Divergent Synthesis of Monosubstituted and Unsymmetrical 3,6‐Disubstituted Tetrazines from Carboxylic Ester Precursors

Since tetrazines are important tools to the field of bioorthogonal chemistry, there is a need for new approaches to synthesize unsymmetrical and 3‐monosubstituted tetrazines. Described here is a general, one‐pot method for converting (3‐methyloxetan‐3‐yl)methyl carboxylic esters into 3‐thiomethyltetrazines. These versatile intermediates were applied to the synthesis of unsymmetrical tetrazines through Pd‐catalyzed cross‐coupling and in the first catalytic thioether reduction to access monosubstituted tetrazines. This method enables the development of new tetrazine compounds possessing a favorable combination of kinetics, small size, and hydrophilicity. It was applied to a broad range of aliphatic and aromatic ester precursors and to the synthesis of heterocycles including BODIPY fluorophores and biotin. In addition, a series of tetrazine probes for monoacylglycerol lipase (MAGL) were synthesized and the most reactive one was applied to the labeling of endogenous MAGL in live cells.     

Massenspektren von 11-Hydroxypregnan-3.20-dionen und 3-Hydroxypregnan-11.20-dionen Zur Lokalisierung funktioneller Gruppen in Steroiden mit Hilfe der Massenspektrometrie, 6. Mitt.

Zusammenfassung 11-Hydroxypregnan-3.20-dione zeigen in ihren Massen-spektren vorzugsweise typische Spaltstücke für Abbaureaktionen desD-Ringsystems. Nur bei Gegenwart einer -konfigurierten Hydroxylgruppe in Stellung 11 und gleichzeitigercis-Verknüpfung desA/B-Ringsystems entsteht ein weiteres Schlüsselbruchstück, das die C-Atome desA-Ringes umfaßt.Im Gegensatz dazu übt die Carbonylgruppe in Stellung 11 der 3-Hydroxypregnan-11.20-dione entscheidenden Einfluß auf die Bruchstückbildung aus. Schlüsselbruchstücke der Masse 206 und 219 erlauben eine eindeutige Festlegung der Stellung der Substituenten. Überdies ist wegen der unterschiedlichen Neigung zur Bruchstückbildung die Konfigurationsbestimmung des Wasserstoffatoms in Stellung 5 möglich. Eine 3-Hydroxygruppe in einem 5-konfigurierten 11-Ketosteroid ist an einem ausgeprägtenM-72-Fragment zu erkennen.

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Mass spectra of 11-hydroxypregnane-3.20-diones and 3-hydroxypregnane-11.20-diones

Mass spectra of 11-hydroxypregnane-3.20-diones show typical fragments for degradation reactions of theD-ring. An additional key fragment is only produced, if the hydroxy group in position 11 has -configuration and if theA/B ring system showscis-junction.In contrast a carbonyl-group in position 11 exerts dominant influence on the fragmentation. Key fragments of mass 206 and 219 allow an unequivocal determination of the position of substituents. Different tendency for fragmentation reactions in isomeres with different junction of theA/B ring system allows the determination of the configuration of the hydrogen in position 5. A -hydroxygroup in position 3 of an 11-ketosteroid with 5-configuration is recognized by intense ions atM-72.

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Mit 8 Abbildungen

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Herrn Prof. Dr.M. Pailer zum 60. Geburtstag gewidmet.

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5. Mitt.:H. Obermann, M. Spiteller-Friedmann undG. Spiteller, Tetrahedron, im Druck.     

Driven torsion pendulum for measuring the complex shear modulus in a steady shear flow

