A Facile One-Pot Synthesis of 3-Methylbenzisoxazoles via a Key Intermediate of ortho-Ethoxyvinyl Nitroaryls by Domino Rearrangement and Their Anti- Inflammatory Activity

Author(s): Bashetti Nagaraju, Jagarlapudi V. Shanmukhakumar, Nareshvarma Seelam, Tondepu Subbaiah, Bethanamudi Prasanna*

Journal Name: Current Organic Synthesis

Volume 16 , Issue 8 , 2019

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Abstract:

Background: Recently, there has been a lot of scientific interest in exploring the syntheses of oxygen and nitrogen-containing heterocyclic compounds due to their pharmacological activities. In addition, benzisoxazoles play a very important role in organic synthesis as key intermediates.

Objective: In this paper, we focused on developing a novel synthetic route for biologically active arylisoxazoles under normal conditions, and simplified it to get high purities and yields, and also reported their anti-inflammatory activities.

Methods: An efficient and simple method has been explored for the synthesis of novel 3-methyl arylisoxazoles from o-nitroaryl halides via o-ethoxyvinylnitroaryls, using dihydrated stannous chloride (SnCl2.2H2O) in MeOH / EtOAc (1:1) via Domino rearrangement in one pot synthesis.

Results: We synthesized novel 3-methylarylisoxazoles from o-nitroarylhalides via o-ethoxyvinylnitroaryls, using dihydrated stannous chloride (SnCl2.2H2O) in MeOH / EtOAc (1:1) via domino rearrangement. In this reduction, nitro group and ethoxy vinyl group change to the functional acyl ketones, followed by hetero cyclization. Here, the reaction proceeds without the isolation of intermediates like 2-acylnitroarenes and 2- acylanilines. All the synthesized compounds were completely characterized by the NMR and mass spectra. The compounds were also explored for their anti-inflammatory activity by carrageenan-induced inflammation in the albino rats (150-200 g) of either sex used in this entire study with the use of Diclofenac sodium as the standard drug. The initial evaluations identified leading targets with good to moderate anti-inflammatory activity.

Conclusion: A simple, one-pot and convenient method has been explored for the synthesis of novel 3- methylarylisoxazoles with high purity and reaction yields. All the compounds 3a, 3c, 3d, 3f, 3g and 3h exhibited 51-64% anti-inflammatory activities.

Keywords: Arylisoxazoles, domino rearrangement, SnCl2.2H2O, anti-inflammatory activities, o-ethoxyvinyl nitro aryls, diclofenac.

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Article Details

VOLUME: 16
ISSUE: 8
Year: 2019
Page: [1161 - 1165]
Pages: 5
DOI: 10.2174/1570179416666190925125450
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