TCI Practical Example: Isoxazole Ring Construction Reaction Using Hydroxylamine Hydrochloride

We are proud to present the isoxazole ring construction reaction using hydroxylamine hydrochloride and 1,3-diphenyl-1,3-propanedione.

Used Chemicals

• 1,3-Diphenyl-1,3-propanedione [D0910]
• Hydroxylamine Hydrochloride [H1581]
• Ethanol

Procedure

Hydroxylamine hydrochloride (396 mg, 6.0 mmol, 1.2 eq.) was added to a solution of 1,3-diphenyl-1,3-propanedione (1.12 g, 5.0 mmol) in ethanol (20 mL) at room temperature. The mixture was refluxed for overnight. Then water (80 mL) was added to the reaction mixture and precipitate was filtered to give 3,5-diphenylisoxazole as a pale red solid (1.09 g, 99% yield).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

3,5-Diphenylisoxazole

¹H NMR (400 MHz, CDCl₃); δ 7.87-7.83 (m, 4H), 7.50-7.46 (m, 6H), 6.82 (s, 1H).

Lead Reference

• Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies
  • A. G. Griesbeck, M. Franke, J. Neudörfl, H. Kotaka, Beilstein J. Org. Chem. 2011, 7, 127.