A zirconocene triazenido hydride complex activates CO.

Starting from the alkyne complex CpZr(py)(η-MeSiCSiMe) (Cp = η-cyclopentadienyl, py = pyridine), the synthesis and complete characterisation of a zirconocene(IV) triazenido hydride complex and its use in the activation of small molecules is reported. The reaction with CO led to the formation of a zirconocene(IV) triazenido-formate complex, which was further investigated for its stability towards different bases with respect to the formation of formic acid. The experimentally observed reaction pathway was investigated computationally using DFT methods, revealing the favourable role of pyridine coordination in the hydrogen transfer from the triazene to the alkyne unit of the zirconocene reagent.

Stronger Together! Mechanistic Investigation into Synergistic Effects during Homogeneous Carbon Dioxide Hydrogenation Using a Heterobimetallic Catalyst.

A series of group 6 heterobimetallic complexes [M;Ir] (M = Cr, Mo, W) were synthesized and fully characterized, and the catalytic behavior was studied. The heterobimetallic complex [Mo;Ir] () was by far the most active and has shown a considerable synergistic effect, with both metals actively participating in homogeneous carbon dioxide hydrogenation, leading to formate salts. Based on theoretical calculations, the synergistic interaction is due to Pauli repulsion, lowering the transition state and thus enabling higher catalytic activity.

Mechanochemical Oxidative Degradation of Thienopyridine Containing Drugs: Toward a Simple Tool for the Prediction of Drug Stability.

The long-term stability of an active-pharmaceutical ingredient and its drug products plays an important role in the licensing process of new pharmaceuticals and for the application of the drug at the patient. It is, however, difficult to predict degradation profiles at early stages of the development of new drugs, making the entire process very time-consuming and costly. Forced mechanochemical degradation under controlled conditions can be used to realistically model long-term degradation processes naturally occurring in drug products, avoiding the use of solvents, thus excluding irrelevant solution-based degradation pathways.

Effect of atmosphere and relative humidity on photodegradation of clopidogrel under artificial solar and indoor light irradiation.

Knowledge of the chemical stability of active pharmaceutical ingredients (APIs) is an important issue in the drug development process. This work describes a methodical approach and a comprehensive protocol for forced photodegradation studies of solid clopidogrel hydrogen sulfate (Clp) under artificial sunlight and indoor irradiation at different relative humidities (RHs) and atmospheres. The results showed that, at low RHs (up to 21%), this API was relatively resistant to simulated sunlight as well as indoor light.

Deoxygenation of chalcogen oxides EO (E = S, Se) with phospha-Wittig reagents.

In here we present the deoxygenation of the chalcogen oxides EO (E = S, Se) with R-P(PMe), so-called phospha-Wittig reagents. The reaction of DABSO (DABCO·2SO) with R-P(PMe) (R = Mes*, 2,4,6-Bu-CH; Ter, 2,6-(2,4,6-Me-CH)-CH) resulted in the formation of thiadiphosphiranes (RP)S (1:R), while selenadiphosphiranes (RP)Se (2:R) were afforded with SeO, both accompanied by the formation of OPMe. Utilizing the sterically more encumbered Ter-P(PMe) (Ter = 2,6-(2,6-iPr-CH)-CH) a different selectivity was observed and (TerP)Se (2:DipTer) along with [Se(μ-PTer)] (3:DipTer) were isolated as the Se-containing species in the reaction with SeO.

Nickel-catalyzed hydrogenative coupling of nitriles and amines for general amine synthesis.

Efficient and general methods for the synthesis of amines remain in high demand in the chemical industry. Among the many known processes, catalytic hydrogenation is a cost-effective and industrially proven reaction and currently used to produce a wide array of such compounds. We report a homogeneous nickel catalyst for hydrogenative cross coupling of a range of aromatic, heteroaromatic, and aliphatic nitriles with primary and secondary amines or ammonia.

Low-Temperature Isolation of a Labile Silylated Hydrazinium-yl Radical Cation, [(Me Si) N-N(H)SiMe ].

The oxidation of silylated hydrazine, (Me Si) N-N(H)SiMe , with silver salts led to the formation of a highly labile hydrazinium-yl radical cation, [(Me Si) N-N(H)SiMe ] , at very low temperatures (decomposition > -40 °C). EPR, NMR, DFT and Raman studies revealed the formation of a nitrogen-centered radical cation along the N-N unit of the hydrazine. In the presence of the weakly coordinating anion [Al{OCH(CF ) } ] , crystallization and structural characterization in the solid state were achieved.

Unveiling a key catalytic pocket for the ruthenium NHC-catalysed asymmetric heteroarene hydrogenation.

