The cocrystallization between thymol (THY) and hexamethylenetetramine (HMT) was studied by in situ X-ray powder diffraction.
Source: BAM, Structure Analysis division
Mechanochemistry uses mechanical energy input to cause substances to react. As solvents are normally not needed, this type of reaction is very environmentally friendly. Cocrystals are compounds in which different molecules are incorporated into the same crystal lattice and held together by intramolecular interactions. Mechanochemistry is an excellent method to synthesize cocrystals. However, the reaction mechanisms during these reactions are still largely unknown. This greatly hinders the large-scale application of mechanochemical cocrystallization in, for example, the pharmaceutical industry. Thymol (THY, an essential oil extracted from thyme) has antibacterial properties, but its volatility and poor water solubility limits its use in agricultural and food chemistry. Cocrystallization with hexamethylenetetramine (HMT) was used to mitigate its negative characteristics.
In this work, the mechanochemical cocrystallization between thymol and hexamethylenetetramine is studied. The reaction proceeds via a low melting eutectic. Time-resolved in situ x-ray powder diffraction performed at the synchrotron BESSY II revealed that the reaction is completed within 5s. The formation of the amorphous eutectic is evident in the increase of the amorphous background. The binary phase diagram of the cocrystal was created. From this, a melting temperature of Tm= 24.38 °C can be extrapolated for the eutectic. The extrapolated melting temperature could be confirmed experimentally by hot stage microscopy and differential scanning calorimetry (DSC). The cocrystal was further characterized by variable temperature x-ray powder diffraction (vt-PXRD).
On the Mechanism of Cocrystal Mechanochemical Reaction via Low Melting Eutectic: A Time-Resolved In Situ Monitoring Investigation
P. P. Mazzeo, M. Prencipe, Torvid Feiler, Franziska Emmerling, A. Bacchi
published in Crystal Growth and Design, Vol. 22, issue 7, pages 4260 - 4267, 2022.
BAM, department Materials Chemistry division Structure Analysis