Page 47 - Pharmaceutical Organic Chemmistry-3 (Theoritical book) 24-25

Clinical Pharmacy PharmD - 2024/2025 Level 2 Pharmaceutical Organic Chemistry-3 (PC 305)
Chemical properties:

• It is very weak base.

• Indoles, like pyrroles, resinify under the effect of acids and form N-salts with alkali,

which undergo different substitution reactions.

• Electrophilic substitution takes place in the 3-position (cf. pyrrole), but if this is

occupied then the 2-position is substituted. If both the 2-and 3-positions are

blocked, then the benzene ring is attacked at the 6-position.

4 3
5 2
6 1
7 N
H

Sites of electrophilic attack

• The transition state in case of 2-and 3-substitution is stabilized through the

following resonance structures without disturbing the electrons in the benzene ring:

+
E + H
2-position N E
H

H E H E
N
H E +
.. + +
3-position N N
H H

• Thus, fusion between benzene and pyrrole rings alters the position of reactivity

towards electrophilic reagents of the pyrrole ring from position 2 to position 3.