It is well known that solvents can have significant effects on rates and equilibrium compositions of chemical reactions. The computer-aided molecular design (CAMD) of solvents for heterogeneous liquid phase reactions is challenging due to multiple solvent effects on reaction and phase equilibria. In this work, we propose a CAMD methodology based on a genetic algorithm (GA) for identifying optimal solvents for liquid phase reactions where the objective is to maximize the reaction equilibrium conversion. In particular, a novel molecular encoding method is introduced to facilitate the construction and evaluation of solvent molecules in a defined structure space. The reliability of the method for fast identification of optimal reaction solvents is demonstrated for a selected biphasic esterification reaction. The proposed approach opens up new perspectives for intensifying extractive reaction processes via the purposeful design of solvent molecules. (C) 2016 American Institute of Chemical Engineers