Synthesis of substituted 5-aminomethyl tetrahydro-isoquinolines and dihydro-isoindoles

The synthesis of ten substituted aminomethylene tetrahydro-isoquinolines is described, proceeding in eight steps from 5-hydroxyisoquinoline via reductive amination of N-Boc tetrahydro-isoquinoline 5-carboxaldehyde. Likewise, reductive amination was used to prepare four substituted dihydro-isoindoles from the corresponding aldehyde. The dihydro-isoindole ring system was conveniently accessed via a 2+2+2 cycloaddition reaction.     

Cyclopentadienyl-ruthenium and -osmium chemistry: XXVIII. Reactions and isomerisation of 1,2-bis(methoxycarbonyl)ethenyl complexes: X-ray structures of Ru{Z)-C(CO2Me)CH(CO2Me)} -(CO)(PPh3)(η-C5H5) · 0.5EtOH,Ru{(E)-C(CO2Me)CH(CO2Me)}(dppe)(η-C5H5) and Ru{C(CO2Me)C(CO2Me)C(CO2Me)CH(CO2Me)} - (PPh3)(η-C5H5)

A reinvestigation of the reaction between C₂(CO₂Me)₂ and RuH(PPh₃)₂(η-C₅H₅) and some related complexes is reported. Initial cis addition is followed by conversion into the trans isomer. In the case of the bis-(PPh₃) complex, isomerisation is followed by chelation of the ester CO group with concomitant displacement of one PPh₃ligand. The resulting chelate complex reacts with CO or CNBu^t to give the (Z)-RuC(CO₂Me)CH(CO₂Me) complexes; the (E)-isomer of the carbonyl complex is obtained by addition of C₂(CO₂Me)₂to RuH(CO)(PPh₃)(η-C₅H₅). The ^1Hand ¹³C NMR spectra are not a reliable guide to assignment of the stereochemistry of the vinyl group. Other products isolated from the initial reaction are the bis-insertion product $\text{Ru{C(CO}{}_2\text{Me)C(CO}{}_2\text{Me)C(CO}{}_2\text{Me)}$CH(CO₂Me)} -(PPh₃)(η-C₅H₅) and the 1/2 PPh₃/C₂(CO₂Me)₂ adduct. The molecular structures of Ru{(Z)-C(CO₂Me)CH(CO₂Me)}(CO)(PPh₃(η-C₅H₅) · 0.5EtOH, Ru{(E)-C(C₂Me)CH(CO₂Me)}(dppe)(η-C₅H₅) and $\text{Ru{C(CO}{}_2\text{Me)C(CO}{}_2\text{Me)C(CO}{}_2\text{-Me)}$CH(CO₂Me)}(PPh₃)(η-C₅H₅) have been determined. The cis isomer is monoclinic, space group P2₁,with a 9.328(8), b 17.385(10), c 10.356(7) Å, β 101.78(3)° and Z = 2; 2107 data with I ≥ 2.5σ(I) were refined to R = 0.076 R_w = 0.085. The trans isomer is triclinic, space group P$\text{1}$, with a 10.404(7) b 11.221(6), c 13.230(9) Å, α 92.67(5), β 110.56(5), γ 106.21(5)° and Z = 2; 2520 data with I ≥ 2.5σ(I) were refined to R = 0.055 R_w = 0.068. The butadienyl complex is monoclinic, space group P2₁/a, with a 19.655(8), b 8.674(4), c 21.060(5) Å, β 116.22(3)° and Z = 4; 2724 data with I ≥ 2.5σ(I) were refined to R = 0.042, R_w = 0.047.     

Generation and reactivity of bis(2,6-diethylphenyl)germanium(II)

The title intermediate ($\text{3a}$) is produced on photolysis of hexakis(2,6-diethyl-phenyl)cyclotrigermane ($\text{1}$) or bis(2,6-diethylphenyl)bis(trimethylsilyl)germane ($\text{4}$) as evidenced by trapping experiments, and thermally dimerizes to tetrakis(2,6-diethyl-phenyl)digermene ($\text{2a}$). Diarylgermylenes such as $\text{3a}$ do not form stable triethylamine adducts (e.g. $\text{5a}$) as has been previously reported.     

Characterization of inclusion complexes of betamethasone-related steroids with cyclodextrins using high-performance liquid chromatography

HPLC was used to study the inclusion complexes formed between various beta- and gamma-cyclodextrins and a series of corticosteroids related to betamethasone. Apparent association constants were measured in acetonitrile-water for a set of 13 steroids. An increase in the stability of the steroid-cyclodextrin complex is observed at lower concentrations of acetonitrile. The effects of the nature of the halide at the 9-position, the location of a double bond within the C-ring, substitution at the 9- and 11-positions, and modification of the D-ring of the steroid backbone were studied. The 11- and 17-positions were found to be critically involved in the inclusion process. Larger apparent association constants were obtained with gamma-cyclodextrin (gamma-CD) than with beta-cyclodextrin (beta-CD) due to the increased diameter of the gamma-CD cavity. Van't Hoff plots were constructed to examine the thermodynamic properties of the inclusion process. Plots constructed using retention factors were found to be nonlinear when gamma-CD was present in the mobile phase. This is due to an increase in the strength of the inclusion complex as temperature decreases. Plots constructed using apparent association constants were linear, indicating that the mechanism of inclusion does not change over the range of temperatures studied (10 to 80 degrees C). Enthalpy-entropy compensation was observed for 11 of the 13 steroids studied. The usefulness of cyclodextrins to achieve the separation of steroids in HPLC is discussed and a practical application for the analysis of a steroid and three potential impurities is described.     

Hydrodynamics of a bounded vertical film with nonlinear surface properties

The drainage of a thin liquid film with an insoluble monolayer down a vertical wall is studied. Lubrication theory is used to develop a model where the film is pinned at the top with a given thickness and the film drains into a bath at the bottom. A nonlinear equation of state is used for the surface tension and the surface viscosity is a nonlinear function of the surfactant concentration; these are appropriate for some aqueous systems. The three partial differential equations are solved via discretization in space and then the resulting differential algebraic system is solved. Results are described for a wide range of parameters, and the conditions under which the free surface is immobilized are discussed.