Iron‐containing ionic liquid as an efficient and recyclable catalyst for the synthesis of C3‐substituted indole derivatives

Abstract

A facile and efficient protocol for the synthesis of C3‐substituted indole derivatives has been developed under mild condition. The iron‐containing ionic liquid, 1‐(2‐hydroxyethyl)‐1,4‐diazabicyclo[2.2.2] octanylium tetrachloroferrate ([Dabco‐C2OH][FeCl4]) as a recyclable catalyst has been successfully used in the synthesis of trisindolines, bis(3‐indolyl) methanes and β‐indolyl alcohols for the first time. The products of trisindolines and bis(3‐indolyl) methanes are easily separated and purified without chromatographic technique. The catalyst was recycled six times without significant activity loss.

Silica-Coated Magnetic-Nanoparticle-Supported DABCO-Derived Acidic Ionic Liquid for the Efficient Synthesis of Bioactive 3,3-Di(indolyl)indolin-2-ones

“…Subsequently, after hydrogen transfer (IV), dehydration takes place to form an intermediate (V) where nucleophilic attack of another activated indole molecule leads to the formation of the targeted product and regenerates the catalyst. 12,30…”

“…Simultaneously, trifluoroacetate accepts an H-bond from the N–H of indole, and thus, facilitates the nucleophilic attack of indole via its C-3 carbon on the electron-deficient carbonyl carbon of activated isatin to generate species (III). Subsequently, after hydrogen transfer (IV), dehydration takes place to form an intermediate (V) where nucleophilic attack of another activated indole molecule leads to the formation of the targeted product and regenerates the catalyst. , …”

“…In this context, scientists have greatly acknowledged their properties in the synthesis of 3,3-di­(indolyl)­indolin-2-ones. A variety of ILs such as imidazolium-based, guanidinium-based, and 1,4-diazabicyclo[2.2.2]­octane (DABCO)-based − cations have served their role as catalysts in the reaction of isatin and indole. Although each and every catalytic system imparts good to excellent yields, they offer large scope for improvement due to associated drawbacks, including slow diffusion of substrates, tedious product isolation, troublesome IL recycling procedures, and their possible degradation during recycling …”

Chemistry of trisindolines: natural occurrence, synthesis and bioactivity

“…After extensive screening, 10 mol% [Dabco-C 2 H 4 OH][FeCl 4 ] 205 emerged as the best catalyst giving the trisindolines 3, 5, 15–17, 22, 27, 31, 33, 37 and 95 in 85–97% yields in ethanol at 50 °C within 1 h ( Scheme 21 ). 69 The reaction showed a wide substrate scope where substituted indoles (halogen, methoxy) and isatins (halogen, nitro, methyl) gave the desired trisindolines in excellent yields. However, the reaction between 4-bromoisatin and indole required longer reaction time of 2 h to afford 81% yield of 95.…”

“…67 The catalyst 205 was recycled and reused six times with a 10% overall decrease in the yield of 3. 69 …”