.
Reactions of
Aromatic Compounds
Based on Solomons , Fryhle
Organic Chemistry 10th. Edition
Created by
Professor William Tam & Dr. Phillis Chang
Ch. 15 - 1
About The Authors
These PowerPoint Lecture Slides were created and prepared by Professor
William Tam and his wife, Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
Ch. 15- 2
1. Electrophilic Aromatic
Substitution Reactions

Overall reaction
H
+
E
E
+
H
+
Ch. 15 - 3
X
SO3H
SO3
H2SO4
X2
FeX3
O
O
R
R
HNO3
Cl
AlCl 3
H2SO4
RCl
AlCl 3
NO2
R
Ch. 15 - 4
2.

A General Mechanism for Electrophilic Aromatic Substitution
Different chemistry with alkene
C
C
+
Br2
+ Br2
Br
C
C
Br
No Reaction
Ch. 15 - 5

Benzene does not undergo electrophilic
addition, but it undergoes electrophilic
aromatic substitution
H
E
A
E
+H
A
(H substituted by E)
Ch. 15 - 6

Mechanism
● Step 1
+
E
E
E
slow
r.d.s.
E
Ch. 15 - 7

Mechanism
● Step 2
E
B
H
fast
E
+ B
H
Ch. 15 - 8
Ch. 15 - 9
3. Halogenation of Benzene

Benzene does not react with Br2 or Cl2
unless a Lewis acid is present (catalytic
amount is usually enough)
Ch. 15 - 10

Examples
Cl
Cl2
FeCl3
25o
HCl
+
HBr
(90%)
Br
Br2
FeCl3
heat
+
(75%)
● Reactivity: F2 > Cl2 > Br2 > I2
Ch. 15 - 11

Mechanism
FeBr3
Br
Br

Br
Br

FeBr3
(weak
electrophile)
Br
+ FeBr4
(very reactive
electrophile)
Ch. 15 - 12

Mechanism (Cont’d)
Br
slow r.d.s.
Br
Br
Br
Ch. 15 - 13

Mechanism (Cont’d)
Br
H
Br
FeBr3
Br
+ Br
H
+ FeBr3
Ch. 15 - 14

F2: too reactive, give mixture of mono-,
di- and highly substituted products
F2
Lewis
acid
F
F
F
F
+
+
F
+ others
Ch. 15 - 15
 I2:
very unreactive even in the
presence of Lewis acid, usually need to
add an oxidizing agent (e.g. HNO3,
2+
Cu , H2O2)
e.g.
I2
I
(86%)
HNO3
I2
CuCl 2
I
(65%)
Ch. 15 - 16
4. Nitration of Benzene
NO2
conc. HNO 3
conc. H2SO4
50-60oC

+ H3O+
(85%)
Electrophile in this case is
(nitronium ion)
+ HSO4

NO2
Ch. 15 - 17

Mechanism
O
HO
S
O
O
H
+
HO
N
O
O
H
HSO4 +
O
O
H
O
N
O
N
O + H2O
(NO2)
Ch. 15 - 18

Mechanism (Cont’d)
NO2
slow r.d.s.
NO2
NO2
NO2
Ch. 15 - 19

Mechanism (Cont’d)
NO2
H
H2O
NO2
+ H3O+
Ch. 15 - 20
5. Sulfonation of Benzene

Mechanism
● Step 1
SO3 + H3O+ + HSO4
2 H2SO4
● Step 2
O
O
S
slow
O
O
O
S
O
H
other
resonance
structures
Ch. 15 - 21
● Step 3
O
O
S
O
fast
O
H
S

HSO4
O
O
+ H2SO4
● Step 4
O
S
O
O
fast
S
O
H
O
H
H
O
H
O
+ H2O
Ch. 15 - 22

Sulfonation & Desulfonation
SO3, conc. H2SO4
o
o
25 C - 80 C
SO3H
dil. H2SO4
H2O, 100oC
Ch. 15 - 23
6. Friedel–Crafts Alkylation
R
X
Lewis acid
(e.g. AlCl3)

