CFB 2043 – ORGANIC CHEMISTRY

REACTION OF AROMATIC
COMPOUNDS
LECTURE 8

TS DR MOHD DZUL HAKIM WIRZAL

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COURSE OUTCOME
This lecture address the following course outcome

Describe the special stability of aromatic compounds and how this

3 affects reactivity.

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LEARNING OUTCOME
At the end of this lecture, students should be able to:

To draw basic electrophilic aromatic substitution of benzene

1 (halogenation, nitration, sulfonation, alkylation, and acylation.

To compare and contrast the effect of the attached-electrophile toward

2 reactivity of aromatic ring.

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 PART 1
BASIC EAS REACTION

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INTRODUCTION
When chemical reaction involves, you shall use structures 1-3

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INTRODUCTION (CONT.)
▪ Basic electrophilic aromatic substitution.

▪ Benzene does not undergo addition reactions like other unsaturated

hydrocarbons, because addition would yield a product that is not aromatic.
Substitution of a hydrogen, on the other hand, keeps the aromatic ring intact.

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INTRODUCTION: REACTIONS MAP

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FIVE (5) BASIC EAS REACTIONS

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HALOGENATION OF BENZENE
X = Halogen
= Fluorine (F), Chlorine (Cl), Bromine (Br),
Iodine (I)

Unlike alkene, benzene does not go addition reaction with Br2

Benzene does go electrophilic aromatic substition with Br2 in

the presence of catalyst FeBr3

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HALOGENATION OF BENZENE (CONT.)
How does it work?

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HALOGENATION OF BENZENE (CONT.)

▪ Fluorination occurs so rapidly , it is hard to stop at mono fluorination of the ring

▪ Fluorobenzene can be made, however, by an indirect method as the following
reaction,

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HALOGENATION OF BENZENE (CONT.)

▪ Iodine is so unreactive that an alternative method must be used.

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NITRATION OF BENZENE (CONT.)

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SULFONATION OF BENZENE
▪ Sulfonation occurs most rapidly using fuming sulfuric acid (concentrated
sulfuric acid that contains SO3.

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SULFONATION OF BENZENE (CONT.)

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SULFONATION OF BENZENE (CONT.)
▪ All of the steps in sulfonation are equilibria, which means that the
overall reaction is reversible.
▪ The position of equilibrium can be influenced by the conditions we
employ.

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FRIEDEL-CRAFT ALKYLATION

▪ The mechanism for the reaction starts with the formation of a

carbocation.
▪ The carbocation then acts as an electrophile and attacks the benzene
ring to form an arenium ion.
▪ The arenium ion then loses a proton.

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FRIEDEL-CRAFT ALKYLATION (CONT.)

▪ When R-X is a primary halide, a simple carbocation probably does not form.
▪ Instead, the aluminum chloride forms a complex with the alkyl halide, and this
complex acts as the electrophile.

▪ These complexes react so much like carbocations that they also undergo typical
carbocation rearrangements

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FRIEDEL-CRAFT ALKYLATION (CONT.)
▪ Friedel–Crafts alkylations are not restricted to the use of alkyl halides and
aluminum chloride.
▪ Other pairs of reagents that form carbocations (or species like carbocations)
may be used in Friedel–Crafts alkylations as well.

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FRIEDEL-CRAFT ACYLATION

R = Acyl group
▪ An acyl group has a carbonyl attached to some R group.
▪ Two common acyl groups are:

Acetyl Benzoyl

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FRIEDEL-CRAFT ACYLATION (CONT.)

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FRIEDEL-CRAFT ACYLATION

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LIMITATION OF FRIEDEL-CRAFT REACTION
1. When the carbocation formed from an alkyl halide, alkene, or alcohol can
rearrange to one or more carbocations that are more stable, it usually does so,
and the major products obtained from the reaction are usually those from the
more stable carbocations.

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LIMITATION OF FRIEDEL-CRAFT REACTION
2. Friedel–Crafts reactions usually give poor yields when powerful electron-
withdrawing groups (Lecture 8.2) are present on the aromatic ring or when
the ring bears an iNH2, iNHR, or iNR2 group. This applies to both alkylations
and acylations.

