Molbank 2008, M572

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ISSN 1422-8599

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Short Note

9-Methyl-2H-chromeno[8,7-d]isoxazol-2-one N-oxide

Antigoni Kotali ^1,*, Ioannis S. Lafazanis ¹ and Philip A. Harris ²

¹ Laboratory of Organic Chemistry, Department of Chemical Engineering, College of Engineering, University of Thessaloniki, Thessaloniki 54124, Greece E-mail: [email protected]

² GlaxoSmithKline, 1250 South Collegeville Road, P.O.Box 5089, Collegeville, PA 19426-0989, USA E-mail: [email protected]

* Author to whom correspondence should be addressed.

Received: 24 April 2007; in revised form: 8 August 2008 / Accepted: 18 August 2008 / Published: 24 August 2008

Keywords: 7-Hydroxy-8-acetylcoumarin, lead tetraacetate, diacetoxy iodobenzene.

As part of a research programme targeting novel molecules derived from nitrogen derivatives of o-hydroxyaryl ketones [1] we synthesised 7-hydroxy-8-acetylcoumarin oxime and we subsequently oxidized it with lead tetraacetate (LTA) as well as with diacetoxy iodobenzene (DIB). The reactions led to the formation of the oxidative cyclisation product, 9-methyl-2H-chromeno[8,7-d]isoxazol-2-one N-oxide , in good yields. It is well known that isoxazole ring possesses interesting biological activity especially as acetyl cholesterinase inhibitor [2] and as antimicrobial agent [3].

7-Hydroxy-8-acetylcoumarin oxime was prepared according to the literature method [4] whereas commercially available lead tetraacetate as well as diacetoxy iodobenzene were supplied by Aldrich.

Method A

1.37 g (3.09 mmol) of LTA are added to a suspension of 0.5 g (2.30 mmol) of 7-hydroxy-8-acetylcoumarin oxime in 20 ml THF in an ice-bath. The mixture was then stirred magnetically at 0-4 ^οC for 2 hrs. Filtration of the precipitate, which was formed, gave a solid which was recrystillised from petroleum ether to afford (0.33 g, 67 %) of the desired as white crystals. The product was identified by its ¹H NMR, ¹³C NMR and MS and elemental analysis.

Method B

0.75 g (2.33 mmol) of DIB are added to a suspension of 0.5 g (2.30 mmol) of 7-hydroxy-8-acetylcoumarin oxime in 20 ml CH₂Cl₂ in an ice-bath. The mixture was then stirred magnetically at r.t. for 24 hrs. Evaporation of the solvent gave an oil which was then subjected to column chromatography (silica gel 70-230 mesh). Elution with a mixture of petroleum ether / ethylacetate 1:1 afforded (0.32 g, 65 %) the desired as white crystals. The product was identified by its ¹H NMR, ¹³C NMR and MS and elemental analysis.

M.p. 208.5-209.5 °C.

¹H NMR (400 MHz, DMSO-d₆): 2.47 (s, 3H), 6.47-6.50 (d, 1H, J=9.7),7.32-7.34 (d, 1H, J=8.6), 7.83-7.85 (d, 1H, J=8.6), 8-11-8.13 (d, 1H, J=9.7).

¹³C NMR (100 MHz, DMSO-d₆): 11.2, 104.7, 109.7, 115.0, 115.2, 128.9, 129.5, 139.7, 145.5, 151.8, 159.5.

MS m/z (ES+): 240 [M+Na]⁺, 217 [M]⁺, 202, 201, 187.

Anal. Calc. for C₁₁H₇NO₄: C 60.83, H 3.25, N 6.45; found: C 60.73, H 3.22, N, 6.39.

References

1. Kotali, A.; Harris, P. A. Org. Prep. Proc. Int. 1994, 26(2), 155.

2. Rangappa, S. Biorganic and Med. Chem. 1994, 37, 2721.

3. Priya, B.S;. Bassappa, S.; Nanjunda, S.; Rangappa, S. Biorganic and Med. Chem. 2005, 13, 2623.

4. Thakkar, K.; Cushman, K. Tetrahedron Lett. 1994, 35 (35), 6441.

© 2008 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).