R
+
HX
R = alkyl group
(not aryl or vinyl)

Electrophile in this case is R
o
o
● R = 2 or 3




o
● Or R ClAlCl 3 (R = 1 )
Ch. 15 - 24

Mechanism
Cl
AlCl 3
Cl
+
AlCl 3
AlCl 4
Ch. 15 - 25

Mechanism (Cont’d)
Ch. 15 - 26

Mechanism (Cont’d)
H
Cl
AlCl 3
+ HCl
+ AlCl3
Ch. 15 - 27

Note: Not necessary to start with alkyl
halide, other possible functional groups
can be used to generate a reactive
carbocation
e.g.
+ H+
via
H+
Ch. 15 - 28
OH
BF3
+
via
60oC
H
O
BF3
Ch. 15 - 29
7. Friedel–Crafts Acylation
O

Acyl group: R
C
O
O
AlCl3
+
R

Cl
R
80oC

Electrophile in this case is R–C≡O
(acylium ion)
Ch. 15 - 30

Mechanism
O
O
+
R
Cl
AlCl 3
R
R
C
O
C
Cl
AlCl 3
R
C
O
Ch. 15 - 31

Mechanism (Cont’d)
R
O
C
O
R
O
O
R
R
Ch. 15 - 32

Mechanism (Cont’d)
O
R
H
O
Cl
AlCl 3
R
+ HCl
+ AlCl3
Ch. 15 - 33

Acid chlorides (or acyl chlorides)
O
R
C
Cl
● Can be prepared by
SOCl2
O
R
C
O
OH
or
PCl5
R
C
Cl
Ch. 15 - 34
8. Limitations of Friedel–Crafts
Reactions

When the carbocation formed from an
alkyl halide, alkene, or alcohol can
rearrange to one or more carbocations
that are more stable, it usually does so,
and the major products obtained from
the reaction are usually those from the
more stable carbocations
Ch. 15 - 35

For example
+
(not formed)
Cl
AlCl 3
AlCl 3
(How is this
Formed?)
Ch. 15 - 36

Reason
Cl + AlCl
3
1o cation (not stable)
H
AlCl 4
+
1,2-hydride
shift
H
3o cation
(more
stable)
Ch. 15 - 37
Friedel–Crafts reactions usually give poor
yields when powerful electron-withdrawing
groups are present on the aromatic ring or
when the ring bears an –NH2, –NHR, or –NR2
group. This applies to both alkylations and
acylations
CF3
These usually give poor yields
in Friedel-Crafts reactions
SO3H
NH2
>
R
>
OH O
>
N(CH3)3
O
>
>
NO2
>

Ch. 15 - 38
The amino groups, –NH2, –NHR, and –NR2,
are changed into powerful electronwithdrawing groups by the Lewis acids used
to catalyze Friedel-Crafts reactions
H
N
H
H
H
N
AlCl 3
>

+
AlCl 3
Does not undergo a
Friedel-Crafts
reaction
Ch. 15 - 39

Aryl and vinylic halides cannot be used as
the halide component because they do not
form carbocations readily
Cl
sp2
, AlCl 3
sp2
Cl , AlCl 3
No Friedel-Crafts
reaction
No Friedel-Crafts
reaction
Ch. 15 - 40

Polyalkylations often occur
+
OH
BF3
+
60oC
(24%)
(14%)
Ch. 15 - 41
9. Synthetic Applications of
Friedel-Crafts Acylations: The
Clemmensen Reduction

Clemmensen ketone reduction
O
R
Zn/Hg
R
HCl
reflux
Ch. 15 - 42

Clemmensen ketone reduction
● A very useful reaction for making
alkyl benzene that cannot be made
via Friedel-Crafts alkylations
e.g.
?
Ch. 15 - 43

Clemmensen ketone reduction
● Cannot use Friedel-Crafts alkylation
Cl
give
AlCl 3
but
NOT
Ch. 15 - 44

