The Gelatinous Pulp of the Fruit of Dillenia indica: An Efficient Catalyst for the Synthesis of Polyfunctionalized Indole Derivatives

Introduction: This study reports a green and sustainable protocol for synthesizing polyfunctionalized indole derivatives. It involves the use of the gelatinous pulp of Dillenia indica fruit as the catalyst. materials and methods: Materials and method: Preparation of the catalyst: Fresh and matured fruits of Dillenia indica were purchased from the local market. The edible parts of the fruit (the pseudosepals) were separated to uncover the pseudocarpels which hold the gelatinous substance inside. The gel with tiny seeds was taken out of the pseudocarpels manually. After removing the seeds, the gelatinous material was used directly as a catalyst without further modification. The pH of the gel from the Dillenia indica fruit was found in the range from 4.6 to 4.9. General procedure for the synthesis of bis(indolyl)methanes (BIM)s A mixture of indole (1, 1 mmol), aryl aldehyde (2, 1 mmol) and the gel of Dillenia indica fruit (0.5 g) was magnetically stirred in a round bottom flask at 60 °C in 10 mL of water. The progress of reactions was monitored by thin-layer chromatography (TLC). After completion of the reaction, the reaction mixture was extracted with ethyl acetate (10 mL x 5). The combined organic layer was dried over anhydrous sodium sulfate, solvent removed under vacuum and the crude product was further purified by column chromatography. The aqueous part containing the catalyst could be further reused until 3rd cycle without significant decrease in the isolated yields. General procedure for the synthesis of ethyl (E)-2-((1H-indol-3-yl)(phenyl)methylene)-3-oxobutanoate derivates A mixture of aryl aldehyde (2, 1 mmol), ethyl acetoacetate (1 mL) and the gel from Dillenia indica fruit (0.75 g) was magnetically stirred in a round bottom flask at 60 °C in 10 mL of water for 30 minutes. After bringing the reaction condition to room temperature, indole (1, 1mmol) was added to the reaction mixture and stirred for another 15 minutes. The progress of reactions was monitored by thin-layer chromatography (TLC) . After completion of the reaction, work up was done using ethyl acetate (10 mL x 5). The combined organic layer was dried over anhydrous sodium sulfate, solvent removed under vacuum and the crude product purified by column chromatography. The aqueous part containing the catalyst could be further reused until 3rd cycle without any significant decrease in the isolated yield. Method: The gelatinous component from fresh and mature fruit of Dillenia indica is directly used as the catalyst. The mixture of the reactants along with the catalyst is magnetically stirred at 60°C in water. After equilibrium is achieved, the product is extracted with ethyl acetate, followed by recrystallization using an ethanol/diethyl ether mixture. Results: Syntheses of twelve compounds in moderate to high yields have been reported. The catalyst can be reused up to the third cycle without compromising yield. The catalytic activity of Dillenia indica fruit gel has been compared with previously reported bio-based catalysts. Discussion: The data clearly indicate that the newly discovered catalyst surpasses other catalysts in several aspects, including energy efficiency, shorter reaction time, catalyst complexity, and the use of green solvents. Without the catalyst, the yield is limited to about 30%, but the catalyst helps to afford yields well over 80%. The catalyst does not work in organic solvents. Conclusion: The catalytic activity of the gel from the fruit of Dillenia indica has been established beyond doubt. The catalyst is inexpensive and reusable. By harnessing the unique catalytic activity of this bio-based catalyst, a sustainable protocol for the synthesis of highly functionalized heterocycles has been developed. The substrate scope of the protocol is broad.