The potential of hydroaminomethylation : directing the cascade

Amino compounds are important building blocks or end products in a broad range of durable and consumer goods in everyday life such as polymers, airbags, textiles, insecticides, and pharmaceuticals. Classical syntheses of amines often lead to large amounts of waste, mainly inorganic salts. One of the most promising new reactions for the production of amines in terms of atom-efficiency, activity, selectivity, and applicability is the hydroaminomethylation of alkenes in which water is the only side product. Especially the possibility to synthesise primary amines atom-efficiently from cheap alkene feedstocks and ammonia by hydroaminomethylation makes this an interesting reaction from an industrial point of view. Although the hydroaminomethylation has been discovered already in 1949 by Reppe at BASF, most research with respect to this reaction has been performed during the last 15 years. In Chapter 1, the most relevant and interesting literature with respect to the hydroaminomethylation reaction, is reviewed. Chapter 2 deals with catalyst recycling in a biphasic ionic liquid system. Hydroaminomethylation reactions were performed successfully in an imidazolium-based ionic liquid using a rhodium/Sulfoxantphos system by reacting piperidine with different n-alkenes, affording yields higher than 95% of the resulting amine with turnover frequencies of up to 8400 h-1, along with high regioselectivity for the linear amines with l/b ratios up to 78. Additionally, facile quantitative catalyst recovery was accomplished and recycling of the catalyst and product separation were achieved by a fast phase separation after the reaction. The product distribution was monitored in time at different temperatures both in an organic solvent and in the ionic liquid in order to investigate and compare the course of the formation of (side) products and intermediates in these reactions. Furthermore, it was shown that the nature of the Rh-precatalyst has a profound effect on the activity and selectivity. Protic organic solvents and ionic liquids containing a C-H acidic bond in the imidazolium part have a beneficial effect on the hydrogenation activity of the catalyst systems. Chapter 3 is dedicated to the very fast and selective hydroaminomethylation with a novel class of ligands. In order to increase the activity and to maintain a good selectivity in the hydroaminomethylation reaction in comparison to Rh/phosphine-catalysed systems, a new p-acidic ligand, the bis-[(dipyrrolyl)phosphino]xanthene, was synthesised. In combination with rhodium, this ligand leads to outstanding activities and selectivities with turnover frequencies of 6200 h-1 and very high l/b ratios exceeding 200. Furthermore, it was shown that the pKa value of the alcohol used in the solvent mixture has a profound effect on the performance of the catalytic systems. Acidic media enhance the activity, while less acidic media increase the regio- and chemoselectivity, as well as the degree of double bond isomerisation. Chapter 4 describes the Rh-catalysed hydroaminomethylation of internal alkenes towards linear amines is described using amino-functionalised ligands. Bulky and rigid substituents were introduced and the ligand backbone was functionalised with a (bisindolyl) phosphine moiety in order to increase the regioselectivity in this process. However, bis-[(dipyrrolyl)phosphino]xanthene, introduced in Chapter 3, again turned out to be the best performing ligand in combination with rhodium. Although the reaction is slower than in case of n-alkenes, catalyst activities are still reasonably high. The influence of catalyst preformation, reaction temperature, solvent mixture, and syngas ratio are described. Furthermore, the effect of adding a monodentate phosphorus ligand (phosphines or phosphites) to the reaction mixture was investigated. Interestingly, the regioselectivity could be increased considerably by addition of triphenylphosphine to the catalyst mixture, which can be explained by changing the isomerisation rate related to ß-hydrogen elimination in this particular way. Chapter 5 involves the coordination chemistry of the novel xanthene-based aminofunctionalised ligands, which were discussed in Chapters 3 and 4, to rhodium and platinum. In combination with rhodium, these compounds display interesting catalytic results in the hydroaminomethylation reaction. In order to clarify their structure/performance relationship, the coordination behaviour was investigated. The structural properties of the ligands were studied by NMR spectroscopy of the corresponding rhodium and platinum complexes, while the electronic properties were examined by studying the IR frequencies of the CO stretch vibrations in the particular rhodium-carbonyl complexes. For two ligands, the corresponding selenides were synthesised. The NMR coupling constant JSe-P can be used as a measure for the s-donor ability of a ligand. Furthermore, the coordination behaviour of the ligands was investigated by high pressure NMR and IR spectroscopic measurements under actual hydroformylation reaction conditions. The ligands have been compared to the diphosphine ligand Xantphos, which performs very well in regioselective hydroformylations. An X-ray crystal structure was determined for a rhodium complex with Xantphos. Although the hydroaminomethylation reaction is a promising and atom-efficient alternative for the classical production process towards amines, this reaction has not been applied on a large scale in industry to date. On the other hand, in recent (patent) literature, more and more publications concerning this interesting reaction can be found. The near absence of hydroaminomethylation in industry might be explained by the fact that most publications mention rhodium, which is a very expensive metal. Moreover, no chemo- and regioselective synthesis of linear primary amines via hydroaminomethylation with NH3 has been reported up to now. Most probably, this reaction will first be applied in fine chemical or pharmaceutical industry, since smaller product volumes and higher added value are common practice in these industries. For bulk chemical application, this reaction needs further optimisation for which intensive and challenging research is necessary. Chapter 6 deals with these possibilities and the future of hydroaminomethylation. Hydroaminomethylation with protected amines and the opportunities of primary amine protection by using ammonium carbamate as a combined substrate/dynamic protection group has been presented

