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The mechanism of mechanochemical PdII-catalyzed selective bromination of the carbon–hydrogen bond in azobenzene by N-bromosuccinimide (NBS) was investigated using in situtime-resolved Raman spectroscopy and quantum-chemical (density functional theory, DFT) calculations. Raman monitoring of the reactions in the presence of different amounts of Pd(OAc)2, p-toluenesulfonic acid (TsOH), and acetonitrile (MeCN) as solid and liquid additives provided direct evidence that the formation of the carbon–halogen bond in the solid state proceeds from catalytically active cyclopalladated intermediates that are monomeric in the presence of MeCN or dimeric without MeCN. The reaction pathway viathe monomeric palladacycle is more efficient than the pathway viathe dimeric palladacycle for the bromination of azobenzene, offering better yields and faster reactions. Both reaction routes require the presence of TsOH, which is involved in the formation of the active PdIIcatalysts and palladacyclic intermediates, as well as in the activation of NBS. Four possible reaction mechanisms for the bromination of cyclopalladated azobenzene were investigated by DFT modeling. Three mechanistic pathways include (i) oxidative addition of the Br to Pd atom and (ii) reductive elimination by the 1,2-displacement of Br to the carbon atom. In one pathway, the transfer of Br to Pd occurs only after the initial displacement of the neutral ligand by NBS. In another, the Pd atom is inserted directly into the N–Br bond of NBS, and in the last one, Br+migrates spontaneously from the protonated NBS to Pd. In all three cases, the subsequent elimination step is remarkably lower in energy. In the fourth mechanism, Br+migrates from free NBS directly to the activated carbon, simultaneously with the Pd–C bond breaking. Besides NBS, the hydrogen bond complex NBS···TsOH was also considered as the bromine source. None of the considered mechanisms can be definitely rejected on the basis of experimental findings and the current modeling level, and more than one could be operative depending on the reaction conditions.

Performing reactions in the solid state offers the largely unexplored possibility of influencing reactivity by manipulating the solid form of the starting reactants. In this work, we explore the use of various solid forms of barbituric acid and its effect on reaction paths and kinetics in a Knoevenagel condensation reaction with vanillin. Modifications of barbituric acid included the use of its desmotrope, a cocrystal, and a salt as the starting reactant. Comparing these reactions with the reaction starting from the commercial keto tautomer of barbituric acid, we find that the reaction kinetics could be accelerated or decelerated, together with a change in the reaction mechanism. Exploring solid forms of reactants can be used as general methodology for manipulating mechanochemical reactivity, further highlighting the benefits of conducting reactions in the solid state, because many of the modifications of solids become unavailable upon dissolution.

Solid-state milling has emerged as an alternative, sustainable approach for preparing virtually all classes of compounds and materials. In situ reaction monitoring is essential to understanding the kinetics and mechanisms of these reactions, but it has proved difficult to use standard analytical techniques to analyze the contents of the closed, rapidly moving reaction chamber (jar). Monitoring by Raman spectroscopy is an attractive choice, because it allows uninterrupted data collection from the outside of a translucent milling jar. It complements the already established in situ monitoring based on powder X-ray diffraction, which has limited accessibility to the wider research community, because it requires a synchrotron X-ray source. The Raman spectroscopy monitoring setup used in this protocol consists of an affordable, small portable spectrometer, a laser source and a Raman probe. Translucent reaction jars, most commonly made from a plastic material, enable interaction of the laser beam with the solid sample residing inside the closed reaction jar and collection of Raman-scattered photons while the ball mill is in operation. Acquired Raman spectra are analyzed using commercial or open-source software for data analysis (e.g., MATLAB, Octave, Python, R). Plotting the Raman spectra versus time enables qualitative analysis of reaction paths. This is demonstrated for an example reaction: the formation in the solid state of a cocrystal between nicotinamide and salicylic acid. A more rigorous data analysis can be achieved using multivariate analysis.