Rearrangements of carbon chain do
not occur in Friedel-Crafts acylations
O
O
AlCl3
+
R
Cl
R
80oC
(no rearrangement
of the R group)
Ch. 15 - 45
O
O
Cl
Zn/Hg
conc. HCl
reflux
AlCl 3
Ch. 15 - 46
10. Substituents Can Affect Both
the Reactivity of the Ring and
the Orientation of the
Incoming Group

Two questions we would like to
address here
● Reactivity
● Regiochemistry
Ch. 15 - 47
● Reactivity
Y
Y
E
faster or
slower than
E
E
E
Y = EDG (electron-donating group) or
EWG (electron-withdrawing group)
Ch. 15 - 48
● Regiochemistry
Y
Y
Y
Y
E
E
E
E
(ortho)
(o)
(meta)
(m)
(para)
(p)
Statistical mixture of o-, m-, pproducts or any preference?
Ch. 15 - 49
G
G

+ E

A
Electrophilic
reagent
A substituted
benzene
E
H
other
resonance
structure
Arenium
ion
Ch. 15 - 50
Z
Y
>
>
Z donates
electrons
The ring is more
electron rich and
reacts faster with
an electrophile
Y withdraws
electrons
The ring is electron
poor and reacts
more slowly with
an electrophile
Ch. 15 - 51
● Reactivity
 Since electrophilic aromatic
substitution is electrophilic in
nature, and the r.d.s. is the

attack of an electrophile (E )
with the benzene p-electrons,
⊖
an increase in e density in the
benzene ring will increase the
reactivity of the aromatic ring
towards attack of an electrophile,
and result in a faster reaction
Ch. 15 - 52
● Reactivity

On the other hand, decrease in
⊖
e density in the benzene ring
will decrease the reactivity of
the aromatic ring towards the
attack of an electrophile, and
result in a slower reaction
Ch. 15 - 53
● Reactivity
Increasing activity
Y
EDG
–H
EWG
Ch. 15 - 54
● Reactivity

EDG (electron-donating group)
on benzene ring
 Increases electron density in
the benzene ring
 More reactive towards
electrophilic aromatic
substitution
Ch. 15 - 55
● Reactivity

EWG (electron-withdrawing
group) on benzene ring
 Decreases electron density in
the benzene ring
 Less reactive towards
electrophilic aromatic
substitution
Ch. 15 - 56
● Reactivity towards electrophilic
aromatic substitution
EDG
EWG
>
>
Ch. 15 - 57

Regiochemistry: directing effect
● General aspects
 Either o-, p- directing or mdirecting
 Rate-determining-step is pelectrons on the benzene ring

attacking an electrophile (E )
Ch. 15 - 58
Y
E
ortho
attack
Y
Y
E
o-I
Y
E
o-II
E
o-III
Ch. 15 - 59
Y
E
meta
attack
Y
m-I
Y
E
m-II
Y
E
m-III
E
Ch. 15 - 60
Y
E
para
attack
Y
E
Y
p-I
E
Y
p-II
p-III
E
Ch. 15 - 61

If you look at these
resonance structures
closely, you will notice
that for ortho- or parasubstitution, each has
one resonance form
with the positive charge
attached to the carbon
that directly attached to
the substituent Y (o-I
and p-II)
Y
E
o-I
Y
p-II
E
Ch. 15 - 62

When Y = EWG, these resonance
forms (o-I and p-II) are highly unstable
and unfavorable to form, thus not
favoring the formation of o- and pregioisomers, and m- product will form
preferentially
Ch. 15 - 63

On the other hand, if Y = EDG, these
resonance forms (o-I and p-II) are
extra-stable (due to positive mesomeric
effect or positive inductive effect of Y)
and favorable to form, thus favoring
the formation of o- and p- regioisomers
Ch. 15 - 64

Classification of different substituents
Y
Y (EDG)
–NH2, –NR2 Strongly

activating
–OH, –O
o-, p-
directing
–NHCOR
–OR
Moderately o-, pactivating
directing
–R (alkyl)
–Ph
Weakly
activating
o-, p-
–H
NA
NA
directing
Ch. 15 - 65

