Transformations of N-heteroarylformamidines and N-heteroarylformamidine oximes new syntheses and transformations of oxazolo[5,4—c]pyridazines

New approaches to the synthesis of oxazolo[5,4—c]pyridazine derivatives7 and15 starting from the substituted N-pyridazin-5-ylformamide oximes5 and13 are described. Under mild conditions the transformations of the amino or substituted amino group at position 2 of the oxazolo[5,4—c]pyridazine system were observed to give the compounds16 and17, while under more drastic reaction conditions the nucleophilic attack at position 2 followed by the ring opening of the oxazole part of the molecule was taking place to give the compounds18, 20, and21.

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Transformationen von N-Heteroarylformamidinen und N-Heteroarylformamidinoximen. Neue Synthesen und Transformationen von Oxazolo[5,4—c]pyridazinen

Zusammenfassung Neue Synthesemöglichkeiten von Oxazolo[5,4—c]pyridazinen7 und15, ausgehend von substitutierten N-Pyridazin-5-ylformamid-oximen5 und13 werden beschrieben. Unter milden Reaktionsbedingungen trat Transformation der Amino- oder substituierten Aminogruppe an der Position 2 des Oxazolo[5,4—c]pyridazin-Systems unter Bildung der Verbindungen16 und17 ein, währenddessen unter drastischeren Reaktionsbedingungen ein nucleophiler Angriff am Kohlenstoff der Position 2, gefolgt von einer Ringöffnung des Oxazol-Teils des Moleküls zu Verbindungen18, 20 und21 führte.

     

Synthesis and Characterization of m‐Terphenyl (1,3‐Diphenylbenzene) Compounds Containing Trifluoromethyl Groups

The bis(silyl)triazene compound 2,6‐(Me₃Si)₂‐4‐Me‐1‐(N?N? NC₄H₈)C₆H₂ ( 4 ) was synthesized by double lithiation/silylation of 2,6‐Br₂‐4‐Me‐1‐(N?N? NC₄H₈)C₆H₂ ( 1 ). Furthermore, 2,6‐bis[3,5‐(CF₃)₂‐C₆H₃]‐4‐Me‐C₆H₂‐1‐(N?N? NC₄H₈)C₆H₂ derivative 6 can be easily synthesized by a C,C‐bond formation reaction of 1 with the corresponding aryl‐Grignard reagent, i.e., 3,5‐bis[(trifluoromethyl)phenyl]magnesium bromide. Reactions of compound 4 with KI and 6 with I₂ afforded in good yields novel phenyl derivatives, 2,6‐(Me₃Si)₂‐4‐MeC₆H₂? I and 2,6‐bis[3,5‐(CF₃)₂? C₆H₃]‐4‐MeC₆H₂? I ( 5 and 7 , resp.). On the other hand, the analogous m‐terphenyl 1,3‐diphenylbenzene compound 2,6‐bis[3,5‐(CF₃)₂? C₆H₃]C₆H₃? I ( 8 ) could be obtained in moderate yield from the reaction of (2,6‐dichlorophenyl)lithium and 2 equiv. of aryl‐Grignard reagent, followed by the reaction with I₂. Different attempts to introduce the ^tBu (Me₃C) or neophyl (PhC(Me)₂CH₂) substituents in the central ring were unsuccessful. All the compounds were fully characterized by elemental analysis, melting point, IR and NMR spectroscopy. The structure of compound 6 was corroborated by single‐crystal X‐ray diffraction measurements.     

