Improved Synthesis of Isatins

28 January 2006

Isatins are important precursors of indole derivatives and are usually prepared via isonitrosoacetanilides — the latter are made from an aniline, chloral hydrate and hydroxylamine hydrochloride. This methodology fails with electron rich anilines, particularly if ortho substituted.

A recent report shows that 2,2 diacetoxyacetyl chloride, prepared from glyoxylic acid in 2 steps, is a superior reagent to chloral hydrate in this synthesis (Rewcastle G W et al, Tetrahedron Lett, 2005, 46, 8719-8721).