Chapter 6 Arenes and Aromaticity
6.1 The Structure of Benzene
1. A resonance theory
2. An orbital hybridization view
3. The molecular obitals
6.2 Nomenclature of Benzene
Derivatives
6.3 Aromaticity and the Huckel(4n + 2)rule
6.3.1 Annulenes(轮烯)
6.3.2 Aromatic ions
6.3.3 Polycyclic aromatic hydrocarbons
6.4 Reactions of Arenes
6.4.1 Aromatic ring as a substituent
1. Halogenation of α - H of arenes
2. Oxidation of Alkylbenzenes
3. Addition Reaction of Alkenylbenzenes
6.4.2 Aromatic Ring as a Functional
Group:
Electrophilic Aromatic Substitution
6.4.3 Halogenation of Benzene
6.4.4 Nitration of Benzene
6.4.5 Sulfonation of Benzene
6.4.6 Friedel-Crafts Alkylation of Benzene
6.4.7 Friedel-Crafts Acylation of Benzene
Clemmensen reduction
Wolff-Kishner reduction
6.4.8 Effects of Substituents on Reactivity
and Orientation
6.4.8.1 Classification of Substituents
6.4.8.2 Substituent Effects in
Electrophilic Aromatic Substitution
6.4.9 Multiple Substituent Effects
6.4.10 Synthetic Applications
Organic compounds
Aliphatic 脂肪族
Aromatic 芳香族
Aromatic compound: Benzene
CH3
C6H6
Toluene
A low ratio
Tolu balsam
hydrogen / carbon.
Estrone
Fragrant: Balsams
( 香脂 )
O
C H oil
雌激素酮
CH3
of bitter
COOH
CHCOOH
CH3CHCH2
almond
CH3
Ibuprofen
Benzaldehyde Benzoic acid
布洛芬
6.1 Structure of Benzene
Three modern theories:
1. A resonance theory(共振论)
The structure of benzene is planar:
regular hexagon(正六边型).
P153,5.3
The bond angles: 120 °
The C–C bond lengths : 1.39Å
sp2–sp2 single bond: 1.46Å
sp2–sp2 double bond: 1.34
A hybrid of the two Kekulé structures:
is equivalent to
Cyclic conjugation in benzene leads to
a great stability.
2. An orbital hybridization view
In a mole. of benzene, all C atoms are
sp2–hybridized.
Resonance
6 C–C σ bonds: sp2–sp2 overlap, energy:
152 kJ/mol
2
6 C –H σ bonds: sp –1s overlap.
The 6 2p orbitals that
are perpendicular to
the σ framework
overlap to form π
orbital.
C C
C H
C
H
The 6 π electrons are
C C
delocalized over all six C.
H
A closed π conjugate system.H
3. The molecular obitals
The 6 overlapping 2p obitals combine to
form a set of 6 π molecular orbitals:
Antibonding orbitals
Bonding orbitals
6.2 Nomenclature of Benzene
Derivatives
P154,5.4
1. Monosubstituted benzenes
A. Benzene as the parent name.
Cl
CH3
Toluene Chlorobenzene
(甲苯)
(氯苯)
NO2
CH3
CHCH3 Nitrobenzene
( 硝基苯)
Isopropylbenzene
B. Benzene as a substituent
CH2
C6H5–, Ph–: phenyl.
Diphenylmethane
CH3
PhC CH
CH2 Cl
CHCH3
PhC
Phenylacetylene
Benzylchloride
2-Phenyl-2-butene
(苯乙炔)
(苄基氯)
2. Disubstituted benzenes
Three isomers:
Br
Br
Br
Br
1,2-Dibromobenzene
o-Dibromobenzene
orthoCH3
CH3
o-Xylene
(0-二甲 苯)
Br
Br
1,3mmeta-
1,4ppara-
3. Polysubstituted Benzenes
NO2
Cl
NO2
Common name: CH3
P155
H3C
CH3
2-Chloro-1,4-dinitrobezene
1,3,5-Trimethylbezene
(1,4- 二硝基-2-氯苯)
( 均三甲苯)
6.3 Aromaticity and the
Huckel (4n + 2) rule
Ch.276
Aromaticity: a special stability.
