The Experiment of Dipolar Cycloaddition of Diphenylisoxazoline

Preparation of Diphenylisoxazoline

The goal of the following experiment is a synthesis of diphenylisoxazoline by means of 1,3- dipolar cycloaddition. At first, the preparation of benzaldehyde oxime must take place.


  • Sodium hydroxide – 3.5g
  • Water – 200 ml
  • Benzaldehyde – 5.1 mL
  • Hydroxylamine hydrochloride – 4.2g
  • Magnesium sulfate – several spoons
  • Styrene – 2.9 mL
  • Trimethylamine – 0.3 mL
  • Oxime – 2.5g
  • Sodium hypochlorite – 25 mL

At first, the sodium hydroxide must be dissolved in water. The solution must be cooled and then the benzaldehyde must be added following the hydroxylamine hydrochloride. The maximum potency was set to the stirrer in order to let the stirring in a vigorous style conduct. The flask with the solutions must be stopped during the stirring.

In five minutes of reaction, other portions of benzaldehyde and hydroxylamine hydrochloride (0.5g each) were added to the conical flask with the solutions. The process must be repeated until the whole amount of reagents (5.1 mL of benzaldehyde and 4.2 g of hydroxylamine hydrochloride) are dissolved fully.

In order to complete the reaction, the solution must be warmed until it becomes homogeneous. This is an indicator that all benzaldehyde is consumed.

The pH indicator should be used to neutralize the mixture with 1.6 mL of glacial acetic acid. Several drops of water can be added to the mixture in order to dissolve the sodium acetate precipitate that could form as the result of neutralization.

Then the solution is needed to be cooled and its upper layer must be extracted with diethyl ether (60 mL). This is an extraction of organic material and is conducted up to a 100 mL beaker. Some MgSO4 are added to the beaker in order to dry out the organic extract. Then the mixture must be filtered off. It must be placed into a round-bottomed flask and then a solvent must be removed on a rotary evaporator.

Inside the fume cupboard, 2.9 mL of styrene and 0.3 mL of trimethylamine are dissolved in 15 mL of dichloromethane in a conical flask. Then, 25 mL of sodium hypochlorite was added. The flask must be placed in an ice bath. 2.5 g of oily oxime were added with the help of Pasteur pipette within 15 minutes. After addition, the mixture stayed in the ice bath for another 45 minutes. Then the lower layer of organic substances was extracted in the separating funnel. The aqueous phase was extracted with 15 mL of dichloromethane.

All organic extracts were combined with MgSO4 for drying out. Then the filter was applied as well as the evaporator to get rid of the dissolvent.


  1. “3,5-Diphenylisoxazole.” 26 Mar. 2005. PubChem, Accessed 23 Apr. 2018.
  2. Karlsson, Staffan. “Asymmetric 1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides, Thiocarbonyl Ylides, and Nitrones.” 2003., Accessed 23 Apr. 2018.
  3. Cheng, Qing-Qing. “Cycloaddition reactions of enoldiazo compounds.” Chemical Society Reviews, vol. 17, no. 46, 2017. Royal Society Of Chemistry,!divAbstract. Accessed 23 Apr. 2018.
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