Palladium C–H bond activation in azobenzenes with R1and R2at parapositions of the phenyl rings (R1= NMe2, R2= H (L1); R1= NMe2, R2= Cl (L2); R1= NMe2, R2= I (L3); R1= NMe2, R2= NO2(L4); R1= H, R2= H (L5)) and their monopalladated derivatives, using cis-[PdCl2(DMF)2], has been studied in detail by in situ1H NMR spectroscopy in N,N-dimethylformamide-d7(DMF-d7) at room temperature; the same processes have been monitored in parallel via time-resolved UV–vis spectroscopy in DMF at different temperatures and pressures. The final goal was to achieve, from a kinetico-mechanistic perspective, a complete insight into previously reported reactivity results. The results suggest the operation of an electrophilic concerted metalation–deprotonation mechanism for both the mono- and dipalladation reactions, occurring from the coordination compound and the monopalladated intermediates, respectively. The process involves deprotonation of the C–H bond assisted by the presence of a coordinated DMF molecule, which acts as a base. For the first time, NMR monitoring provides a direct evidence of all the intermediate stages: that is, (i) coordination of the azo ligand to the PdIIcenter, (ii) formation of the monopalladated species, and (iii) coordination of the monopalladated species to another PdIIunit, which finally result in the (iv) formation of the dipalladated product. All of these species have been identified as intermediates in the dipalladation of azobenzenes, evidenced also by UV–vis spectroscopy time-resolved monitoring. The data also confirm that the cyclopalladation of asymmetrically substituted azobenzenes occurs by two concurrent reaction paths. In order to identify the species observed by NMR and by UV–vis spectroscopy, the final products, intermediates, and the PdIIprecursor have been prepared and characterized by X-ray diffraction and IR and NMR spectroscopy. DFT calculations have also been used in order to explain the isomerism observed for the isolated complexes, as well to assign their NMR and IR spectra.

Here we describe real-time, in situmonitoring of mechanochemical solid-state metathesis between silver nitrate and the entire series of sodium halides, on the basis of tandem powder X-ray diffraction and Raman spectroscopy monitoring. The mechanistic monitoring reveals that reactions of AgNO3with NaX (X = Cl, Br, I) differ in reaction paths, with only the reaction with NaBr providing the NaNO3and AgX products directly. The reaction with NaI revealed the presence of a novel, short-lived intermediate phase, while the reaction with NaCl progressed the slowest through the well-defined Ag2ClNO3intermediate double salt. While the corresponding iodide and bromide double salts were not observed as intermediates, all three are readily prepared as pure compounds by milling equimolar mixtures of AgX and AgNO3. The in situobservation of reactive intermediates in these simple metathesis reactions reveals a surprising resemblance of reactions involving purely ionic components to those of molecular organic solids and cocrystals. This study demonstrates the potential of in situreaction monitoring for mechanochemical reactions of ionic compounds as well as completes the application of these techniques to all major compound classes.

The solvent-free ball-milling method for substitution of anionic ligands in organopalladium compounds was developed. Reactions of acetate, acetylacetonate, chloride, or tetrafluoroborate of mono- or dicyclopalladated azobenzenes with alkali salts of chloride, acetate and acetylacetonate yielded target products, some of which could not be obtained via direct C–H bond activation by Pd(II) precursors. The formation of products was monitored in situby Raman spectroscopy and ex situby NMR and IR spectroscopies and PXRD. The reported solid-state pathway provides easy access to organopalladium derivatives in high yields and in shorter reaction times than solvent-based protocols.

Using tandem in situ monitoring and isotope-labeled solids, we reveal that mechanochemical ball-milling overcomes inherently slow solid-state diffusion through continuous comminution and growth of milled particles. This process occurs with or without a net chemical reaction and also occurs between solids and liquid additives that can be practically used for highly efficient deuterium labeling of solids. The presented findings reveal a fundamental aspect of milling reactions and also delineate a methodology that should be considered in the study of mechanochemical reaction mechanisms.

We have applied in situ monitoring of mechanochemical reactions by high-energy synchrotron powder X-ray diffraction to study the role of liquid additives on the mechanochemical synthesis of the archetypal metal–organic framework (MOF) HKUST-1, which was one of the first and is still among the most widely investigated MOF materials to be synthesized by solvent-free procedures. It is shown here how the kinetics and mechanisms of the mechanochemical synthesis of HKUST-1 can be influenced by milling conditions and additives, yielding on occasion two new and previously undetected intermediate phases containing a mononuclear copper core, and that finally rearrange to form the HKUST-1 architecture. On the basis of in situ data, we were able to tune and direct the milling reactions toward the formation of these intermediates, which were isolated and characterized by spectroscopic and structural means and their magnetic properties compared to those of HKUST-1. The results have shown that despite the relatively large breadth of analysis available for such widely investigated materials as HKUST-1, in situ monitoring of milling reactions can help in the detection and isolation of new materials and to establish efficient reaction conditions for the mechanochemical synthesis of porous MOFs.

N–H bond activation of gaseous ammonia is achieved at room temperature in a reversible solvent-free reaction using a solid dicyclopalladated azobenzene complex. Monitoring of the gas–solid reaction in real-time by in situsolid-state Raman spectroscopy enabled a detailed insight into the stepwise activation pathway proceeding to the final amido complex via a stable diammine intermediate. Gas–solid synthesis allowed for isolation and subsequent structural characterization of the intermediate and the final amido product, which presents the first dipalladated complex with the PdII−(μ-NH2)−PdIIbridge. Gas–solid reaction is readily followed via color changes associated with conformational switching of the palladated azobenzene backbone. The reaction proceeds analogously in solution and was characterized by UV–vis and NMR spectroscopies showing the same stepwise route to the amido complex. Combining the experimental data with density functional theory calculations we propose a stepwise mechanism of this heterolytic N–H bond activation assisted by exogenous ammonia.

