Three-phase reversible mechanochemical interconversion of hydrogen-bonded melamine : barbiturate co-crystals: from rosette to linear tape polymorphs†

Ball milling an equimolar ratio of melamine and barbiturate under liquid assisted grinding (LAG) with acetonitrile forms a rosette co-crystal (form A), while under neat grinding (NG) forms an amorphous form. A new co-crystal (form B) is formed from form A or from the amorphous form by LAG with water. The 2 crystalline polymorphs and the amorphous form can be interconverted by ball milling under the conditions favouring their formation. Surprisingly, on milling the co-formers with water, we obtained a linear tape co-crystal (form C), leading to the disappearance of form B. Form C takes now the role previously executed by form B in the reversible turnover cycle. This work is the experimental evidence that full reversibility between multiple phases under milling conditions is a general phenomenon.