A mixed-integer nonlinear programming (MINLP) formulation for the molecular design optimization of ionic liquids (ILs) to recuperate ethanol with a purity of 99 mol % or greater from a E85 system (a mixture containing 85 and IS mol % of ethanol and water, respectively) is presented. The reason why the ethanol/water separation is difficult is because of the azeotropic behavior of this system. Therefore, the IL is designed to feature water affinity such that it can break the ethanol/water azeotrope, allowing the high-purity separation to take place. The MINLP formulation is based on the development of a superstructure that contains a set of cations and anions, whose combination forms different kinds of ILs that have the potential to separate azeotropic systems such as the ethanol/water system. Because most of the Its to be optimally designed are novel solvents, their physical and thermodynamic properties are estimated by group contribution methods. The optimization formulation is composed of a set of constraints featuring vapor liquid equilibrium conditions as well as constraints dealing with structural and allowed cation anion combinations. We assume that the separation will take place at atmospheric pressure. For the sake of simplicity, the optimal IL is first synthesized in a single separation stage, although the separation was also addressed using a reboiled absorption column. The results indicate that the optimally designed IL is capable of performing the required separation meeting the high-purity ethanol constraint.