Structures of Highly Twisted Amides Relevant to Amide N−C Cross‐Coupling: Evidence for Ground‐State Amide Destabilization

Herein, we show that acyclic amides that have recently enabled a series of elusive transition‐metal‐catalyzed N?C activation/cross‐coupling reactions are highly twisted around the N?C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N‐glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α‐carbon atom. The ¹⁵N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground‐state twist as a blueprint for activation of amides toward N?C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non‐planar amide bonds.     

The Forgotten Pyrazines: Exploring the Dakin–West Reaction

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin–West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α-acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal–organic frameworks.     

Electrophilicity Scale of Activated Amides: 17O NMR and 15N NMR Chemical Shifts of Acyclic Twisted Amides in N−C(O) Cross-Coupling

The structure and properties of amides are of tremendous interest in organic synthesis and biochemistry. Traditional amides are planar and the carbonyl group non-electrophilic due to n_N→π*_C=O conjugation. In this study, we report electrophilicity scale by exploiting ¹⁷O NMR and ¹⁵N NMR chemical shifts of acyclic twisted and destabilized acyclic amides that have recently received major attention as precursors in N-C(O) cross-coupling by selective oxidative addition as well as precursors in electrophilic activation of N-C(O) bonds. Most crucially, we demonstrate that acyclic twisted amides feature electrophilicity of the carbonyl group that ranges between that of acid anhydrides and acid chlorides. Furthermore, a wide range of electrophilic amides is possible with gradually varying carbonyl electrophilicity by steric and electronic tuning of amide bond properties. Overall, the study quantifies for the first time that steric and electronic destabilization of the amide bond in common acyclic amides renders the amide bond as electrophilic as acid anhydrides and chlorides. These findings should have major implications on the fundamental properties of amide bonds.     

A comparison between parallelization approaches in molecular dynamics simulations on GPUs

We test the relative performances of two different approaches to the computation of forces for molecular dynamics simulations on graphics processing units. A “vertex‐based” approach, where a computing thread is started per particle, is compared to an “edge‐based” approach, where a thread is started per each potentially non‐zero interaction. We find that the former is more efficient for systems with many simple interactions per particle while the latter is more efficient if the system has more complicated interactions or fewer of them. By comparing computation times on more and less recent graphics processing unit technology, we predict that, if the current trend of increasing the number of processing cores—as opposed to their computing power—remains, the “edge‐based” approach will gradually become the most efficient choice in an increasing number of cases. © 2014 Wiley Periodicals, Inc.     

Probenecid and benzamide: DSC applied to the study of an “impossible” pharmaceutical system

Journal of Thermal Analysis and Calorimetry - The study of the binary system probenecid–benzamide is an excellent example of the power and the limits of thermal analysis applied to the...     

The Physico-Chemical Properties of Glipizide: New Findings

The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.     

Numerical Analysis of Structural Systems Subjected to Non-Gaussian Random Fields

This paper deals with the stochastic response of structures loaded by non-Gaussian random fields. A finite element model is used to describe a cantilever beam assuming both linear and non-linear behavior. The cross-correlated stochastic field is generated by a numerical procedure based on the translation processes theory. The marginal distribution of the load is assumed to be lognormal and the correlation structure is based on the second-order Markov process. The statistical analysis of the results highlights the effects of the involved non-linearity and non-Gaussianity properties on the structures response.     

The effect of boundary conditions by the side of the nozzle of a low Reynolds number jet

The near flow field of an axially symmetric water jet at Reynolds numbers from about 1,000 to 10,000 is investigated using laser-induced fluorescence (LIF), laser Doppler anemometry and particle tracking velocimetry. Spanwise and streamwise vortices are detected on the longitudinal plane and on cross-sections. Attention is focused onto the effects of rigid or free boundaries sideways to the nozzle outlet (no-slip or free-slip conditions), and particularly on the start up, growth and interaction of large vortical structures. On average, for the free-slip jet these structures develop more gradually and closer to the nozzle than for the no-slip jet; the local mixedness (derived from LIF measurements) is also higher for the free-slip case. Moreover, the measured velocity field decreases more slowly, with a longer potential core and a higher shear layer (momentum) thickness for the free-slip rather than for the no-slip conditions. The relation between spanwise and streamwise large-scale vortices is clarified by the observation that the ejection of fluid in cross-sections through streamwise vortices is coupled to the pairing of spanwise vortices on the longitudinal section.     

Permanent Waves in Slow Free-Surface Flow of a Herschel–Bulkley fluid

Unsteady flow of a viscoplastic fluid on an inclined plane is examined. The fluid is described by the three-parameter Herschel–Bulkley constitutive equation. The set of equations governing the flow is presented, recovering earlier results for a Bingham fluid and steady uniform motion. A permanent wave solution is then derived, and the relation between wave speed and flow depth is discussed. It is shown that more types of gravity currents are possible than in a Newtonian fluid; these include some cases of flows propagating up a slope. The speed of permanent waves is derived and the possible surface profiles are illustrated as functions of the flow behavior index.     

An exact solution for one-dimensional unsteady nonlinear groundwater flow

After a brief review of the validity of Darcy's law, a nonlinear flow law is adopted for the analytical solution of a groundwater flow problem. A one-dimensional unsteady flow in plane geometry, with prescribed head at the boundaries, is studies. The solution of the analogous linear case is reviewed through the use of Boltzmann's transformation. A solution for nonlinear flow is obtained through a generalization of this transformation. Detailed expressions for specific discharge and drawdown are derived for two significant values of the exponent of the flow law. All results are presented in dimensionless form for a comparative analysis. Some significant cases are plotted. Finally, some implications of the adoption of a nonlinear flow law are discussed.

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Sommario Dopo un breve riepilogo sui limiti di validità della legge di Darcy, si adotta una formulazione non lineare della legge del moto per la risoluzione analitica di un problema di filtrazione. Si studia un moto non stazionario monodimensionale in geometria piana, con carico assegnato al contorno. Viene richiamata la soluzione dell'analogo caso lineare, tramite l'applicazione della trasformata di Boltzmann. Una soluzione per il moto non lineare è ottenuta mediante la generalizzazione di tale trasformazione. Si ricavano le espressioni della velocità apparente di filtrazione e del drawdown per due valori significativi dell'esponente della legge del moto. Tutti i risultati sono presentati in forma adimensionale per una analisi comparativa. Alcuni casi significativi sono diagrammati. In conclusione, sono discusse alcune implicazioni dell'adozione di una legge del moto non lineare.