Page 46 - Pharmaceutical Organic Chemmistry-3 (Theoritical book) 24-25

Clinical Pharmacy PharmD - 2024/2025 Level 2 Pharmaceutical Organic Chemistry-3 (PC 305)
Fused Heterocyclic Systems of Pyrrole, Furan

and Thiophen with Benzene

Bicyclic systems:

b c X
a a
X

X

1-benzopyrrole (indole) NH 2-benzopyrrole (isoindole)

1-benzofuran (coumarone) O 2-benzofuran (isobenzofuran)

1-benzothiophene (thionaphthene) S 2-benzothiophene (isothionaphthen)

Indole

o
• Indole (1-benzopyrrole), Solid, mp 52 C, occurs in coal-tar and the volatile oils of
Jasmine and orange.

Synthesis of indole:

1) Fischer indole synthesis:

It involves cyclization of a phenylhydrazone of a suitable aldehyde or ketone with zinc

chloride, sulphuric acid or BF 3.

2) Madelung synthesis:

It is an intramolecular condensation of an o-acylaminotoluene by means of strong

bases as potassium t-butoxide or sodamide.

CH 3
O t-BuOK or NaNH 2
C R R
N - H O N
2
H H
o-acylaminotoluene R = H : o-formamidotoluene indole
CH : o- acetamidotoluene 2-methylindole
3