Microwave Assisted ZrSiO2 Mediated One-Pot Synthesis of Spiro[chromene- 4,3’-indoline] Derivatives

Author(s): Mayuri A. Borad, Manoj N. Bhoi, Bhakti N. Patel, Hitesh D. Patel.

Journal Name: Current Microwave Chemistry

Volume 3 , Issue 3 , 2016

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Abstract:

Background: Microwave-assisted organic synthesis has been a powerful and expedient tool for quick organic synthesis which has vital advantages such as simplicity in process, cumulative rate of reaction, high reaction yields, and less amount of side product etc. Multicomponent reactions have developed chemical transformations for powerful bond-forming in organic, combinatorial and medicinal chemistry. The spirooxindole system possesses prominent biological properties and played a very vital role as a core structure of many synthetic pharmaceuticals. Isatin and its derivatives are a leading molecule for designing latent bioactive agents. Isatin and its derivatives are used as precursors due to having numerous applications and great biological characteristics. Fused chromenes derivatives have established more attention because of their high potential biological application. Here, we have described a one-pot synthesis of diverse spiro[chromene-4,3’-indoline] derivatives using ZrSiO2 mediated three-component reactions of substituted phenols with isatin and malononitrile.

Methods: We have used microwave assisted method for synthesis. We have taken mixture of phenol derivatives, Isatin, Malononitrile, the catalyst, ZrSiO2 (10 mol %) and 5 ml methanol was placed into a 25 mL round bottomed flask. The reaction mixture was irradiated under microwave radiations at 100 °C, 300 W for 3-7 min. The progress of the reaction was monitored by thin layer chromatographic plate. After consumption of all starting materials the mixture was poured into water and then extracted with ethyl acetate. The organic layer was washed with brine and evaporated under reduced pressure. The combined aqueous layer was filtered to recycle the catalyst. Filtered catalyst washed with methanol two or three times to remove the strains and tars, and then dried in an oven. Compounds were isolated by column chromatography, elution gradient 15% Ethyl acetate: hexane as pure yellow solid with 80-90% of yield. The catalyst was reused up to three cycles with slight decrease of catalytic activity. Antibacterial activity of synthesized compound was carried out on Nutrient- agar plates by well-diffusion assay against test culture.

Results: The one pot three-component cyclization reaction of phenol derivatives, isatin and malononitrile in the presence of ZrSiO2 (10 mol %) as catalyst in methanol was performed and the reaction was completed in 3-7 minutes by using microwave irradiation to afford 2-amino-2'-oxospiro [chromene-4,3’-indoline]-3-carbonitrile 4a in good yields.

First, we optimized catalyst for finding best catalyst in very short reaction time with high yields. Reactions using ZrSiO2 in methanol give desirable yield with 88 % in very short time. A sensible decrease in the product yield was observed only after the third recycle of the catalyst. The structures of all the newly synthesized compounds were confirmed by various spectroscopy techniques. All the synthesized compounds were screened through antibacterial activity. Most of the synthesized compounds found to be active against Gram negative bacteria and Gram positive bacteria.

Conclusion: We have presented a series of 2-amino-2'-oxospiro[chromene-4,3'-indoline]-3-carbonitrile derivatives that have been synthesized by microwave assisted reaction by isatin, malononitrile and various phenol derivatives. We have described a facile, one pot, three component, and environmentally benign protocol using ZrSiO2 as a prompt catalyst which can be reused. Most important of all, the synthesized derivatives can be used for the development of new antibacterial drugs because compounds 4f, 4b and 4d exhibited promising activity as compared to streptomycin.

Keywords: Isatin, microwave-assisted synthesis, multi-component reactions, spiro compound, ZrSiO2.

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2016
Page: [187 - 193]
Pages: 7
DOI: 10.2174/2213335602666150903211701
Price: $58

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