Domino one-pot multicomponent synthesis of 3,5-disubstituted isoxazoles
SyntheticPage 728
DOI:
Submitted: March 15, 2014, published: March 24, 2014
Authors
Anil Padala (anil.p.iiim@gmail.com)
Rammohan R. Yadav (rammohanryadav@gmail.com)
Sandip Bharate (sbharate@iiim.ac.in)
A contribution from
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Chemicals
p-Anisaldehyde (Sigma Aldrich), 98%, A88107
Hydroxylamine hydrochloride (SD Fine Chemicals Ltd)
Sodium hydroxide (SD Fine Chemicals Ltd)
N-Chlorosuccinimide (Sigma Aldrich), 98%, 109681
Phenyl acetylene (Sigma Aldrich), 98%, 117706
Clay-Cu(II) catalyst (preparation provided below)
Sodium azide (Sigma Aldrich), ReagentPlus, ≥99.5%, S2002
Procedure
Synthesis of 3-(4-methoxyphenyl)-5-phenylisoxazole: The aqueous solution of p-anisaldehyde (100 mg, 1 mmol) and hydroxylamine hydrochloride (61 mg, 1.2 mmol) was stirred at room temperature for 30 minutes. After complete conversion of aldehyde to oxime (monitored by TLC), N-chlorosuccinimide (127 mg, 1.3 mmol) was added to the reaction mixture and was allowed to stir for 3 hours. The clay-Cu(II)/NaN3 mixture [prepared by stirring 15 mol% clay-Cu catalyst (15 mg) and 7.5 mol% NaN3 (4 mg) in water (3 ml) until the color changes from brown to black] and phenyl acetylene (104 µl, 1.3 mmol) was added and the reaction mixture was further stirred for another 3 hours. After completion of reaction, the reaction mixture was filtered through filter paper, and residue was washed with EtOAc. Organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by silica gel (mesh 100-200) column chromatography using EtOAc: hexane as eluting solvent to get 3-(4-methoxyphenyl)-5-phenylisoxazole (71 mg, 55% yield). The product was characterized by comparison of NMR data with literature values (Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210-216. http://dx.doi.org/10.1021/ja0471525)
Author Comments
Data
3-(4-methoxyphenyl)-5-phenylisoxazole: White solid; m.p. 121-123 °C; Rf (5% EtOAc: n-hexane): 0.2;
1H NMR (CDCl3, 400 MHz) δ ppm: 7.85-7.80 (m, 4H), 7.51-7.45 (m, 3H), 7.00 (d, J = 8.0 Hz, 2H), 6.78 (s, 1H), 3.87 (s, 3H);
13C NMR (CDCl3, 125 MHz) δ ppm: 170.16, 162.61, 161.01, 130.18, 129.02, 128.23, 127.55, 125.84, 121.62, 114.33, 97.29, 55.40;
IR (neat)): 3400, 3115, 2921, 2851, 1613, 1570, 1529, 1494, 1447, 1430, 1299, 1253, 1178, 1116, 1073, 1032 cm-1;
ESI-MS: m/z 252.00 [M+H]+.
Lead Reference
Other References
- Hansen, T. V.; Wu, P.; Fokin, V. V. J. Org. Chem. 2005, 70, 7761-7764. http://dx.doi.org/10.1021/jo050163b ·
- Waldo, J. P.; Larock, R. C. Org. Lett. 2005, 7, 5203-5205. http://dx.doi.org/10.1021/ol052027z
Supplementary Information
Keywords
1, 3-dipolar cycloaddition, aldehydes, heterocyclic compounds, heterogeneous, isoxazoles, Montmorillonite clay, multicomponent