This is Power Point Presentation on Topic "Electrophilic Aromatic Substitution Reactions" as per syllabus of "University of Mumbai" for S.Y. B. Pharmacy (Sem.: IV) students.

1. Electrophilic Aromatic
Substitution Reactions
Dr. Firoz Khan
Assistant Professor
AIKTC, School of Pharmacy,
Panvel, Navi Mumbai, India.
https://scholar.google.co.in/citations?user=FkGHPWQAAAAJ&hl=en

2. Generalized electrophilic aromatic
substitution:

3. Nitration Reaction:
Mechanism
σ Complex
Nitro group can
often be reduced to
the amine group using
tin or iron and HCl.
Ar-NO2 Ar-NH2
σ Complex

4. Sulfonation Reaction:
Mechanism

5. Halogenation Reaction:
Mechanism

6. Friedel-Crafts Alkylation
Mechanism

7. Friedel-Crafts Acylation
Mechanism

8. Kolbe reaction
It is also known as Kolbe-Schmitt reaction (named after
Hermann Kolbe and Rudolf Schmitt).
When Phenol reacts with Sodium hydroxide, gives
Sodium phenoxide which undergoes electrophilic
substitution with CO2 and Salicylic acid is formed.
Reaction

9. Reaction Mechanism
Application: Salicylic acid is used as Precursor/ starting material for synthesis of Aspirin.

10. Reimer-Tiemann Reaction
Reimer-Tiemann reaction is an chemical reaction where
Phenol is converted into an ortho-hydroxy
benzaldehyde (Salicylaldehyde) using chloroform and
base.
Reaction
Application: It is starting material for synthesize coumarin and
which is used to synthesize Warfarin.

11. Reaction Mechanism

12. Orientation and Reactivity of mono and di-
substituted Benzenes
Orientation

13. Mechanism of Electrophilic Aromatic Substitution
Without any substituents
With a substituent group G
Depending on the nature of the substituent, the substituent G
may stabilize the carbocation intermediate and therefore speed the
reaction. Substituents that make the ring react faster (than
benzene) with electrophiles are called activators; those that make
the ring react slower (than benzene) are called deactivators.

14. Products of Nitration

15. Substituent Effects
All activators direct incoming electrophiles to the ortho- and the
para-positions.
Most deactivators direct incoming electrophiles to the meta
position. The exceptions are the halogens, which are weakly
deactivating yet ortho-para directing.
Classification of Substituents
H
F
Cl
Br
I
Benzene
o,p-directing
deactivators
o,p-directing
activators
Ar
R
NHCOCH3
OR NH2
OH
CHOCO2H
COR
O
CR
O
CN
SO3HNO2
NR3
+
m-directing
deactivators
more activatingmore deactivating

16. 3º, especially stable
3º, especially stable
p
m
o
E
E
E
CH3
CH3
HE
CH3
H
H
E
CH3
H
HE
CH3
H
E
CH3
HE
CH3
H
H
E
CH3
H
H
E
CH3
H
E
CH3
H
H
E
CH3
H
CH3
o & p-Activators (alkyl & aryl groups)
Inductive effect and stability of carbocation will direct the
electrophile for o & p substitution.

17. o,p-Activators with a lone pair of electrons
More
number of
resonating
structures,
more is the
stability

18. o,p-Deactivators (Halogens)
Cl
H
E
Cl
H
E
Cl
H
E
Cl
H
E
H
E
Cl
HE
Cl
H
E
Cl
HE HE
Cl
HE
Cl
Cl
Cl
E
E
E
HE
Cl
Cl
Cl
H
E
4 resonance forms
4 resonance forms
o-
m-
p-
Chlorine is electronegative element and therefore it will donate the paired
electrons towards positive centre.

19. Summary for o & p directing groups (Activators)
 When the substituent is R (alkyl) or Ar (aryl), the
resonance hybrid cation intermediate has three
resonance forms. For attack of the electrophile at the
ortho or para positions, one of these is a 3º carbocation,
which is especially stable. This lowers the energy of the
intermediate, thus facilitates (speeds) the substitution
reaction at the o- and p- positions.
 When the substituent has a lone pair of electrons, such
as the halogens, oxygen (OH) or nitrogen (NH2), the
resonance hybrid for attack of the electrophile at the
ortho and para positions has four resonance forms. This
lowers the energy of the those intermediates, thus
facilitates (speeds) the substitution reaction at the o- and
p- positions.

20. meta-directing Deactivators
CN
H
E
CN
H
E
CN
H
E
CN
H
E
CN
HE
CN
H
E
CN
HE
CN
HE
H
E
CN
HE
CN
CN
CN
E
E
E
Especially UNSTABLE**
Especially UNSTABLE**
o-
m-
p-
Carbocations formed are unstable because of the electron
withdrawing effect.

21. Summary for meta (m) directing groups
(Deactivators)
 It will not form the o & p substitution product because of the
formation of unstable carbocation (energy level will be too
high).
 Meta substitution product will be formed. Energy level will be
less as compared to o & p substitutions. But reaction will be
slow one.
N
O O
E
H
SO OH
E
H
O
C
O CH3
E
H
E
H
N
C
nitro group sulfonic acid ketone nitrile

22. Rule 1:
If the directing effects of two substituents
reinforce each other, the predicted product
predominates.
CH3
CO2H
CH3
CO2H
NO2
HNO3
H2SO4
(o,p)
(m)

23. Rule 2:
If the directing effects of two substituents
oppose each other, the more activating group
dominates, but mixtures often result.
NH2
CH3
NH2
CH3
Br
Br2
(FeBr3 cat
not needed)
(o,p; STRONG activator)
(o,p;
weak activator)
Ortho to CH3-
product will be
formed but in
very less
quantity.

24. Rule 3:
Substitution almost never occurs between two
substituents meta to each other.
CH3
Cl
CH3
SO3H
Cl
SO3
H2SO4
CH3
Cl
HO3S
CH3
Cl
SO3H
+
but not:
(o,p)
(o,p)
X (too crowded)

25. Rule 4:
With a bulky o,p- director and/or a bulky
electrophile, para substitution predominates.
Ortho- product
will be formed
but in very less
quantity.