The chiral ruthenium(ii)bis-SINpEt complex is a versatile and powerful catalyst for the hydrogenation of a broad range of heteroarenes. This study aims to provide understanding of the active form of this privileged catalyst as well as the reaction mechanism, and to identify the factors which control enantioselectivity. To this end we used computational methods and NMR spectroscopy to study the hydrogenation of 2-methylbenzofuran promoted by this system.

HCOOH disproportionation to MeOH promoted by molybdenum PNP complexes.

Molybdenum(0) complexes with aliphatic aminophosphine pincer ligands have been prepared which are competent for the disproportionation of formic acid, thus representing the first example so far reported of non-noble metal species to catalytically promote such transformation. In general, formic acid disproportionation allows for an alternative access to methyl formate and methanol from renewable resources. MeOH selectivity up to 30% with a TON of 57 could be achieved while operating at atmospheric pressure.

Ball milling - a new concept for predicting degradation profiles in active pharmaceutical ingredients.

A method for forced oxidative mechanochemical degradation of active pharmaceutical ingredients (APIs) using clopidogrel hydrogensulfate as a model compound is presented. Considerable and selective formation of degradants occurs already after very short reaction times of less than 15 minutes and the nature of the products is strongly dependent on the used oxidant.

Selective Oxidation of Clopidogrel by Peroxymonosulfate (PMS) and Sodium Halide (NaX) System: An NMR Study.

A selective transformation of clopidogrel hydrogen sulfate (CLP) by reactive halogen species (HOX) generated from peroxymonosulfate (PMS) and sodium halide (NaX) is described. Other sustainable oxidants as well as different solvents have also been investigated. As result of this study, for each sodium salt the reaction conditions were optimized, and four different degradation products were formed.

Mechanistic Understanding of the Heterogeneous, Rhodium-Cyclic (Alkyl)(Amino)Carbene-Catalyzed (Fluoro-)Arene Hydrogenation.

Recently, chemoselective methods for the hydrogenation of fluorinated, silylated, and borylated arenes have been developed providing direct access to previously unattainable, valuable products. Herein, a comprehensive study on the employed rhodium-cyclic (alkyl)(amino)carbene (CAAC) catalyst precursor is disclosed. Mechanistic experiments, kinetic studies, and surface-spectroscopic methods revealed supported rhodium(0) nanoparticles (NP) as the active catalytic species.

1-Titanacyclobuta-2,3-diene - an elusive four-membered cyclic allene.

The synthesis of an unusual 1-metalla-2,3-cyclobutadiene complex [-(ebthi)Ti(MeSiCSiMe)] (-ebthi = -1,2-ethylene-1,1'-bis(η-tetrahydroindenyl)), a formal metallacyclic analogue of a non-existent four-membered 1,2-cyclobutadiene, is described. By variation of the cyclopentadienyl ligand of the titanocene precursor it was possible to stabilise this highly exotic compound which selectively reacts with ketones and aldehydes to yield enynes by oxygen transfer to titanium. Analysis of the bonding and electronic structure of the metallacycle shows that the complex is best described as an unusual antiferromagnetically coupled biradicaloid system, possessing a formal Ti(iii) centre coordinated with a monoanionic radical ligand.

Stereoselective Synthesis of Highly Substituted Conjugated Dienes via Pd-Catalyzed Carbonylation of 1,3-Diynes.

The stereoselective synthesis of conjugated dienes was realized for the first time via Pd-catalyzed alkoxycarbonylation of easily available 1,3-diynes. Key to success is the utilization of the specific ligand 1,1'-ferrocenediyl-bis(tert-butyl(pyridin-2-yl)phosphine) (L1), which allows this novel transformation to proceed at room temperature. A range of 1,2,3,4-tetrasubstituted conjugated dienes are obtained in this straightforward access in high yields and selectivities.

Simple ruthenium-catalyzed reductive amination enables the synthesis of a broad range of primary amines.

The production of primary benzylic and aliphatic amines, which represent essential feedstocks and key intermediates for valuable chemicals, life science molecules and materials, is of central importance. Here, we report the synthesis of this class of amines starting from carbonyl compounds and ammonia by Ru-catalyzed reductive amination using H. Key to success for this synthesis is the use of a simple RuCl(PPh) catalyst that empowers the synthesis of >90 various linear and branched benzylic, heterocyclic, and aliphatic amines under industrially viable and scalable conditions.

Diffusion ordered NMR spectroscopy measurements as screening method of potential reactions of API and excipients in drug formulations.

In the development of new pharmaceutical formulations it is important to consider the possible interactions between the active pharmaceutical ingredient (API) and excipients which is a well-known problem. The objective of the work presented here was to investigate such reactions by means of diffusion ordered NMR spectroscopy (DOSY). The known reaction of 5-aminosalicylic acid (5-ASA) and the excipient citric acid was studied.

Visiting the Limits between a Highly Strained 1-Zirconacyclobuta-2,3-diene and Chemically Robust Dizirconacyclooctatetraene.

