REACTIONS

REACTIONS OF
OF BENZENE
BENZENE
AND
AND ITS
ITS DERIVATIVE
DERIVATIVE
Group 5:
Lê Thị Diễm Quyên
Viên Hồng Nhung
Đào Ngọc Thái
Nguyễn Anh Quốc
 Outlines
Introdution
Electrophilic Aromatic Substitution
Disubstitution and Polysubstitution
Nucleophilic Aromatic Substitution
 Introdution to benzene
function groups

The Halogen
The Nitro group (-NO2)
The Sulfonic acid group (-SO3H)
The Alkyl group (-R)
The Acyl group (RCO-)
 Electrophilic Aromatic Substitution

• The characteristic reaction of benzene is electrophilic aromatic

substitution—a hydrogen atom is replaced by an electrophile (E+)
Mechanism
All occur by a common three-step mechanism
Step 1: Generation of the electrophile

Step 2: Reaction of the electrophile with the ring

H H H
H
+ slow
+ E E E E

Resonance-stabilized cation intermediate

Step 3: Proton transfer to regenerate the aromatic ring

H E
fast + Base-H
E + Base
• Benzene does not undergo addition reactions like other
unsaturated hydrocarbons, because addition would
yield a product that is not aromatic.
• Substitution of a hydrogen keeps the aromatic ring
intact.
 Chlorination and Bromination
Step 1: Formation of a chloronium ion (E+)

Cl
Cl Cl + Fe Cl
Cl
Chlorine Ferric chloride
(a Lewis base) (a Lewis acid)

+ Cl Cl
- + -
Cl Cl Fe Cl Cl Cl Fe Cl
Cl Cl
A molecular complex with An ion pair containing
a positive charge on chlorine a chloronium ion
and a negative charge on iron
Step 2: Reaction of the chloronium ion with the aromatic ring

slow, rate
+
determining
+ Cl

+
H H H
+
Cl Cl + Cl
Resonance-stabilized cation intermediate
Step 3: Proton transfer to FeCl4- forms HCl, regenerates the Lewis
acid catalyst, and gives chlorobenzene
+
H Cl
- fa s t
+ Cl Fe Cl
Cl Cl
Cation
intermediate
Cl
Cl + H-Cl + Fe Cl
Cl
Chlorobenzene
 Nitration and Sulfonation
Nitration
Nitration and sulfonation introduce two different functional
groups into the aromatic ring.
Nitration is especially useful because the nitro group can be
reduced to an NH2 group.
The electrophile is NO2+, generated in this way

H
H O NO2 + H O SO3 H H +O NO2 + HSO4
Conjugate acid
Nitric acid of nitric acid

H H
+ +
H O NO2 H O + NO2
The nitronium
ion
A particular value of nitration is that the nitro group can be
reduced to a 1° amino group.

Reduction occurs with other reagents such as an active metal

(Fe, Sn or Zn) in HCl.

COOH COOH

Ni
+ 3 H2 + 2 H2 O
(3 atm)
NO2 NH2
4-Nitrobenzoic acid 4-Aminobenzoic acid
Sulfonation

Carried out using concentrated sulfuric acid

containing dissolved sulfur trioxide.
Concentrated sulfuric acid containing dissolved sulfur
trioxide is fuming sulfuric acid.

SO3H
H2SO4
+ SO3

Benzene Benzenesulfonic acid

 Friedel-Crafts Alkylation
Friedel-Crafts alkylation forms a new C-C bond between an
aromatic ring and an alkyl group.
Mixing benzene and alkyl halide, AlCl3 catalyst, form alkyl
benzene and HX

AlCl3
+ Cl + HCl

Benzene 2-Chloropropane Cumene

(Isopropyl chloride) (Isopropylbenzene)
 Step 1: Formation of an alkyl cation as an ion pair.
Cl Cl
+
-
R Cl + Al Cl R Cl Al Cl R+ AlCl4 -
Cl Cl
A molecular An ion pair containing
complex a carbocation

Step 2: Attack of the alkyl cation on the ring.

+
H H H
+ R+ +
R R R
+
A resonance-stabilized cation

Step 3: Proton transfer regenerates aromaticity.