To investigate the viscoelastic behavior of fluid dispersions under steady shear flow conditions, an apparatus for parallel superimposed oscillations has been constructed which consists of a rotating cup containing the liquid under investigation in which a torsional pendulum is immersed. By measuring the resonance frequency and bandwidth of the resonator in both liquid and in air, the frequency and steady-shear-rate-dependent complex shear modulus can be obtained. By exchange of the resonator lumps it is possible to use the instrument at four different frequencies: 85, 284, 740, and 2440 Hz while the steady shear rate can be varied from 1 to 55 s^–1. After treatment of the theoretical background, design, and measuring procedure, the calibration with a number of Newtonian liquids is described and the accuracy of the instrument is discussed.Notation a radius of the lump - A geometrical constant - b inner radius of the sample holder - c constant - C ₁, C ₂ apparatus constants - D damping of the pendulum - e _x , e _y , e _z Cartesian basis - e _r , e , e _z orthonormal cylindrical basis - E geometrical constant - E _t , ⁰ E _t , _t relative strain tensor - f function of shear rate - F _t relative deformation tensor - G (t) memory function - G ^* complex shear modulus - G Re(G ^* ) - G Im(G ^* ) - h distance between plates - H ^* transfer function - , functional - i imaginary unit: i ²= – 1 - I moment of inertia - J _exc excitation current - J ₀ amplitude of J _exc - k ^* = k – ik complex wave number - K torsional constant - K fourth order tensor - l length of the lump - L mutual inductance - M _dr driving torque - M _liq torque exerted by the liquid - ⁰ M _liq, _liq steady state and dynamic part of Mliq - n power of the shear rate - p isotropic pressure - Q quality factor - r radial position - R,R ₀, R _c Re(Z ^*, Z ₀ ^* , Z _c ^* ) - s time - t, t time - T temperature - T, ⁰ T, stress tensor - u velocity - U lock-in output - ₀ velocity - V _det detector output voltage - V _sig, V _cr signal and cross-talk part of V _det - x Cartesian coordinate - X , X ₀, X _c Im(Z ^*, Z ₀ ^* , Z _c ^* ) - y Cartesian coordinate - z Cartesian coordinate, axial position     

Intramolecular meta photocycloaddition of 6-arylhex-2-enes Part 2

The course of the intramolecular meta photocycloaddition of ring-substituted (E)- and (Z)- 6-phenylhex-2-enes depends on the position and nature of the substituent. In this paper, the effects of methyl and cyano groups and the fluorine atom are described. The results are in agreement with a reaction mechanism in which the excited phenyl ring becomes polarized when it is approached by the alkene. The dipolar character becomes particularly apparent in the case of fluorine which, depending on its position, can stabilize either the negative charge through its inductive effect or the positive charge through its mesomeric effect. The configuration of the terminal methyl group sterically influences the photoreaction. The Z alkenes readily undergo the 1′,3′-addition, but fail to add in the 2′,6′-mode, even if substituents which strongly promote this mode are present. The E alkenes seem to suffer from steric hindrance in the 2′,6′- and the 1′,3′-mode, but the electronic effects of activating substituents provide compensation and substituents may have a pronounced influence on the ratio of the two modes.     

Capillary Stokes drift: a new driving mechanism for mixing in AC-electrowetting

We studied the flow fields generated inside sessile drops that oscillate periodically between states of high and low contact angle under the influence of alternating electric fields of variable frequency and amplitude. Following the motion of dye patches, we show that the number of oscillation cycles required to achieve mixing scales logarithmically with the Péclet number as expected for chaotic mixing. High speed movies reveal an asymmetry of the drop shape between the spreading and receding phase of the oscillations. This results in net internal flow fields that we characterize by tracing the motion of colloidal seed particles. The strength and frequency dependence of the flow are explained in terms of Stokes drift driven by capillary waves that emanate from the oscillating contact line.     

Removal of Chromium(VI) from Groundwater Using Oil Shale Ash Supported Nanoscaled Zero-valent Iron

Oil shale ash(OSA) supported nanoscaled zero-valent iron(OSA-nZVI) was used as a rapid and efficient reductant for Cr(VI) reduction. The optimal mass ratio of nZVI to OSA and the optimal dosage were explored. The effects of initial pH, reaction temperature, initial Cr(VI) concentration, and common cations and anions in groundwater on Cr(VI) reduction were determined in batch experiments. The results show that the optimum initial pH is 5.0. The reaction temperature has a positive effect on Cr(VI) reduction while the real groundwater has a negative effect. Additionally, 84.22% Cr(VI) was still reduced by 3 g/L OSA-nZVI(1:2)(mass ratio of OSA to Fe⁰ was 1:2) within 120 min for 50 mg/L Cr(VI) under conditions of 10℃ and unadjusted pH.     

Excitation of Lamb-waves in plates

Lamb waves show great potential in the detection of structural defects in plate and shell structures. In the sense of the adaptive structures concept the wave generation takes place with help of integrated piezoelectric ceramics. For a steel plate with adhered piezoelectric actuator, analytical calculations, FEM simulations, and experimental results are in good agreement. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Synthesis of selenoacetals

This paper reports our results concerning the syntheses of various bis(alkylseleno)alkanes and some of their arylseleno analogues by different methods. The scope and limitation of each of them are presented.