On the basis of the calculation by MO. Theory,
Huckel (4n + 2) rule:
a. The monocyclic and fully conjugated
polyenes.
b. All atoms in the ring are coplanar.
c. The Mole. possesses(4 n+2) π electrons.
6.3.1 Annulenes(轮烯)
cyclobutadiene
cyclooctatetraene
π electrons 4 [6]-Annulene [8]-Annulene
[4]-Annulene
Tub-mole.
Eric Hückel
1896
"Eric Hückel received his PhD in experimental
Physics in 1921 at the University of Göttingen.
After spending a year with David Hilbert
in mathematics and Max Born, he left Göttingen
for a position at the ETH Federal Institute of
Technology in Zurich with Peter Debye.
While at Zurich, Hückel and Debye
developed the Debye-Hückel theory of strong
electrolytes. In 1930 Hückel received
an appointment in chemical physics
at the Technical Institute in Stuttgart.
In 1937 he was appointed a professor of theoretical
physics at the University of Marburg,
where he remained until his retirement in 1962."
(Source: DA McQuarrie "Quantum Chemistry",
University Science Books, 1983)
In the quantum chemistry community,
Hückel is best known for introducing in 1930
a simple theory for the treatment of
conjugated molecules and aromatic molecules.
This theory came to be known as"Hückel molecular
orbital theory" or simply"Hückel Theory".
This was later extended by Roald Hoffmann
and has been widely used in organic
and inorganic chemistry.
H H
Cyclodecapentaene
(环癸五烯)
6.3.2 Aromatic ions
H
H
strong
base
2
sp
CH2:
H
cyclopentadiene Cyclopentadienyl
π electrons: 6
anion
sp3
H
Ch.P278
H H
H
Cycloheptatriene Cycloheptatrienyl
cation
(环庚三 烯)
6.3.3 Polycyclic aromatic hydrocarbons
8
1
8
7
2
6
3
5
4
9
9 10
1
7
6
2
5
10
4
3
1
8
7
P279
2
6
5
4
3
Naphthalene Anthracene Phenanthrene
(萘)
(蒽)
(菲)
The hybrid of three resonance forms
• following Hückel rule
• Aromaticity
6.4 Reactions of Arenes
6.4.1 Aromatic ring as a substituent
CCl3
CHCl2
Ex. CH3
CH2Cl
Cl2
Cl2
Cl2
h
h
h
1. Halogenation of α - H of arenes
O
CH2CH3 +
N Br
O
O
O
O
PhCOOCPh
CCl4, 80°C
CHCH3 +
N H
Br
O
Ethylbenzene N-Bromosuccinimide (87%)
N-溴代丁二酰亚胺
(NBS)
Allylic halogenation:
CH3 CH CH2
NBS
h,CCl4
CH2 CH CH2
Br
2. Oxidation of Alkylbenzenes P170,5.11
The alkyl side chain with α - H on a
benzene ring is oxidized to benzoic acid
by chromic acid(铬酸) or KMnO4:
CH2CH2R
Na2Cr2O4
COOH
H2O,H2 SO4,heat
COOH
CH3
Na2Cr2O4
H2O,H2SO4,heat
NO2
NO2
CH3
C CH3
CH3
Oxidant:
KMnO4
(86%)
Na2Cr2O4
H2O,H2 SO4,heat
t-Butylbenzene
NO reaction
3. Addition Reaction of Alkenylbenzenes
6.4.2 Aromatic Ring as a Functional
Group:
Electrophilic Aromatic Substitution
(芳环上的亲电取代反应)
P157
When the aromatic ring of benzene reacts
with a electrophilic reagent, the substitution
reaction occurs:
A benzene ring with
6 π electrons
+E Y
in a cyclic conjugated system is a site
Electron donor: benzene ring of electron-rich.
Electron acceptor: E+, a Lewis
acid.


E
+H Y
Aromatic electrophilic substitution reactions:
The electrophlic part of a reagent
replaces a hydrogen atom from aromatic
ring.
Sulfonation
Alkylation
SO3H
Nitration
R
NO2
Acylation
Halogenation
X
P157
(酰基化)
H
O
C R
Figure 1 Types of electrophilic
aromatic substitution of benzene
6.4.3 Halogenation of Benzene
H
+
Br
Fe
Br2 heat
+ HBr
(75%)
The Lewis acids most commonly used are
FeCl3, FeBr3 and AlCl3.
