Electrochemical synthesis and crystal structure of cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes with 2-pyridinecarbaldehyde-(2′-aminosulfonylbenzoyl)hydrazone

A new hydrazonic Schiff base ligand, 2-pyridinecarbaldehyde-(2′-aminosulfonylbenzoyl)hydrazone (HL), has been prepared and characterized, and its coordinative properties were studied. [ML₂] complexes, M = Co, Ni, Cu, Zn or Cd have been synthesised by electrochemical oxidation of the anodic metal in a cell containing an acetonitrile solution of the ligand. The compounds obtained have been characterized by microanalysis, IR, NMR and UV–Vis spectroscopy, mass spectrometry and also by X-ray diffraction. The structural studies show that the metal is in a distorted octahedral environment with the monoanionic ligand acting as a meridional tridentate (N,N,O) chelate system.     

Enantiodivergent synthesis of pyrrolo[2,1-a]isoquinolines based on diastereoselective Parham cyclization and alpha-amidoalkylation reactions

Enantiodivergent synthesis of C-10b-substituted pyrrolo[2,1-a]isoquinolines starting from an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide 3a, with a 2-exo-hydroxy-10-bornylsulfinyl group as a chiral auxiliary, has been developed. The key transformations are derived from diastereoselective intramolecular cyclization of aryllithiums and alpha-amidoalkylation reactions, with the ethylidene bridge of the norbornene moiety dictating the stereochemical outcome in both types of reactions. Thus, the organolithium addition-intramolecular alpha-amidoalkylation sequence on imide 3a afforded stereoselectively the R configuration at C-12b, whereas the tandem Parham cyclization-intermolecular alpha-amidoalkylation reactions on the corresponding iodinated imide 3b occurred with complete control of stereoselectivity, leading to the epimer at C-12b. Subsequent reductive removal of the chiral auxiliary and retro-Diels-Alder reaction afforded (10bS)- and (10bR)-pyrroloisoquinolines 1 in high yields and optical purities (>99% ee).     

An integrated multiphase flow sensor for microchannels

The flow regimes of microscale multiphase flows affect the yield and selectivity of microchemical systems, and the heat transfer properties of micro heat exchangers. We describe an integrated optical sensor that uses total internal reflection to detect the structure of multiphase flows in microchannels. The non-intrusive sensor enables detection of individual slugs, bubbles, or drops, and can be used to continuously determine their number and velocity. The sensor performance is modeled using ray-tracing techniques, and tested for several channel geometries. Both gas-liquid and liquid-liquid flows are investigated in microchannels with rectangular and triangular cross-sections. Statistical properties of the flow, derived from the sensor signal, compare favorably to commonly-used dynamic pressure measurements. We demonstrate the integration of the sensor into a planar multichannel microreactor. An existing glass layer used as a waveguide allows us to monitor flows in optically inaccessible channels. This sensor configuration can be integrated into layers of vertically-stacked multichannel microreactors.

List of symbols

Roman symbols a Radius of largest sphere inscribed in channel [m] - A_ch Channel cross-sectional area [m²] - Ca Capillary number [-] - Critical capillary number [-] - d_h Hydraulic diameter [m] - d_sensor Distance prism surface-sensor origin [m] - E₀ Incident light energy [J] - E_r Emerging light energy [J] - f(t_pass) Probability density function (PDF) of slug dwell times [1/s] - f Focal length [m] - f_slug Slug frequency [Hz] - F(t_pass) Probability distribution of slug dwell times [-] - g(t) Arbitrary function of time [-] - h Liquid film thickness [m] - j_G Superficial gas velocity [m/s] - j_L Superficial liquid velocity [m/s] - l Slug length [m] - N Number of samples [-] - n Refractive index [-] - N_c Number of channel corners [-] - n_i Refractive index of incident medium [-] - n_r Number of reflections [-] - n_t Refractive index of transmitting medium [-] - n_slug Number of slugs [-] - p Gas inlet pressure [Pa] - r Reflectance [-] - R_XX(x,) Autocorrelation function [-] - R_Xp(x,) Cross correlation function [-] - r Slug radius at infinite distance from leading slug tip [m] - s Standard deviation of measured slug dwell times [s] - t Time [s] - t Measurement time interval [s] - t_pass Slug dwell time [s] - U_b Slug (bubble) velocity [m/s] - W Bin size of slug dwell time histogram [-] - x Streamwise coordinate [m] - X(x,t) Phase density function [-] - Y Surface tension of the gas-liquid interface [N/m] - Volumetric gas flow rate [m³/s] - Volumetric liquid flow rate [m³/s] - Volumetric oil flow rate [m³/s] - Volumetric water flow rate [m³/s] - z Normal coordinate [m]Greek symbols Void fraction [-] - _c Critical angle for total internal reflection [^°] - _i Incident angle [^°] - Laser wavelength [m] - µ Liquid viscosity [Pa s] - Normalization factor [-] - _h Dimensionless liquid film thickness [-] - _r Dimensionless radius [-] - _x Dimensionless streamwise position [-] - _r Dimensionless slug radius at infinite distance from leading slug end [-] - Standard deviation of the slug dwell time distribution [s] - Time shift [s] - Contact angle [^°]     

