Electrophilic
Aromatic Substitution
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Sect. 22.1 Nomenclature
CH 3
benzene
Cl
chlorobenzene
toluene
aniline
NO 2
OH
nitrobenzene
phenol
O
O
NH 2
OH
benzoic acid
H
benzaldehyde
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Nomenclature-- examples
Group
ortho or 2
meta or 3
para or 4
O
O
H
OH
Cl
NO 2
3-nitro benzoic acid (IUP AC)
m-nitrobenzoic acid (common)
4-chlorobenzaldehyde (IUPAC)
p-chlorobenzaldehyde (common)
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Chapter 22: Aromatic Substitutions,
Monosubstitution reactions on benzene
Sect. 22.2 Electrophilic aromatic substitution
mechanism
Sect. 22.5 Nitration
Sect. 22.6. Halogenation
Sect. 22.7 Friedel-Crafts Reactions
Sect. 22.8 Sulfonation Reactions (skip fall 2006)
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Sect. 22.2 Electrophilic aromatic
substitution.
H
E+
H
H
H
SLOW
E
E
E
resonance stabilized cation
E
+ HB
H
re-aromatize
E
:B
"base"
delocalized
cation
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Sect. 22.5: Nitration
• conc. HNO3 and H2SO4 react to make electrophile, NO2+
• nitro aromatics are important intermediates
• reduction of nitro groups give anilines
HNO3
NO2
+ H2O
H2SO4
HSO4
H2SO4
H
NO2
NO2
O N O
nitronium ion
NO2
reduce
NH2
reducing agents: LiAlH4 or H2 / Pd(C) or Sn / HCl or Fe / HOAc
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Mechanism of Aromatic Nitration
Step 1: Where does the electrophile
come from?
H
O
HO
+
N
H2SO4
O
O
H
N
O
O
H
H
HSO4
O
O
N
O
N
O
O
+
H
O
H
Nitronium ion
Nitronium ion (NO2+) is the electrophile that reacts
with the benzene ring.
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Mechanism of Aromatic
Nitration (Step 2)
H
+
NO2
H
slow
H
NO2
NO2
H
NO2
a resonance-stabilized arenium ion
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Mechanism of Aromatic
Nitration (Step 3)
H
NO2
fast
+
NO2 + HSO4
H2SO4
this represents the
resonance hybrid
of the arenium ion
H
O
O -S
NO2
O
NO2
OH
O
H-O
S
OH
O
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Sect. 22.6: Halogenation
• active electrophile is a bromonium or chloronium ion
• need Lewis acid catalyst ( FeX3 ) to activate X2
Br
Br2
+ HBr
FeBr3
mechanism:
Br2 + FeBr3
Br + FeBr4
Br
HBr
H
Br
Br
Br
bomonium ion
Cl2
Cl
+ HCl
FeCl3
(iodination requires special conditions)
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Sect. 22.7: Friedel-Crafts
Alkylation
• alkyl halide + AlCl3 -->carbocation + AlCl3X• watch out for carbocation rearrangements!
• more than one alkylation can occur --> mixtures!
+
+
AlCl3 (cat)
Br
CH2Cl2
AlCl3 (cat)
Br
CH2Cl2
HBr
+
+
HBr
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Friedel-Crafts Acylation
•
•
•
•
acid chloride + AlCl3 --> acylium ion + AlCl4cation rearrangements are NOT observed!
acylation will only occur ONCE...
reaction VERY sensitive to substituents-- an acyl group
prevents further reaction
O
O
AlCl3 (cat)
+
+ HCl
Cl
O
AlCl3
O
C O
Cl
AlCl4
an acylium ion
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H
O
H
Two other
resonance
structures
O
_
H+
O
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Aromatic substitution on
Benzene
• Sect. 22.8:
• Sect. 22.9:
Sulfonation (skip, fall 06)
Summary
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Sect. 22.10 and 22.11: Directing
effects
• methoxy group releases electrons by
resonance effect: ortho and para director
• nitro group withdraws electrons by
inductive and resonance effect: meta
director
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These are ortho and para
directors! All are electron
releasing!!
..
-O-H
..
..
-O-R
..
O
..
-O-C-R
..
..
-NR2
-R
.. .
-X
.. .
R = H or alkyl
O
..
-N-C-R
H
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All ortho/para directing groups have pairs of
electrons next to the benzene ring!
The only exception are alkyl groups. They are
also ortho/para directors.
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Why do ortho/para groups direct as
they do? Resonance!!
O
O
H3C
AlCl3
Cl
H
AlCl4
H3C
O CH 3
O
O
CH 3
CH 3
H
CH 3
_
O
CH 3
CH 3
H
O
O
Meta won't work!
can't put + next
to O-CH3
O
H
O
CH 3
CH 3
H
O
CH 3
Extra resonance
structure from lone
pair on oxygen!
Ortho would work
CH 3 too.
O
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These are meta directors! All are
electron withdrawing!!
O
O
R
CH 3
N CH 3
CH 3
O
H
F
C F
F
O
O-R
O
N
O
NH 2
O
S OH
O
C
N
Notice! These groups have electronegative elements next to the
benzene ring! There are NO non-bonded electrons next to the ring!
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Now let’s look at a meta directing
group
O
O
C
CH3
C
H2SO4
O
+
H
HNO3
CH3
O
+
15°C
H 2O
NO2
This is an example of Electrophilic Aromatic
Substitution (EAS).
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Why does the nitration reaction take
place preferentially at the meta
position?
Let’s ask a “what if” question.
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O
OCH3
O
OCH3
C
H
O
H
NO2
OCH3
O
C
BAD!
NO2
O
OCH3
OCH3
C
C
O
H
H
H
NO2
NO2
NO2
OCH3