The rate of WD-WD head-on collisions in isolated triples is too low to explain standard type Ia supernovae

Type Ia supernovae (Ia-SNe) are thought to arise from the thermonuclear explosions of white dwarfs (WDs). The progenitors of such explosions are still highly debated; in particular the conditions leading to detonations in WDs are not well understood in most of the suggested progenitor models. Nevertheless, direct head-on collisions of two WDs were shown to give rise to detonations and produce Ia-SNe - like explosions, and were suggested as possible progenitors. The rates of such collisions in dense globular clusters are far below the observed rates of type Ia SNe, but it was suggested that quasi-secular evolution of hierarchical triples could produce a high rate of such collisions. Here we used detailed triple stellar evolution populations synthesis models coupled with dynamical secular evolution to calculate the rates of WD-WD collisions in triples and their properties. We explored a range of models with different realistic initial conditions and derived the expected SNe total mass, mass-ratio and delay time distributions for each of the models. We find that the SNe rate from WD-WD collisions is of the order of 0.1% of the observed Ia-SNe rate across all our models, and the delay-time distribution is almost uniform in time, and is inconsistent with observations. We conclude that SNe from WD-WD collisions in isolated triples can at most provide for a small fraction of Ia-SNe, and can not serve as the main progenitors of such explosions.Comment: 13 pages, 4 figures, submitted to A&

A triple origin for the lack of tight coplanar circumbinary planets around short-period binaries

Transiting circumbinary planets are more easily detected around short-period than long-period binaries, but none have yet been observed by {\it Kepler} orbiting binaries with periods shorter than seven days. In triple systems, secular Kozai-Lidov cycles and tidal friction (KLCTF) have been shown to reduce the inner orbital period from $\sim 10^4$ to a few days. Indeed, the majority of short-period binaries are observed to possess a third stellar companion. Using secular evolution analysis and population synthesis, we show that KLCTF makes it unlikely for circumbinary transiting planets to exist around short-period binaries. We find the following outcomes. (1) Sufficiently massive planets in tight and/or coplanar orbits around the inner binary can quench the KL evolution because they induce precession in the inner binary. The KLCTF process does not take place, preventing the formation of a short-period binary. (2) Secular evolution is not quenched and it drives the planetary orbit into a high eccentricity, giving rise to an unstable configuration, in which the planet is most likely ejected from the system. (3) Secular evolution is not quenched but the planet survives the KLCTF evolution. Its orbit is likely to be much wider than the currently observed inner binary orbit, and is likely to be eccentric and inclined with respect to the inner binary. These outcomes lead to two main conclusions: (1) it is unlikely to find a massive planet on a tight and coplanar orbit around a short-period binary, and (2) the properties of circumbinary planets in short-period binaries are constrained by secular evolution.Comment: Revised to match MNRAS publication. 24 pages, 22 figure

Quantitative Validation: An Overview and Framework for PD Backtesting and Benchmarking.