Classification of different substituents
Y
Y (EWG)
–Halide
(F, Cl, Br, I)
Weakly
o-, pdeactivating directing
–COOR, –COR,
Moderately m–CHO, –COOH,
deactivating directing
–SO3H, –CN
–CF3 , –CCl3 ,
–NO2 , –⊕NR3
Strongly
mdeactivating directing
Ch. 15 - 66
11. How Substituents Affect
Electrophilic Aromatic
Substitution: A Closer Look
Ch. 15 - 67
11A. Reactivity: The Effect of
Electron-Releasing and
Electron-Withdrawing Groups

If G is an electron-releasing group (relative to
hydrogen), the reaction occurs faster than the
corresponding reaction of benzene
G
G
>
>


+ E
H
G releases
electrons.

E
Transition state
is stabilized
G
>



H
E
Arenium ion
is stabilized
When G is
electron
donating,
the
reaction is
faster
Ch. 15 - 68
If G is an electron-withdrawing group,
the reaction is slower than that of
benzene
G


+ E
H
G withdraws
electrons

E
Transition state
is destabilized
G
>

>
G
>



H
E
Arenium ion
is destabilized
When G is electron withdrawing,
the reaction is slower
Ch. 15 - 69
Ch. 15 - 70
11B. Inductive and Resonance Effects:
Theory of Orientation

Two types of EDG
OR
NR2
(i)
or
CH3
>
(ii)
by positive
mesomeric effect
(donates electron
towards the benzene
ring through
resonance effect)
by positive inductive
effect (donates
electron towards the
benzene ring through
s bond)
Ch. 15 - 71

Two types of EDG
● Positive mesomeric effect is usually
stronger than positive inductive
effect if the atoms directly attacked
to the benzene ring is in the same
row as carbon in the periodic table
Ch. 15 - 72

Similar to EDG, EWG can withdraw
electrons from the benzene ring by
resonance effect (negative mesomeric
effect) or by negative inductive effect
O
C
CH3
e.g.
Deactivate the ring by
resonance effect
>
F
>
C> F
F
Deactivate the ring by
negative inductive effect
Ch. 15 - 73
11C. Meta-Directing Groups
EWG
EWG
E
(EWG ≠ halogen)
E
(major)

EWG = –COOR, –COR, –CHO, –CF3,
–NO2, etc.
Ch. 15 - 74

For example
CF3
NO2
(ortho)
CF3
CF3
NO2
CF3
NO2
CF3
NO2
- H+
(ortho)
(not favorable)
NO2
(highly unstable due
to negative inductive
effect of –CF3)
Ch. 15 - 75
CF3
(highly unstable due to negative
inductive effect of –CF3)
CF3
CF3
CF3
- H+
NO2
(para)
NO2
NO2
NO2
CF3
(para)
(not favorable)
NO2
Ch. 15 - 76
(positive charge never
attaches to the carbon
directly attached to the
EWG: –CF3)  relatively
more favorable
CF3
NO2
(meta)
CF3
CF3
NO2
CF3
NO2
NO2
CF3
- H+
(relatively more
favorable than o-, p- products)
(meta)
NO2 Ch. 15 - 77
11D. Ortho–Para-Directing Groups
EDG
EDG
EDG
E
E
+
E
para
ortho
(major)

EDG = –NR2, –OR, –OH, etc.
Ch. 15 - 78

For example
OCH3
NO2
(ortho)
OCH3
OCH3
OCH3
NO2
NO2
OCH3
NO2
(ortho)
(favorable)
+
-H
OCH3
NO2
NO2
(extra resonance
structure due to
positive mesomeric
effect of –OCH3)
Ch. 15 - 79
OCH3
OCH3
OCH3
(para)
- H+
NO2
NO2
NO2
NO2
OCH3
OCH3
OCH3
NO2
NO2
(extra resonance structure due to positive
mesomeric effect of –OCH3)
(para)
(favorable)
Ch. 15 - 80
OCH3
NO2
(meta)
OCH3
(3 resonance structures
only, no extra stabilization
by positive mesomeric
effect of –OCH3)  less
favorable
OCH3
NO2
OCH3
NO2
NO2
OCH3
- H+
(meta)
(less favorable)
NO2
Ch. 15 - 81

