The strecker reaction of benzaldehyde, amines and cyanide: some mechanistic and synthetic studies

The Strecker reaction involves the formation of aminonitriles by the reaction of an aldehyde with an amine in the presence of cyanide ions. In this work kinetic, equilibrium and synthetic measurements have been made using benzaldehyde, or 4-nitrobenzaldehyde, as the aldehyde and benzylamine or allylamine as the amine. A side reaction involves the formation of a cyanohydrin from benzaldehyde and cyanide ion. The equilibria involved m the reaction and their pH dependence have been examined. For comparison values for the equilibrium constants for the reaction of benzaldehyde with sulfite are also reported. The syntheses and structural characterisations of N-benzylidene benzylamine, N-benzylidene allylamine and N-(4-nitro)-benzylidene benzylamine are reported. A major part of the thesis is concerned with the kinetics and equilibria involved in the reaction of N-benzylidene benzylamine and N-benzylidene allylamine with cyanide in aqueous solutions. The results are compatible with the rate-determining step involving reaction of the corresponding iminium ions with cyanide ions. The pH profile is bell-shaped with a plateau between pH = 6.5 and 8.5 defined by the pK(_a) values of the iminium ions and hydrogen cyanide. pK(_a) values of 6.14 ± 0.1 and 6.05 ± 0.1 have been calculated for N- benzylidene benzyliminium and N-benzylidene allyliminium ions respectively. Rate constants for reaction of cyanide ion with these cations are 6.70x10(^3) and 1.03x10(^4) dm(^3)mol(^-1)s(^-1) respectively. The hydrolysis reactions of imines to yield benzaldehyde have also been quantitatively investigated. The relatively low reactivity found for those iminium ions may be attributed to charge delocalisation in the aromatic ring. An important aspect of the Strecker reaction is the possibility of forming enantiomerically pure products. The asymmetric catalysis by Salen metal complexes of the reaction of the imines with trimethylsilyl cyanide in organic solvents has been investigated. Various methods for the determination of the enantiomeric excess were tested and the most reliable was found to be use of camphorsulfonic acid. The reaction carried out in the presence of a Salen V(V) complex was optimised to yield aminonitriles in a 80% e.e. at -30 C and 69% e.e. at room temperature. Trifluoroacetic anhydride (TFFA) has been reported in the literature as a reagent for reaction with aminonitriles to allow the separation of enantiomers. Here the reaction of imines with TFAA in acetonitrile and in benzene has been investigated In each solvent there are strong reactions yielding hifluoroacetylated derivatives which are thought to exist in both ionic and covalentiy-bound forms

Contrôle par microjets impactants d'un jet à Mach 0.9 : influence du nombre de microjets sur le développement des structures tourbillonnaires générées par le contrôle.

Des essais menés en chambre anéchoïque ont permis d'effectuer la détection des structures cohérentes longitudinales induites par un système de microjets impactant un jet subsonique à haut nombre de Mach et haut nombre de Reynolds. Une analyse statistique d'acquisitions par PIV stéréoscopique a été menée en utilisant le critère topologique Gamma2. La localisation de ces structures dans la couche de mélange et leurs propriétés statistiques (nombre, enstrophie) sont examinées pour déterminer l'influence aérodynamique du nombre de microjets. Le nombre de microjets, qui s'est révélé présenter une valeur optimale pour la réduction du bruit, s'avère dans le même temps imposer le développement des structures dans la couche de mélange

Merging the Structural Motifs of Functionalized Amino Acids and α-Aminoamides: Compounds with Significant Anticonvulsant Activities

Functional amino acids (FAAs) and α-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4′-((3″-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED50 values of 13, 14, ~10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases

Etude de la dynamique d'un nuage de bulles généré par ultrasons focalisés de forte intensité

Nous présentons une étude expérimentale sur la dynamique des nuages de bulles générés par ultrasons focalisés de forte intensité. En utilisant des mesures optiques en ombroscopie, on a pu suivre le développement de nuages de cavitation. Les images numériques sont numérisées et analysées. Les résultats mettent en évidence des variations du comportement du nuage de bulles en fonction des paramètres ultrasonores d'excitation. Ces variations apparaissent corrélées à l'efficacité destructrice de la cavitation ultrasonore dans les applications thérapeutiques

Comparative study of the microstructure between a laser beam melted 17-4PH stainless steel and its conventional counterpart