The reaction of the allene precursor Li (Me SiC SiMe ) with [Cp ZrCl ] (Cp=cyclopentadienyl) was examined. The selective formation of hitherto unknown linear, allene-bridged dizirconocene complexes [(Cp ZrCl) {-μ-(Me Si)C (SiMe )-}] and [(Cp Zr) {-μ-(Me Si)C (SiMe )-} ] was observed. Upon σ coordination of the allenediyl unit to {Cp Zr}, pyrophoric Li (Me SiC SiMe ) is tamed stepwise to yield a surprisingly robust 1,5-dizirconacyclooctatetra-2,3,6,7-ene with cumulated double bonds.

Children's First Experience of Taking Anabolic-Androgenic Steroids can Occur before Their 10th Birthday: A Systematic Review Identifying 9 Factors That Predicted Doping among Young People.

Taking performance-enhancing drugs (PEDs) can cause serious and irreversible health consequences, which can ultimately lead to premature death. Some young people may take PEDs without fully understanding the ramifications of their actions or based on the advice from others. The purpose of this systematic review was to identify the main factors that predicted doping among young people.

Selective Hydrogenation of α,β-Unsaturated Aldehydes and Ketones by Air-Stable Ruthenium NNS Complexes.

The selective hydrogenation of the carbonyl functionality of α,β-unsaturated aldehydes and ketones is catalysed by ruthenium dichloride complexes bearing a tridentate NNS ligand as well as triphenylphosphine. The tridentate ligand backbone is flexible, as evidenced by the equilibrium observed in solution between the cis- and trans-isomers of the dichloride precatalysts, as well as crystal structures of several of these complexes. The complexes are activated by base in the presence of hydrogen and readily hydrogenate carbonyl functionalities under mild conditions.

Low-Temperature Hydrogenation of Carbon Dioxide to Methanol with a Homogeneous Cobalt Catalyst.

Herein we describe the first homogeneous non-noble metal catalyst for the hydrogenation of CO to methanol. The catalyst is formed in situ from [Co(acac) ], Triphos, and HNTf and enables the reaction to be performed at 100 °C without a decrease in activity. Kinetic studies suggest an inner-sphere mechanism, and in situ NMR and MS experiments reveal the formation of the active catalyst through slow removal of the acetylacetonate ligands.

Impact of material and morphological parameters on the mechanical response of the lumbar spine - A finite element sensitivity study.

Finite element models are frequently used to study lumbar spinal biomechanics. Deterministic models are used to reflect a certain configuration, including the means of geometrical and material properties, while probabilistic models account for the inherent variability in the population. Because model parameters are generally uncertain, their predictive power is frequently questioned.

Unravelling the Mechanism of Basic Aqueous Methanol Dehydrogenation Catalyzed by Ru-PNP Pincer Complexes.

Ruthenium PNP complex 1a (RuH(CO)Cl(HN(CHPi-Pr))) represents a state-of-the-art catalyst for low-temperature (<100 °C) aqueous methanol dehydrogenation to H and CO. Herein, we describe an investigation that combines experiment, spectroscopy, and theory to provide a mechanistic rationale for this process. During catalysis, the presence of two anionic resting states was revealed, Ru-dihydride (3) and Ru-monohydride (4) that are deprotonated at nitrogen in the pincer ligand backbone.

Multiple and Highly Selective Alkyne-Isonitrile C-C and C-N Couplings at Group 4 Metallocenes.

Reactions of the group 4 metallocene alkyne complexes [Cp'2 M(η(2) -Me3 SiC2 SiMe3 )] [Cp'2 =rac-(ebthi)=rac-1,2-ethylene-1,1'-bis(η(5) -tetrahydroindenyl): M=Ti, Zr, Hf; Cp'2 =Cp*2 (Cp*=η(5) -pentamethylcyclopentadienyl): M=Zr] with 2,6-dimethylphenyl isocyanide (2-xylyl isonitrile, XyNC) were investigated. Depending on the metal, the Cp' ligand, and/or the stoichiometry, as well as the reaction temperature and time, different products were obtained. The products included simple end-on coordination compounds of XyNC in addition to those of the coupling of Me3 SiC2 SiMe3 with two, three, or four isonitriles to form enimine complexes, aza-metallacycloallenes, and fused heterocyclic systems, respectively.

Selective Catalytic Hydrogenations of Nitriles, Ketones, and Aldehydes by Well-Defined Manganese Pincer Complexes.

Hydrogenations constitute fundamental processes in organic chemistry and allow for atom-efficient and clean functional group transformations. In fact, the selective reduction of nitriles, ketones, and aldehydes with molecular hydrogen permits access to a green synthesis of valuable amines and alcohols. Despite more than a century of developments in homogeneous and heterogeneous catalysis, efforts toward the creation of new useful and broadly applicable catalyst systems are ongoing.