For halogens, two opposing effects
Cl
>
Cl
negative inductive effect
withdrawing electron
density from the
benzene ring
positive mesomeric effect
donating electron
density to the
benzene ring
Ch. 15 - 82

Overall
● Halogens are weak deactivating
groups
 Negative inductive effect >
positive mesomeric effect in this
case)
Ch. 15 - 83

Regiochemistry
Cl
NO2
(ortho)
Cl
Cl
Cl
NO2
NO2
Cl
NO2
(ortho)
(favorable)
+
-H
Cl
NO2
NO2
(extra resonance
structure due to
positive mesomeric
effect of –Cl)
Ch. 15 - 84
Cl
Cl
Cl
(para)
- H+
NO2
NO2
NO2
NO2
Cl
Cl
Cl
NO2
NO2
(extra resonance structure due to positive
mesomeric effect of –Cl)
(para)
(favorable)
Ch. 15 - 85
Cl
NO2
(meta)
Cl
(3 resonance structures
only, no extra stabilization
by positive mesomeric
effect of –Cl)  less
favorable
Cl
NO2
Cl
NO2
NO2
Cl
- H+
(meta)
(less favorable)
NO2
Ch. 15 - 86
11E. Ortho–Para Direction and
Reactivity of Alkylbenzenes
R
R
>
>


+ E

H
R
>




E
Transition state
is stabilized

H
E
Arenium ion
is stabilized
Ch. 15 - 87

Ortho attack
CH3
Relatively
stable
contributor
E
CH3
CH3
E
E
>
CH3
E
Ch. 15 - 88

Meta attack
CH3
E
CH3
CH3
CH3
E
E
E
Ch. 15 - 89

Para attack
CH3
E
E
CH3
CH3
E
E
>
CH3
Relatively
stable
contributor
Ch. 15 - 90
12. Reactions of the Side Chain
of Alkylbenzenes
CH3
Methylbenzene
(toluene)
Ethylbenzene
Isopropylbenzene
(cumene)
Phenylethene
(styrene or
vinylbenzene)
Ch. 15 - 91
12A. Benzylic Radicals and Cations
R
H CH2
CH2
- RH
Methylbenzene
(toluene)
C
C
The benzyl
radical
C
Benzylic radicals are stabilized by resonance
C
Ch. 15 - 92
C
LG
C
- LG
A benzyl
cation
C
C
C
Benzylic cations are stabilized by resonance
C
Ch. 15 - 93
12B. Halogenation of the Side Chain:
Benzylic Radicals
O
O
CH3
+
N
O
NBS

Br
CCl4
light
Br
+
Benzyl bromide
(-bromotoluene)
(64%)
N
H
O
N-Bromosuccinimide (NBS) furnishes a
low concentration of Br2, and the
reaction is analogous to that for allylic
bromination
Ch. 15 - 94

Mechanism
● Chain initiation
X
X
peroxides
heat or
light
2X
● Chain propagation
H
C6H5
C
H
H
H + X
C6H5
+ H
C
X
H
Ch. 15 - 95
● Chain propagation
H
H
C6H5
+
C
X
X
H
C6H5
C
X +X
H
● Chain termination
H
H
C6H5
+
C
H
X
C6H5
C
X
H
Ch. 15 - 96

e.g.
(more stable
benzylic radicals)
Br
Br
NBS
+
h
(major)
(very little)
o
(less stable 1 radicals)
Ch. 15 - 97
13. Alkenylbenzenes
13A. Stability of Conjugated Alkenylbenzenes

Alkenylbenzenes that have their side-chain
double bond conjugated with the benzene
ring are more stable than those that do not
non-conjugated
system
C
C
conjugated
system
C
is more
stable than
C
C
C
Ch. 15 - 98

Example
H+
OH
heat
(not observed)
- Ha
Ha
Hb
- Hb
Ch. 15 - 99
13B. Additions to the Double Bond of
Alkenylbenzenes
HBr
Br
RO OR
heat
Br
HBr
(no
peroxides)
Ch. 15 - 100

