The feasibility of employing reversible reactions to convert the separation of ethanediol (EG) and 1,2-butanediol (1,2-BDO) azeotropic system was analyzed in our previous work. This article aims at systematically screening the feasible reactants for the reaction-assisted separation process. A screening principle was brought up and applied. Through preliminary screening, acetic acid, acrylic acid, acetaldehyde, propionaldehyde, propanol, and butanone were obtained as potential reactants. Propionaldehyde was chosen as the proper one after fully comparing the reaction selectivity difference and conversion of EG and 1,2-BDO in the reaction process, the separation efficiency in the purification process, and final EG yield. The separation efficiency was predicted based on the relative volatility of EG, 1,2-BDO, and their corresponding products and was verified by distillation experiments. The stratification appeared in the reaction was found beneficial to the coupling of reaction and separation.