Transcript Ch. 5-2, Chemistry o..

Chapter 5-2.
Chemistry of Benzene:
Electrophilic Aromatic Substitution
Substitution Reactions of Benzene
and Its Derivatives
 Benzene is aromatic: a cyclic conjugated
compound with 6  electrons
 Reactions of benzene lead to the retention of
the aromatic -system
 Electrophilic aromatic substitution replaces a
proton on benzene with another electrophile
2
3
Bromination of Aromatic Rings
 Benzene’s  electrons participate as a Lewis base in
reactions with Lewis acids
 The product is formed by loss of a proton, which is
replaced by bromine
4
Bromination of Aromatic Rings
 FeBr3 is added as a catalyst to polarize the
bromine reagent
5
Cationic Intermediate in
Bromination
 The addition of bromine occurs in two steps
 In the first step the  electrons act as a
nucleophile toward Br2 (in a complex with
FeBr3)
6
This forms a cationic addition
intermediate
The intermediate
is not aromatic
and therefore
high in energy
7
Formation of Product from
Intermediate
 The cationic addition
intermediate transfers a
proton to FeBr4- (from
Br- and FeBr3)
 This restores aromaticity
(in contrast with
addition in alkenes)
8
9
Other Aromatic Substitutions
 The reaction with bromine
involves a mechanism that is
similar to many other
reactions of benzene with
electrophiles
 The cationic intermediate
was first proposed by G. W.
Wheland of the University of
Chicago and is often called
the Wheland intermediate
10
Aromatic Chlorination and Iodination
 Chlorine and iodine (but not fluorine, which is too
reactive) can produce aromatic substitution in the
presence of Lewis acids.
 Chlorination requires FeCl3
11
Aromatic Chlorination and Iodination
 Iodine must be oxidized to form a more powerful I+
species (with Cu+ or peroxide)
12
Aromatic Nitration
 The combination of nitric acid and sulfuric
acid produces NO2+ (nitronium ion), which
is isoelectronic with CO2
13
Aromatic Nitration
 The reaction with benzene produces
nitrobenzene
14
Reduction of nitro compounds
to amines
15
Aromatic Sulfonation
 Substitution of H by SO3 (sulfonation)
 Reaction with a mixture of sulfuric acid and
SO3 (fuming sulfuric acid)
 Reactive species is sulfur trioxide or its
conjugate acid
16
Aromatic Sulfonation
 Sulfur trioxide, or its conjugate acid, react
by the usual mechanism:
17
Useful reactions of sulfonic acids
 Sulfonic acids are useful as intermediates in the
synthesis of sulfa drugs and phenols:
18
Alkylation of Aromatic Rings: The
Friedel–Crafts Reaction
 Aromatic substitution of “R+” for H,
alkylating the ring
19
Alkylation of Aromatic Rings: The
Friedel–Crafts Reaction
 Aromatic
substitution of a R+
for H
 Aluminum chloride
promotes the
formation of the
carbocation
 Wheland
intermediate forms
20
Limitations of the Friedel-Crafts
Alkylation
 Only alkyl halides can be used (F, Cl, I, Br)
 Aryl halides and vinylic halides do not react
(their carbocations are too hard to form)
21
Control Problems
 Multiple alkylations can occur because the
first alkylation is activating
22
Carbocation Rearrangements During
Alkylation
 Similar to those that occur during electrophilic
additions to alkenes
23
24
Similar reactions:
Mechanism?
25
Solution:
26
Another variation:
27
Acylation of Aromatic Rings
 Reaction of an acid chloride (RCOCl) and an
aromatic ring in the presence of AlCl3
introduces acyl group, COR
28
Mechanism of Friedel-Crafts Acylation
 Similar to alkylation; reactive electrophile is a
resonance-stabilized acyl cation, which does
not rearrange
29
Problem: acid chloride reactant?
