The reactions of alcohols and alkyl halides to synthesize di-ether compounds under phase-transfer catalysis conditions were carried out in an alkaline solution/organic solvent two-phase medium. Accordingly, the concentrations of alkyl halide, di-ether compound, active intermediate ( QOR), and hydration number of active intermediate ( QOR) were measured during these reactions. The fractional factorial design ( FFD) method was first employed to study the effects of single factors and the effects of their interactions on the PTC reaction. The following reaction conditions ( or factors) were investigated in the present FFD analysis: amount of alkaline salt, temperature, amount of water, amount of catalyst, volume of organic solvent, and agitation speed. A polynomial model and an analysis of variance table ( ANOVA) were developed to connect the reaction conditions and the conversion from statistical results. Plots of the partition coefficient of alcohol between organic and aqueous phase, the concentration of active intermediate ( QOR), and the hydration number of active intermediate ( QOR) were used to elucidate the reasons for interactions between factors.