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LIMITATION OF FRIEDEL-CRAFT REACTION
3. Aryl and vinylic halides cannot be used as the halide component because they
do not form carbocations readily.

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LIMITATION OF FRIEDEL-CRAFT REACTION
4. Polyalkylations often occur. Alkyl groups are inductive electron-releasing
groups, and once one is introduced into the benzene ring, it activates the ring
toward further substitution (see Lecture 8.2):

Polyacylations are not a problem in Friedel–Crafts acylations. The acyl group

(RCOi ) by itself is an electron-withdrawing group, and when it forms a complex
with AlCl3 in the last step of the reaction (Lecture 8.2), it is made even more
electron withdrawing. This strongly inhibits further substitution and makes
monoacylation easy.
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SYNTHETIC APPLICATIONS OF FRIEDEL-CRAFTS ACYLATIONS
▪ The Clemmensen Reduction is a chemical reaction described as a reduction of
ketones or (aldehyde) to alkanes using zinc amalgam and HCl.
▪ This reaction is named after Erik Christian Clemmensen, a Danish chemist

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SYNTHETIC APPLICATIONS OF FRIEDEL-CRAFTS ACYLATIONS
▪ The Wolff–Kishner Reduction is a reaction used in organic chemistry to
convert carbonyl functionalities into methylene groups.

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CLASS ACTIVITY 8.1
1. Starting with benzene and the appropriate acyl chloride or acid anhydride,
outline a synthesis of each of the following:

2. Predict the product (or products) formed from the following reactions

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SUMMARY OF FIRST EAS

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SUMMARY OF BASIC EAS REACTIONS

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SUMMARY OF BASIC EAS REACTIONS

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 PART 2
SECOND (AND FURTHER) EAS REACTION

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PREVIOUS CLASS

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ADVANCE EAS
▪ First substitution replaces any of 6 hydrogen atoms in aromatic ring.

E
E

▪ How about second substitution? Which hydrogen will be replaced?

E E
E ? ?

? ?

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ADVANCE EAS

E E
E ? ?

? ?

▪ The first electrophile will determine the reactivity of the ring as well as to
direct the second electrophile.

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ACTIVATION & DEACTIVATION OF AROMATIC RING
▪ Aromatic ring of benzene

The aromatic ring is

π-electron rich

▪ The presence of substituent (resulted from electrophilic aromatic

substitution) affect the “properties” and “reactivity” of benzene

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ACTIVATION & DEACTIVATION OF AROMATIC RING
▪ Example 1: Chlorination of monosubstituted benzene

Aromatic compound Relative Rate

Benzene 1
Anisole 109
Toluene 600
N,N-dimethylaniline 1014

The ring becomes more electron-rich making

the reaction faster

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ACTIVATION & DEACTIVATION OF AROMATIC RING
▪ Example 2: Nitration of monosubstituted benzene

Aromatic compound Relative Rate

Phenol 1000
Benzene 1
Chlorobenzene 0.033
Nitrobenzene 6 x 10-8

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ACTIVATION & DEACTIVATION OF AROMATIC RING
▪ Electron-releasing (donating) and electron-withdrawing group

Electron-releasing group Electron-withdrawing group

▪ The aromatic ring
becomes MORE partially
negative.
▪ MORE reactive toward
EAS reaction
▪ The aromatic ring
becomes LESS partially
negative.
▪ LESS reactive toward EAS
reaction

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ACTIVATION & DEACTIVATION OF AROMATIC RING
1. Groups that have an unshared electron pair on the atom attached to the
aromatic ring directly bonded to the ring, are powerful activating groups.

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ACTIVATION & DEACTIVATION OF AROMATIC RING
▪ Electron donation to the ring by resonance is reduced when there is an
alternative resonance pathway away from the ring
Resonance

More powerful
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ACTIVATION & DEACTIVATION OF AROMATIC RING
▪ Contribution of electron density to the benzene ring through resonance is
generally stronger than through an inductive effect.
Resonance

More powerful
Inductive

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ACTIVATION & DEACTIVATION OF AROMATIC RING
2. Groups that DO NOT have an unshared electron pair on the atom attached to
the aromatic ring directly bonded to the ring and/or have electronegative
atom in the vicinity are powerful deactivating groups.