The aim of credit risk models is to identify and quantify future outcomes of a set of risk measurements. In other words, the model's purpose is to provide as good an approximation as possible of what constitutes the true underlying risk relationship between a set of inputs and a target variable. These parameters are used for regulatory capital calculations to determine the capital needed that serves a buffer to protect depositors in adverse economic conditions. In order to manage model risk, financial institutions need to set up validation processes so as to monitor the quality of the models on an ongoing basis. Validation is important to inform all stakeholders (e.g. board of directors, senior management, regulators, investors, borrowers, …) and as such allow them to make better decisions. Validation can be considered from both a quantitative and qualitative point of view. Backtesting and benchmarking are key quantitative validation tools. In backtesting, the predicted risk measurements (PD, LGD, CCF) will be contrasted with observed measurements using a workbench of available test statistics to evaluate the calibration, discrimination and stability of the model. A timely detection of reduced performance is crucial since it directly impacts profitability and risk management strategies. The aim of benchmarking is to compare internal risk measurements with external risk measurements so to allow to better gauge the quality of the internal rating system. This paper will focus on the quantitative PD validation process within a Basel II context. We will set forth a traffic light indicator approach that employs all relevant statistical tests to quantitatively validate the used PD model, and document this complete approach with a reallife case-study.Framework; Benchmarking; Credit; Credit scoring; Control;

Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47

Recent studies suggest that exposure to endocrine-disrupting compounds (EDCs) may play a role in the development of obesity. EDCs such as the flame retardant 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) have been shown to enhance adipocyte differentiation in the murine 3T3-L1 model. The mechanisms by which EDCs direct preadipocytes to form adipocytes are poorly understood. Here, we examined transcriptional and epigenetic mechanisms underlying the induction of in vitro adipocyte differentiation by BDE-47. Quantitative high content microscopy revealed concentration-dependent enhanced adipocyte differentiation following exposure to BDE-47 or the antidiabetic drug troglitazone (TROG). BDE-47 modestly activated the key adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) in COS7 cells, transiently transfected with a GAL4 reporter construct. Increased gene expression was observed for Pparγ2, leptin (Lep), and glucose-6-phophatase catalytic subunit (G6pc) in differentiated 3T3-L1 cells after BDE-47 exposure compared to TROG. Methylation-sensitive high resolution melting (MS-HRM) revealed significant demethylation of three CpG sites in the Pparγ2 promoter after exposure to both BDE-47 and TROG in differentiated 3T3-L1 cells. This study shows the potential of BDE-47 to induce adipocyte differentiation through various mechanisms that include Pparγ2 gene induction and promoter demethylation accompanied by activation of PPARγ, and possible disruption of glucose homeostasis and IGF1 signaling

Toward a Partnership in the Transition from Home to a Nursing Home: The TRANSCIT Model

The transition from home to a nursing home can be stressful and traumatic for both older persons and informal caregivers and is often associated with negative outcomes. Additionally, transitional care interventions often lack a comprehensive approach, possibly leading to fragmented care. To avoid this fragmentation and to optimize transitional care, a comprehensive and theory-based model is fundamental. It should include the needs of both older persons and informal caregivers. Therefore, this study, conducted within the European TRANS-SENIOR research consortium, proposes a model to optimize the transition from home to a nursing home, based on the experiences of older persons and informal caregivers. These experiences were captured by conducting a literature review with relevant literature retrieved from the databases CINAHL and PubMed. Studies were included if older persons and/or informal caregivers identified the experiences, needs, barriers, or facilitators during the transition from home to a nursing home. Subsequently, the data extracted from the included studies were mapped to the different stages of transition (pre-transition, mid-transition, and post-transition), creating the TRANSCITmodel. Finally, results were discussed with an expert panel, leading to a final proposed TRANSCIT model. The TRANSCIT model identified that older people and informal caregivers expressed an overall need for partnership during the transition from home to a nursing home. Moreover, it identified 4 key components throughout the transition trajectory (ie, pre-, mid-, and post-transition): (1) support, (2) communication, (3) information, and (4) time. The TRANSCIT model could advise policy makers, practitioners, and researchers on the development and evaluation of (future) transitional care interventions. It can be a guideline reckoning the needs of older people and their informal caregivers, emphasizing the need for a partnership, consequently reducing fragmentation in transitional care and optimizing the transition from home to a nursing home