Synthesis of 4-Substituted Indole Derivatives
Heterocycles – January 01, 1977
Source: OpenAlex
Summary
A novel Chemistry approach precisely synthesizes 4-substituted indole derivatives, vital in Medicinal chemistry for compounds like LSD. Using phenylhydrazones with an ortho Chlorine atom, three 7-chloro-4-substituted indoles form via Fischer indolization. Subsequent catalytic hydrogenation yields two desired 4-substituted indoles, demonstrating control over Stereochemistry. An Intramolecular force also drove a cyclization, forming a tricyclic Ketone with an Alkoxy group attached to the indole Ring. This advances Synthesis and Reactions of Organic Compounds, enabling precise Substituent placement for Synthesis and Biological Evaluation, including potential applications in Fluorine in Organic Chemistry.
Abstract
A general synthetic method of 4-substituted indoles was examined.The Fischer indolization of phenylhydrazones (2, 3, 7, and 8) having chlorine on & position gave 7-chloro-4-substituted indoles (4, 9, and lo), which were converted to 4-substituted indoles (5 and 13) by catalytic hydrogenation.Cyclization of 3-(2-ethoxy~arbonyl-7-chloroindol-4-yl)propionic acid (10) with polyphosphoric acid (PPA) took place at the 5-position of indole ring to give a tricyclic ketone (14).4-Substituted indole derivatives have ken of interest for many years because of the psychotamimetic activity of ampunds such as lysergic acid diethylamide CUD) and psilocybin.2The intramolecular cyclization reaction to 4-position of indole ring has been reported recently."However introduction of a certain substituent to 4-position by intermolecular reaction seem mre difficult.4In this paper we wish to report the useful syretic method of 4-substituted indole derivatives.The Fischer indolization of 3-substituted phenylhydrazone gives a mixture of 4-and 6-substituted indoles.' 4-Substituted indoles m y be selectively obtained from the phenylhydrazones (such as 2, 3, 7, and 8) having chlorine atom on the one ortho position.6Rawever, it was reported by Ishii et that the Fischer