H
+ Cl AlCl3 R + AlCl3 + HCl
R
 Friedel-Crafts Acylation of Benzene

Friedel-Crafts acylation forms a new C-C bond

between a benzene ring and an acyl group.
O
O AlCl3
+ CH3 CCl + HCl

Benzene Acetyl Acetophenone

chloride

O
Cl O
AlCl3 + HCl

4-Phenylbutanoyl -Tetralone
chloride
• The electrophile is an acylium ion.
• A special value of Friedel-Crafts acylations is
preparation of unrearranged alkylbenzenes.
O
A lCl 3
+ Cl

2-Methylpropanoyl
chloride
O

N 2 H 4 , KOH
diethylene
glycol
2-Methyl-1- Isobutylbenzene
phenyl-1-propanone

Wolff-Kishner reduction
 Other Electrophilic Aromatic Alkylations

Carbocations are also generated from alkenes and

alcohols by treatment of an alkene with a protic
acid, most commonly H2SO4, H3PO4, or HF/BF3

H3 PO4
CH3 CH=CH2
+

Benzene Propene Cumene

 By treating an alkene with a Lewis acid,

AlCl3
+

Benzene Cyclohexene Phenylcyclohexane

By treating an alcohol with H2SO4 or H3PO4.

H3PO4
+ + H 2O
HO

Benzene 2-Methyl-2-propanol 2-Methyl-2-phenylpropane

(tert-Butyl alcohol) (tert-Butylbenzene)
 Di- and Polysubstitution
• Two characteristics of a substituent
– Orientation:
• Certain substituents direct preferentially to ortho & para positions; others
to meta positions.
• Substituents are classified as either ortho-para directing or meta directing
toward further substitution.
– Rate:
• Certain substituents cause the rate of a second substitution to be greater
than that for benzene itself; others cause the rate to be lower.
• Substituents are classified as activating or deactivating toward further
substitution.
Di- and Polysubstitution
-OCH3 is ortho-para directing.
OCH3 OCH3 OCH3
NO2
+ HNO3 + + H2 O
CH3 COOH
NO2
Anisole o-Nitroanisole p-Nitroanisole
(44%) (55%)

-COOH
COOH is meta directing.
COOH COOH COOH
H2 SO4 NO2
+ HNO3 + +
100°C
NO2
Benzoic NO2
acid o-Nitro- p-Nitro-
m-Nitro-
benzoic benzoic benzoic
acid acid acid
(18%) (80%) (2%)
Table 1.1. Directing effects of substitution on futher substitution

Strongly

:
:

:
activating N H2 N HR N R2 OH OR
Ortho-para Directing

:
:
O O O O
Moderately

:
:

:
activating N HCR N HCAr OCR OCAr

:
Weakly
activating R

Weakly
:

:
:
deactivating F: Cl : Br : I:
:

:
O O O O
Meta Directing

CH CR COH COR
Moderately
deactivating O
CNH 2 S O3 H C N
Strongly
+
deactivating N O2 N H3 CF3 CCl3
 Di- and Polysubstitution
• Generalizations:
– Directivity: Alkyl, phenyl, and all substituents in which
the atom bonded to the ring has an unshared pair of
electrons are ortho-para directing. All other substituents
are meta directing.

– Activation: All ortho-para directing groups except the

halogens are activating toward further substitution. The
halogens are weakly deactivating.
 Di- and Polysubstitution.
– The order of steps is important.
CH3 o,p COOH
HNO3 K2 Cr2 O7
H2 SO4 H2 S O4
o,p
CH3 NO2 NO2
p-Nitrobenzoic
acid
m m
COOH COOH
K2 Cr2 O7 HNO3
H2 SO4 H2 S O4
NO2
m-Nitrobenzoic
acid

Note the key point: transformation of o,p director

into m director.
Theory of Directing Effects
• The rate of EAS is limited by the slowest step
in the reaction
• For almost every EAS, the rate-determining
step is attack of E+ on the aromatic ring to give
a resonance-stabilized cation intermediate
• The more stable this cation intermediate, the
faster the rate-determining step and the faster
the overall reaction
Theory of Directing Effects
-OCH3 is directing: assume ortho-para attack.
Here only para attack is shown.
OCH3 OCH3

+ N O2 + slow

+ N O2
:

:
:

:
: OCH3 : OCH3 OCH3 : OCH3
fast
+ - H+
+ +
H N O2 H N O2 H N O2 H N O2
(d) (e) (f) (g)
Theory of Directing Effects
-OCH3: assume ortho-para attack
OCH3 OCH3

+ N O2 + slow

+ N O2
:

:
:

:
: OCH3 : OCH3 OCH3 : OCH3
fast
+ - H+
+ +
H N O2 H N O2 H N O2 H N O2
(d) (e) (f) (g)
Theory of Directing Effects
-CO2H is directing; assume meta attack.

