Abstract
Background: Organic synthesis using microwave is one of the good alternative method for becoming progressively more extensive in the modern organic synthesis. It shows numerous advantages like reduce the reaction time, decrease energy consumption, reduces side reactions, improve reproducibility and increases the product yields. Multicomponent Reactions (MCRs) are one of the method for convenient and facile conversion of simple readily available substrates into novel and extremely diverse compound libraries by the use of one-pot synthesis. MCRs are influenced by microwave and as a potent green alternative over the conventional synthesis.
Many researcher have done tremendous research work on Spiroheterocyclic compounds. Coumarin is one of the major classes of naturally occurring compounds and having continues interest in chemistry because of its usefulness as biologically active agents.
Synthesis of new and desired compounds have an endless demand. As a part of our ongoing research in the area of synthesis of spirooxindole derivative, We described a rapid, efficient, one-pot three component microwave assisted method for the synthesis of chromenylspiro[indoline-3,2'-pyrrolidin]-2-one derivatives from the reaction between isatin, sarcosine and 4-(allyloxy)-2H-chromen-2-one derivatives by using p-TSA as an prompt catalyst. All the synthesized compounds are subjected to in-vitro antibacterial activity using four different bacterial stain.
Methods: A mixture of 4-(allyloxy)-2H-chromen-2-one derivatives (3a-3c) (0.01 mmol), isatin (0.01 mmol) and sarcosine (0.01 mmol) in 5 ml methanol were irradiated in microwave (CEM microwave) at 300 W for 10-25 minutes in the presence of p-TSA (10 mol%). The completion of the reaction was indicated by TLC (30% ethyl acetate-hexane). The reaction mixture was allowed to cool at room temperature and was then poured into ice water. The resulting solid residues were filtered off, dried to get the crude product which was further recrystallized from methanol or ethanol to get targeted product 1'-methyl-4'-(((2-oxo-2H-chromen-4-yl)oxy)methyl) spiro[indoline-3,2'-pyrrolidin]-2-one derivatives (6a-6i) in very good yield.
Results: In the recent study, it has been understood that the catalysts have a major role in the organic synthesis. We optimized the reaction conditions, The one-pot, three-component cyclization reaction of 4-(allyloxy)-2H-chromen-2- one derivatives, various isatins, and sarcosine in the presence of p-TSA (10 mol%) as catalyst in methanol and complete reaction in only 12 minutes by using microwave irradiation to afford 1'-methyl-4'-(((2-oxo-2H-chromen-4- yl)oxy)methyl) spiro[indoline-3,2'-pyrrolidin]-2-one 6a in good yields.
To achieve suitable conditions for the synthesis of targeted compound, various reaction conditions and catalysts have been investigated for reaction. Results showed that the reaction proceeds in the presence of all catalysts of the series and also reaction yields were better with p-TSA. The results were good in terms of yields and product purity in the presence of p-TSA as an inexpensive and easily available catalyst and so, it can be proved better than the others.
The structure of the products were elucidated with the help of IR, 1H-NMR, mass spectral data, and elemental analysis.
All the synthesized compounds were screened for their antibacterial activity out on Nutrient-agar plates by welldiffusion assay against test culture. Compounds 6g and 6i exhibited better zone of inhibition against Enterobacter aerogens gram negative bacteria. When compound 6c shows parallel activity to standard drug against Escherichia coli. For Micrococcus luteus, compounds 6f found to be very active than all other compounds in the series. Moreover, the compounds 6b and 6g displayed good activity against Bacillus cereus gram positive bacteria.
Conclusion: In summary, we have reported an efficient, novel, one pot, three component protocol for the synthesis of chromenyl spiro[indoline-3,2'-pyrrolidin]-2-one derivatives by the reaction of isatin, sarcosine with diversified 4- (allyloxy)-2H-chromen-2-one derivatives using p-TSA as a quick catalyst under microwave assisted reaction. The main benefits of this present practice are the simplicity of the method, good yields, simple work up, and the ease of product isolation. Additionally, the existence of three different important heterocyclic moieties such as chromen, indoline, and spiro rings in one molecule is fantastic as a result of the prospective applications of these derivatives in biological as well as pharmacological activities. Furthermore, The Pharmacokinetic characterization and optimization of this series are under process in our laboratory.
Keywords: 1, 3-dipolar cycloaddition, antibacterial activity, azomethine ylide, coumarin, isatin, microwave-assisted synthesis, multicomponent reactions, sarcosine, spiro compound.
Graphical Abstract
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