Transcript Lecture 11 and 12

Treatment of cyclooctatetrene with potassium gives you a
dianion. Classify the starting material and product as
aromatic, antiaromatic or nonaromatic?
2K
1
2
Classify cyclononatetrene and it’s various ions as
either aromatic, antiaromatic or nonaromatic.
3
4
Electrophilic Aromatic Substitution
Background
• The characteristic reaction of benzene is electrophilic aromatic
substitution—a hydrogen atom is replaced by an electrophile.
5
• Benzene does not undergo addition reactions like other
unsaturated hydrocarbons, because addition would yield
a product that is not aromatic.
• Substitution of a hydrogen keeps the aromatic ring
intact.
• There are five main examples of electrophilic aromatic
substitution.
6
7
• Regardless of the electrophile used, all electrophilic aromatic
substitution reactions occur by the same two-step mechanism—
addition of the electrophile E+ to form a resonance-stabilized
carbocation, followed by deprotonation with base, as shown
below:
8
• The first step in electrophilic aromatic substitution forms a
carbocation, for which three resonance structures can be
drawn. To help keep track of the location of the positive
charge:
9
• The energy changes in electrophilic aromatic substitution are
shown below:
10
Halogenation
• In halogenation, benzene reacts with Cl2 or Br2 in the
presence of a Lewis acid catalyst, such as FeCl3 or
FeBr3, to give the aryl halides chlorobenzene or
bromobenzene respectively.
• Analogous reactions with I2 and F2 are not synthetically
useful because I2 is too unreactive and F2 reacts too
violently.
11
• Chlorination proceeds by a similar mechanism.
12
Nitration and Sulfonation
• Nitration and sulfonation introduce two different functional
groups into the aromatic ring.
• Nitration is especially useful because the nitro group can be
reduced to an NH2 group.
13
• Generation of the electrophile in nitration requires
strong acid.
14
• Generation of the electrophile in sulfonation requires
strong acid.
15
Friedel-Crafts Alkylation and Friedel-Crafts Acylation
• In Friedel-Crafts alkylation, treatment of benzene with an
alkyl halide and a Lewis acid (AlCl3) forms an alkyl
benzene.
16
• In Friedel-Crafts acylation, a benzene ring is treated with
an acid chloride (RCOCl) and AlCl3 to form a ketone.
• Because the new group bonded to the benzene ring is
called an acyl group, the transfer of an acyl group from
one atom to another is an acylation.
17
Friedel-Crafts Alkylation and Friedel-Crafts Acylation
18
19
• In Friedel-Crafts acylation, the Lewis acid AlCl3 ionizes the
carbon-halogen bond of the acid chloride, thus forming a
positively charged carbon electrophile called an acylium ion,
which is resonance stabilized.
• The positively charged carbon atom of the acylium ion then goes
on to react with benzene in the two step mechanism of
electrophilic aromatic substitution.
20
Three additional facts about Friedel-Crafts alkylation
should be kept in mind.
[1] Vinyl halides and aryl halides do not react in FriedelCrafts alkylation.
21
[2] Rearrangements can occur.
These results can
rearrangements.
be
explained
by
carbocation
22
23
Rearrangements can occur even when no free carbocation
is formed initially.
24
[3] Other functional groups that form carbocations can
also be used as starting materials.
25
Each carbocation can then go on to react with benzene to
form a product of electrophilic aromatic substitution. For
example:
26
Starting materials that contain both a benzene ring and an
electrophile are capable of intramolecular Friedel-Crafts
reactions.
27
For Monday, do problems 18.1-18.11.
28
1) Why is benzene less reactive than an alkene?
The pi electrons of benzene are delocalized over 6
atoms, thus making benzene more stable and less
available for electron donation.
While an alkene’s electrons are localized between two
atoms, thus making it more nucleophillc and more
reactive toward electrophiles.
29
2) Show how the other two resonance structures can be
deprotonated in step two of electrophillic aromatic
substitution.
H
E
B
E
H
B
E
E
30
H
B
E
E
31
3) Draw a detailed mechanism of the chlorination of
benzene.