2Fe + 3X2
2FeX3
The mechanism for bromination of benzene:
Step 1 Polarization of Br2.
Br Br + FeBr3

Br

Br FeBr3
The formation of the bromine-iron(III)
bromide complex.
Step 2 The attack of polarized bromine
to benzene ring .
Br

+ Br
Br FeBr3 slow
H + Br
FeBr3
The formation of nonaromatic carbocation.
Allylic cation: p- π conjugation
Delocalization of π - electrons generates
the resonance forms:
Br
H
Br
H
Br
H
Step 2 is rate-determining.
Step 3 The loss of a proton to restore the
aromatic system.
Br
H + Br
FeBr3
Br
+ HBr + FeBr3
Step 1. Polarization of Br2.
Step 2 The attack of polarized bromine
to benzene ring .
Step 3 The loss of a proton to restore the
aromatic system.
Reactivity : F2 > Cl2 > Br2 > I2
Iodination has to carry out in the presence
CH3
of an oxidizing agent:
NO2
O2N
I
HNO3
Ex.
+ I2
NO2
Iodobenzene(86%) Trinitrotoluene
(TNT)
6.4.4 Nitration( 硝化反应) of Benzene
Aromatic rings can be nitrated by
reaction with a mixture of concentrated
nitric acid and sulfuric acid:
+
H2 SO4
HNO3 50 - 55 °C
NO2
+ H3O + HSO4
Nitrobenzene(85%)
The generation of electrophile, E+:
HNO3 + 2H2SO4
NO2 + H3O + 2HSO4
Nitronium ion(
)
6.4.5 Sulfonation(磺化反应) of Benzene
Benzene reacts with fuming sulfuric acid
to produce benzene sulfonic acid:
H
O
O
+
25 °C
concd H2SO4
S
O
O
S
OH
O
Sulfur trioxide Benzenesulfonic acid
(苯磺酸)(56%)
Fuming H2SO4: a mixture of H2SO4 and SO3.
Mechanism of the reaction:
Step 1 Generation of the electrophile:
2H2SO4
SO3 + H3O + 2HSO4
Step 2. Sulfur trioxide as a electrophile
attacksO benzene inSOthe rate-determing step.
H
3
slow
+
H
S
O
An antibiotic O
S
O
Step 3. The loss of a proton to
restore the aromatic system.
H2N
Step 4. A rapid proton transfer to produce
benzenesulfonic acid.
+ H2SO4
NH2
Sulfanilamide
SO3
+ H2SO4 (磺胺)
SO3
fast
H + HSO4
SO3
O
fast
SO3H
+ HSO4
The sulfonation of benzene is reversible.
Sulfonation is favored in strong acid,
Desulfonaton is favored in hot,dilute aqueous
acid.
6.4.6 Friedel-Crafts Alkylation
of Benzene
Benzene reacts with alkyl halide in the
presence of AlCl3 as catalyst:
+ CH3CHCH3
AlCl3
CHCH3
+ HCl
CH3
Cl
Cumene(枯烯)
Mechanism of the reaction: Isopropylbenzene
Step 1. The formation of carbocation:
CH3
CH3
CH Cl + AlCl3
CH3
CH3
CH + Cl AlCl3
Step 2. The carbocation as a electrophile attacks
benzene ring, a C–C bond is formed:
H
CH3
slow
+ CH
CH3
CH3
CHCH3
H
Step 3. Loss of a proton to produce
CH3
the alkylbenzene
CHCH3
H
+ Cl AlCl3 fast
CHCH3 + HCl + AlCl3
CH3
• CH3X and RCH2X do not form the carbocation,
they form the complex:
RCH2 X AlX3
• The rearrangement can occur when
especially a primary halides are used:
H
+ (CH3)2CHCH2Cl
C(CH3)3
AlCl3
0 °C
(66%)
H
CH3 C
+ HCl
CH2 Cl AlCl3
CH3
CH3 C
CH3 + Cl AlCl3
CH3
• Friedel-Crafts alkylation can be availble to
other systems that generate a carbocation:
H2SO4
Ex.
+
Cyclohexyl benzene(65%)
A alkene and a acid.
+ HO
BF3
60°C
A alcohol and a acid.
