Organic Chemistry

For USTH Students

Lecture
Benzene and Aromatic systems

Dr. Doan Duy Tien

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 Contents

+ Interesting aromatic systems

+Aromaticity: Cyclic, planar, complete conjugation, Huckel’s Rule
+ Nomenclature
+ Preparation
+ Electrophilic substitution in Aromatic systems:
- The General Mechanism
- Halogenation
- Nitration and Sulfonation
- Substituted Benzenes: Inductive Effects, Resonance Effects
- Electrophilic Aromatic Substitution of Substituted Benzenes
- Application : Synthesis of the hallucinogenic effects of LSD
Interesting benzene rings

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 Background of Benzene
• Benzene (C6H6) is the simplest aromatic hydrocarbon
(aromatic compounds are called arenes).
• Benzene has four degrees of unsaturation, making it
a highly unsaturated hydrocarbon.
• Whereas unsaturated hydrocarbons such as alkenes,
alkynes and dienes readily undergo addition
reactions, benzene does not.

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 Historical: Structure of Benzene
• August Kekulé proposed that benzene was a rapidly
equilibrating mixture of two compounds, each
containing a six-membered ring with three
alternating  bonds.
• In the Kekulé description, the bond between any two
carbon atoms is sometimes a single bond and
sometimes a double bond.
• These structures are known as Kekulé structures.

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Structure and bonding of () Bond
Pi () Bond * In the Ground State, the
Antibonding MO is empty.

Antibonding MO

Energy . .
2p AO 2p AO

 In the Ground State, the

Bonding MO has two
Bonding MO electrons
Structure of Benzene and Aromaticity

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 Aromaticity-Hückel’s Rule?

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2 diabetes; that increases the that reduces fever
body’s ability to lower blood
sugar levels,
8
 Aromaticity-Hückel’s Rule?
5 7
3 4 6 8
2

1 N N 9

20 10
Mg
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19 N N
N@C60 Buckyball-Ideal Cage 18
12
17 16 14 13
15

MeOOC O
O
O phytyl 1
chlorophyll a Molecule of life

phytyl = E R R

Buckminsterfullerene, C60 9
 Nomenclature of Benzene Derivatives

• To name a benzene ring with one substituent, name

the substituent and add the word benzene.

• Common names used for monosubstituted benzenes:

Toluene, Phenol, Aniline, Anisole

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 Nomenclature of Benzene Derivatives

• There are three different ways that two groups can be

attached to a benzene ring, so the prefixes: ortho,
meta, or para are used to designate the relative
position of the two substituents.

ortho-dibromobenzene meta-dibromobenzene para-dibromobenzene

or or or
o-dibromobenzene m-dibromobenzene p-dibromobenzene
or 1,2-dibromobenzene or 1,3-dibromobenzene or 1,4-dibromobenzene
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 Nomenclature of Benzene Derivatives
• If the two groups on the benzene ring are different,
alphabetize the names of the substituents preceding
the word benzene.
• If one substituent is part of a common root, name the
molecule as a derivative of that monosubstituted
benzene.

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 Nomenclature of Benzene Derivatives

For three or more substituents on a benzene ring:

1. Number to give the lowest possible numbers
around the ring.
2. Alphabetize the substituent names.
3. When substituents are part of common roots,
name the molecule as a derivative of that
monosubstituted benzene. The substituent that
comprises the common root is located at C1.

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 Nomenclature of Benzene Derivatives

• Other common monosubstituted benzenes:

benzaldehyde, benzoic acid, acetophenone & styrene
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 Nomenclature of Benzene Derivatives

• A benzene substituent is called a phenyl group, and it

can be abbreviated in a structure as “Ph-”.

• Therefore, benzene can be represented as PhH, and

phenol would be PhOH.

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 Nomenclature of Benzene Derivatives

• The benzyl group, another common substituent that

contains a benzene ring, differs from a phenyl group.

• Substituents derived from other substituted aromatic

rings are collectively known as aryl groups.

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Reaction of benzene
and aromatic systems

Electrophilic Aromatic Substitution

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 Electrophilic Aromatic Substitution
Background:
• The characteristic reaction of benzene is electrophilic aromatic
substitution: a hydrogen atom is replaced by an electrophile.

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 Electrophilic Aromatic Substitution
Background:
• 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.
• There are five common examples of electrophilic
aromatic substitution.

