
ƒ Rearrangements are possible.
ƒ The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
Chapter 17
48
R
Rearrangements
t
Chapter 17
49
Solved Problem 2
Devise a synthesis of p-nitro-t-butylbenzene from benzene.
Solution
To make p-nitro-t-butylbenzene, we would first use a Friedel–Crafts reaction to make tb t lb
butylbenzene.
Nit
Nitration
ti gives
i
th
the correctt product.
d t If we were tto make
k nitrobenzene
it b
fifirst,
t the
th
Friedel–Crafts reaction to add the t-butyl group would fail.
Chapter 17
50
F i d l C ft Acylation
Friedel–Crafts
A l ti
ƒ Acyl chloride is used in place of alkyl chloride.
ƒ The product is a phenyl ketone that is less
reactive than benzene.
Chapter 17
51
M h i
Mechanism
off A
Acylation
l ti
Step 1: Formation of the acylium ion.
Step 2: Electrophilic attack to form the sigma complex.
Chapter 17
52
Cl
Clemmensen
Reduction
R d ti
ƒ Th
The Clemmensen
Cl
reduction
d ti is
i a way tto
convert acylbenzenes to alkylbenzenes by
t t
treatment
t with
ith aqueous HCl and
d
amalgamated zinc.
Chapter 17
53
Nucleophilic
p
Aromatic
Substitution
ƒ A nucleophile replaces a leaving group on the
aromatic ring.
ƒ This is an addition–elimination reaction
reaction.
ƒ Electron-withdrawing substituents activate the
ring for nucleophilic substitution
substitution.
Chapter 17
54
Mechanism of Nucleophilic
p
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
55
A ti t d Positions
Activated
P iti
ƒ Nitro groups ortho and para to the halogen
stabilize the intermediate (and the transition
state leading to it).
ƒ Electron-withdrawing groups are essential for
the reaction to occur.
Chapter 17
56
Benzyne
y Reaction: EliminationAddition
ƒ Reactant is halobenzene with no electronwithdrawing groups on the ring
ring.
ƒ Use a very strong base like NaNH2.
Chapter 17
57
B
Benzyne
Mechanism
M h i
ƒ Sodium amide abstract a proton.
ƒ The benzyne intermediate forms when the bromide is
expelled and the electrons on the sp2 orbital adjacent
p with the empty
p y sp
p2 orbital of the carbon
to it overlap
that lost the bromide.
ƒ Benzynes are very reactive species due to the high
strain of the triple bond
bond.
Chapter 17
58
Nucleophilic
p
Substitution on the
Benzyne Intermediate
Chapter 17
59
Chl i ti off B
Chlorination
Benzene
ƒ Addition to the
benzene ring may
occur with excess of
chlorine under heat
and pressure.
ƒ The
Th first
fi t Cl2 addition
dditi iis
difficult, but the next
t
two
moles
l add
dd rapidly.
idl
Chapter 17
An insecticide
60
C t l ti H
Catalytic
Hydrogenation
d
ti
CH 3
CH 3
3 H 2, 1000 psi
Ru, 100°C
CH 3
CH 3
ƒ El
Elevated
t dh
heatt and
d pressure iis required.
i d
ƒ Possible catalysts: Pt, Pd, Ni, Ru, Rh.
ƒ Reduction cannot be stopped at an
intermediate stage.
g
Chapter 17
61
Bi h R
Birch
Reduction
d ti
H
H
H
H
Na or Li
NH3 (l), ROH
H
H
H
H
H
H
H
H
H
H
ƒ Thi
This reaction
ti reduces
d
the
th aromatic
ti ring
i tto a
nonconjugated 1,4-cyclohexadiene.
ƒ The reducing agent is sodium or lithium in a
mixture of liquid ammonia and alcohol.
Chapter 17
62
Mechanism of the Birch Reduction
Chapter 17
63
Li it ti
Limitations
off th
the Bi
Birch
hR
Reduction
d ti
Chapter 17
64
Sid Ch i Oxidation
Side-Chain
O id ti
CH2CH3
KMnO4, NaOH
H2O, 100oC
CO2H
(or Na2Cr2O7, H2SO4 , heat)
ƒ Alkylbenzenes are oxidized to benzoic acid by
heating in basic KMnO4 or heating in
Na2Cr2O7/H2SO4.
ƒ The benzylic carbon will be oxidized to the carboxylic
acid.
Chapter 17
65
Sid Ch i H
Side-Chain
Halogenation
l
ti
Br
CH2CH3
Br2 or NBS
hν
CHCH3
ƒ Th
The benzylic
b
li position
iti iis th
the mostt reactive.
ti
ƒ Br2 reacts only at the benzylic position.
ƒ Cl2 is not as selective as bromination, so
results in mixtures.
Chapter 17
66
Mechanism of Side-Chain
Halogenation
Chapter 17
67
SN1 R
Reactions
ti
ƒ Benzylic carbocations are resonancestabilized, easily formed.
ƒ Benzyl halides undergo SN1 reactions
reactions.
CH 2Br
C H 3 CH 2 O H, heat
Chapter 17
C H 2 O CH 2C H 3
68
SN2 R
Reactions
ti
ƒ Benzylic halides are
100 ti
times more
reactive than
primary
i
h
halides
lid via
i
SN2.
ƒ The transition state
is stabilized by a
ring.
Chapter 17
69
O id ti off Phenols
Oxidation
Ph
l
OH
O
Cl
Cl
Na2Cr2O7
H2SO4
O
2-chloro-1,4-benzoquinone
ƒ Phenol will react with oxidizing agents to produce
quinones.
ƒ Quinones
Q i
are conjugated
j
t d1
1,4-diketones.
4 dik t
ƒ This can also happen (slowly) in the presence of air.
Chapter 17
70