Indole: Heterocyclic Compounds

1.1 Introduction
A cyclic organic compound containing all carbon atoms in ring formation is referred to as a carbocyclic compound. If at least one atom other than carbon forms a part of the ring system then it is designated as a heterocyclic compound [1]. Generally nitrogen, oxygen and sulphur are known to be the part of heterocyclic ring. Out of the known approximately 20 million compounds, almost half are heterocyclic. From biological, industrial point of view as well as in the improvement of quality of life and life process, the contribution of heterocyclic compounds is significant. Wide variety of drugs, biologically active compounds having antitumor, antibiotic, anti-inflammatory, antidepressant, antiviral, antimalarial, anti-HIV, antimicrobial,

1.4: Indole

Principally, indole (9) was extracted from coal tar and first obtained by Adolf Baeyer [4] by the pyrolysis of oxindole (10) with zinc dust in 1886. Oxindole was obtained from the reduction of isatin was obtained from oxidizing the natural insoluble dark blue dye called indigo [Scheme1.1]. Scheme1.1: Preparation of Indole from Indigo.

Physical Properties
1) Molecular Formula : C8H7N
2) Molar mass : 117.15 g/mol
3) Appearance : White solid
4) Melting point : 52-540C, 325-327K.
5) Boiling point : 253-2540C, 526-527K.
6) Solubility in Water : 0.19 g/100 ml (200C)
The protonation of indole requires strong acidic condition due to its weak basic nature. The protonation of indole offers three possible cations. Out of the three cations, (11b) is thermodynamically most stable whereas (11a) is kinetically favorable [Fig.1.5].

Fig.1.5: Cationic forms of Indole

1.3 Synthesis of indole Over the past few years, the vast abundance of indole ranging from lysergic acid to vincristine have enthused organic synthetic chemists to develop new methods for its synthesis. These new methods have been reported across the literature and reviews [5]. Taber et al, [6] reviewed the synthesis of indole and proposed nine strategies for indole construction

These strategies cover all significant contribution of researcher in the synthesis of indole. There are several name reactions associated with indole synthesis. Amongst these several name reactions, very few are discussed along with the modern synthetic routes.

1.3.1 Fischer Indole