Electrophilic Attack
Electrophilic Aromatic Substitution
Electrophile substitutes for a hydrogen on
the benzene ring.
Mechanism
=>
Bromination of Benzene
• Requires a stronger electrophile than Br2.
• Use a strong Lewis acid catalyst, FeBr3.
Br Br
FeBr3
Br
Br
H
H
H
H
H
FeBr3
H
H
H
Br
Br
Br
FeBr3
+
H
H
H
H
Br
+
HBr
_
+ FeBr4
Energy Diagram for Bromination
=>
Chlorination and Iodination
• Chlorination is similar to bromination. Use
AlCl3 as the Lewis acid catalyst.
• Iodination requires an acidic oxidizing agent,
like nitric acid, which oxidizes the iodine to
an iodonium ion.
+
H
+ HNO3 + 1/2 I2
+
I
+
NO2 + H2O
Nitration of Benzene
Use sulfuric acid with nitric acid to form the
nitronium ion electrophile.
O
H O
S
O H
O
H O
H O N
H O N
+
O
O
O
H O
H O N
+
O
O
H2O +
N+
O
_
+ HSO4
NO2+ then forms a
sigma complex with
benzene, loses H+ to
form nitrobenzene. =>
Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric acid is
the electrophile.
_
O
O
S
S+
O
O
O
O
O
S+
_
O
O
_
O
S
O
O
H O
S O
+
O
H
O
_
S +
O
O
HO
O
S
O
benzenesulfonic acid
Nitration of Toluene
• Toluene reacts 25 times faster than benzene.
The methyl group is an activator.
• The product mix contains mostly ortho and
para substituted molecules.
Sigma Complex
Intermediate
is more
stable if
nitration
occurs at
the ortho
or para
position.
Energy Diagram
=>
Friedel-Crafts Alkylation
• Synthesis of alkyl benzenes from alkyl halides
and a Lewis acid, usually AlCl3.
• Reactions of alkyl halide with Lewis acid
produces a carbocation which is the
electrophile.
• Other sources of carbocations:
alkenes + HF or alcohols + BF3.
Examples of Carbocation Formation
Cl
CH3
CH CH3
+ AlCl3
_
CH3 +
C Cl AlCl3
H3C H
_
H2C CH CH3
OH
H3C CH CH3
BF3
HF
+ BF3
H O
H3C CH CH3
F
+
H3C CH CH3
_
+
H3C CH CH3 + HOBF3
=>
Formation of Alkyl Benzene
CH3
H
+C H
+
CH3
CH(CH3)2
H
F
H
CH(CH3)2
+
H
F
B OH
CH3
F-
CH
+
CH3
HF
F
F
B OH
Limitations of Friedel-Crafts
• Reaction fails if benzene has a substituent
that is more deactivating than halogen.
• Carbocations rearrange. Reaction of
benzene with n-propyl chloride and AlCl3
produces isopropylbenzene.
• The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
Friedel-Crafts Acylation
• Acyl chloride is used in place of alkyl chloride.
• The acylium ion intermediate is resonance
stabilized and does not rearrange like a
carbocation.
• The product is a phenyl ketone that is less
reactive than benzene.
Mechanism of Acylation
O
R C Cl
O
+ _
R C Cl AlCl3
AlCl3
O
+ _
R C Cl AlCl3
_
AlCl4
+
+
R C O
O
O
C
C+
R
+
H
H
R
Cl
_
AlCl3
+
R C O
O
C
HCl
R +
AlCl3
Clemmensen Reduction
Acylbenzenes can be converted to alkylbenzenes
by treatment with aqueous HCl and
amalgamated zinc.
O
O
+ CH3CH2C Cl
1) AlCl3
2) H2O
C CH2CH3
Zn(Hg)
aq. HCl
CH2CH2CH3
Gatterman-Koch Formylation
• Formyl chloride is unstable. Use a high
pressure mixture of CO, HCl, and catalyst.
• Product is benzaldehyde.
O
H C Cl
CO + HCl
+
AlCl3/CuCl
O
O
C+
C H
H
_
+
H C O AlCl4
+
HCl
Activating, O-, P-Directing Substituents
• Alkyl groups stabilize the sigma complex
by induction, donating electron density
through the sigma bond.
