Ball-milling Mechanochemical Synthesis of Coordination Bonds: Discrete Units, Polymers and Porous Materials - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 167

suggesting a rational strategy to mechanochemically screen for hydrated
coordination polymers. 71 Formation of solid hydrates is of particular im-
portance in developing pharmaceutical formulations and new solid forms of
pharmaceuticals. Consequently, control of water activity in LAG was exploited
in the pharmaceutical context, as a strategy to explore the phase space of
hydrated magnesium complexes of the drug naproxen: deliberate variation of
water activity in the grinding liquid enabled the LAG discovery of new mag-
nesium derivatives of naproxen formed directly from MgO and the drug
(Figure 7.6c). 72
7.5.5 Mechanochemical Dehydration
Liquid-assisted grinding offers an interesting alternative to grinding-
annealing for achieving the formal dehydration of small molecule complexes
and their association into extended structures. As demonstrated by Wang
and co-workers, 73 mechanochemical milling of zinc oxide or copper( II )
acetate monohydrate in the presence of water leads to the formation of
corresponding hydrated metal isonicotinates, as small discrete complexes of
composition M(ina) 2 (H 2 O) 4 (where M ¼ Zn or Cu). A second round of mil-
ling, but now in the presence of methanol, a solvent well known to greatly
reduce the activity of water, leads to dehydration of the monomeric tetra-
hydrate complexes and their reversible polymerization into either the non-
porous triply interpenetrated MOF Zn(ina) 2 with a diamondoid topology or
the open 2D framework Cu(ina) 2 (Figure 7.7a). Thus, it appears that LAG
with a liquid exhibiting a particularly high anity for water can be used as a
means of non-thermal dehydration and polymerization of small molecule
complexes into MOFs. Notably, such mechanochemical LAG dehydration is
readily reversed by milling the two MOFs with water, yielding again the
M(ina) 2 (H 2 O) 4 complexes.
7.5.6 One-pot Multi-component Strategies
Whereas applications of mechanochemical reactivity are, to a very large
extent, focused on a particular chemical reaction, there is growing interest
in the potential of mechanochemistry for conducting multi-component,
multi-step reactions. Such potential, if realized, would further enhance the
synthetic benefits of mechanochemical reactions by allowing rapid and
solvent-free assembly of increasingly complex products directly from the
simplest reactants. In the context of metal-organic materials, an early
investigation of multi-component, one-pot reactivity involved the synthesis
and screening for inclusion behavior of wheel-and-axle lattice hosts based on
cobalt( II ) and nickel( II ) dibenzoylmethanates. 74 Milling of either nickel( II )or
cobalt( II ) dibenzoylmethanate dihydrate with nicotinamide and a suitable
guest liquid quantitatively yielded metal-organic inclusion compounds in
which a small molecule guest was trapped through weak van der Waals
forces within an extended host structure based on coordination bonds and