Formation of Electrophile
Cl
FeCl3
Cl
Cl
Cl
FeCl3
Electrophillic Additon
H
H
Cl
Cl
FeCl3
H
Cl
+ FeCl4
Cl
H
Cl
32
Deprotonation
H
Cl
FeCl4
Cl
+ HCl + FeCl3
33
4) Draw stepwise mechanism for the sulfonation of A.
a
SO3
H2SO4
b
SO3H
Formation of Electrophile
O
H
S
O
OSO3H
SO3H
+
HSO4
O
34
Electrophillic Addition
R
R
R
SO3H
H
H
H
SO3H
SO3H
R
H
Deprotonation
SO3H
R
HSO4
H
SO3H
R
+ H2SO4
SO3H
35
5) What product is formed when benzene is reacted with
each of the following alkyl halides?
a)
CH(CH3)2
+
(CH3)2CHCl
AlCl3
b)
Cl
+
AlCl3
36
c)
O
O
+ H CH C
3
2
AlCl3
CH2CH3
Cl
37
6) What acid chloride is necessary to produce each
product from benzene using a Friedal-Crafts acylation?
a)
O
O
CH2CH2CH(CH3)2
Cl
CH2CH2CH(CH3)2
b)
O
O
Cl
38
c)
O
O
Cl
39
7) Draw a stepwise mechanism for the following
friedal-Crafts alkylation?
CH2CH3
+
CH3CH2Cl
AlCl3
Formation of Electrophile
CH3CH2Cl
AlCl3
H3CH2C
Cl
AlCl3
40
Electrophillic Additoon
H
H
H
CH2CH3
H3CH2C
Cl
CH2CH3
AlCl3
H
Protonation
CH2CH3
Cl
H
AlCl3
CH2CH3
CH2CH3
+ HCl + AlCl3
41
8) Which of these halides are reactive in a Friedal-Crafts
alkylation?
Br
Br
Br
Br
C
B
A
D
Br
Br
B
D
Look at the carbon to which the halogen is
attached and determine its hybridization. If sp2 its
unreactive, while sp3 is reactive.
42
9) Draw a stepwise mechanism for the following
reaction.
C(CH3)3
+ (CHe)2CHCH2Cl
+ HCl + AlCl3
AlCl3
Formation of Electrophile
CH3
CH3
H2
C
H3C
Cl
AlCl3
H2
C
H3C
H
Cl
AlCl3
H
1,2 H shift
CH3
H3C
CH3
+ AlCl4
43
Electrophillic Additon
CH3
H3C
CH3
H
H
C(CH3)3
H
C(CH3)3
H
C(CH3)3
Deprotonation
AlCl4
H
C(CH3)3
C(CH3)3
+ AlCl3 + HCl
44
10) Draw the product of each reaction
a)
+
H2SO4
b)
C(CH3)3
+
(H3C)2C
CH2
H2SO4
45
c)
OH
+
d)
H2SO4
OH
+
H2SO4
46
11) Draw a stepwise mechanism for the intermolecular
Friedal-Crafts acylation below
Cl
Cl
Cl
Cl
AlCl3
O
+ HCl + AlCl3
Cl
O
47
Formation of Electrophile
Cl
Cl
Cl
Cl
Cl
O
AlCl3
Cl3Al
Cl
O
Cl
Cl
Cl
Cl
+ AlCl4
O
O
48
Electrophillic addition
Cl
Cl
Cl
Cl
H
O
O
Cl
Cl
Cl
H
O
Cl
H
O
49
Deprotonation
Cl
Cl
Cl
H
AlCl4
Cl
O
O
+ HCl + AlCl3
50
Substituted Benzenes
Many substituted benzene rings undergo electrophilic
aromatic substitution.
Each substituent either increases or decreases the
electron density in the benzene ring, and this affects the
course of electrophilic aromatic substitution.
51
Considering inductive effects only, the NH2 group
withdraws electron density and CH3 donates electron
density.
52
Resonance effects are only observed with substituents
containing lone pairs or  bonds.
An electron-donating resonance effect is observed
whenever an atom Z having a lone pair of electrons is
directly bonded to a benzene ring.
53
• An electron-withdrawing resonance effect is observed in
substituted benzenes having the general structure
C6H5-Y=Z, where Z is more electronegative than Y.
• Seven resonance structures can be drawn for
benzaldehyde (C6H5CHO). Because three of them place a
positive charge on a carbon atom of the benzene ring,
the CHO group withdraws electrons from the benzene
ring by a resonance effect.
54
• To predict whether a substituted benzene is more or less
electron rich than benzene itself, we must consider the
net balance of both the inductive and resonance effects.
• For example, alkyl groups donate electrons by an
inductive effect, but they have no resonance effect
because they lack nonbonded electron pairs or  bonds.
• Thus, any alkyl-substituted benzene is more electron
rich than benzene itself.
55
• The inductive and resonance effects in compounds having the
general structure C6H5-Y=Z (with Z more electronegative than Y)
are both electron withdrawing.
56
• These compounds represent examples of the general
structural features in electron-donating and electron
withdrawing substituents.
57
Electrophilic Aromatic Substitution and Substituted
Benzenes.
•
Electrophilic aromatic substitution is a general reaction
of all aromatic compounds, including polycyclic
aromatic hydrocarbons, heterocycles, and substituted
benzene derivatives.
