Molbank
2008, M572
molbank
ISSN 1422-8599
www.mdpi.org/molbank
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,
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/).