30
Substituent Effects in Aromatic Rings
 Substituents can cause a compound to be
(much) more or (much) less reactive than
benzene
31
Substituent Effects in Aromatic Rings
 Substituents affect the orientation of the reaction – the
positional relationship is controlled
 ortho- and para-directing activators, ortho- and
para-directing deactivators, and meta-directing
deactivators
32
33
Origins of Substituent Effects
 An interplay of inductive effects and
resonance effects
 Inductive effect - withdrawal or donation of
electrons through a s bond
 Resonance effect - withdrawal or donation
of electrons through a  bond due to the
overlap of a p orbital on the substituent
with a p orbital on the aromatic ring
34
Inductive Effects
 Controlled by electronegativity and the polarity
of bonds in functional groups
 Halogens, C=O, CN, and NO2 withdraw
electrons through s bond connected to ring
 Alkyl groups donate electrons
35
Resonance Effects – Electron
Withdrawal
 C=O, CN, NO2 substituents withdraw electrons
from the aromatic ring by resonance
36
Resonance Effects – Electron
Withdrawal
37
Resonance Effects – Electron
Donation
 Halogen, OH, alkoxyl (OR), and amino
substituents donate electrons
 Effect is greatest at ortho and para
38
Resonance Effects – Electron
Donation
39
Contrasting Effects
 Halogen, OH, OR, withdraw electrons
inductively so that they deactivate the
ring
 Resonance interactions are generally
weaker, affecting orientation
 The strongest effects dominate
40
An Explanation of Substituent
Effects
 Activating groups donate electrons to
the ring, stabilizing the Wheland
intermediate (carbocation)
 Deactivating groups withdraw electrons
from the ring, destabilizing the Wheland
intermediate
41
42
Electron Donation & Withdrawal
from Benzene Rings
43
Ortho- and Para-Directing
Activators: Alkyl Groups
 Alkyl groups activate: direct further
substitution to positions ortho and para
to themselves
 Alkyl group is most effective in the ortho
and para positions
44
45
Ortho- and Para-Directing
Activators: OH and NH2
 Alkoxyl, and amino groups have a strong,
electron-donating resonance effect
 Most pronounced at the ortho and para
positions
46
47
Ortho- and Para-Directing
Deactivators: Halogens
 Electron-withdrawing inductive effect
outweighs weaker electron-donating
resonance effect
 Resonance effect is only at the ortho and
para positions, stabilizing carbocation
intermediate
48
49
Meta-Directing Deactivators
 Inductive and resonance effects
reinforce each other
 Ortho and para intermediates
destabilized by deactivation from
carbocation intermediate
 Resonance cannot produce
stabilization
50
51
Summary Table: Effect of
Substituents in Aromatic Substitution
52
Trisubstituted Benzenes: Additivity
of Effects
 If the directing effects of the two groups
are the same, the result is additive
53
Substituents with Opposite
Effects
 If the directing effects of two groups
oppose each other, the more powerful
activating group decides the principal
outcome
54
Meta-Disubstituted Compounds Are
Unreactive between the two groups
 The reaction site is too hindered
55
Prob.: Substitution at which positions?
56
Prob.: Major substitution product(s)?
57
Oxidation of Aromatic Compounds
 Alkyl side chains can be oxidized to CO2H
by strong reagents such as KMnO4 and
Na2Cr2O7 if they have a C-H next to the ring
 Converts an alkylbenzene into a benzoic
acid
58
Prob.: Oxidation products?
59
Reduction of Aromatic Compounds
 Aromatic rings are inert to catalytic hydrogenation under
conditions that reduce alkene double bonds
 Can selectively reduce an alkene double bond in the
presence of an aromatic ring
 Reduction of an aromatic ring requires more powerful
reducing conditions (high pressure or rhodium catalysts)
60
61
Reduction of Aryl Alkyl Ketones
 Aromatic ring activates neighboring carbonyl
group toward reduction
 Ketone is converted into an alkylbenzene by
catalytic hydrogenation over Pd catalyst
62
Synthesis Strategies
 These syntheses require planning and
consideration of alternative routes
 Work through the practice problems in this
section following the general guidelines for
synthesis and retrosynthetic analysis.
63
Practice Problem:
Synthesize From Benzene:
64
Solutions:
65
Practice Problem:
Synthesize From Benzene:
66
67
How can we make m-chloropropylbenzene?
68
Putting it all together:
69
Prob.: What’s wrong with these
syntheses?
70
Prob.: What’s wrong with these
syntheses?
71
Prob.: Synthesize from benzene
72
Prob.: Identify the reagents
73