• Polyalkylation
Ch. P252
+ (CH3)3CCl
(56%)
Another limitation
to alkylation on ring
C(CH3)3
AlCl3
+
Major
product
C(CH3)3
+
C(CH3)3
Minor
product
Charles Friedel
(1832-1899)
Charles Friedel was born in
Strabourg, Frans,and studied
at the Sorbonne in Paris. He was
among the first to attempt
manufacture synthetic diamonds.
He was professor of chemistry
at the Sorbonne(1884-1889).
James Mason Crafts
(1839-1917)
James Mason Crafts was
born in Boston, Massachusetts,
and graduated from Harvard in
1858. He served as president in
the Massachusetts Institute of
Technology (1897-1900).
6.4.7 Friedel-Crafts Acylation of Benzene
Benzene reacts with a (酰基化反应)
acyl halide (酰卤) in the presence of AlCl3,
to produce a acylbenzene(酰基苯). O
O
H
+ CH3C Cl
AlCl3
excess benzene
80°C
CCH3 + HCl
Acetophenone(苯乙酮)(97%)
Reagents: Acyl chloride (or acid chloride):
Carboxylic acids react with thionyl chloride
(亚硫酰氯) or PCl5:
Ch. P252
O
O
CH3C OH + SOCl2
80°C
CH3C Cl + SO2 + HCl
Carboxylic acid anhydrides(酸酐)O:
O
O
H
+ CH3C O CCH3
AlCl3
excess benzene
80°C
O
CCH3 + CH3C OH
(83%)
• Limitation to Friedel-Crafts Reactions:
Friedel-Crafts reactions do not occur
when powerful electron-drawing groups
are present on the aromatic ring.
+
-NO
,
-SO
H,
RCO-,-COOH,
-NR
ect..
2
3
3
NH
2
+R X
AlCl3
NO reaction
NH2 + AlCl3
NH2
AlCl3
• Application of acylation to aromatic ring
Preparation of unbranched alkyl
O
O
benzene:
AlCl
+ CH3CH2CH2CCl
3
CCH2CH2CH3 + HCl
1-Pheny-1-butanone
(1-苯基1-丁酮)(86%)
Clemmensen reduction:
The ketone can be reduced to alkylbenzene
by refluxing with HCl containing
amalgamated
zinc(锌汞齐):
O
Ch.P355
CCH2CH2CH3
HCl
Zn(Hg)
CH2CH2CH2CH3
Butylbenzene(73%)
Wolff-Kishner reduction:
O
C
CH2
Heating with hydrazine(肼) and hydroxide
O
H 2NNH2,KOH
CCH2CH3 triethylene glycol
1-Pheny-1-propanone 175°C
(1-苯基-1-丙酮)
CH2CH2CH3
Propylbezene
( 丙苯)(82%)
Triethylene glycol
HOCH2CH2OCH2CH2OCH2CH2OH( 三甘醇 or 三 缩 乙二醇 )
6.4.8 Effects of Substituents on P164, 5.9
Reactivity and Orientation
Y
To substituted benzenes:
the substituent on the ring affects both
the rate of the reaction and the site of attack.
Effect of substituents on the reactivity
and orientation or regioselectivity.
6.4.8.1 Classification of Substituents
Substituents can be classified into
three groups:
1. Ortho and para Directing activators
（邻、对定位致活基团）
Substituents in first category(第一类定位基团)
• Making the ring more reactive than benzene.
OH
H
Hydroxyl group
is a activitor
Relative rate 1000
of nitration
NO2
Cl
1 0.033 6 × 10-8
Reactivity
• Directing substitution primarily to the ortho
and para position to themselves
CH3
CH3
CH3
HNO3
HOAc
NO2
+
CH3
+
NO2
o-
p-
m-
63%
34%
3%
NO2
2. Meta directing deactivators
(间位定位致钝基团)
Substituents in second category(第二类定位基团)
• Making the ring less reactive than benzene.
Ex. –NO2, –CF3 etc.(et cetera[it´setr ])
• Directing substitution primarily to the meta
position to themselves
CF3
CF3
CF3
NO2
HNO3
H2SO4
+
CF3
+
NO2
NO2
6%
3%
91%
3. Ortho and para directing deactivators
–X:
Cl
Cl
Cl
Cl
NO2
HNO3
H2 SO4
+
+
NO2
NO2
30%
69%
1%
FIGURE 6.1 Classification of substituent
effects in electrophilic aromatic substitution.
