Indoles 93Reactivity of side-chain substituents
The electron-rich character of indoles gives rise to some special properties of side-chain substituents.
3-Dialkylaminomethyl-indoles, easily produced in Mannich substitutions (page 88), can be utilised in further elabora-
tions, because the amine group (or an ammonium group derived by selective side-chain amine quaternisation) can
be easily displaced by nucleophiles. These are not direct displacements but involve ring-N-hydrogen deprotonation by
the nucleophile, acting as a base, leading to elimination of the side-chain nitrogen and an intermediate 3-alkylidene-
indolenine; the nucleophile then adds, in a conjugate fashion.
A related sequence is involved in the lithium aluminium hydride reduction of indol-3-ylcarbinols (or the correspond-
ing ketones) constituting a useful synthesis of 3-alkylindoles.