Isoxazole
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| Names | |||
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| Preferred IUPAC name
1,2-Oxazole[1] | |||
| Other names
isoxazole
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| Identifiers | |||
3D model (JSmol)
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| ChEMBL | |||
| ChemSpider | |||
| ECHA InfoCard | 100.005.472 | ||
PubChemCID
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CompTox Dashboard(EPA)
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| Properties | |||
| C3H3NO | |||
| Molar mass | 69.06202 g/mol | ||
| Density | 1.075 g/ml | ||
| Boiling point | 95 °C (203 °F; 368 K) | ||
| Acidity(pKa) | -3.0 (of conjugate acid)[2] | ||
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
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Isoxazoleis an electron-richazolewith anoxygenatomnext to thenitrogen.It is also the class of compounds containing this ring.Isoxazolylis theunivalentfunctional groupderived from isoxazole.
Occurrence
[edit]Isoxazole rings are found in some natural products, such asibotenic acidandmuscimol.
Synthesis
[edit]Isoxazole can be synthesised via a variety of methods.[3][4] Examples include via a1,3-dipolar cycloadditionofnitrile oxideswithalkynes;or the reaction ofhydroxylaminewith1,3-diketonesor derivatives ofpropiolic acid.[5]
Photochemistry
[edit]The photolysis of isoxazole was first reported in 1966.[6]Due to the weak N-O bond, the isoxazole ring tends to collapse under UV irradiation, rearranging to oxazole through azirine intermediate. Meanwhile, the azirine intermediate can react with nucleophiles, especially carboxylic acids. Given the photoreactions, isoxazole group is developed as a native photo-cross-linker for photoaffinity labeling and chemoproteomic studies.[7][8]
Pharmaceuticals and herbicides
[edit]Isoxazoles also form the basis for a number ofdrugs,[9]including the COX-2 inhibitorvaldecoxib(Bextra) and aneurotransmitteragonistAMPA.A derivative,furoxan,is anitric oxidedonor. An isoxazolyl group is found in manybeta-lactamase-resistant antibiotics,such ascloxacillin,dicloxacillinandflucloxacillin.Leflunomide is an isoxazole-derivative drug. Examples ofAAScontaining the isoxazole ring includedanazolandandroisoxazole.A number ofpesticidesare isoxazoles.[10]
See also
[edit]- Oxazole,an analog with thenitrogenatomin position 3
- Pyrrole,an analog without theoxygenatom
- Furan,an analog without the nitrogen atom
- Simple aromatic rings
References
[edit]- ^International Union of Pure and Applied Chemistry(2014).Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013.The Royal Society of Chemistry.p. 140.doi:10.1039/9781849733069.ISBN978-0-85404-182-4.
- ^Zoltewicz, J. A. & Deady, L. W. Quaternization of heteroaromatic compounds. Quantitative aspects. Adv. Heterocycl. Chem. 22, 71-121 (1978)
- ^Dasa S, Chanda K (2021)."An overview of metal-free synthetic routes to isoxazoles: the privileged scaffold".RSC Adv(11): 32680–32705.doi:10.1039/D1RA04624A.PMC9042182.
- ^Morita, Taiki; Yugandar, Somaraju; Fuse, Shinichiro; Nakamura, Hiroyuki (March 2018). "Recent progresses in the synthesis of functionalized isoxazoles".Tetrahedron Letters.59(13): 1159–1171.doi:10.1016/j.tetlet.2018.02.020.
- ^Hossain M, Khan M, Kim S, Le H (2022)."Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides".Beilstein J. Org. Chem.(18): 446–458.doi:10.3762/bjoc.18.47.PMC9039522.PMID35529890.
- ^Edwin F. Ullman (1966). "Photochemical Transposition of Ring Atoms in Five-Membered Heterocycles. The Photorearrangement of 3,5-Diphenylisoxazole".J. Am. Chem. Soc.88(8): 1844–1845.doi:10.1021/ja00960a066.
- ^Cheng, K.; Qi, J.; Ren, X.; Zhang, J.; Li, H.; Xiao, H.; Wang, R.; Liu, Z.; Meng, L.; Ma, N.; Sun, H. (2022). "Developing Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics".Angew. Chem. Int. Ed.61(47): e202209947.doi:10.1002/anie.202209947.
- ^Lougee, M.; Pagar, V.; Kim, H.; Pancoe, S.; Chia, W.; Mach, R.; Garcia, B.; Petersson, E. (2022)."Harnessing the Intrinsic Photochemistry of Isoxazoles for the Development of Chemoproteomic Crosslinking Methods".Chem. Comm.58(65): 9116–9119.doi:10.1039/D2CC02263J.PMC9922157.
- ^Zhu, Jie; Mo, Jun; Lin, Hong-zhi; Chen, Yao; Sun, Hao-peng (2018). "The recent progress of isoxazole in medicinal chemistry".Bioorganic & Medicinal Chemistry.26(12): 3065–3075.doi:10.1016/j.bmc.2018.05.013.
- ^Clemens Lamberth (2018). "Oxazole and Isoxazole Chemistry in Crop Protection".Journal of Heterocyclic Chemistry.55(9): 2035–2045.doi:10.1002/jhet.3252.