1 - Introduction

Abstract

The chapter discusses the indole derivatives, which have found their use as drugs such as indomethacin, one of the first non-steroidal anti-inflammatory agents, sumatriptan, which is used in the treatment of migraine headaches and pindolol, one of the β-adrenergic blockers. The dimeric vinca alkaloid vincristine and closely related compounds were among the first of the antimitotic class of chemotherapeutic agents for cancer. Indole is classified as n-excessive aromatic compound. It is isoelectronic with naphthalene, with the heterocyclic nitrogen atom donating two of the ten π-electrons. The reactivity pattern underlies a group of important synthetic methods, in which α-substituent is displaced by a nucleophile by an elimination–addition mechanism. Even substituents, which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. As is broadly true for aromatic compounds, α- or benzylic position of alkyl substituents exhibits special reactivity. This includes susceptibility to radical reactions, because of the stabilization provided the radical intermediates. In indole derivatives, the reactivity of α-substituents towards nucleophilic substitution is greatly enhanced by participation of the indole nitrogen. This effect is strongest at C3, but is also present at C2 and to some extent in the carbocyclic ring. The effect is enhanced by N-deprotonation.