Synthesis of new 3-[(alkylthio)methyl]-1-hydroxy-2-(4'-substituted phenyl)indoles and their mechanistic studies on substituent effects

Abstract

The synthesis and mechanistic studies of new 3-[(alkylthio)methyl]-1-hydroxy-2-(4'-substituted phenyl)indoles 1 were presented. New substrates 2 were prepared by the application of efficient three-step synthesis with minor modifications, and used to produce target 1-hydroxyindoles 1. Substrates 2 were reacted with thiol nucleophiles in the presence of SnCl2·2H2O and 4Å molecular sieves to afford sixteen novel 1-hydroxyindoles 1, by a consecutive process involving nitro reduction, intramolecular cyclization, and nucleophilic 1,5-addition. Studies on the mechanistic aspects of these reactions with focus on the effects of p-substituent (X) in phenyl ring at C(1) in 2 were performed.

One-Pot Synthesis of Novel Multisubstituted 1-Alkoxyindoles

“…Previously, the 1-hydroxyindole derivative was successfully applied for the total synthesis of nocathiacin [ 9 ]. We also reported methods to synthesize 2,3-disubstituted 1-hydroxyindole compounds [ 10 , 11 , 12 , 13 ]. Other methods by reduction of the indole system to 2,3-dihydroindole, followed by an oxidation (Na 2 WO 4 /H 2 O 2 ) were applied to give 1-hydroxyindoles [ 14 ].…”

One-pot, regioselective synthesis of functionalized indole derivatives: a three-component domino reaction of arylamine, arylglyoxal, and 4-hydroxycoumarin or 4-hydroxy-6-methyl-2-pyrone

“…23 Recently, new strategies have been developed for the synthesis of indole derivatives; these include: various metal-catalyzed, [24][25][26][27][28][29] multi-component method, 30 cyclization reaction, 31 Wittig reactions, 32 and various other methods. [33][34][35][36] Most of these protocols appear to suffer from some drawbacks such as tedious experimental procedures, difficult reaction conditions, multiple synthetic steps, low yields, and usage of expensive catalysts and reagents. Therefore, the development of more economic, convenient and efficient approaches to the regioselective synthesis of substituted indoles under mild conditions is still an attractive proposition.…”