3,5-Diarylisoxazoles: Individualized Three-Step Synthesis and Isomer Determination Using 13C NMR or Mass Spectroscopy

As a multistep synthetic project for the second-semester organic laboratory, the three-step synthesis and definitive characterization of a 3,5-diarylisoxazole via the chalcone and the chalcone dibromide is described. As each student prepares a differently substituted chalcone, and thus isoxazole, the project is individualized with regard to compound purification, characterization, and literature searches. To determine which isoxazole isomer was obtained from the synthesis, students compare their experimental 13C NMR data for C4 of the isoxazole to that predicted for each isomer. The predicted values are calculated using a formula that utilizes Hammett constants for estimating substituent NMR-shift effects on C4. Isomer determination can also be accomplished through interpretation of the fragmentation pattern observed in the mass spectrum.