Mechanochemistry: A Force of Synthesis

[Image: see text] The past decade has seen a reawakening of solid-state approaches to chemical synthesis, driven by the search for new, cleaner synthetic methodologies. Mechanochemistry, i.e., chemical transformations initiated or sustained by mechanical force, has been advancing particularly rapidly, from a laboratory curiosity to a widely applicable technique that not only enables a cleaner route to chemical transformations but offers completely new opportunities in making and screening for molecules and materials. This Outlook provides a brief overview of the recent achievements and opportunities created by mechanochemistry, including access to materials, molecular targets, and synthetic strategies that are hard or even impossible to access by conventional means

Effect of fluorination on molecular conformation in the solid state: tuning the conformation of cocrystal formers

We present a detailed analysis of the effect of fluorination on the conformation of perfluorosuccinic acid in the solid state, using database analysis, crystal structure determination, and computational analysis of molecular conformations. Our results indicate that perfluorosuccinic acid exhibits strikingly different conformational preferences to its hydrocarbon analogue despite similarity in molecular size. This difference in conformational behavior also extends to the pair of adipic and perfluoroadipic acids. A search of the Cambridge Structure Database indicates that our analysis is valid for neutral molecules, salts, cocrystals, and metal-organic materials, suggesting fluorination as a general means to modify the shape of a molecular building block without changing its size. The difference in molecular shape between hydrocarbon and perfluorocarbon molecules is expected to lead to significant differences in solid-state structures of the resulting materials. We illustrate this by comparing the structures of new multicomponent crystals involving the model pharmaceutical ingredient caffeine and perfluorosuccinic or perfluoroadipic acid with the structures of analogous crystals based on the hydrocarbon diacids. Unlike hydrocarbon-based succinic and adipic acids which provide structurally similar hydrogen-bonded cocrystals and inclusion hosts with caffeine, perfluorosuccinic acid provides a salt and perfluoroadipic acid yields a cocrystal. Combined crystal structure analysis, solid-state and solution NMR analysis, single molecule conformational analysis, and calculations of acid dissociation energies indicate that the different solid-state behaviors of perfluoro- and hydrocarbon acids toward caffeine should be interpreted as a result of their distinct conformational properties rather than differences in pKa values

A Large Family of Halogen-Bonded Cocrystals Involving Metal–Organic Building Blocks with Open Coordination Sites

We demonstrate a design for halogen-bonded metal–organic cocrystals involving coordinatively unsaturated square-planar Cu­(II) and Ni­(II) centers, by utilizing a Schiff base ligand whose pendant acetyl group enables halogen bonding. The robustness of this design is evident by the assembly of a large family of eight cocrystals based on zero-, one-, and two-dimensional halogen bonded architectures involving mono- or ditopic halogen bond donors based on iodine or bromine

Mechanochemical Synthesis, Accelerated Aging, and Thermodynamic Stability of the Organic Mineral Paceite and Its Cadmium Analogue

We demonstrate the use of ball milling mechanochemistry for rapid, simple, and materials-efficient synthesis of the organic mineral paceite CaCu­(OAc)4·6H2O (where OAc– is the acetate ion), composed of coordination polymer chains containing alternating Ca2+ and Cu2+ ions, as well as its cadmium-based analogue CaCd­(OAc)4·6H2O. While the synthesis of paceite in aqueous solutions requires a high excess of the copper precursor, mechanochemistry permits the use of stoichiometric amounts of reagents, as well as the use of poorly soluble and readily accessible calcium carbonate or hydroxide reactants. As established by thermochemical measurements, enthalpies of formation of both synthetic paceite and its cadmium analogue relevant to the mechanochemical reactions are highly exothermic. Reactions can also be conducted using accelerated aging, a synthetic technique that mimics geological processes of mineral weathering. Accelerated aging reactivity involving copper­(II) acetate monohydrate (hoganite) and calcium carbonate (calcite) provides a potential explanation of how complex organic minerals like paceite could form in a geological environment

Shaping Crystals with Light: Crystal-to-Crystal Isomerization and Photomechanical Effect in Fluorinated Azobenzenes

