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.