Mechanochemical halogenation of unsymmetrically substituted azobenzenes.

The direct and selective mechanochemical halogenation of C-H bonds in unsymmetrically substituted azobenzenes using N-halosuccinimides as the halogen source under neat grinding or liquid-assisted grinding conditions in a ball mill has been described. Depending on the azobenzene substrate used, halogenation of the C-H bonds occurs in the absence or only in the presence of PdII catalysts. Insight into the reaction dynamics and characterization of the products was achieved by in situ Raman and ex situ NMR spectroscopy and PXRD analysis. A strong influence of the different 4,4'-substituents of azobenzene on the halogenation time and mechanism was found.

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions.

In the search for versatile reagents compatible with mechanochemical techniques, in this work we studied the reactivity of N-fluorobenzenesulfonimide (NFSI) by ball milling. We corroborated that, by mechanochemistry, NFSI can engage in a variety of reactions such as fluorinations, fluorodemethylations, sulfonylations, and amidations. In comparison to the protocols reported in solution, the mechanochemical reactions were accomplished in the absence of solvents, in short reaction times, and in yields comparable to or higher than their solvent-based counterparts.

A Detailed Kinetico-Mechanistic Investigation on the Palladium C-H Bond Activation in Azobenzenes and Their Monopalladated Derivatives.

Palladium C-H bond activation in azobenzenes with R1 and R2 at para positions 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 situ 1H 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 PdII center, (ii) formation of the monopalladated species, and (iii) coordination of the monopalladated species to another PdII unit, 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 PdII precursor 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.

Controlling the Polymorphism and Topology Transformation in Porphyrinic Zirconium Metal-Organic Frameworks via Mechanochemistry.

Tetratopic porphyrin-based metal-organic frameworks (MOFs) represent a particularly interesting subclass of zirconium MOFs due to the occurrence of several divergent topologies. Control over the target topology is a demanding task, and reports often show products containing phase contamination. We demonstrate how mechanochemistry can be exploited for controlling the polymorphism in 12-coordinated porphyrinic zirconium MOFs, obtaining pure hexagonal PCN-223 and cubic MOF-525 phases in 20-60 min of milling. The reactions are mainly governed by the milling additives and the zirconium precursor. In situ monitoring by synchrotron powder X-ray diffraction revealed that specific reaction conditions resulted in the formation of MOF-525 as an intermediate, which rapidly converted to PCN-223 upon milling. Electron spin resonance measurements revealed significant differences between the spectra of paramagnetic centers in two polymorphs, showing a potential of polymorphic Zr-MOFs as tunable supports in spintronics applications.

Protonation and Anion Binding Properties of Aromatic Bis-Urea Derivatives-Comprehending the Proton Transfer.

A series of aromatic bis-urea derivatives was prepared and their proton dissociation, as well as anion binding properties in DMSO were investigated. To this end, UV/Vis and 1 H NMR spectroscopies and computational methods were employed. The synthesized molecules differed in the relative position of the urea moieties (ortho- and meta-derivatives) and in the functional groups (-H, -CH3 , -OCH3 , -NO2 ) in the para-position of the pendant phenyl groups. Remarkably high acidities of the compounds (logK1 H ≈14), were ascribed primarily to the stabilizing effect of the aromatic subunits. Quantum chemical calculations corroborated the conclusions drawn from experimental data and provided information from the structural point of view. Knowledge regarding protonation properties proved to be essential for reliable quantitative determination of anion binding affinities. Studied receptors were selective for acetate and dihydrogen phosphate among several anions. Formation of their complexes of 1:1 and 1:2 (ligand/anion) stoichiometries was quantitatively characterized. Proton transfer was taken into account in the course of data analysis, which was especially important in the case of AcO- . ortho-Receptors were proven to be more efficient acetate binders, achieving coordination with all four NH groups. The meta-analogues preferred dihydrogen phosphate, which acted as both hydrogen bond donor and acceptor. Cooperative binding was detected in the case of 1:2 H2 PO4 - complexes, which was assigned to formation of interanionic hydrogen bonds.

Isotope Labeling Reveals Fast Atomic and Molecular Exchange in Mechanochemical Milling Reactions.

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.

Mechanochemical carbon-carbon bond formation that proceeds via a cocrystal intermediate.

We report the first cocrystal as an intermediate in a solid-state organic reaction wherein molecules of barbituric acid and vanillin assume a favorable orientation for the subsequent Knoevenagel condensation.

Mechanism of Mechanochemical C-H Bond Activation in an Azobenzene Substrate by PdII Catalysts.

Mechanism of C-H bond activation by various PdII catalysts under milling conditions has been studied by in situ Raman spectroscopy. Common PdII precursors, that is PdCl2 , [Pd(OAc)2 ]3 , PdCl2 (MeCN)2 and [Pd(MeCN)4 ][BF4 ]2 , have been employed for the activation of one or two C-H bonds in an unsymmetrical azobenzene substrate. The C-H activation was achieved by all used PdII precursors and their reactivity increases in the order [Pd(OAc)2 ]3

Neutral glycoconjugated amide-based calix[4]arenes: complexation of alkali metal cations in water.

Cation complexation in water presents a unique challenge in calixarene chemistry, mostly due to the fact that a vast majority of calixarene-based cation receptors is not soluble in water or their solubility has been achieved by introducing functionalities capable of (de)protonation. Such an approach inevitably involves the presence of counterions which compete with target cations for the calixarene binding site, and also rather often requires the use of ion-containing buffer solutions in order to control the pH. Herein we devised a new strategy towards the solution of this problem, based on introducing carbohydrate units at the lower or upper rim of calix[4]arenes which comprise efficient cation binding sites. In this context, we prepared neutral, water-soluble receptors with secondary or tertiary amide coordinating groups, and studied their complexation with alkali metal cations in aqueous and methanol (for the comparison purpose) solutions. Complexation thermodynamics was quantitatively characterized by UV spectrometry and isothermal titration calorimetry, revealing that one of the prepared tertiary amide derivatives is capable of remarkably efficient (log K ≈ 5) and selective binding of sodium cations among alkali metal cations in water. Given the ease of the synthetic procedure used, and thus the variety of accessible analogues, this study can serve as a platform for the development of reagents for diverse purposes in aqueous media.

Dehydroacetic Acid Derivatives Bearing Amide or Urea Moieties as Effective Anion Receptors.

Derivatives of dehydroacetic acid comprising amide or urea subunits have been synthesized and their anion-binding properties investigated. Among a series of halides and oxyanions, the studied compounds selectively bind acetate and dihydrogen phosphate in acetonitrile and dimethyl sulfoxide. The corresponding complexation processes were characterized by means of 1 H NMR titrations, which revealed a 1:1 complex stoichiometry in most cases, with the exception of dihydrogen phosphate, which formed 2:1 (anion/ligand) complexes in acetonitrile. The complex stability constants were determined and are discussed with respect to the structural properties of the receptors, the hydrogen-bond-forming potential of the anions, and the characteristics of the solvents used. Based on the spectroscopic data and results of Monte Carlo simulations, the amide or urea groups were affirmed as the primary binding sites in all cases. The results of the computational methods indicate that an array of both inter- and intramolecular hydrogen bonds can form in the studied systems, and these were shown to play an important role in defining the overall stability of the complexes. Solubility measurements were carried out in both solvents and the thermodynamics of transfer from acetonitrile to dimethyl sulfoxide were characterized on a quantitative level. This has afforded a detailed insight into the impact of the medium on the complexation reactions.