A rapid, efficient and versatile green synthesis of 3,3'-diindolylmethanes

Abstract

The natural product 3,3'-diindolylmethane (DIM) exhibits anti-cancer and immunostimulatory properties. We report an operationally simple, efficient and versatile synthesis of DIM derivatives by reaction of indoles with aldehydes in the presence of sulfuric acid in water. Short reaction times of only 5 min, simple work-up procedure, avoidance of hazardous organic solvents, and excellent yields are apparent advantages of this method. The synthetic protocol tolerates a broad range of functional groups allowing fast and straightforward access to a large variety of DIM derivatives, including 20 new compounds not previously described in literature, which have potential as anti-cancer drugs.

2,2,2‐Trifluoroethanol‐mediated hydroarylation of fluorinated alkynes with indoles: Application to diindolylmethanes

“…As part of our ongoing efforts to produce bioactive indole derivatives, [26][27][28][29][30][31] we describe an efficient synthesis of numerous β-trifluoromethyl indole-3-acrylates in trifluoroethanol (TFE) at room temperature (rt) without the use of any catalysts or additives (see Scheme 1b). Atom economy, high yields, a broad substrate scope, and multiscale synthesis are advantages of this process.…”

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.…”

Bis-indolylation of aldehydes and ketones using silica-supported FeCl3: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites

“…Consequently, several methods have been reported for the synthesis of these compounds. A variety of reagents such as protic acid, 28 Lewis acids, 29 transition and non-transitional metal salts, 30 solid acidic catalysts 31 and ionic liquids 32 have been employed to accomplish this transformation. However, many of these methods suffer from disadvantages such as unsatisfactory yields, expensive catalysts, long reaction times, toxic organic solvents, laborious work-up procedures, requirement of special apparatus, and harsh reaction conditions.…”