TsOH&amp;#183;H&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;O-Catalyzed Friedel-Crafts of Indoles of 3-Hydroxyisobenzofuran-1(3&amp;lt;i&amp;gt;H&amp;lt;/i&amp;gt;)-One with Indoles: Highly Synthesis of 3-Indolyl-Substituted Phthalides

Hongying Tang,Airu Song,Zhongbiao Zhang,Xinyu Zhang

doi:10.4236/mrc.2012.12002

Abstract

An efficient and facile method for the synthesis of 3-indolyl-substituted phthalides by Friedel-Crafts alkylation of indoles with 3-hydroxyisobenzofuran-1(3H)-one has been developed. Using only 2 mol-% TsOH·H2O as the catalyst, various substituted indoles can react smoothly at room temperature to give the corresponding phthalides products in good to excellent yields (up to 96%).

Highlights

The chemistry of phthalides has attracted much attention from many research groups, as they are the key skeleton for a number of synthetic and naturally occurring bioactive molecules [1,2,3,4,5]
(-)-Alcyopterosin E which contains phthalides bone shows mild cytotoxicity toward Hep-2 cell line [6]; 3-Butylphthalides isolated from the basidiomycete Phanerochaete velutina CL6387 appear to be specific for Helicobacter pylori [7]; and Cytosporone E has antifungal activities [8]; Fuscinarin isolated from soil fungas was found to compete effecttively with macrophage inflammatory protein (MIP)-1α for binding to human CCR5, an important anti HIV-1 target that interferes with HIV entry into cells [9]
The potential biological activities of phthalides and indoles promoted us to develop a synthesis of an interesting type of heterocyclic compounds via their combination

Summary

Introduction

The chemistry of phthalides has attracted much attention from many research groups, as they are the key skeleton for a number of synthetic and naturally occurring bioactive molecules [1,2,3,4,5]. Develop a synthesis of an interesting type of heterocyclic compounds via their combination. It probably offers great opportunities for the lead compound discovery. The synthesis of this type compounds is mainly restricted to the reaction of indoles with 2-forylbenzoic acids either at high temperature (T > 100 ̊C) [16,17,18] or in the presence of an acidic cation exchange resin Amberlyst 15 [19]. We report an efficient substitution reaction of 3-hydroxyisobenzofuran-1(3H)-one [24,25,26], which can be prepared via the reduction of readily available phthalic anhydride, and indoles using the TsOH·H2O as a catalyst at room temperature for the synthesis of 3-indolyl substituted phthalides with high yields

General Information

Results and Discussion

Conclusion