ARYL HALIDES

Ch. 21 - 1
1. Electrophilic Aromatic
Substitution Reactions
❖ Overall reaction

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3
2. A General Mechanism for Electro-
philic Aromatic Substitution

❖ Different chemistry with alkene

4
❖ Benzene does not undergo electrophilic
addition, but it undergoes electrophilic
aromatic substitution

5
❖ Mechanism
● Step 1

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❖ Mechanism
● Step 2

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3. Halogenation of Benzene

❖ Benzene does not react with Br2 or Cl2

unless a Lewis acid is present (catalytic
amount is usually enough)

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❖ Examples

● Reactivity: F2 > Cl2 > Br2 > I2

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❖ Mechanism

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❖ Mechanism (Cont’d)

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❖ Mechanism (Cont’d)

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❖ F2: too reactive, give mixture of mono-,
di- and highly substituted products

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❖ I2:very unreactive even in the presence
of Lewis acid, usually need to add an
2+
oxidizing agent (e.g. HNO3, Cu , H2O2)

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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

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 ● Reactivity

faster or
slower than

Y = EDG (electron-donating group) or

EWG (electron-withdrawing group)
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● Regiochemistry

Statistical mixture of o-, m-, p-

products or any preference?
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 + -
d d

Electrophilic
reagent Arenium
A substituted ion
benzene

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Z donates Y withdraws
electrons electrons

The ring is more The ring is electron

electron rich and poor and reacts
reacts faster with more slowly with an
an electrophile electrophile

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● Reactivity
⧫ Since electrophilic aromatic
substitution is electrophilic in
nature, and the r.d.s. is the attack
Å
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
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● 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

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● Reactivity
Y

EDG
Increasing activity

–H

EWG
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● Reactivity

⧫ EDG (electron-donating group) on

benzene ring
❑ Increases electron density in the
benzene ring
❑ More reactive towards
electrophilic aromatic
substitution

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● Reactivity

⧫ EWG (electron-withdrawing group)

on benzene ring
❑ Decreases electron density in the
benzene ring
❑ Less reactive towards
electrophilic aromatic
substitution

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● Reactivity towards electrophilic
aromatic substitution

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❖ Regiochemistry: directing effect

● General aspects
⧫ Either o-, p- directing or m-
directing
⧫ Rate-determining-step is p-
electrons on the benzene ring
Å
attacking an electrophile (E )

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27
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29
❖ If you look at these
resonance structures
closely, you will notice
that for ortho- or para-
substitution, 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)
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❖ 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 p- regioisomers,
and m- product will form preferentially

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❖ 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

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❖ Classification of different substituents
Y (EDG)

–NH2, –NR2 Strongly

- o-, p-directing
–OH, –O activating

–NHCOR Moderately
o-, p-directing
–OR activating

–R (alkyl) Weakly
o-, p-directing
–Ph activating

–H NA NA

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❖ Classification of different substituents

Y (EWG)

–Halide Weakly o-, p-

(F, Cl, Br, I) deactivating directing

–COOR, –COR,
Moderately
–CHO, –COOH, m-directing
deactivating
–SO3H, –CN

–CF3 , –CCl3 , Strongly

m-directing
–NO2 , –⊕NR3 deactivating

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11B. Inductive and Resonance Effects:
Theory of Orientation
❖ Two types of EDG
by positive mesomeric
(i) effect (donates
electron towards the
benzene ring through
resonance effect)

(ii) by positive inductive

effect (donates electron
towards the benzene
ring through s bond)
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❖ 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

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❖ Similar to EDG, EWG can withdraw
electrons from the benzene ring by
resonance effect (negative mesomeric
effect) or by negative inductive effect

Deactivate the ring by

resonance effect

Deactivate the ring by

negative inductive effect
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11C. Meta-Directing Groups

(EWG ≠ halogen)

❖ EWG = –COOR, –COR, –CHO, –CF3,

–NO2, etc.

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❖ For example

(highly unstable due

to negative inductive
effect of –CF3)
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(highly unstable due to negative
inductive effect of –CF3)

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(positive charge never
attaches to the carbon
directly attached to the
EWG: –CF3) Þ relatively
more favorable

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11D. Ortho–Para-Directing Groups

❖ EDG = –NR2, –OR, –OH, etc.

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❖ For example

(extra resonance
structure due to
positive mesomeric
effect of –OCH3)
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(extra resonance structure due to positive
mesomeric effect of –OCH3) 44
(3 resonance structures
only, no extra stabilization
by positive mesomeric
effect of –OCH3) Þ less
favorable

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❖ For halogens, two opposing effects

negative inductive effect positive mesomeric effect

withdrawing electron donating electron
density from the density to the
benzene ring benzene ring

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❖ Overall
● Halogens are weak deactivating
groups
⧫ Negative inductive effect > positive
mesomeric effect in this case)

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❖ Regiochemistry

(extra resonance
structure due to
positive mesomeric
effect of –Cl)
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(extra resonance structure due to positive
mesomeric effect of –Cl) 49
(3 resonance structures
only, no extra stabilization
by positive mesomeric
effect of –Cl) Þ less
favorable

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Aryl Halides and Nucleophilic
Aromatic Substitution
Cl

H2O
+ NaOH NO substitution
heat

H2O
Cl + NaOH NO substitution
heat
X
Nu: X NO reaction
Ch. 21 - 51
X X X

X Ch. 21 - 52
X
11A. Nucleophilic Aromatic Substitution
by Addition–Elimination:
The SNAr Mechanism

v Nucleophilic aromatic substitution can

occur when strong electron-
withdrawing groups are ortho or para
to the halogen atom
Cl OH
NO2 + NO2
aq. NaHCO3 H3O
+ OH
130oC

Ch. 21 - 53
Cl OH
NO2 + NO2
aq. NaHCO3 H3O
+ OH
130oC

NO2 NO2
Cl
O2N NO2
aq. NaHCO3
+ OH o
130 C OH
Ch. 21 - 54
+ O2N NO2
NO2 H3O

NO2
vThe mechanism that operates in
these reactions is an addition–
elimination mechanism involving
the formation of a carbanion with
delocalized electrons, called a
Meisenheimer intermediate. The
process is called nucleophilic
aromatic substitution (SNAr)

Ch. 21 - 55
 vThe SNAr mechanism
Cl
Cl OH

addition
+ OH
slow
elimination
NO2 NO2 fast

O OH
Ch. 21 - 56

OH
HOH + Cl +

NO2 NO2
HO Cl HO Cl HO Cl

N N N
O O O O O O

HO Cl

N
O O
Ch. 21 - 57