Pharmaceutical Chemistry 2 2020 Extra notes on EArS reactions

EXTRA NOTES ON MECHANISM OF ELECTROPHILIC AROMATIC

SUBSTITUTION REACTIONS:
Use the information in the table on page 60 in the notes. The two shaded columns are important
for the first step:
Reaction name Reagents Electrophile M- that will A product formed
produced from abstract the H from benzene
the reagents in the last
step (p.62)
Br- Halobenzene aka
halogenation X2 and FeX3 X+ arylhalide e.g.
bromobenzene
H2SO4 and
+
HSO4-
nitration HNO3 both NO2 nitrobenzene
concentrated
sulfonation H2SO4 SO3 HSO4- Benzenesulfonic
acid
Friedel Crafts Alkyl halide + + X- Alkylbenzene e.g.
alkylation and AlCl3 R e.g. CH3 - ethylbenzene
e.g. Cl
O X-
Friedel Crafts Acyl halide Acylbenzene, e.g.
acylation and AlCl3 e.g. Cl- acetophenone
R

In the “Reagents” column you will see the reagents that are used to create the electrophiles in
the column. You do not need to know how the electrophiles are formed. It will not be examined.
The memo for the mechanism of the chlorination of benzene is as follows:
Step 1.
Use the template in the notes on page 61 in the notes:

M
E
H H
E draw all the resonance forms
H H

+ HM
H
Pharmaceutical Chemistry 2 2020 Extra notes on EArS reactions

Here is the same mechanism with a few extra notes:

2. A negative ion in the reaction

mixture removes the H-atom from
M the same carbon atom to which the
E electrophile is attached.
H H

E draw all the resonance forms

H
3. The cation that is formed as a
H
result of the electrophilic addition
1. Two p-electrons of the
has three resonance forms.
aromatic system form a bond
If an entity has resonance forms, it is
with the electrophile.
relatively stable.
This is called electrophilic
addition.
E

+ HM
H

Step 2.
Find the electrophile related to the reagents in the table:
Reaction name Reagents Electrophile M- that will A product formed
produced from abstract the H from benzene
the reagents in the last
step (p.62)
Halobenzene aka
halogenation X2 and FeX3 + - arylhalide e.g.
X X
bromobenzene

The halogen used in this reaction is chlorine, so the reagents will be Cl2 and FeCl3. The
electrophile will be Cl+.
Pharmaceutical Chemistry 2 2020 Extra notes on EArS reactions

Now replace the “E+” in the reaction mechanism on page 60 with Cl+ and the M- with Cl- :

Cl
Cl
H H

Cl draw all the resonance forms

H H

Cl

+ HCl
H
The product of the reaction is chlorobenzene

The resonance forms of the carbocation intermediate are:

Cl Cl Cl
H H H

H H H

Please note :
NO2+ : the N-atom will form the new bond with a carbon atom on the benzene ring.

SO3 : the S-atom will form the new bond with a carbon atom on the benzene ring.
Friedel Craft’s Reactions: The carbocation of the electrophile will form a new bond with a
carbon atom of the benzene ring.
Pharmaceutical Chemistry 2 2020 Extra notes on EArS reactions

ADDITIONAL NOTES ON FRIEDEL CRAFTS REACTIONS:

Friedel Crafts reactions are the last two types of reaction in the table on page 60.
An acyl halide is any carboxylic acid where the -OH group has been replaced with a halide
atom such as chlorine or bromine. The most common acyl halides that you might encounter are
those with chlorine and bromine atoms. You only need to know the name and structure of
benzoyl chloride below.

O O O

Cl Br Cl

Benzoyl chloride
Pharmaceutical Chemistry 2 2020 Extra notes on EArS reactions

An acyl benzene is a benzene ring where a carbonyl group is directly attached to a carbon atom
of the benzene ring, such as acetophenone:

O O O

acetophenone

You do not have to know the names of all the above structures, only acetophenone.