Abstract

Aim and Objective: To explore the use of naturally occurring biodegradable organic acids as a catalyst in organic synthesis. The development of a simple, inexpensive, highly efficient yet ecofriendly catalyst for the synthesis of bis(indolyl)methanes is explored.

Materials and Method: A mixture of indole 1a (1.0 g, 8.53 mmol), benzaldehyde 2a (0.45 g. 4.26 mmol), and itaconic acid (0.12 g, 0.92 mmol, 20 mol%), in H2O (5.0 mL) was refluxed at 100°C for indicated time. After the completion of the reaction (TLC check), the reaction mixture was cooled to room temperature and extracted with ethyl acetate (3 × 5.0 mL), organic layer was dried over Na2SO4 and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel using ethyl acetate:hexane as an eluent.

Results: Initially optimal reaction conditions were developed for the synthesis of bis(indolyl)methanes by selecting model reaction between indole and benzaldehyde. It was found that optimal conditions for the synthesis of bis(indolyl)methanes are use of indole (1.0 mmol), aldehyde (0.5 mmol) and catalyst 20 mol% in water as a solvent, under air atmosphere and at 100°C. Moreover, it was found that aqueous solution of the catalyst can be reused with the same catalytic efficiency for ten times without any pre-treatment. This is an important achievement with regard to the efficiency and reusability of the catalyst in synthesis.

Conclusion: We have shown that itaconic acid in water can be used as an excellent green catalyst with high reusability. It efficiently catalyzes electrophillic substitution reaction of indoles (ESRI) with various aldehydes to give the corresponding BIMs in an efficient manner. Therefore, itaconic acid in water as a catalyst can be a good alternative for the use of hazardous mineral acid and Lewis acid catalyst.

Keywords: Itaconic acid, catalysis, green chemistry, Bis(indolyl)methanes, biodegradable, electrophillic substitution reaction of indoles.

Graphical Abstract