Computer-aided reaction solvent design considering inertness using group contribution-based reaction thermodynamic model

Abstract

Solvents have been widely used in process manufacturing industries. When involved in liquid-phase organic synthesis reactions, solvents can reduce the activation energy of reactions between the reactants and the transition state through solvation effects. However, undesirable side reactions can also be performed between solvents and the reaction system (the reactants and products), which should be avoided for producing unnecessary byproducts in the reaction system. In this paper, an optimization-based methodology is proposed for inert reaction solvent design. In this method, first, a Group Contribution (GC)-based reaction thermodynamic model is developed to quantitatively identify the thermodynamic feasibility of side reactions between solvents and the reaction system. Then, the SMARTS (SMiles Arbitrary Target Specification)-based reaction generation algorithm is employed to generate possible side reactions between solvents and the reaction system, helping to integrate the developed GC-based reaction thermodynamic model with the Computer-Aided Molecular Design (CAMD) problem for designing inert reaction solvents through the formulation and solution of the Mixed-Integer Non-Linear Programming (MINLP) model. Due to the nonlinear equations in the MINLP model, a decomposition-based solution strategy is employed to solve the optimization problem. Finally, two case studies are presented to demonstrate the feasibility and effectiveness of the proposed optimization-based methodology for promising inert reaction solvent design.