Cocrystal Phase Diagrams for Systems Formed by Succinic Acid, Fumaric Acid, and Benzoic Acid in Ethanol with Tebuconazole

Abstract

The solid–liquid phase equilibriums composed of succinic acid + tebuconazole + ethanol and fumaric acid + tebuconazole + ethanol at 298.15, 313.15, and 323.15 K and benzoic acid + tebuconazole + ethanol at 278.15, 288.15, and 298.15 K under atmospheric pressure were determined using the isothermal saturation method. Nine isothermal phase diagrams for these systems were constructed. The influence of temperature on the crystallization region of a cocrystal was investigated. In addition, interactions between tebuconazole and succinic acid/fumaric acid/benzoic acid were calculated via quantum chemical calculations, together with an independent gradient model based on Hirshfeld partition analysis. The results can be used to explain the cocrystalline behavior of tebuconazole–succinic acid/fumaric acid/benzoic acid cocrystals in ethanol and to make sense of the discovery of tebuconazole cocrystals with organic acids.