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 Electrophilic Aromatic Substitution

Mechanism:

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 Electrophilic Aromatic Substitution
Background:
• The energy changes in electrophilic aromatic
substitution are shown below:
Energy diagram for electrophilic aromatic substitution:
PhH + E+ → PhE + H+

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 Electrophilic Aromatic Substitution
Five examples
of electrophilic
aromatic
substitution

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Electrophilic Aromatic Substitution

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 Electrophilic Aromatic Substitution
Nitration and Sulfonation:
• 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.

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Electrophilic Aromatic Substitution

Synthesis detergent by sulfonation:

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 Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
• In Friedel-Crafts alkylation, treatment of benzene with
an alkyl halide and a Lewis acid (AlCl3) forms an alkyl
benzene.

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 Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
• In Friedel-Crafts acylation, a benzene ring is treated
with acid chloride (RCOCl) and AlCl3 to form a ketone.
• The new group bonded to the benzene ring is an acyl
group, the transfer of an acyl group from one atom to
another is an acylation.

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 Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation: Mechanism

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 Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation:

Carbocation rearrangements can occur.

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 Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation Involving Carbocation Rearrangement

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 Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
Each carbocation can then go on to react with benzene
to form a product of electrophilic aromatic substitution.
For example:

Starting materials that contain both a benzene ring and

an electrophile are capable of intramolecular Friedel-
Crafts reactions.

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 Electrophilic Aromatic Substitution
Substituted Benzenes: inductive effect, hyperconjugation

+ Considering the inductive effect, the NH2 group

withdraws electron density.
+ The CH3 donates electron density through
hyperconjugation.

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 Electrophilic Aromatic Substitution
Substituted Benzenes:
Resonance effects are only observed with substituents
containing lone pairs or  bonds.

An electron-donating resonance effect is observed

whenever an atom Z having a lone pair of electrons is
directly bonded to a benzene ring.

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 Electrophilic Aromatic Substitution
Substituted Benzenes:
• An electron-withdrawing resonance effect is observed
in substituted benzenes having the general structure
C6H5-Y=Z, where Z is more electronegative than Y.
• Seven resonance structures can be drawn for
benzaldehyde (C6H5CHO). Because three of them place
a positive charge on a carbon atom of the benzene ring,
the CHO group withdraws electrons from the benzene
ring by a resonance effect.

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 Electrophilic Aromatic Substitution
Substituted Benzenes:

• The inductive and resonance effects in compounds

having the general structure C6H5-Y=Z (with Z more
electronegative than Y) are both electron withdrawing.

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 Electrophilic Aromatic Substitution
Substituted Benzenes:
• These compounds represent examples of the general
structural features in electron-donating and electron
withdrawing substituents.

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 Electrophilic Aromatic Substitution
EAS and Substituted Benzenes:

• Toluene reacts faster than benzene in all substitution

reactions.
• The electron-donating CH3 group activates the
benzene ring to electrophilic attack.
• Ortho and para products predominate.
• The CH3 group is called an ortho, para director.

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 Electrophilic Aromatic Substitution
EAS and Substituted Benzenes:
• Nitrobenzene reacts more slowly than benzene in all
substitution reactions.
• The electron-withdrawing NO2 group deactivates the
benzene ring to electrophilic attack.
• The meta product predominates.
• The NO2 group is called a meta director.

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 Electrophilic Aromatic Substitution
Orientation Effects in Substituted Benzenes:

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 Electrophilic Aromatic Substitution
Orientation Effects in Substituted Benzenes:
• There are two general types of ortho, para directors
and one general type of meta director.
• All ortho, para directors are R groups or have a
nonbonded electron pair on the atom bonded to the
benzene ring.
• All meta directors have a full or partial positive charge
on the atom bonded to the benzene ring.

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 Electrophilic Aromatic Substitution
Limitations in Electrophilic Aromatic Substitutions:
• Benzene rings activated by the strong electron-
donating groups, OH, NH2, and their derivatives (OR,
NHR, and NR2), undergo polyhalogenation when
treated with X2 and FeX3.

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 Electrophilic Aromatic Substitution
Limitations in Electrophilic Aromatic Substitutions:
• A benzene ring deactivated by strong electron-
withdrawing groups (the meta directors) is not
electron rich enough to undergo Friedel-Crafts
reactions.

• Friedel-Crafts reactions also do not occur with NH2

groups because the complex that forms between the
NH2 group and the AlCl3 catalyst deactivates the ring
towards Friedel-Crafts reactions.