COOH
+ slow
+ NO2

COOH COOH COOH COOH

fast
+
H H H -H
NO2
NO2 NO2 NO2
(a) (b) (c)
Theory of Directing Effects
-CO2H is directing: assume ortho-para attack.
COOH
+ slow
+ NO2

COOH COOH COOH COOH

fast
+
-H
H NO2 H NO2 H NO2 NO2
(d) (e) (f)
The most disfavored
contributing structure
 Activating-Deactivating
• Any resonance effect,
effect such as that of -NH2, -OH,
and -OR, that delocalizes the positive charge on
the cation intermediate lowers the activation
energy for its formation, and has an activating
effect toward further EAS
• Any resonance or inductive effect,
effect such as that of
-NO2, -CN, -CO, or -SO3H, that decreases
electron density on the ring deactivates the ring
toward further EAS
Nucleophilic Aromatic Substitution

 Aryl halides, don’t undergo substitution by either of the

SN1 or SN2 pathways that are characteristic of nucleophilic
aliphatic substitution

 Undergo nucleophilic aromatic substitution under certain

condition but by mechanisms quite different from those for
nucleophilic aliphatic substitution

 Nucleophilic aromatic substitutions are far less common

than electrophilic aromatic substitutions
 Benzyne Intermediates
 When heated at 3000C under hight pressure with aqueous
NaOH, chlorobenzene is converted to sodium phenoxide.
Neutralization of this salt with aqueous Acid gives phenol
- +
Cl O Na
H2 O
+ 2 NaOH + NaCl + H2 O
o
pressure, 300 C
Chloro- Sodium
benzene phenoxide
 Benzyne Intermediates
 At pressure high and temperature at 5000C reaction
appears to involve nucleophilic substitution of group OH for
group Cl on the benzene ring
CH3 CH3 CH3
Cl OH
1 . NaOH, heat, pressure
+
2 . HCl, H2 O OH
2-Methylphenol 3-Methylphenol
(o-Cresol) (m-Cresol)

 For example o-chlorotoluene under these conditions

gives a mixture of o-cresol and m-cresol
 Benzyne Intermediates
 The same type of reaction can be brought about using
of sodium amide in liquid ammonia
 Under these condition p-chlorotoluene gives a mixture
of 4-methylaniline and 3-methylaniline

CH3 CH3 CH3

NH3 (l) + NaCl
+ NaNH2 o
+
(-33 C)
NH2
Cl NH2
4-Methylaniline 3-Methylaniline
(p-Toluidine) (m-Toluidine)
 Benzyne Intermediates
Mechainsm
Step1: Dehydrohalogenation of the benzene ring gives a
benzyne intermediate

When elimination of HX gives a benzyne intermediate, that

then adds the nucleophile to give new products
 Benzyne Intermediates

Step 2: Addition to either carbon of the “triple” is possible

Step 3: Proton transfer from ammonia to the carbanion

 Addition- elimination

 Aromatic halides are normally inert to the

types of nucleophiles that readily displace
halide ions from alkyl halides

 When an aryl halide contains electron-

withdrawing NO2 groups ortho and/or para to X,
nucleophilic aromatic substitution takes place
readily
 Addition- elimination

 When 1-chloro-2,4-dinitrobenzene is heated at reflux in aqueous Na2CO3

- +
Cl O Na
NO2 Na2 CO3 , H2 O NO2
o
100 C
NO2 NO2
1-Chloro-2,4- Sodium 2,4-dinitro-
dinitrobenzene phenoxide

 Hence product react with acid

form 2,4-dinitrophenol
 Addition- elimination

Mechainsm

Step 1: the nucleophile adds to the aromatic ring at the carbon

bearing the halogen

Step 2:Elimination of halide ion regenerates the aromatic ring and

gives the observed product
 Problems
Problem 22.23: Mechanism
2,6-di-tert-butyl-4-
methylphenol
OH
Or Butylated
hydroxytoluene (BHT)
In food industry, it is an
antioxidation in food to
“retard spoilage”
2,6-di-tert-butyl-4-methylphenol
Starting materials :
4-methylphenol (p-cresol)
2-methylpropene
OH
H3PO4 catalyst

2-methylpropene
p-cresol
 Summary

Reaction s
of
Benzene
Summary
• References
Thank for your
attention