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We present SpeedMixing, a rapid blending technology, as an approach for fast mechanosynthesis and discovery of model pharmaceutical cocrystals through rapid spinning in the absence of bulk solvents and milling/grinding media. Syntheses of pharmaceutical cocrystals based on the active pharmaceutical ingredients (APIs) carbamazepine, dihydrocarbamazepine, and nicotinamide demonstrate SpeedMixing as a method for rapid, scalable, as well as controllable and selective synthesis of cocrystals, cocrystal polymorphs and stoichiomorphs, including the discovery of an unexpected methanol solvate of the archetypal cocrystal of carbamazepine and saccharin, which has eluded extensive screens over 20 years. [ABSTRACT FROM AUTHOR]

The "disappearing polymorph" phenomenon is well established in organic solids, and has had a profound effect in pharmaceutical materials science. The first example of this effect in metal‐containing systems in general, and in coordination‐network solids in particular, is here reported. Specifically, attempts to mechanochemically synthesize a known interpenetrated diamondoid (dia) mercury(II) imidazolate metal–organic framework (MOF) yielded a novel, more stable polymorph based on square‐grid (sql) layers. Simultaneously, the dia‐form was found to be highly elusive, observed only as a short‐lived intermediate in monitoring solvent‐free synthesis and not at all from solution. The destabilization of a dense dia‐framework relative to a lower dimensionality one is in contrast to the behavior of other imidazolate MOFs, with periodic density functional theory (DFT) calculations showing that it arises from weak interactions, including structure‐stabilizing agostic C−H⋅⋅⋅Hg contacts. While providing a new link between MOFs and crystal engineering of organic solids, these findings highlight a possible role for agostic interactions in directing topology and stability of MOF polymorphs. [ABSTRACT FROM AUTHOR]

Recent structural studies of organic minerals, coupled with the intense search for new carbon‐containing mineral species, have revealed naturally occurring structures analogous to those of advanced materials, such as coordination polymers and even open metal–organic frameworks exhibiting nanometre‐sized channels. While classifying such 'non‐conventional' minerals represents a challenge to usual mineral definitions, which focus largely on inorganic structures, this overview highlights the striking similarity of organic minerals to artificial organic and metal–organic materials, and shows how they can be classified using the principles of coordination chemistry and crystal engineering. The discovery of naturally occurring metal–organic framework (MOF) minerals highlights the connection between crystal engineering and mineralogy. It is shown how classification of such organic minerals rests on concepts of supramolecular chemistry, coordination chemistry and crystal engineering. [ABSTRACT FROM AUTHOR]

The regioselective functionalization of monosaccharides is notoriously achieved using metal catalysis, lengthy synthetic strategies requiring protection/deprotection, various enzymes, or other methods that target cis-diols (and thus cannot be used with glucopyranose derivatives), In this paper, we report a new method using selected boronic acids as temporary protecting groups, and describe its application to the regioselective functionalization of methyl α- d-glucopyranoside, the most difficult monosaccharide to functionalize regioselectively. Generally, reactions of glucopyranosides may lead to a plethora of mono- and polyfunctionalized derivatives, yet our method gave the 3- O-acetylated, 2- O-benzoylated, and 2- O-pivaloylated derivatives of methyl α- d-glucopyranoside as major products. We focused on the use of recyclable and green temporary protecting groups (in a one-pot reaction) and on the modulation of the intramolecular hydrogen-bonding network using selected arylboronic acids. A complete scalable procedure leading to a single regioisomer from unprotected methyl α- d-glucopyranoside is presented. [ABSTRACT FROM AUTHOR]

Cover Feature: Disappearing Polymorphs in Metal-Organic Framework Chemistry: Unexpected Stabilization of a Layered Polymorph over an Interpenetrated Three-Dimensional Structure in Mercury Imidazolate (Chem. Eur. J. 8/2020) Keywords: mechanochemistry; mercury; metal-organic frameworks; polymorph; solid state Mechanochemistry, mercury, metal-organic frameworks, polymorph, solid state. [Extracted from the article]