• Substituents with a lone pair of electrons
stabilize the sigma complex by resonance.
OCH3
+
OCH3
NO2
NO2
+
H
H
The Amino Group
Aniline reacts with bromine water (without a
catalyst) to yield the tribromide. Sodium
bicarbonate is added to neutralize the HBr
that’s also formed.
NH2
NH2
Br
Br
3 Br2
H2O, NaHCO3
Br
=>
Summary of Activators
Deactivating Meta-Directing Substituents
• Electrophilic substitution reactions for
nitrobenzene are 100,000 times slower
than for benzene.
• The product mix contains mostly the
meta isomer, only small amounts of the
ortho and para isomers.
• Meta-directors deactivate all positions
on the ring, but the meta position is less
deactivated.
Ortho Substitution on Nitrobenzene
Para Substitution on Nitrobenzene
=>
Meta Substitution on Nitrobenzene
Energy Diagram
Structure of Meta-Directing Deactivators
• The atom attached to the aromatic ring
will have a partial positive charge.
• Electron density is withdrawn inductively
along the sigma bond, so the ring is less
electron-rich than benzene.
Summary of Deactivators
More Deactivators
Halobenzenes
• Halogens are deactivating toward
electrophilic substitution, but are ortho, paradirecting!
• Since halogens are very electronegative,
they withdraw electron density from the ring
inductively along the sigma bond.
• But halogens have lone pairs of electrons
that can stabilize the sigma complex by
resonance.
Sigma Complex for Bromobenzene
Para attack
Ortho attack
Br
Br
+
(+)
+
E
Br
Br
(+)
H
E
(+)
+
(+)
(+)
+
E
(+)
H E
Ortho and para attacks produce a bromonium ion
and other resonance structures.
Meta attack
Br
Br
H
(+)
+
+
H
E
(+)
E
No bromonium ion
possible with meta attack.
Energy Diagram
Summary of Directing Effects
Multiple Substituents
The most strongly activating substituent will
determine the position of the next substitution.
May have mixtures.
OCH3
OCH3
SO3H
SO3
O2N
H2SO4
OCH3
+
O2N
O2N
SO3H
II. Electrophilic Addition
“Loose” p electrons are nucleophilic (Lewis bases),
react with electrophiles (Lewis acids).
electrophile
+ Y Z
C C
Z
Y
Y
C C
C C
nucleophile
37
Z
II. Electrophilic Addition
A. Addition of hydrogen halides
H X
C C
+ H X
(X = Cl, Br, I)
C C
Reactivity: HI > HBr > HCl >> HF (stronger acid = better e
+ H X
H
C C
RLS
X
C C
H X
C C
fast
HBr
Br
HI
I
38
II. Electrophilic Addition
A. Addition of hydrogen halides
1. Markovnikov’s rule
In the addition of HX to an alkene, the H goes to the carbon w
CH3
CH CH2
Br
HBr
CH3
CH CH3
but not CH3
CH2
CH2 Br
Question 6-2. Draw the products. Click on the arrow to check a
HI
HCl
HBr
Check Answer
HI
39
II. Electrophilic Addition
A. Addition of hydrogen halides
1. Markovnikov’s rule
In the addition of HX to an alkene, the H goes to the carbon w
CH3
CH CH2
Br
HBr
CH3
CH CH3
but not CH3
Answer 6-2.
HI
I
Cl
HCl
HBr
Br
I
HI
and
I
40
CH2
CH2 Br
II. Electrophilic Addition
A. Addition of hydrogen halides
2. mechanism
H Br
CH3
CH CH2
CH3 CH CH3
2º carbocation
more stable
CH3 CH2 CH2
1º carbocation
less stable
Br
Br
Br
Br
Mechanistic interpretation of Markovnikov’s rule: The
reaction proceeds through the more stable
carbocation intermediate.
41
II. Electrophilic Addition
A. Addition of hydrogen halides
2. mechanism
lower Ea 
faster rate of
formation
Br
Br
Br
+ HBr
Br
42