Ball-milling Mechanochemical Synthesis of Coordination Bonds: Discrete Units, Polymers and Porous Materials - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 173

Figure 7.10 Examples of mechanochemical synthesis of ionic co-crystals: (a) by
kneading of potassium bromide and barbituric acid with methanol 88
and (b) by kneading of lithium chloride with the API piracetam in the
presence of methanol as the kneading liquid. 89,90
piracetam, brivaracetam and seletracetam, as well as small organic mol-
ecules oxamide, nicotinamide (vitamin B6), malonamide and diacetamide
(Figure 7.10). 89,90
An example of using mechanochemistry to synthesize metallodrugs is the
ILAG synthesis of bismuth subsalicylate, 56 the active component of the
popular gastrointestinal drug Pepto-Bismol s . In addition to providing a
clean and rapid route to the known API directly from the inexpensive metal
oxide Bi 2 O 3 , variation of the reaction composition allowed the selective
synthesis of two further bismuth salicylates. Quantitative yield and product
purity facilitated the structural characterization of bismuth disalicylate
monohydrate, an outstanding target from the 2002 Second Structure De-
termination by Powder Diffractometry Round Robin challenge (SDPDRR-2),
from X-ray powder diffraction data. 91 The crystal structure revealed a non-
porous 2D framework and corrected a previously proposed chemical