Dissecting the Solvate Formation Behavior of 3,5-Dihydroxybenzoic Acid: Why So Many Solvate-Hydrates and How to Obtain Pure Solvates?

Crystallographic analysis of solvate structures formed by 3,5-dihydrohybenzoic acid demonstrates that the high propensity of this compound to form solvate-hydrates is a result of the highly efficient crystal structure framework obtained by the inclusion of water molecules. On the contrary, pure solvates can be obtained with a limited number of organic solvents, only with relatively small solvents providing efficient hydrogen bonding. The crystal structure analysis shows that the steric characteristics of the solvent molecules notably affect the crystal structure framework. In all of the cases where the formation of alternative crystal forms is possible, the water content present in the crystallization medium directly influences the obtained crystal form. Exploration of the formation of two ethyl acetate solvate-hydrates indicates that the water content present in the crystallization medium and packing characteristics in the crystal structure mostly influence the phase appearance frequency.