Molbank 2008, M573

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ISSN 1422-8599

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Short Note

3-(1-Phenyl-1H-pyrazol-4-yl)-1,2-benzisoxazole 2-oxide

Antigoni Kotali

Laboratory of Organic Chemistry, Department of Chemical Engineering, College of Engineering, University of Thessaloniki, Thessaloniki 54006, Greece E-mail: [email protected]

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

Keywords: (2-hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone oxime, diacetoxy iodobenzene, oxidation, cyclisation.

It is well known that both isoxazole ring as well as pyrazole ring possess various biological activities and they both show interesting antimicrobial activity [1-3]. Therefore, it is not unreasonable to believe that a molecule bearing both moieties would possible show combined activity. Having this in mind we designed the synthesis of 3-(1-phenyl-1H-pyrazol-4-yl)-1,2-benzisoxazole 2-oxide as shown below. Nitrogen derivatives of o-hydroxyaryl ketones have been proved valuable starting materials in organic synthesis[4]. Thus, we synthesised (2-hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone oxime and we subsequently oxidized it with diacetoxy iodobenzene (DIB). The reaction led to the formation of the oxidative cyclisation product, giving the desired 3-(1-phenyl-1H-pyrazol-4-yl)-1,2-benzisoxazole 2-oxide, in 61% yield.

(2-Hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone oxime was prepared according to the literature methods by refluxing (2-hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone and hydrochloric hydroxylamine in ethanol in the presence of pyridine whereas commercially available diacetoxy iodobenzene were supplied by Aldrich.

Oxidation of (2-hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone oxime

0.58 g (1.79 mmol) of DIB are added to a suspension of 0.5 g (1.79 mmol) of (2-hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone oxime in 20 ml CH₂Cl₂ in an ice-bath. The mixture was then magnetically stirred for 3 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 3:1 afforded the desired 3-(1-phenyl-1H-pyrazol-4-yl)-1,2-benzisoxazole 2-oxide as white crystals (0.30 g, 61 %). The product was identified by its ¹H NMR, ¹³C NMR and MS and elemental analysis.

M.p. 179-180 °C.

¹H NMR (400 MHz, DMSO-d₆): 7.44-7.52 (m, 3H), 7.58-7.70 (m, 3H), 8.04-8.07(m, 2H), 8.32-8.34(d, J=8.0Hz, 1H), 8.67(s, 1H), 9.36(s, 1H).

¹³C NMR (100 MHz, DMSO-d₆): 107.7, 109.5, 118.9, 119.9, 120.1, 121.6, 125.1, 127.3, 127.7, 128.1, 129.6, 130.2, 139.5, 139.7, 149.1, 150.5.

MS m/z (ES+): 300 [M+Na]⁺, 277 [M]⁺, 261, 247.

Anal. Calc. for C₁₆H₁₁N₃O₂: C 69.31, H 4.00, N 15.15; found: C 69.22, H 3.88, N, 15.10

References

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

2. Menozzi, G.; Merello, L.; Fossa, P.; Schenome, S.; Ranise, A.; Mosti, L.; Bondavalli, F.; Loddo, R.; Murgioni, C.; Mascia, V.; La Colla, P.; Tamburini, E. Bioorg. Med. Chem. 2004, 12(20), 5465.

3. Bekhit, A.A.; Ashour, H.M.; Guemei, A.A.; Arch Pharm (Weinheim) 2005, 338(4), 167.

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

© 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/).