A method to predict binary eutectic mixtures for mechanochemical syntheses and cocrystallizations

Abstract

The prediction of the phase behaviour of a mixture of solid components when they come into contact is of high interest in fast growing research fields such as mechanochemistry and deep eutectic solvents (DESs). This paper provides a friendly predictive tool (PoEM, i.e. Predictor of Eutectic Mixtures), along with some guidelines and quantitative references, to quickly estimate the variation in the melting point due to the mixture of reactants for a mechanochemical process. An empirical model that estimates the ideal eutectic point and includes deviation from ideality based on intermolecular interactions is presented here, allowing for the design of synthetic procedures for solvent-less cocrystallization processes. PoEM calculations are validated by comparing the prediction with experimental behaviour of a number of mixtures with a low melting eutectic mixture. Finally, as a working example we consider how to identify coformers for the synthesis of a cocrystal containing thymol such that the cocrystallization would proceed through the formation of a metastable liquid phase.