Bisindolization Reaction Employing Phthalimide-N-sulfonic Acid as an Efficient Catalyst

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Author(s): Hoda Banari, Hamzeh Kiyani*, Ali Reza Pourali.

Journal Name: Current Organocatalysis

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Aims: The aim is to use phthalimide-N-sulfonic acid in the synthesis of BIMs and also to search for the best conditions for the synthesis of above-mentioned biheterocycles.

Background: Bis(indolyl)methanes(BIMs) are valuable biheterocyclic compounds, which can be found in natural products and marine sources. BIMs possess biological properties such as anticancer, antioxidant, and antimicrobial activities.

Objective: Applications of phthalimide-N-sulfonic acid in the Synthesis of BIMs

Method: Indole derivative 1 (2 mmol), substituted aldehyde 2 (1 mmol), and PISA (10 mol%) were stirred in ethanol at room temperature. After completion of the reaction (using TLC analysis), hot ethyl acetate was added to the resulting mixture and then cooled to RT and the catalyst was recovered by filtration and washed thoroughly with ethyl acetate and then diethyl ether. After this, the organic phase was concentrated by evaporation, distilled water was added to the residue, and the solid thus obtained. The resulting solid product was filtered off, washed with distilled water, dried, and recrystallized from hot ethanol to afford the targeted compounds.

Result: The bis(indolyl)methane derivatives were easily obtained via bisindolization reaction (BIR) of two indoles (2-methylindole and indole) with a series of aryl and heteroaryl aldehydes. The BIR was efficiently catalyzed at room temperature using phthalimide-N-sulfonic acid (PISA) as a solid acidic organocatalyst.

Conclusion: The reactions were implemented in simple manner and were completed within acceptable reaction times. The expected BIM products were obtained in satisfactory yields. The catalyst can be recovered and reused several times in the template reaction. This approach provides the benefits of convenience, simple operational procedure, no use of hazardous organic solvents, cheapness and ease of preparation of catalyst.

Other: It is comparable in terms of yields and reaction times and not requires any solvent or inert atmosphere. It also does not require the use of some organic solvents such as acetonitrile, THF, and methanol. This method can also avoid the reflux conditions or the use of special devices such as microwave and ultrasound.

Keywords: Bis(indolyl)methanes, Green synthesis, Indole, Phthalimide-N-sulfonic acid, Aryl aldehyde, Organocatalyst

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(E-pub Ahead of Print)
DOI: 10.2174/2213337206666191022110730