Project 5 Procedure

Generic synthesis of chalcone epoxides.

1. In a 250 mL Erlenmeyer flask equipped with a magnetic stir bar, combine acetophenone (5 mmol), benzaldehyde (5 mmol), and methanol (15 mL).

2. Add aqueous sodium hydroxide (30% m/v, 2.0 mL) dropwise.

3. Stir the reaction mixture at room temperature for 20 minutes, then heat it on the hot plate to a gentle reflux for 5 minutes.

4. Add methanol (65 mL) and stir the flask to dissolve as much solid as possible.

5. Allow the mixture to cool completely to room temperature. {Hint: Place an ice-water bath on the hot plate to quickly cool the surface of the plate while your reaction mixture is cooling.}

6. Return the flask to the stir plate. To the continuously stirred solution, add aqueous hydrogen peroxide (30% m/v, 5.7 mL) dropwise over a period of 3-5 minutes.

7. Stir the mixture at room temperature for 1 hour.

8. Chill the reaction mixture in an ice bath, then add ice-cold water (100 mL) slowly to precipitate the product.

9. Collect the solid product by vacuum filtration, washing it with cold water. The crystals often are highly pure and may be used in the next reaction without further purification. If necessary, the solid may be recrystallized from 95% ethanol.

10. Save the solid in an OPEN beaker. It must be as dry as possible for the next reaction to be successful!


Generic synthesis of isoxazoles.

Note: The chalcone epoxide and all glassware/materials used in this reaction must be as dry as possible. Do not use a wet flask! If necessary, rinse it with acetone and thoroughly dry it before setting up your reaction.

In a 25 mL round bottom flask, copper (II) triflate (0.044 g, 0.12 mmol) was added to a solution of chalcone epoxide (0.514 g, 2.29 mmol) in dichloromethane (5 mL). The reaction was monitored by TLC (8:2 hexane:ethyl acetate). After 30 minutes, the epoxide had been consumed. Hydroxylamine hydrochloride (0.180 g, 2.59 mmol) and 95% ethanol (5 mL) were added to the reaction mixture. The solution was refluxed for 45 minutes, then the solvent was removed by rotary evaporation. The resulting residue was partitioned between ethyl acetate (20 mL) and water (20 mL). The organic layer was washed sequentially with water and brine, dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The product was obtained as a yellow oil (0.486 g, 98%).