Unusually long thermal half-lives of perhalogenated <i>cis</i>-azobenzenes enabled their structural characterization and the first evidence of a crystal-to-crystal <i>cis</i> → <i>trans</i> azobenzene isomerization. Irradiation with visible light transforms a perhalogenated <i>cis</i>-azobenzene single crystal into a polycrystalline aggregate of its <i>trans</i>-isomer in a photomechanical transformation that involves a significant, controllable, and thermally irreversible change of crystal shape. This is the first demonstration of permanent photomechanical modification of crystal shape in an azobenzene

Shaping Crystals with Light: Crystal-to-Crystal Isomerization and Photomechanical Effect in Fluorinated Azobenzenes

Unusually long thermal half-lives of perhalogenated <i>cis</i>-azobenzenes enabled their structural characterization and the first evidence of a crystal-to-crystal <i>cis</i> → <i>trans</i> azobenzene isomerization. Irradiation with visible light transforms a perhalogenated <i>cis</i>-azobenzene single crystal into a polycrystalline aggregate of its <i>trans</i>-isomer in a photomechanical transformation that involves a significant, controllable, and thermally irreversible change of crystal shape. This is the first demonstration of permanent photomechanical modification of crystal shape in an azobenzene

Shaping Crystals with Light: Crystal-to-Crystal Isomerization and Photomechanical Effect in Fluorinated Azobenzenes

Unusually long thermal half-lives of perhalogenated <i>cis</i>-azobenzenes enabled their structural characterization and the first evidence of a crystal-to-crystal <i>cis</i> → <i>trans</i> azobenzene isomerization. Irradiation with visible light transforms a perhalogenated <i>cis</i>-azobenzene single crystal into a polycrystalline aggregate of its <i>trans</i>-isomer in a photomechanical transformation that involves a significant, controllable, and thermally irreversible change of crystal shape. This is the first demonstration of permanent photomechanical modification of crystal shape in an azobenzene

Shaping Crystals with Light: Crystal-to-Crystal Isomerization and Photomechanical Effect in Fluorinated Azobenzenes

Unusually long thermal half-lives of perhalogenated <i>cis</i>-azobenzenes enabled their structural characterization and the first evidence of a crystal-to-crystal <i>cis</i> → <i>trans</i> azobenzene isomerization. Irradiation with visible light transforms a perhalogenated <i>cis</i>-azobenzene single crystal into a polycrystalline aggregate of its <i>trans</i>-isomer in a photomechanical transformation that involves a significant, controllable, and thermally irreversible change of crystal shape. This is the first demonstration of permanent photomechanical modification of crystal shape in an azobenzene

Testing the sensitivity of terahertz spectroscopy to changes in molecular and supramolecular structure: a study of structurally similar cocrystals

Terahertz time-domain-spectroscopy (THz-TDS) has emerged as a versatile spectroscopic technique, and an alternative to powder X-ray diffraction in the characterization of molecular crystals. We tested the ability of terahertz spectroscopy to distinguish between chiral and racemic hydrogen-bonded cocrystals that are similar in molecular and supramolecular structure. Terahertz spectroscopy readily distinguished between the isostructural cocrystals of theophylline with chiral and racemic forms of malic acid which are almost identical in molecular structure and supramolecular architecture. Similarly, the cocrystals of theophylline with chiral and racemic forms of tartaric acid, which are similar at the molecular level but dissimilar in crystal packing, were distinguished unequivocally. The investigation of the same cocrystals using X-ray powder diffraction and Raman spectroscopy suggested that THz-TDS is comparable in sensitivity to diffraction methods and more sensitive than Raman spectroscopy to changes in cocrystal architecture. The differences in spectra acquired by THz-TDS could be further enhanced by cooling the samples to 109 K.<br/

Mechanochemical Ruthenium-Catalyzed Olefin Metathesis

We describe the development of a mechanochemical approach for Ru-catalyzed olefin metathesis, including cross-metathesis and ring-closing metathesis. The method uses commercially available catalysts to achieve high-yielding, rapid, room-temperature metathesis of solid or liquid olefins on a multigram scale using either no or only a catalytic amount of a liquid