Neat grinding

The effect of metal impurities from wear on the appearance of i H NMR spectrum of A/-(3-nitrophenyl)-A/ -phenylurea (30). (A) Crude product from neat grinding (red) and iron-free LAG product. (B) The precipitated iron particles after solubilization of the urea product from LAG reaction. 

In a different smdy by the same group, SEM was utilized to investigate the differences between neat grinding and LAG synthesis of another MOF system Cu3(BTC)2 (BTC=1,3,5-benzenetricarboxylate), commonly known as HKUST-1 [55]. In accordance with a previous study, it was found that LAG provides better defined crystallites with a typical size in the range 50-100nm. In an attempt to activate the product... 

The real-time in situ synchrotron PXRD technique found its next application in the mechanistic study of mechanochemically promoted co-crystallization of carbamazepine and nicotinamide as representatives of active pharmaceutical ingredients (API) [62], In the case of carbamazepine saccharin co-crystal, in situ analysis confirmed previous studies by cryomiUing that neat grinding led to amorphization while LAG synthesis rapidly produced the co-crystal. The other investigated system involved two-step neat grinding synthesis of nicotinamide suberic acid 2 1 co-crystal. The ex situ PXRD analysis had revealed a stepwise mechanism with the 1 1 cocrystal as the intermediate. Whereas LAG synthesis was too fast for ex situ approach, in situ monitoring enabled the discovery of an unknown phase that preceded the rapid formation of the 1 1 intermediate (Fig. 1.28). However, the authors were not successful at full characterization of the new phase due to its pronounced instability. 

A) An experimental setup for real-time in situ Raman spectroscopy monitoring of mechanochemical reactions. Time-resolved Raman spectra for CdCl2-cnge neat grinding... 

The simplest mechanochemical method for pharmaceutical co-crystallisation is by neat grinding of two or more co-crystal components. The first examples of neat grinding co-crystallisation of pharmaceutically relevant molecules were... 

Stoichiometric ratio nicotinamide acid Co-crystallisation from solution 1 1 2 1 Co-crystallisation from the melt 1 1 2 1 Neat grinding 1 1 2 1 LAG 1 1 2 1... 

Figure 8.14 Mechanochemical co-crystallisation by neat grinding of carbamazepine and saccharin involving an amorphous intermediate.

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