Mechanism (top reaction)
RO
OR
RO
+ H
2 RO
+ RO
Br
Br
H
Br
+
Br
Br
(more stable
benzylic radical)
Br
+
H
Br
(less stable)
Br
Ch. 15 - 101

Mechanism (bottom reaction)
H
H
 
H Br
(more stable
benzylic cation)
(less stable)
Br
Br
Ch. 15 - 102
13C. Oxidation of the Side Chain
O
CH3
-
1. KMnO4, OH , 
OH
2. H3O+
(100%)
Ch. 15 - 103
O
1. KMnO4, OH-, 
OH
2. H3O+
O
1. KMnO4, OH-, 
OH
2. H3O+
O
1. KMnO4, OH-, 
OH
2. H3O+
O
O
1. KMnO4, OH-, 
2. H3O+
OH
Ch. 15 - 104
Using hot alkaline KMnO4, alkyl, alkenyl,
alkynyl and acyl groups all oxidized
to –COOH group
o
 For alkyl benzene, 3 alkyl groups resist
oxidation

1. KMnO4, OH-, 
2. H3O+
No Reaction
● Need benzylic hydrogen for alkyl
group oxidation
Ch. 15 - 105
13D. Oxidation of the Benzene Ring
R
1. O3, CH3CO2H
2. H2O2
O
R
OH
Ch. 15 - 106
14. Synthetic Applications
CH3
How?
NO2
Ch. 15 - 107
CH3 group: ortho-, para-directing
 NO2 group: meta-directing

CH3
CH3
CH3Cl
conc. HNO 3
AlCl 3
conc. H2SO4
heat
NO2
CH3
NO2
+
Ch. 15 - 108

If the order is reversed  the wrong
regioisomer is given
conc. HNO 3
CH3Cl
conc. H2SO4
heat
AlCl 3
NO2
CH3
NO2
NOT
CH3
NO2
Ch. 15 - 109
COOH
NO2
We do not know how to substitute a
hydrogen on a benzene ring with a
–COOH group. However, side chain
oxidation of alkylbenzene could provide
the –COOH group
 Both the –COOH group and the NO2
group are meta-directing

Ch. 15 - 110

Route 1
CH3
conc. HNO 3
CH3Cl
conc. H2SO4
heat
AlCl 3
NO2
NO2
COOH
1. KMnO4, OH-, 
NO2
2. H3O+
Ch. 15 - 111

Route 2
CH3
COOH
CH3Cl
1. KMnO4, OH-, 
AlCl 3
2. H3O+
COOH
conc. HNO 3
NO2
conc. H2SO4
heat
Ch. 15 - 112

Which synthetic route is better?
● Recall “Limitations of Friedel-Crafts
Reactions, Section 15.8”


Friedel–Crafts reactions usually give
poor yields when powerful electronwithdrawing groups are present on
the aromatic ring or when the ring
bears an –NH2, –NHR, or –NR2
group. This applies to both
alkylations and acylations
Route 2 is a better route
Ch. 15 - 113
Br
Both Br and Et groups are ortho-, paradirecting
 How to make them meta to each
other?
 Recall: an acyl group is meta-directing
and can be reduced to an alkyl group
by Clemmensen ketone reduction

Ch. 15 - 114
O
Cl
AlCl 3
O
Br
Br2
FeBr3
Br
Zn/Hg
HCl, heat
O
Ch. 15 - 115
14A. Use of Protecting and Blocking
Groups

Protected amino groups
● Example
NH2
NH2
?
Br
Ch. 15 - 116
Problem
 Not a selective synthesis, o- and pproducts + dibromo and tribromo
products
NH2
NH2
Br2
NH2
+
Br
Br
Br
NH2
+
+ others
Br
Br
Ch. 15 - 117
Solution
 Introduction of a deactivated group
on –NH2
O
NH2
CH3
H
Cl
pyridine
N
O
CH3
(an amide)
Ch. 15 - 118