NH2
OH
O
F
Br
H
CF3
CCl3
NR3 NO2
Reactivity
NHCOCH3 OCH3 CH3
Cl I C H(R) C OH C OR SO3H C N
O
O
O
P166 Ortho- and
Ortho- and
para- directing para- directing
deactivitors
activitors
Metadirecting
deactivitors
6.4.8.2 Substituent Effects in electrophilic
Aromatic substitution
Substituent Effects
Ortho- and para- directing
Electron-releasing
activitors
Meta-directing
deactivitors
X
Electron-withdrawing
–I, +C
1. Ortho and para directing activitors
Activiting effect: • Electron-releasing groups
increase the density of electron
CH3
CH3
cloud to favor electrophilic
E
attack.
H E
• stabilize the carbocation.
Orientation effect:
OH
OH
Para
attack
P168,
OH
E H
Meta OH
attack
E
H
E
H
E
H
E
H
Ortho
attack
OH
OH
OH
OH
OH
OH
E H E H
OH
E H
OH
E
H
E
H
E
H
Most stable
resonance
structure
Para and ortho
attacks are
primary.
2. Meta directing deactivitors
Deactiviting effect: • Electron-drawing groups
CF3
CF3
decrease the density of electron
cloud of aromatic ring.
E
E • Making intermedias highly
H
unstable
Orientation effect: CF
CF3
CF3
3
Ortho
attack
CF3
E
H
CF3
CF3
CF3
Para
attack
Meta
attack
CF3
E
H
Most unstable
intermeidate
E H
E H
E H
E
H
E
H
CF3
E
H
CF3
E
H
Meta
attack is
primary
3. Halogens
X Halogen as a substituent on aromatic ring
possesses both electron-drawing inductive
effect(-I) and electron-releasing conjugative
effect(+C).
Inductive effect of halo-group
X -I > +C
deactivates aromatic ring.
OH
Halo-group stabilizes the interOR -I < +C mediate relative to that from ortho
NH2
and para attack deactivates aromatic
ring by donating unshared pair of
electrons in the same way as –OH.
Ch.P262
Cl
Cl
Cl
Cl
E H
E H
E H
E H
6.4.9 Multiple Substituent Effects
X
Further electrophilic substitution of
a disubstituted bezene is governed by
Additivity(累加性) of effects.
Y 1. If the directing effects of the two groups
reinforce( 增强) each other, there is no
problem.
CH3
CH3
Ch. P266
NO
2
HNO3
H2SO4
NO 2
NO2
2. If the directing effects of the two groups are
oppose each other, the more powerful
activiting group has the dominant influence.
NHCH3
Br
NHCH3
Br2
HOAc
Cl
CH3
Cl
CH3
CH3
O2N
HNO3
+
COOH
H2SO4
COOH
COOH
NO2
3. When two positions are comparably actived
by alkyl group, substitution usually occurs
at the less hindered site.
CH3
CH3
HNO3
NO2
H2SO4
CH
CH3
CH3
CH
CH3
CH3
(88%)
6.4.10 Synthetic
Applications
NO
2
Ex. 1
Ch.172,5.13
CH2CH2CH3
Cl
4-Chloro-1-nitro-2-propylbenzene(2-丙基-4-氯硝基苯)
Cl
Retrosynthetic analysis
NO2
O
Cl
Cl
Cl
NO2
Synthetic route:
O
( CH3CH2CCl )
( AlCl3 )
(H2NNH2 ) Cl
(
( KOH )
m-Chloropropiophenone
NO2
O
(间-氯苯基乙基(甲)酮
( Cl2 )
( Cl
( FeCl3 )
)
(HNO3)
(H2SO4)
O
)
Cl
NO2
Chapter 6 to Problems
P178,
5.22 (a), (c)
5.23 (c), (f)
5.26 (b)
5.27
5.28 (b) (苯基腈 或氰基苯)
5.32 (b) (邻-甲基苯酚)
5.33 (c)
5.39
5.40 (b)
5.41(b)
5.42
5.44
5.45
5.48
5.49
5.50
5.51