Project 5 Procedure

Dr. O’Neal is collecting data on the success of Project 4. After you have isolated your products and finished your analysis, please report your yields and any comments in this data table.

Part A: Chalcone Synthesis

Generic synthesis of chalcones.

Acetophenone (5 mmol), benzaldehyde (5 mmol), and methanol (15 mL) were combined in a 250 mL Erlenmeyer flask equipped with a magnetic stir bar. Aqueous sodium hydroxide (30% m/v, 2.0 mL) was added dropwise. The reaction mixture was stirred at room temperature for 20 minutes at which point a solid precipitated. The flask was then chilled in an ice-water bath, then water (~50 mL) was added. The precipitate was collected by vacuum filtration and recrystallized from 95% ethanol.


1. If no solid precipitates after stirring the reaction mixture at room temperature for 30 minutes, heat the mixture to a gently reflux for 5-10 minutes. Solid should then precipitate upon cooling. If not, try adding a little water to induce precipitation.

2. Chalcones typically can be recrystallized from ethanol or methanol. The best solvent depends on the exact structure of the chalcone. You may wish to experiment with solvents to optimize your yield.

3. Remember that you need to make a convincing argument for the structure of your chalcone. You may decide which characterization data to obtain in order to support your argument. Most chalcones are known compounds with characterization data already reported in the literature.

Part B: Isoxazole Synthesis

Generic synthesis of isoxazoles.

Chalcone (2.4 mmol) was dissolved in methanol (11 mL). Iodobenzene diacetate (2.5 mmol) was added, then 50% sulfuric acid in methanol (2 mL) was added dropwise. The reaction mixture was stirred at room temperature until TLC (80:20 hexanes:ethyl acetate) indicated that the starting material was consumed (30 min). Hydroxylamine hydrochloride (3.6 mmol), ammonium acetate (3.6 mmol), and distilled water (5 mL) were added, and the reaction mixture was refluxed for 45 minutes. The flask was cooled to room temperature. The mixture was poured into water (25 ml) and extracted with ethyl acetate (2 × 20 mL). The combined organic layers were washed sequentially with saturated sodium bicarbonate and brine, dried over sodium sulfate, gravity filtered, and concentrated by rotary evaporation. The resulting oil was dissolved in methanol (2-3 mL) and poured into a 100 mL beaker. Upon standing, the product solidified. Recrystallization from hexane gave the isoxazole.


1. If the chalcone does not dissolve, additional methanol may be used.

2. If the oxidative rearrangement reaction is not complete after 30 minutes, continue to stir the mixture at room temperature and monitor the progress at 20 minute intervals by TLC. Seek additional guidance from your instructor.

3. The 45 minute timeframe for the cyclization is arbitrary. You may think about whether it would be wise to monitor the progress of this reaction in some way.

4. The oil obtained after rotary evaporation is a mixture of product and iodobenzene generated during the oxidative rearrangement. The iodobenzene complicates the isolation of the isoxazole and solidification may take a long time. This is a good stopping point for Week 2 of the project. Leave the open beaker in the back of your hood for the week to allow the product to crystallize. If there is still no solid when you return for Week 3, you may need to isolate your product by column chromatography.