Polymorphism of Mechanochemically Synthesized Cocrystals: A Case Study

Abstract

The liquid-assisted grinding cocrystallization of theophylline with benzamide leading to polymorphic compounds was investigated. A solvent screening with 17 different solvents was performed. The dipole moment of the solvent used in the synthesis determines the structure of the polymorphic product. A detailed investigation leads to the determination of the kinetically and thermodynamically favored product. In situ observations of the formation pathway during the grinding process of both polymorphs show that the thermodynamically favored cocrystal is formed in a two-step mechanism with the kinetic cocrystal as an intermediate.

Solvation and surface effects on polymorph stabilities at the nanoscale

“…For system (i), the procedure described by Fischer et al 29 was used to prepare 1 : 1 tp  :  bzm co-crystal in forms I and II. For system (ii), dbu-free form B was quantitatively prepared by crystallizing compound (ii) after its synthesis by means of method (a).…”

The effect of ball mass on the mechanochemical transformation of a single-component organic system: anhydrous caffeine

“…Many examples are now available where mechanical treatment has been shown to be a method providing access to novel molecular materials or has been used to enhance the selectivity and the rates of product formation [6][7][8][9]. In recent years, attention has largely turned towards the use of mechanical treatment as a tool for synthesis of new organic and coordination compounds, including pharmaceuticals, as well as for control of their polymorphism [10][11][12][13][14].…”

Mechanistic Insights into a Sustainable Mechanochemical Synthesis of Ettringite

“…Mechanochemistry is an effective solid‐state approach for the rapid synthesis of materials in high yields . Extensive reviews of mechanosyntheses are available, highlighting their particular benefit of avoiding solvent waste.…”