indoles

Indole is a bicyclic aromatic heterocycle consisting of a six-member benzene ring fused to a five-membered nitrogen-containing pyrrole ring, giving the indole framework. Its formula is C8H7N. The N-H in the pyrrole ring makes it a weak acid and a hydrogen bond donor. The ring system is highly conjugated and planar.

In terms of reactivity, indoles are more reactive at C3 toward electrophilic substitution, though the N-H can participate in hydrogen bonding; the nitrogen is not strongly basic. Substitution patterns and protective groups influence chemoselectivity in synthesis and functionalization.

Occurrence and biosynthesis: Indole is a central motif in many natural products. The amino acid tryptophan contains an indole ring; serotonin (5-hydroxytryptamine) and melatonin are derived from tryptophan. Indole-3-acetic acid is a plant growth hormone. Indole-containing alkaloids are widespread in nature and contribute to the chemical diversity of many organisms.

Synthesis and derivatives: The Fischer indole synthesis is a classic method to prepare many indole derivatives from phenylhydrazines and carbonyl compounds via the indole ring construction. Other routes include metal-catalyzed annulations and dehydrogenation of indolines. Indole chemistry also features substituted indoles for pharmaceuticals and dyes.

Applications: Indole cores are common in pharmaceuticals, including serotonin receptor ligands and many natural product–inspired drugs; indole derivatives are used in dyes, with indigo being a famous example, consisting of two indole units. The indole framework also appears in agrochemicals and functional materials.