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 Electrophilic Aromatic Substitution
Disubstituted Benzenes:

1. When the directing effects of two groups reinforce,

the new substituent is located on the position
directed by both groups.

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 Electrophilic Aromatic Substitution
Disubstituted Benzenes:
2. If the directing effects of two groups oppose each
other, the more powerful activator controls the
reaction.

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 Electrophilic Aromatic Substitution
Disubstituted Benzenes:

3. No substitution occurs between two meta

substituents because of crowding.

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 Electrophilic Aromatic Substitution
Planning Synthesis of Benzene Derivatives:
In a disubstituted benzene, the directing effects indicate
which substituent must be added to the ring first.

Let us consider the consequences of bromination first

followed by nitration, and nitration first, followed by
bromination.
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 Electrophilic Aromatic Substitution
Pathway I, in which bromination precedes nitration, yields the
desired product. Pathway II yields the undesired meta isomer.

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 Electrophilic Aromatic Substitution
Halogenation of Alkyl Benzenes:
Note that alkyl benzenes undergo two different
reactions depending on the reaction conditions:

• With Br2 and FeBr3 (ionic conditions), electrophilic

aromatic substitution occurs, resulting in replacement
of H by Br on the aromatic ring to form o and p isomers.
• With Br2 and light or heat (radical conditions),
substitution of H by Br occurs at the benzylic carbon48of
the alkyl group.
 Electrophilic Aromatic Substitution
Oxidation and Reduction of Substituted Benzenes:
Arenes containing at least one benzylic C—H bond are
oxidized with KMnO4 to benzoic acid.

Substrates with more than one alkyl group are

oxidized to dicarboxylic acids. Compounds without
a benzylic hydrogen
are inert to oxidation.

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 Electrophilic Aromatic Substitution
Oxidation and Reduction of Substituted Benzenes:
We now know two different ways to introduce an alkyl
group on a benzene ring:
1. A one-step method using Friedel-Crafts alkylation.
2. A two-step method using Friedel-Crafts acylation to
form a ketone, followed by reduction.
Two methods to
prepare an alkyl
benzene

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 Electrophilic Aromatic Substitution
Oxidation and Reduction of Substituted Benzenes:
Although the two-step method is longer, it must be
used to synthesize certain alkyl benzenes that
cannot be prepared by the one-step Friedel-Crafts
alkylation because of possible rearrangements.

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 Electrophilic Aromatic Substitution
Oxidation and Reduction of Substituted Benzenes:

A nitro group (NO2) that has been introduced on a

benzene ring by nitration with strong acid can
readily be reduced to an amino group (NH2) under a
variety of conditions.

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Electrophilic substitution in Aromatic systems
Synthesis of the hallucinogenic effects of LSD

The synthesis of the female sex hormone estrone

Electrophilic substitution in Aromatic systems

• Application: Swimming pool test kit for

chlorine
NH2 NH2
CH3 Cl2 (aq.) Cl CH3

o-toluidine Cl
bright yellow!

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Electrophilic substitution in Aromatic systems
Naproxen production: Albemarle Company

Heck Coupling: Nobel prize 2010: Anti-inflammatory drug

KEY CONCEPTS

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KEY CONCEPTS

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KEY CONCEPTS

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KEY CONCEPTS

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Problems

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Problems

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Problems

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Problems

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Reaction of Carbocations
 Reaction of Carbocations
Structure Formation

Empty obital
Formation

Stability
 Rearrangement of carbocations
Carbocations can rearrange:
by 1,2-hydride or by 1,2-methyl shifts:
  [1,2-H]  
--C—C--  --C—C–
+   +
H H

  [1,2-CH3]  
--C—C--  --C—C–
+   +
CH3 CH3
Rearrangement of carbocations
Carbocations can rearrange by 1,2-hydride or 1,2-
methyl shifts but only do so when the resultant
carbocation is more stable.
1o carbocation will rearrange to 2o
1o carbocation will rearrange to 3o
2o carbocation will rearrange to 3o
(only goes “down hill”)
 Rearrangement of carbocations

Example
CH3 CH3
H2O
CH3 C CHCH3 CH3 C CH2CH3

H Br OH (93%)
 Rearrangement of carbocations
CH3 Example CH3

CH3 C CHCH3 CH3 C CH2CH3

H Br OH (93%)

H2O

CH3 CH3

CH3 C CHCH3 CH3 C CHCH3

+ +
H H