Mechanochemical Synthesis of Multicomponent Crystals: One Liquid for One Polymorph? A Myth to Dispel

Identifying as many polymorphs as possible for a molecular compound is important in the design of materials with desired properties. In this paper we demonstrate, using a simple experimental procedure, how the amount of liquid present during liquid-assisted mechanochemical reactions can be used to rapidly explore polymorph diversity. Through detailed experimental evidence it is concluded that for the specific (multicomponent) crystal system investigated (caffeine–anthranilic acid) the commonly accepted rule “one liquid for one specific polymorph” is not correct. Additionally we demonstrate that through modification of the amount of added liquid it is possible to form a polymorph previously obtained only by a desolvation reaction. We believe that while the results raise many mechanistic questions the approach is advantageous as a means of rapidly screening for polymorph diversity as well as being a simple screening methodology. While we focus here on a cocrystal system, we believe a similar approach will be advantageous for single component systems.