AROMATIC SUBSTITUTION

1
AROMATIC SUBSTITUTION REACTIONS
Double bonds in a benzene ring do not react
like those in an alkene.
36 kcal/mol resonance
easier
E
Instead of addition reactions, benzene rings give
substitution reactions (resonance preserved).
More powerful electrophiles are required. A few
of the common aromatic substitution reactions are
on the next slide.
E
more difficult
2
Some Substitution Reactions of Benzene
Halogenation

Friedel-Crafts Alkylation

Friedel-Crafts Acylation

-


Nitration

-
Sulfonation

3
MECHANISMS
All of the reactions follow the same pattern of
mechanism.
The reagents combine to form a strong
electrophile E ,and its partner (X ), which
react as follows
ELECTROPHILIC AROMATIC SUBSTITUTION
()

HX
()

slow
X
intermediate
restores ring resonance
benzenium ion
resonance structures are shown by the () symbols
also called a benzenonium ion
4
ENERGY PROFILE FOR AROMATIC SUBSTITUTION
()
benzenium intermediate
Transition state 1

()
Transition state 2
intermediate
Ea
activation energy


H
slow
fast
STEP 1
STEP 2
5
HALOGENATION - 1
Formation of the Chloronium Ion Complex
..
..




d
..
..
..
..
..
..
d-





..
..
..
..
..
..




..
..
sp2
..


..
..
..

-



..
..
..


..
chloronium ion complex
6
HALOGENATION - 2
Chlorination of Benzene
-
Cl2 AlCl3
-




benzenium ion
chloronium ion complex
HAlCl4
HCl AlCl3
7
FRIEDEL-CRAFTS ALKYLATION - 1
Formation of a Carbocation Complex
..
..




d
..
..
..
..
d-



..
..
..
..




..
..
Other aliphatic R-Cl may be used
..


..
..
-



..
..


..
carbocation
8
FRIEDEL-CRAFTS ALKYLATION - 2
Friedel-Crafts Alkylation
-
CH3Cl AlCl3
-




HAlCl4
HCl AlCl3
9
FRIEDEL-CRAFTS ALKYLATION - 3
REARRANGEMENTS ARE COMMON IN FRIEDEL-CRAFTS
ALKYLATION
AlCl3
-

-

carbocation rearrangement
AlCl3

10
FRIEDEL-CRAFTS ACYLATION - 1
Formation of an Acylonium Complex
..
..




..
..
..
..
d
d-



..
..
..
..




..
..
..
Other acid chlorides (RCOCl) may be used


..
..
-


..
..



..
acylium ion
(acylonium ion)
Rearrangements DO NOT occur
11
FRIEDEL-CRAFTS ACYLATION - 2
Friedel-Crafts Acylation
-
AlCl3
-




HAlCl4
HCl AlCl3
12
NITRATION - 1
Formation of Nitronium Ion
nitronium ion
..

Powerful Electrophile

Reacts with benzene.

..
13
NITRATION - 2
Nitration of Benzene

..
..
..

HNO3






H2SO4
..
-

..
..

..


..
-
14
SULFONATION - 1
Fuming Sulfuric Acid
.
H2SO4 SO3
..
..


..
..

..
..


..
..
sulfur trioxide
15
SULFONATION - 2
Sulfonation of Benzene
-
.
H2SO4 SO3

H3O
D
can be reversed in boiling water or steam
(acidic)
H2SO4
16
DIRECTIVITY AND RING ACTIVATION /
DEACTIVATION
17
ortho, meta and para Positions
m-nitrotoluene
3-nitrotoluene
ipso
1
ortho
o-
2
6
1-methyl-3-nitrobenzene
meta
m-
3
5
4
para
p-dichlorobenzene
p-
1,4-dichlorobenzene
18
Nitration of Anisole
HNO3

H2SO4
ortho
para
anisole
ACTIVATED
The -OCH3 group when placed on the ring gives
only ortho and para products, and no meta
Substituents that cause this result are called
o,p directors
and they usually activate the ring.
19
Nitration of Methyl Benzoate
HNO3
H2SO4
meta
methyl benzoate
Reacts slower than benzene
DEACTIVATED
The -COOMe group when placed on the ring gives
only meta, and no ortho or para products
Substituents that cause this result are called
m directors
and they usually deactivate the ring.
20
SUBSTITUENT CATEGORIES
Most ring substituents fall into one of these two
categories
O,P ACTIVATE
M DEACTIVATE
o,p - directors
m- directors
activate the ring
deactivate the ring
We will look at one of each kind in order
to understand the difference..
21
NITRATION OF ANISOLE
22
Nitration of Anisole
ortho
meta
para
Activated ring
actual products
para
ortho

23

ortho
EXTRA!
energy lowered
meta

para
EXTRA!
24
Energy Profiles
NITRATION OF ANISOLE
benzenium intermediate
meta
benzenium intermediates have more resonance
ortho
para
ortho-para director
25
NITRATION OF METHYL BENZOATE
26
Nitration of Methyl Benzoate
ortho
meta
para
Deactivated ring
actual product
meta
27
d-
d
BAD!
ortho
energy raised
meta
d-
d
para
BAD!
energy raised
28
Energy Profiles
NITRATION OF METHYL BENZOATE
some benzenium resonance structures have a
bad situation
ortho
para
meta
meta director
29
DIRECTIVITY OF GROUPS
30
ortho, para - Directing Groups
Groups that donate electron density to the ring.
PROFILE

E
increased reactivity
I Substituent
R Substituent
..
CH3-O-
These groups also activate the ring, or make it
more reactive.
..
CH3-
..
R-
CH3-N-
..
-NH2
..
The R groups activate the ring more
strongly than I groups.
-O-H
..
31
meta - Directing Groups
Groups that withdraw electron density from the
ring.
PROFILE
d
d-
E
decreased reactivity
-I Substituent
-R Substituent
These groups also deactivate the ring, or make
it less reactive.


-
-SO3H
32
EXCEPTION
Halides - o,p Directors / Deactivating
Halides represent a special case
..


They are o,p directing groups that are
deactivating
E
They are o,p directors (R effect )
They are deactivating ( -I effect )
Most other other substituents fall into one of
these four categories
R / -I / o,p / deactivating
1) R / o,p / activating
-F -Cl -Br -I
2) I / o,p / activating
3) -R / m / deactivating
4) -I / m / deactivating
33
GROUPS ACTING IN CONCERT
steric crowding
o,p director
m-director
very little formed
HNO3
H2SO4
When groups direct to the same positions it is
easy to predict the product.
major product
34
GROUPS COMPETING
o,p-directing groups win over m-directing groups
too crowded
X
HNO3

H2SO4
35
RESONANCE VERSUS INDUCTIVE EFFECT
R
HNO3
H2SO4
major product
I
resonance effects are more important than
inductive effects
36
SOME GENERAL RULES
1) Activating (o,p) groups (R, I) win over
deactivating (m) groups (-R, -I).
2) Resonance groups (R) win over inductive
(I) groups.
3) 1,2,3-Trisubstituted products rarely form due
to excessive steric crowding.
4) With bulky directing groups, there will
usually be more p-substitution than
o-substitution.
5) The incoming group replaces a hydrogen, it
will not usually displace a substituent
already in place.