O

C
C
H
OCH3
H
NO2
para

C
C
ortho
meta

O
NO2
H
OCH3
O
OCH3
C
BAD!
NO2
H
NO2
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meta substitution preferred because
the + charge is never next to the
CO2R group
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Activation during substitution
All ortho and para directing groups are activating
relative to benzene, except halogen substituents.
Halogens are weakly deactivating but are still o, pdirectors.
G
Electron releasing groups (G) help stabilize
the + in the ring introduced by the electrophile.
This increases the rate of substitution!
+
H
E
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Deactivation during substitution
• All meta directors are strongly deactivating
relative to benzene.
G
Electron withdrawing groups (G) intensify
the + in the ring introduced by the electrophile.
This slows the substitution reaction!
+
H
E
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Sect. 22.12 and 22.17: Some
synthetic examples involving
aromatic substitution
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• ortho/para directors can work together with
meta directors. They reinforce each other.
O-CH 3
O-CH 3
HNO 3
HNO 3
H2SO4
H2SO4
NO 2
ortho/ para director
O-CH 3
NO 2
NO 2
ortho/para
meta
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Strong o/ p directors win over weak o, p
and meta directors.
OH
OH
Br
Br2
CH 3
FeBr3
CH 3
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Substitution RARELY occurs in-between two
substituents--too hindered!
O
CH 3
nothing here!
CH 3
H3C
Cl
CH 3
AlCl3
CH 3
O
CH 3
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Some groups can be modified to change their
directing effects.
O
CH 3
OH
KMnO 4
Br2
ortho/para
director
meta director
Br2
FeBr3
FeBr3
CH 3
CH 3
Br
O
OH
Br
KMnO 4
O
OH
KMnO 4
O
OH
Br
3-bromobenzoic acid
Br
2-bromobenzoic acid
Br
4-bromobenzoic acid
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Good stuff! Order of reaction is critical!
CH 3
O
OH
KMnO 4
HNO 3
H2SO4
HNO 3
H2SO4
CH 3
CH 3
NO 2
KMnO 4
O
OH
NO 2
KMnO 4
O
OH
O
OH
NO 2
NO 2
2-nitrobenzoic acid
NO 2
4-nitrobenzoic acid
3-nitrobenzoic acid
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Some more good stuff!
O
H3C
O
Cl
O
CH 3
CH 3
Br2
FeBr3
AlCl3
Br
meta director
O
Br2
O
CH 3
H3C
FeBr3
Cl
Br
ortho/para director
AlCl3
Br
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An explosive!
CH 3
O2N
NO 2
NO 2
2,4,6-trinitrotoluene (TNT)
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CH 3
CH 3
CH 3
CH 3
HNO 3
H2SO4
Easy!
NO 2
HNO 3
NO 2
H2SO4
CH 3
NO 2
more difficult
Heat it!
HNO 3
O2N
NO 2
H2SO4
NO 2
NO 2
Even more difficult
so really heat it!
2,4,6-Trinitrotoluene = TNT
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Some miscellaneous examples
•
•
•
•
Nitration of 3-nitrobenzoic acid
Acylation of 1,3-dimethylbenzene
Acylation of 1,4-dimethylbenzene
Make 2-methyl-1-phenylpropane
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Sect. 22.16 Aromaticity and
Huckel’s Rule
Aromatic compounds 4n + 2 pi electrons
n=1
6 pi electrons systems
+
Cation
:
_
Anion
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Empty
p-orbital
H
H
6-pi electrons
This is a n = 1
with 6 pi electrons
H
Aromatic!
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Other n = 1 aromatics
H
:
N
6 electrons
: :
S
6 electrons, one pair
not involved!
:
:
O
6 electrons, one
pair not involved!
All are aromatic!
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rehydridize the oxygen
3
2
atom from sp to sp
O
Oxygen has two pairs, but only one pair is in the
pi system (p-orbital).
This system is a n = 1 system, with 6 pi electrons
This compound is AROMATIC!
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n = 0 aromatic: 2 pi electrons
+
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H
H
2 pi electrons
Aromatic!
H
H
H
H
Cyclopropene is not aromatic, you
need p orbital at all positions!
H
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Some Antiaromatic compounds
: _
4 electrons
4 electrons
8 electrons
Not aromatic!
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Diazonium ions, Azo Dyes and
the Sandmeyer Reaction- from
Chapter 23 (not covered 06)
Sect 23.16: Diazonium ion formation
Sect 23.17: Sandmeyer reaction
Sect 23.19: Azo dyes
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