Ivan Halasz group | Milling and monitoring

September 15, 2021.

This paper explores manipulating mechanochemical reaction mechanisms and kinetics by modifications of solids.

In solution, one can change solvents and change solvation of reacting molecules. In mechanochemistry, the use of additives has become ubiquitous and its effects were recognised a long time ago (e.g. Watanabe, Senna, Tetrahedron Lett., 2005, 46, 6815; Watanabe, Hiraoka, Senna, Tetrahedron Lett., 2006, 47, 4481; Shan, Toda, Jones, Chem Commun. 2002, 2372).

Mechanochemical reactions environment is dynamic and rich. Inspired by the chemistry of the living cell where reaction are often coupled, we couple reactions in the solid state.

We take the reaction of barbituric acid (barb, in the keto form) and vanillin (that we have studied before: Chem. Commun. 2018, 13216) and modify the solid form of barb. We made the desmotrope of barb, it salt and its cocrystal.

For example, barb forms a salt with melamine which reacted much slower that the parent barb. This is probably because melamine must leave the salt and form as a separate phase. But if this reaction is coupled by immediately reacting the nascent melamine in a favourable reaction, the whole transformation becomes much faster. Here we have used cyanuric acid to achieve a reaction that was, remarkably, even faster the the parent reaction of pure barb and van.

On the other hand, making a cocrystal of barb with urea had accelerated the reaction by itself (see Figure).