Enantioselective separation of thalidomide on an immobilized α1-acid glycoprotein chiral stationary phaseglycoprotein chiral stationary phase

Summary An easy and rapid enantioselective separation for assay of racemic thalidomide on an immobilized α₁-acid glycoprotein chiral stationary phase (GPA CSP) is described. The effects of tetrahydrofuran (THF) as organic modifier, buffer concentration to control the ionic strenth, and mobile phase pH were studied. These variations have consequences in terms of chromatographic retention (k), resolution (R _s), selectivity (α), and peak asymmetry (USP tailing factor). The main condition affecting chromatographic retention was mobile phase pH. At pH 4.5, no separation of thalidomide enantiomers was achieved whereas at pH 7.9 chiral separation was optimum. Peak tailing was directly related to changes in pH and to addition of THF as mobile phase modifier. Results also indicated that the resolution factor is THF concentration-dependent, and that the separation factor (α) is the best parameter for evaluating enantioselectivity. The best mobile phase was pH 7.0, 30 mM ammonium acetate containing 0.3% THF. Under these conditions validation including linearity, recovery, and precision was performed. The suitability of this method has been successfully proved in a limited in-vivo study after intravenous administration of thalidomide to a New Zealand male rabbit.     

Conformational analysis,part 43. A theoretical and LIS/NMR investigation of the conformations of substituted benzamides

A refined Lanthanide‐Induced‐Shift Analysis (LISA) is used with molecular mechanics and ab initio calculations to investigate the conformations of benzamide ( 1 ), N‐methylbenzamide ( 2 ), N,N‐dimethylbenzamide ( 3 ) and the conformational equilibria of 2‐fluoro ( 4 ), 2‐chloro ( 5 ) and N‐methyl‐2‐methoxy benzamide ( 6 ). The amino group in 1 is planar in the crystal but is calculated to be pyramidal with the CO/phenyl torsional angle (ω) of 20–25°. The LISA analysis gave acceptable agreement factors (Rcryst ≤ 1%) for the ab initio geometries when ω was decreased to 0°, the other geometries were not as good. In 2 , the N‐methyl is coplanar with the carbonyl group in all the geometries. Good agreement was obtained for the RHF geometries, with ω 25°, the other geometries were only acceptable with increased values of ω. In 3 , good agreement for the RHF and PCModel geometries was found when ω was changed from the calculated values of 40° (RHF) and 90° (PCModel) to ca. 60°, the X‐ray and B3LYP geometries were not as good. The two substituted compounds 4 , 5 and 6 are interconverting between the cis (O,X) and trans (O,X) conformers. The more stable trans conformer is planar in 4 and 6 but the cis form non‐planar. Both the cis and trans conformers of 5 are non‐planar. There is an additional degree of freedom in 6 due to the 2‐methoxy group, which can be either planar or orthogonal to the phenyl ring in both conformers. The conformer ratios were obtained from the LISA analysis to give Ecis‐Etrans in 4 > 2.3 kcal/mol (CDCl₃) and 1.7 kcal/mol (CD₃CN), in 5 0.0 kcal/mol (CD₃CN) and in 6 > 2.5 kcal/mol (CDCl₃) and 2.0 kcal/mol (CD₃CN). These values were used with the observed versus calculated ¹H shifts to determine the conformer ratios and energies in DMSO solvent to give Ecis‐Etrans 1.1, ?0.1 and 1.8 kcal/mol for ( 4 ), ( 5 ) and ( 6 ). Comparison of the observed versus calculated conformer energies show that both the MM and ab initio calculations overestimate the NH..F hydrogen bond in ( 4 ) by ca. 2 kcal/mol. Copyright © 2015 John Wiley & Sons, Ltd.     

Aldehyde‐Assisted Hydrogen Transfer during the Formation of Hydride–Iridafurans from Alkynes and Aldehydes

The bis(ethylene) Ir^I complex [TpIr(C₂H₄)₂] ( 1 ; Tp=hydrotris(3,5‐dimethylpyrazolyl)borate) reacts with two equivalents of aromatic or aliphatic aldehydes in the presence of one equivalent of dimethyl acetylenedicarboxylate (DMAD) with ultimate formation of hydride iridafurans of the formula [TpIr(H){C(R¹)?C(R²)C(R³)O }] (R¹=R²=CO₂Me; R³=alkyl, aryl; 3 ). Several intermediates have been observed in the course of the reaction. It is proposed that the key step of metallacycle formation is a C? C coupling process in the undetected Ir^I species [TpIr{η¹‐O‐R³C(?O)H}(DMAD)] ( A ) to give the trigonal‐bipyramidal 16 e^? Ir^III intermediates [TpIr{C(CO₂Me)?C(CO₂Me)C(R³)(H)O }] ( C ), which have been trapped by NCMe to afford the adducts 11 (R³=Ar). If a second aldehyde acts as the trapping reagent for these species, this ligand acts as a shuttle in transfering a hydrogen atom from the γ‐ to the α‐carbon atom of the iridacycle through the formation of an alkoxide group. Methyl propiolate (MP) can be used instead of DMAD to regioselectively afford the related iridafurans. These reactions have also been studied by DFT calculations.