Gas-liquid interface of microdroplets leads to huge differences from the bulky reactor to drive reaction acceleration and even novel reaction pathways including enthalpy effects of partial solvation, entropy effects, fast solvent evaporation, fast diffusion, ultrahigh electric field, extreme pH, etc. We speculated that extremely low pH of microdroplets in this study facilitated the protonation of the imidazoline 1a. Protonated 1a and cationic intermediates (1a' and 1a-1) may be ordered oriented at the interface to decrease the entropy due to electrostatic repulsion, facilitating the thermodynamically unfavorable C-N cleavage of 1,3-diazolidine (a barrier of 16.9 kcal mol -183 ). It needs to be investigated more in the future to exactly uncover the mechanisms inherent from the gas-liquid interface leading to this extraordinary reactivity in both organic and aqueous microdroplets from more emerging examples. Notably, these remarkable reactivities may also be helpful to other interface-rich studies such as aerosol chemistry, 2 on-water chemistry, 1 biomedical, 4 industrial, and energy. 7