•
A substituent affects two aspects of the electrophilic
aromatic substitution reaction:
1. The rate of the reaction—A substituted benzene
reacts faster or slower than benzene itself.
2. The orientation—The new group is located either
ortho, meta, or para to the existing substituent.
The identity of the first substituent determines the
position of the second incoming substituent.
58
• Consider toluene—Toluene reacts faster than benzene
in all substitution reactions.
• The electron-donating CH3 group activates the benzene
ring to electrophilic attack.
• Ortho and para products predominate.
• The CH3 group is called an ortho, para director.
59
• Consider nitrobenzene—It reacts more slowly than
benzene in all substitution reactions.
• The electron-withdrawing NO2 group deactivates the
benzene ring to electrophilic attack.
• The meta product predominates.
• The NO2 group is called a meta director.
60
All substituents can be divided into three general types:
61
62
• Keep in mind that halogens are in a class by
themselves.
• Also note that:
63
• To understand how substituents activate or deactivate the ring,
we must consider the first step in electrophilic aromatic
substitution.
• The first step involves addition of the electrophile (E+) to form a
resonance stabilized carbocation.
• The Hammond postulate makes it possible to predict the relative
rate of the reaction by looking at the stability of the carbocation
intermediate.
64
• The principles of inductive effects and resonance effects can
now be used to predict carbocation stability.
65
The energy diagrams below illustrate the effect of electronwithdrawing and electron-donating groups on the transition state
energy of the rate-determining step.
Figure 18.6 Energy diagrams comparing the rate of electrophilic substitution of substituted benzenes
66
67
Orientation Effects in Substituted Benzenes
• There are two general types of ortho, para directors and
one general type of meta director.
• All ortho, para directors are R groups or have a
nonbonded electron pair on the atom bonded to the
benzene ring.
• All meta directors have a full or partial positive charge
on the atom bonded to the benzene ring.
68
To evaluate the effects of a given substituent, we can use
the following stepwise procedure:
69
• A CH3 group directs electrophilic attack ortho and para to itself
because an electron-donating inductive effect stabilizes the
carbocation intermediate.
70
• An NH2 group directs electrophilic attack ortho and para to itself
because the carbocation intermediate has additional resonance
stabilization.
71
• With the NO2 group (and all meta directors) meta attack occurs
because attack at the ortho and para position gives a
destabilized carbocation intermediate.
72
Figure 18.7
The reactivity and directing
effects of common substituted
benezenes
73
For Wednesday:
Draw out stepwise mechanisms for 10b and c.
18.12-18.20 as well.
74
10b)
C(CH3)3
+
(H3C)2C
CH2
H2SO4
Formation of Electrophile
(H3C)2C
CH2
H
O
SO3H
(H3C)2C
CH3
HSO4
Electrophillic Addition
C(CH3)3
H
H
C(CH3)3
C(CH3)3
H
H
Deprotonation
C(CH3)3
H
C(CH3)3
HSO4
+ H2S04
C(CH3)3
10c)
OH
+
H2SO4
Formation of Electrophile
OH
H
O
SO3H
OH2
+ HSO4
+ H2O + HSO4
Electrophillic Addition
H
H
H
H
Deprotonation
HSO4
H
12)Identify each group as having an electron
donating or electron withdrawing inductive effect.
a) CH3CH2CH2CH2-
Electron donating
b) Br-
Electron withdrawing
c) CH3CH2O-
Electron withdrawing
13) Draw the resonance structures and use them to
determine whether there is an electron donating or
withdrawing resonance effect.
OCH
a)
3
OCH3
OCH3
OCH3
OCH3
OCH3
Negative charge on ring, electron donating effect
b)
O
O
O
O
O
O
O
O
Positive charge, electron
withdrawing
14)Identify as electron donating or electron withdrawing.
a)
OCH3
Lone pair on oxygen, electron
donating
b)
c)
I
C(CH3)3
Halogen, electron
withdrawing
Alkyl group, electron
donating
15)Predict the products.
a)
OCH3
OCH3
CH3CH2Cl
+
AlCl3
b)
Br
HNO3
OCH3
CH2CH3
Br
Br
+
H2SO4
NO2
H3CH2C
O2N
c)
NO2
NO2
Cl2
FeCl3
Cl
16)Predict the products when reacted with HNO3 and
H2SO4. Also state whether the reactant is more or less
reactive than benzene.
a)
O
O
Less
NO2
b)
N
N
O2N
Less
c)
OH
OH
OH
+
NO2
O2N
More
d)
Cl
Cl
Cl
+
NO2
Less
O2N
d)
CH2CH3
CH2CH3
CH2CH3
+
NO2
More
O2N
17)Label each compound as less or more reactive
than benzene.
a)
C(CH3)3
more
b)
OH
more
OH
c)
O
less
OCH2CH3
d)
N(CH3)3
less
18) Rank each group in order of increasing reactivity.
a)
Cl
2
3
OCH3
1
b)
NO2
2
3
CH3
1
19) Draw the resonance structures of ortho attack by NO2.
