As determined by X-ray crystallography, isoxazol-5(4H)-one derivatives 12–19 feature dihedral angles around the exocyclic C4=C6 double bonds of 26–90°. In the most highly twisted bis-tert-butylamino derivatives 18 and 19, the C4–C6 bonds are essentially single bonds. Density functional theory calculations at the B3LYP/6-31G(d) level with inclusion of a simulated solvent field, which helps stabilize zwitterionic structures, are in good agreement with the experimental crystallographic data. A good correlation between bond lengths and calculated π/π* orbital occupation quotients is observed. A good correlation between the twisting angle and the charge separation, measured by the calculated negative charge on the isoxazolone moiety, is also observed. Low barriers to rotation about the twisted exocyclic double bonds C4=C6 in compounds 13, 20, and 21 (ΔG ^‡ = 15–16 kcal mol^–1 (63–67 kJ mol^–1)) were determined by dynamic ¹H NMR coalescence measurements. The rotational barrier for 17 was estimated to be less than 10 kcal mol^–1. The rotational barriers for compounds 10 and 18 were calculated to be ~8 kcal mol^–1.