This article presents a simultaneous integration of entrainer selection and solvent recycling for the batch distillation synthesis problem for the first time. The industrial case study used here is to separate acetonitrile from an aqueous acetonitrile waste mixture, a challenging problem because of the thermodynamic complexity of the mixture. Two batch distillation campaigns have been designed using coupled heuristics and optimization approaches and investigated with complex batch column configurations. The first campaign for fast removal of highly pure water identified batch stripper and middle vessel column as the optimal column configurations. In the second campaign, effective entrainer molecules were generated by a computer-aided molecular design approach, and the proposed entrainer was continuously charged at a specified fraction into the middle vessel column to obtain pure acetonitrile and water. Two candidate entrainers, propyl amine, having high relative volatility, and acetone, having low relative volatility, were proposed and compared. A multiobjective optimization programming framework and trade-off are also presented for further complete analysis.