Page 34 - Org 3 theoritical book 2024-25

Clinical Pharmacy PharmD - 2024/2025 Level 2 Pharmaceutical Organic Chemistry-3 (PC 305)
Electrophilic substitution reactions:

In general, furan, thiophene and pyrrole undergo electrophilic substitution

preferentially at the - (2- ) position; if occupied, then at the - (3- ) position. This is

attributed to the higher stability of the arenium ion resulting from -attack due to its

more resonating structures than in case of -attack.

Of the three, pyrrole is the most susceptible to electrophilic attack. The electrophilic

substitution is facilitated by electron release from the heteroatom and as a result,

pyrroles are more reactive than furans which are in turn more reactive than thiophenes.

pyrrole > furan > thiophene > benzene (SE)

This is shown through the following reactions:

Ac O
2
COCH 3
S O H PO 4 S O
3

S DMF S CHO
POCl 3 N
N
H H

Substituents on five-membered rings have their orienting effect on further substitution

in a similar way as they do on the benzene ring as shown:

minor minor
o/p director

major o/p director minor major
X X

major
m director

minor m director major
X X