Synthesis of Bis(indolyl)methanes Using Recyclable PEG-Supported Sulfonic Acid as Catalyst

Abstract

An operationally simple, efficient and environmentally benign synthetic method to bis(indolyl) methanes has been developed in good yields (80-96%) by electrophilic substitution reactions of indole with aldehydes or ketones in methanol in the presence of 5 mol% of poly (ethylene-glycol) (PEG) supported sulfonic acid with respect to indole under mild conditions. Recovery and recycling of the poly (ethylene-glycol)-supported catalyst were also described.

Catalyst Free Synthesis of Bis(Indolyl)Methanes and 3,3‐Bis(Indolyl)oxindoles in Aqueous Ethyl Lactate

“…Owing to their versatile biological and medicinal activities as well as their prevalence in natural resources, syntheses of BIMs have continued to be of intense interest. In general, the condensation of indoles and carbonyl compounds catalyzed by Lewis acids, heteropoly acids, solid acids, ionic liquids, metal complexes or biocatalysts is the most traditional and practical method for the synthesis of BIMs. Even though these protocols have demonstrated their efficiency in the synthesis of BIMs, they also suffer from limitations such as long reaction times, the use of expensive or toxic metal ions, the difficulty of recovering high‐boiling solvents, high temperatures, the need for special efforts for the preparation of catalysts as well as harsh conditions.…”

A simple and efficient preparation of bis(indolyl)methanes catalyzed by HCl/silica gel under solvent-free conditions

“…Among numerous methods, the Friedel-Crafts acylation reaction or electrophilic substitution reaction of indoles with aldehydes or ketones under a variety of reaction conditions is a classical strategy. Numerous reagents and reaction conditions were developed and reported to access BIMs including Brønsted or Lewis acid, [22][23][24][25][26][27][28][29][30] iodine, 31 methanol, 32 cyclodextrin/electrolysis, 33 metal salts, 22,[34][35][36][37] ionic liquids, 22,[38][39][40] visible light, [41][42] surfactants, 43 vitamin B1 44 and enzymes. 45 Moreover, the preparation of BIMs by using solid acidic catalysts including amberlyst, zeolite, sulfated zirconia, silica sulfuric acid, montmorillonite clay K-10, AlPW12O40, H3PW12O40, TiO2, ZrOCl2/SiO2, HClO4-SiO2, P2O5/SiO2 and Lewis acid-surfactant-SiO2 has also been investigated.…”

Humic acid: A Biodegradable Organocatalyst for Solvent‐free Synthesis of Bis(indolyl)methanes, Bis(pyrazolyl)methanes, Bis‐coumarins and Bis‐lawsones

“… [20] The widely used protocol to design this important molecule is very straightforward and it can easily obtained by the reaction between aldehydes and indole following the Friedel‐Craft alkylation type pathway. A few protocols are reported in literature using various catalyst and solvent such as enzymes, [21] meglumine, [22] thiamine hydrochloride, [23] graphene oxide, [24] ethyl lactate, [25] sulphated polyborate, [26] Lewis acids, [27–32] Brønsted acids, [33] heteropoly acids, [34–36] solid acids, [37–42] ionic liquids, [43] metal complexes, [44–46] 4‐sulfophthalic acid [47] and Iodine/tert‐Butyl Hydroperoxide [48] . Recently, a number of methodologies have been developed in this field [49–68] .…”