Label any resonance structure that is especially stable or
unstable.
a)
C(CH3)3
C(CH3)3
C(CH3)3
NO2
NO2
C(CH3)3
NO2
C(CH3)3
Most stable
NO2
b)
OH
OH
OH
NO2
NO2
OH
OH
NO2
OH
Most stable
NO2
NO2
c)
O
O
O
NO2
NO2
O
NO2
O
O
Vey
unstable
NO2
NO2
20) Show why chlorine is an ortho para director.
Cl
Cl
Cl
E
E
E
Cl
Cl
E
E
Especially stable, every atom has an octet
Cl
Cl
Cl
E
E
E
Cl
E
Cl
Cl
Cl
E
E
E
Cl
Especially stable, every
atom has an octet
E
Limitations in Electrophilic Aromatic Substitutions
• Benzene rings activated by strong electron-donating groups—
OH, NH2, and their derivatives (OR, NHR, and NR2)—undergo
polyhalogenation when treated with X2 and FeX3.
98
• A benzene ring deactivated by strong electron-withdrawing
groups (i.e., any of the meta directors) is not electron rich
enough to undergo Friedel-Crafts reactions.
• Friedel-Crafts reactions also do not occur with NH2 groups
because the complex that forms between the NH2 group and the
AlCl3 catalyst deactivates the ring towards Friedel-Crafts
reactions.
99
• Treatment of benzene with an alkyl halide and AlCl3
places an electron-donor R group on the ring. Since R
groups activate the ring, the alkylated product (C6H5R) is
now more reactive than benzene itself towards further
substitution, and it reacts again with RCl to give
products of polyalkylation.
• Polysubstitution does not occur with Friedel-Crafts
acylation.
100
Disubstituted Benzenes
1. When the directing effects of two groups reinforce, the
new substituent is located on the position directed by
both groups.
101
2. If the directing effects of two groups oppose each
other, the more powerful activator “wins out.”
102
3. No substitution occurs between two meta substituents
because of crowding.
103
Synthesis of Benzene Derivatives
In a disubstituted benzene, the directing effects indicate
which substituent must be added to the ring first.
Let us consider the consequences of bromination first
followed by nitration, and nitration first, followed by
bromination.
104
Pathway I, in which bromination precedes nitration, yields the
desired product. Pathway II yields the undesired meta isomer.
105
Halogenation of Alkyl Benzenes
Benzylic C—H bonds are weaker than most other sp3 hybridized
C—H bonds, because homolysis forms a resonance-stabilized
benzylic radical.
As a result, alkyl benzenes undergo selective bromination at the
weak benzylic C—H bond under radical conditions to form the
benzylic halide.
106
107
Note that alkyl benzenes undergo two different reactions
depending on the reaction conditions:
• With Br2 and FeBr3 (ionic conditions), electrophilic aromatic
substitution occurs, resulting in replacement of H by Br on the
aromatic ring to form ortho and para isomers.
• With Br2 and light or heat (radical conditions), substitution of H
by Br occurs at the benzylic carbon of the alkyl group.
108
Oxidation and Reduction of Substituted Benzenes
Arenes containing at least one benzylic C—H bond are oxidized
with KMnO4 to benzoic acid.
Substrates with more than one alkyl group are oxidized to
dicarboxylic acids. Compounds without a benzylic hydrogen are
inert to oxidation.
109
Ketones formed as products of Friedel-Crafts acylation can be
reduced to alkyl benzenes by two different methods:
1. The Clemmensen reduction—uses zinc and mercury in the
presence of strong acid.
2. The Wolff-Kishner reduction—uses hydrazine (NH2NH2) and
strong base (KOH).
110
We now know two different ways to introduce an alkyl group on a
benzene ring:
1. A one-step method using Friedel-Crafts alkylation.
2. A two-step method using Friedel-Crafts acylation to form a
ketone, followed by reduction.
Figure 18.8
Two methods to prepare an
alkyl benzene
111
Although the two-step method seems more roundabout, it must be
used to synthesize certain alkyl benzenes that cannot be prepared
by the
one-step
Friedel-Crafts
alkylation
because of
rearrangements.
112
A nitro group (NO2) that has been introduced on a benzene
ring by nitration with strong acid can readily be reduced to
an amino group (NH2) under a variety of conditions.
113
For next time, 18.21-18.30