The amide group is less activating
than –NH2 group
● No problem for over bromination

The steric bulkiness of this group also
decreases the formation of o-product
Ch. 15 - 119
NH2
NH2
Br
O
(hydrolysis
of amide)
Cl
pyridine
NHCOCH 3
Br2, FeBr3
1. H2SO4,
H2O, 
2. OH-
NHCOCH 3
Br
Ch. 15 - 120
NH2
NH2
Br
Problem
 Difficult to get o-product without
getting p-product
 Over nitration
Ch. 15 - 121
Solution
 Use of a –SO3H blocking group at the
p-position which can be removed later
NH2
NH2
NO2
O
1. dil. H2SO4
100oC
Cl
2. OH-
pyridine
NHCOCH 3
SO3
conc. H2SO4 HO3S
60oC
NHCOCH 3
HNO3
H2SO4 HO3S
NHCOCH 3
NO2
Ch. 15 - 122
14B. Orientation in Disubstituted
Benzenes

Directing effect of EDG usually
outweighs that of EWG

With two EDGs, the directing effect is
usually controlled by the stronger EDG
Ch. 15 - 123
Examples (only major product(s) shown)
CH3
CH3
NO2
NO2
(i)
CF3
CF3
OMe
OMe
COCH 3
Br
OMe
COCH 3
COCH 3
+
(ii)
Br
Br
Ch. 15 - 124

Cl
Substitution does not occur to an
appreciable extent between metasubstituents if another position is open
Cl
X
NO2
O2N
HNO3
Br
Cl
Cl
+
+
H2SO4
Br
Br
Br
NO2
62%
37%
1%
Ch. 15 - 125
NHCOCH 3
NHCOCH 3
NO2
(iii)
COOMe
COOMe
NO2
+
NHCOCH 3
O2N
COOMe
Ch. 15 - 126
OCH3
CH3
(iv)
Cl
OCH3
OCH3
CH3
Cl
CH3
+
Cl
Ch. 15 - 127
Cl
Br
(v)
NO2
Cl
Cl
Br
+
NO2
NO2
Br
Ch. 15 - 128
15. Allylic and Benzylic Halides in
Nucleophilic Substitution Reactions
H
CH2X
C
C
C
1o Allylic
C
C
X
C
C
H
1o Benzylic
Ar
C
C
C
X
3o Allylic
H
X
R'
R
2o Allylic
H
Ar
R
R
X
R
2o Benzylic
Ar
C
X
R'
3o Benzylic
Ch. 15 - 129

A Summary of Alkyl, Allylic, & Benzylic
Halides in SN Reactions
● These halides give mainly SN2
reactions:
H3C
X
R
CH2
X
R
CH
X
R'
● These halides may give either SN1
or SN2 reactions:
CH2
Ar
CH2
X
Ar
CH
X
C
C
H
X
C
C
C
R
X
R
Ch. 15 - 130

A Summary of Alkyl, Allylic, & Benzylic
Halides in SN Reactions
● These halides give mainly SN1
reactions:
R
R'
C
R"
R
R
X
Ar
C
R'
X
C
C
C
X
R'
Ch. 15 - 131
16. Reduction of Aromatic
Compounds
H2/Ni
slow
benzene
+
cyclohexadienes
H2/Ni
fast
cyclohexene
H2/Ni
fast
cyclohexane
Ch. 15 - 132
16A. The Birch Reduction
Na
NH3, EtOH
benzene
1,4-cyclohexadiene
Ch. 15 - 133

Mechanism
Na
etc.

benzene

benzene radical anion
EtOH
Na
H
H
H
cyclohexadienyl radical

H
H
H
etc.
H

H
cyclohexadienyl anion
etc.
EtOH
H
H
H
H
1,4-cyclohexadiene
Ch. 15 - 134

Synthesis of 2-cyclohexenones
OCH3
OCH3
Li
liq. NH 3
EtOH
(84%)
H3O+
H2O
O
2-cyclohexenone
Ch. 15 - 135
 END OF CHAPTER 15 
Ch. 15 - 136