The crystal structure of copper(ii) citrate monohydrate (C6H4O7Cu2?H2O) has been solved from a mixture powder diffraction pattern. Approach to indexing, structure solution and Rietveld refinement of multiphase diffraction patterns is discussed. Rietveld refinement is carried out employing free-atom refinement and rigid body refinement.

We describe the only currently available protocol for in situ, real-time monitoring of mechanochemical reactions and intermediates by X-ray powder diffraction. Although mechanochemical reactions (inducing transformations by mechanical forces such as grinding and milling) are normally performed in commercially available milling assemblies, such equipment does not permit direct reaction monitoring. We now describe the design and in-house modification of milling equipment that allows the reaction jars of the operating mill to be placed in the path of a high-energy (∼90 keV) synchrotron X-ray beam while the reaction is taking place. Resulting data are analyzed using conventional software, such as TOPAS. Reaction intermediates and products are identified using the Cambridge Structural Database or Inorganic Crystal Structure Database. Reactions are analyzed by fitting the time-resolved diffractograms using structureless Pawley refinement for crystalline phases that are not fully structurally characterized (such as porous frameworks with disordered guests), or the Rietveld method for solids with fully determined crystal structures (metal oxides, coordination polymers).

The Schiff base derived from salicylaldehyde and 2‐amino‐3‐hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol‐imino (D1 aand D1 b) and keto‐amino (D2 aand D2 b) desmotropes. The isolated phases, identified by IR spectroscopy, X‐ray crystallography, and 13C cross‐polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the OH⋅⋅⋅N (D1) or NH⋅⋅⋅O (D2) type. A change in the position of the proton within this O⋅⋅⋅H⋅⋅⋅N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent‐free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form (D1 a) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature‐resolved powder X‐ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.

The crystal structures of two members of the solid solution series Mg(OH)xClyx+y = 2, Mg(OH)1.7Cl0.3(P$\tilde {3}$m1, a= 3.169(2) Å, c= 5.530(12), V= 48.1(1) Å3at T= 365 °C) and MgOHCl (R$\tilde {3}$m, a= 3.3877(4) Å, c= 17.534(4) Å, V= 174.27(6) Å3at T= 625 °C) were determined from in situsynchrotron powder diffraction data at high temperature upon dehydration of 3Mg(OH)2·MgCl2·8H2O (F3) and 5Mg(OH)2·MgCl2·8H2O (F5) phases. The crystal structures of Mg(OH)1.7Cl0.3(example of ss‐type‐OH) and MgOHCl (example of ss‐type‐Cl) can be related to the C19 (CdCl2) and C6 (CdI2) structure type, respectively, with the disordered chloride and hydroxide anions occupying the same crystallographic site in layers.

A report of the facile separation of C2‐C82(3) fullerene is given, which has resulted in the isolation of isomerically pure C82(3) on a preparative scale, avoiding time consuming recycling procedures. By single‐crystal X‐ray analysis of C82(3)·Ni(OEP) (Nickel octaethylporphyrine) the first crystal structure containing pristine C82(3) has been revealed.

Fein gemahlen: Auf mechanochemischem Weg wurden der Pharmaka‐Bestandteil Bismutsubsalicylat sowie Bismutdisalicylat und ‐trisalicylat direkt aus Bismutoxid hergestellt. Durch Röntgenpulverbeugung gelang die erste Strukturaufklärung eines Bismutsalicylats ohne organische Hilfsliganden (siehe Bild: Bi gelb, O rot, C grau; Salicylat‐Ionen in zwei Koordinationsmodi: rosa und grün).

Ground out: Mechanochemical methods gave the pharmaceutical ingredient bismuth subsalicylate, as well as bismuth disalicylate and trisalicylate directly from bismuth oxide. Structure determination by powder X‐ray diffraction gave the first structure of a bismuth salicylate without auxiliary organic ligands (see picture: Bi yellow, O red, C gray, two salicylate ion coordination modes are shown in purple and green).

A simulated annealing like optimization method has been successfully applied for the determination of global minimum of equation of state (EoS) parameters. The approach is tested using the program TOPAS on a high precision variable pressure data set of quartz [R.J. Angel, D.R. Allan, R. Miletich, L.W. Finger: J. Appl. Cryst. Vol 30 (1997) p. 461] It is evidenced that least-squares refinement finds the global minimum for all EoS except for the Birch-Murnaghan EoS of fourth order for which it is shown that a clearly distinguished global minimum does not exist, at least for the used data set. The method presented herein serves as a fast test for the global minimum verification for the EoS parameters but should be applicable also to other optimisation problems.