More powerful
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ACTIVATION & DEACTIVATION OF AROMATIC RING

More powerful
There is always an exception for any rule
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CLASS ACTIVITY 8.2
1. Using their resonance structures, explain whether the following group is
electron-releasing or electron-withdrawing group :
a. Phenol d. benzoic acid
b. Toluene e. chlorobenzene.
c. benzaldehyde

2. Label each of the following aromatic rings as activated or deactivated based on

the substituent attached

a b c

d e f

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REGIOSELECTIVITY
▪ Example 2: Nitration of monosubstituted benzene

Aromatic compound Relative Rate

Phenol 1000
Benzene 1
Chlorobenzene 0.033
Nitrobenzene 6 x 10-8

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REGIOSELECTIVITY

For the first EAS reaction, the electrophile can

substitute any hydrogen-atom .

For the second EAS reaction, the position of E2 is directed by the E1.

ortho- meta- para-

1,2- 1,3- 1,4-

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REGIOSELECTIVITY

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REGIOSELECTIVITY
Example 1: Nitration of toluene

HNO3
H2SO4

Electron-donating
group

Ortho- and para- director

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REGIOSELECTIVITY
Example 1: Nitration of toluene

Ortho attacks

Relatively
stable
contributor

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REGIOSELECTIVITY
Example 1: Nitration of toluene

Meta attacks

NO stable contributor

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REGIOSELECTIVITY
Example 1: Nitration of toluene

Para attacks

Relatively
stable
contributor

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REGIOSELECTIVITY
Example 2: Bromination of aniline and phenol
Very strong activating group

Every ortho- and para-H is replaced

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REGIOSELECTIVITY
Example 3: Bromination of phenol
Very strong activating group

No catalyst

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REGIOSELECTIVITY
Example 4: Nitration of trifluoromethylbenzene
Very strong deactivating group

~100%

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CLASS ACTIVITY 8.2
1. Provide mechanism for the following reaction and explain whether it occurs
faster or slower than of benzene
a. c.

b.

2. Construct chemical reaction to produce the following compounds

a. b. c. d.

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SUMMARY OF SUBSTITUENT EFFECTS

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POLY-SUBSTITUTED BENZENE
Example 1

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POLY-SUBSTITUTED BENZENE
Answer 1
▪ Nitro is strong meta director, so the next substituent will be directed to meta-
position relative to nitro

▪ Alkyl is weak ortho- and para- director

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POLY-SUBSTITUTED BENZENE
Example 2

▪ Nitro is strong meta director, so the next substituent will be directed to meta-
position relative to nitro.
▪ Alkyl is weak ortho- and para- director

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POLY-SUBSTITUTED BENZENE
Example 3

▪ Nitro is strong meta director, so the next substituent will be directed to meta-
position relative to nitro.
▪ Alkyl is weak ortho- and para- director

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CLASS ACTIVITY 8.3
1. Starting with toluene, outline synthesis of
(a) 1-bromo-2-trichloromethylbenzene
(b) 1-bromo-3-trichloromethylbenzene
(c) 1-bromo-4-trichloromethylbenzene

2. Determine the product(s) of the chlorination of the following compounds:

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SUPPLEMENTARY REACTION

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REACTION OF THE SIDE CHAIN (OF ALKYLBENZENE
1. Benzylic Radicals and Cations

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REACTION OF THE SIDE CHAIN (OF ALKYLBENZENE
2. Benzylic Halogenation of the Side Chain

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REACTION OF THE SIDE CHAIN (OF ALKYLBENZENE
3. Additions to the double bond of alkylbenzenes

Markovnikov’ rule, stable carbocation

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REACTION OF THE SIDE CHAIN (OF ALKYLBENZENE
4. Oxidation of the Side Chain

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REACTION OF THE SIDE CHAIN (OF ALKYLBENZENE
5. Oxidation of Benzene Ring

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 END OF CLASS
(REALLY, THIS IS THE LAST CHAPTER FOR ORGANIC CHEMISTRY)

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