The aim of this work was to compare the microstructures of 17-4PH martensitic stainless steels (MSSs) obtained by conventional manufacturing (CM), and additive manufacturing (AM) using laser beam melting (LBM) process. Both materials were studied after the same H900 heat treatment. Significant differences in microstructure were observed between the two MSSs, with a higher austenite content for the AM-H900 sample, as compared to the CM-H900 sample. Transmission electron microscopy (TEM) analyses allowed to identify both retained and reversed austenite in the AM-H900 sample, but most part of the austenite detected was found to be reversed austenite. The high amount of reversed austenite in the AM-H900 sample was attributed to a heterogeneous distribution in austenite-stabilising elements in the solution heat treated AM sample, leading to a decrease in Ms value and subsequent increase in the driving force for the martensite to austenite transformation during the ageing at 480 °C. Moreover, TEM analyses highlighted thinner martensite laths for the AM-H900 steel as compared to the CM-H900 one. This was interpreted as an increase in both nucleation sites and growth rate for reversed austenite. Despite those differences in microstructure, the AM-H900 and CM-H900 samples showed similar tensile behaviour, with similar UTS and Rp0.2 values, but a decrease in the strain to fracture was observed for the AM-H900 sample, probably related to the pores and/or to intergranular carbides

Synthesis and Anticonvulsant Activities of ( R )- N -(4′-Substituted)benzyl 2-Acetamido-3-methoxypropionamides

The structure-activity relationship (SAR) for the N-benzyl group in the clinical antiepileptic agent (R)-lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-3) has been explored. Forty-three compounds were prepared and then evaluated at the National Institute of Neurological Disorders and Stroke Anticonvulsant Screening Program for seizure protection in the maximal electroshock (MES) and subcutaneous Metrazol models. Comparing activities for two series of substituted aryl regioisomers (2′, 3′, 4′) showed that 4′-modified derivatives had the highest activity. Significantly, structural latitude existed at the 4′-site. The SAR indicated that non-bulky 4′-substituted (R)-3 derivatives exhibited superb activity, independent of their electronic properties. Activities in the MES test of several compounds were either comparable with or exceeded that of (R)-3, and surpassed the activities observed for the traditional antiepileptic agents phenytoin, phenobarbital, and valproate

Geosciences Roadmap for Research Infrastructures 2025 - 2028 by the Swiss Geosciences Community

This roadmap is the product of a grassroots effort by the Swiss Geosciences community. It is the first of its kind, outlining an integrated approach to research facilities for the Swiss Geosciences. It spans the planning period 2025-2028. Swiss Geoscience is by its nature leading or highly in-volved in research on many of the major national and global challenges facing society such as climate change and meteorological extreme events, environmental pol-lution, mass movements (land- and rock-slides), earth-quakes and seismic hazards, global volcanic hazards, and energy and other natural resources. It is essential to under- stand the fundamentals of the whole Earth system to pro-vide scientific guidelines to politicians, stakeholders and society for these pressing issues. Here, we strive to gain efficiency and synergies through an integrative approach to the Earth sciences. The research activities of indivi- dual branches in geosciences were merged under the roof of the 'Integrated Swiss Geosciences'. The goal is to facilitate multidisciplinary synergies and to bundle efforts for large research infrastructural (RI) requirements, which will re-sult in better use of resources by merging sectorial acti- vities under four pillars. These pillars represent the four key RIs to be developed in a synergistic way to improve our understanding of whole-system processes and me- chanisms governing the geospheres and the interactions among their components. At the same time, the roadmap provides for the required transition to an infrastructure adhering to FAIR (findable, accessible, interoperable, and reusable) data principles by 2028.The geosciences as a whole do not primarily profit from a single large-scale research infrastructure investment, but they see their highest scientific potential for ground-break-ing new findings in joining forces in establishing state-of-the-art RI by bringing together diverse expertise for the benefit of the entire geosciences community. Hence, the recommendation of the geoscientific community to policy makers is to establish an integrative RI to support the ne- cessary breadth of geosciences in their endeavor to ad-dress the Earth system across the breadth of both temporal and spatial scales. It is also imperative to include suffi-cient and adequately qualified personnel in all large RIs. This is best achieved by fostering centers of excellence in atmospheric, environmental, surface processes, and deep Earth projects, under the roof of the 'Integrated Swiss Geosciences'. This will provide support to Swiss geo-sciences to maintain their long standing and internatio- nally well-recognized tradition of observation, monitor-ing, modelling and understanding of geosciences process-es in mountainous environments such as the Alps and beyond