Molecular motion by refinement of TLS matrices from high resolution laboratory powder diffraction data: implementation in the program TOPAS and application to crystalline naphthalene

No Abstract

Eine Prise Salz: Kleine Salzmengen beschleunigen und steuern den mechanochemischen Aufbau Metall‐organischer Gerüste (MOFs) aus einem Metalloxid (siehe Schema; ILAG= ionen‐ und flüssigkeitsunterstütztes Mahlen). Dieses Raumtemperaturverfahren belegt, dass die Mechanosynthese von Metall‐organischen Verbindungen mit Templaten gesteuert werden kann und dass es durch Mechanochemie möglich ist, ionische Gäste in neutrale MOFs einzuschließen.

The past two decades have witnessed a rapid emergence of interest in mechanochemistry–chemical and materials reactivity achieved or sustained by the action of mechanical force–which has led to application of mechanochemistry to almost all areas of modern chemical and materials synthesis: from organic, inorganic, and organometallic chemistry to enzymatic reactions, formation of metal–organic frameworks, hybrid perovskites, and nanoparticle-based materials. The recent success of mechanochemistry by ball milling has also raised questions about the underlying mechanisms and has led to the realization that the rational development and effective harnessing of mechanochemical reactivity for cleaner and more efficient chemical manufacturing will critically depend on establishing a mechanistic understanding of these reactions. Despite their long history, the development of such a knowledge framework for mechanochemical reactions is still incomplete. This is in part due to the, until recently, unsurmountable challenge of directly observing transformations taking place in a rapidly oscillating or rotating milling vessel, with the sample being under the continuous impact of milling media. A transformative change in mechanistic studies of milling reactions was recently introduced through the first two methodologies for real-time in situmonitoring based on synchrotron powder X-ray diffraction and Raman spectroscopy. Introduced in 2013 and 2014, the two new techniques have inspired a period of tremendous method development, resulting also in new techniques for mechanistic mechanochemical studies that are based on temperature and/or pressure monitoring, extended X-ray fine structure (EXAFS), and, latest, nuclear magnetic resonance (NMR) spectroscopy. The new technologies available for real-time monitoring have now inspired the development of experimental strategies and advanced data analysis approaches for the identification and quantification of short-lived reaction intermediates, the development of new mechanistic models, as well as the emergence of more complex monitoring methodologies based on two or three simultaneous monitoring approaches. The use of these new opportunities has, in less than a decade, enabled the first real-time observations of mechanochemical reaction kinetics and the first studies of how the presence of additives, or other means of modifying the mechanochemical reaction, influence reaction rates and pathways. These studies have revealed multistep reaction mechanisms, enabled the identification of autocatalysis, as well as identified molecules and materials that have previously not been known or have even been considered not possible to synthesize through conventional approaches. Mechanistic studies through in situpowder X-ray diffraction (PXRD) and Raman spectroscopy have highlighted the formation of supramolecular complexes (for example, cocrystals) as critical intermediates in organic and metal–organic synthesis and have also been combined with isotope labeling strategies to provide a deeper insight into mechanochemical reaction mechanisms and atomic and molecular dynamics under milling conditions. This Account provides an overview of this exciting, rapidly evolving field by presenting the development and concepts behind the new methodologies for real-time in situmonitoring of mechanochemical reactions, outlining key advances in mechanistic understanding of mechanochemistry, and presenting selected studies important for pushing forward the boundaries of measurement techniques, data analysis, and mapping of reaction mechanisms.

Colloidal bismuth therapeutics have been used for hundreds of years, yet remain mysterious. Here we report an X-ray pair distribution function (PDF) study of the solvolysis of bismuth disalicylate, a model for the metallodrug bismuth subsalicylate (Pepto-Bismol). This reveals catalysis by traces of water, followed by multistep cluster growth. The ratio of the two major species, {Bi9O7} and {Bi38O44}, depends on exposure to air, time, and the solvent. The solution-phase cluster structures are of significantly higher symmetry in comparison to solid-state analogues, with reduced off-center Bi3+displacements. This explains why such “magic-size” clusters can be both stable enough to crystallize and sufficiently labile for further growth.

The dehydration of 3Mg(OH)2·MgCl2·8H2O and 5Mg(OH)2·MgCl2·8H2O phases and the crystal structures of the products Mg(OH)1.7Cl0.3(I) and MgOHCl (II) are studied by in situ synchrotron poder diffraction data at high temperature.

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