Kinetic modeling of the thermal degradation of polyethylene and polystyrene mixtures

One possible process for recovering valuable chemical and petrochemical products from plastic waste is the stepwise thermal degradation of polymer mixtures. This potentially allows the step by step simultaneous separation of the different product fractions generated by the polymers of the blend. The aim of this paper is to investigate the effect of the mixing scale of the polymers and their interactions in the melt. Several thermogravimetric analyses were performed on small samples of polyethylene (PE) and polystyrene (PS) mixtures. Two types of operating conditions were adopted: the first one is a dynamic analysis with a linear increase of the temperature over time, the latter consists of two sequential isothermal steps. The experimental results confirm that if the mixing scale is poor, the decomposition of each polymer behaves independently of the presence of the other one. Conversely, when the mixing of the two polymers reaches the molecular scale, a co-pyrolysis takes place with partial interactions. A two phase system is assumed: one phase characterized by a larger PS fraction, the other one by a prevailing PE amount. In order to properly predict the kinetic interactions typical of the mixed phases, it was necessary to extend the detailed kinetic model already developed and validated for the single polymers. The resulting two phase model gives a satisfactory explanation of several experimental data from the thermal degradation of PE–PS mixtures.     

Computation of local radius of information in SM-IBC identification of nonlinear systems

System identification consists in finding a model of an unknown system starting from a finite set of noise-corrupted data. A fundamental problem in this context is to asses the accuracy of the identified model. In this paper, the problem is investigated for the case of nonlinear systems within the Set Membership—Information Based Complexity framework of [M. Milanese, C. Novara, Set membership identification of nonlinear systems, Automatica 40(6) (2004) 957–975]. In that paper, a (locally) optimal algorithm has been derived, giving (locally) optimal models in nonlinear regression form. The corresponding (local) radius of information, providing the worst-case identification error, can be consequently used to measure the quality of the identified model. In the present paper, two algorithms are proposed for the computation of the local radius of information: The first provides the exact value but requires a computational complexity exponential in the dimension of the regressor space. The second is approximate but involves a polynomial (quadratic) complexity.     

Extension of Hilbert's inequality

In this paper we make some further extensions of discrete Hilbert's inequality by using Euler-Maclaurin summation formula. We give the improvements of some previously obtained results and also compare our results with some previously known from the literature.     

Transitive Permutation Groups with Cyclic Point Stabilizers of Maximum Order

We prove that a transitive permutation group of degree n with a cyclic point stabilizer and whose order is n(n-1) is isomorphic to the affine group of degree 1 over a field with n elements. More generally we show that if a finite group G has an abelian and core-free Hall subgroup Q, then either Q has a small order (2|Q|² < |G|) or G is a direct product of 2-transitive Frobenius groups.     

Development and Validation of a Densitometric HPTLC Method for Quantitative Analysis of Levofloxacin in Human Plasma

JPC – Journal of Planar Chromatography – Modern TLC -     

Electron ionization mass spectrometry of the ryanodine receptor‐based Ca2+‐channel stabilizer S‐107 and its implementation into routine doping control

New insights into the biochemistry of cardiac arrhythmia and skeletal muscle fatigue have yielded new drug candidates to counteract these phenomena. Major biological targets have become ryanodine receptor (RyR)‐based Ca²⁺‐release channels, which tend to ‘leak’ under various circumstances including strenuous exercise and, thus, cause aberrant calcium sparks that entail impaired muscle function. Therapeutics, which are referred to as rycals, are currently being developed to treat cardiac arrhythmia via enhancement of calstabin‐ryanodine affinities that causes a stabilization of the RyR. These therapeutics possess potential for misuse in sports, and an early implementation of target analytes such as the benzothiazepine derivatives S‐107 and JTV‐519 or putative metabolites into doping control screening procedures is recommended. Reference compounds, deuterated analogues, and a putative metabolic product were synthesized, and electron ionization mass spectra of these products were studied and dissociation pathways elucidated by means of tandem mass spectrometry (MS/MS) and accurate mass measurements. The characterized analytes were incorporated into existing sports drug testing assays based on liquid‐liquid extraction and subsequent gas chromatography/mass spectrometry (GC/MS) analysis, and specificity, lower limit of detection (4–6 ng/mL), intraday and interday precision (1.5–17.2%), as well as recovery (63–66%) were determined. The established procedure proved suitable for routine doping control analysis to detect a potential misuse of the drug candidate S‐107 in elite sport. Copyright © 2009 John Wiley & Sons, Ltd.