Using the density functional theory calculations, the nature of the effects of electron-donating substituents on pseudopericyclic ring-opening reactions of oxazole derivatives have been explained. The reactions involve interactions in two kinds of orthogonal pi-systems at the transition states. A 2-amino group interacts with a horizontal pi-system at the transition state, while a 5-alkoxy group interacts with a vertical one. Owing to these substituent effects, the barrier of the ring-opening reactions are reduced cumulatively.