Oxazoline chemistry. Part 12: A metal-mediated synthesis of DMU-212; X-ray diffraction studies of an important anti-cancer agent

An improved synthesis of the anti-cancer agent DMU-212 (trans-3,4,5,4′-tetramethoxystilbene) is described. The methodology involves the use of a Pd-oxazoline catalyst as a mediator of a regio-selective (Heck) C-C bond formation reaction. A simple isolation step is then used to obtain the title material. The compound has been further characterised in the solid-state by X-ray diffraction methods.     

Formation of organolithium hetero-aggregates [Li4Ar2(nBu)2] (Ar=C6H4CH(Me)NMe2-2) during the directed ortho-lithiation of [1-(dimethylamino)ethyl]benzene

(R)-[1-(Dimethylamino)ethyl]benzene reacts with nBuLi in a 1:1 molar ratio in pentane to quantitatively yield a unique hetero-aggregate (2 a) containing the lithiated arene, unreacted nBuLi, and the complexed parent arene in a 1:1:1 ratio. As a model compound, [Li(4)(C(6)H(4)CH(Me)NMe(2)-2)(2)(nBu)(2)] (2 b) was prepared from the quantitative redistribution reaction of the parent lithiated arene Li(C(6)H(4)CH(Me)NMe(2)-2) with nBuLi in a 1:1 molar ratio. The mono-Et(2)O adduct [Li(4)(C(6)H(4)CH(Me)NMe(2)-2)(2)(nBu)(2)(OEt(2))] (2 c) and the bis-Et(2)O adduct [Li(4)(C(6)H(4)CH(Me)NMe(2)-2)(2)(nBu)(2)(OEt(2))(2)] (2 d) were obtained by re-crystallization of 2 b from pentane/Et(2)O and pure Et(2)O, respectively. The single-crystal X-ray structure determinations of 2 b-d show that the overall structural motifs of all three derivatives are closely related. They are all tetranuclear Li aggregates in which the four Li atoms are arranged in an almost regular tetrahedron. These structures can be described as consisting of two linked dimeric units: one Li(2)Ar(2) dimer and a hypothetical Li(2)nBu(2) dimer. The stereochemical aspects of the chiral Li(2)Ar(2) fragment are discussed. The structures as observed in the solid state are apparently retained in solution as revealed by a combination of cryoscopy and (1)H, (13)C, and (6)Li NMR spectroscopy.     

Recent advances in the homogeneous polymerisation of olefins mediated by nickel complexes

A brief overview is presented on recent advances in the application of nickel coordination complexes as mediators of olefin polymerisation; in some cases involving stereo-regular polymer formation where appropriate. Emphasis is also given on recent findings concerning di- and tri-nuclear Ni clusters with details on ethylene, methyl methacrylate or styrene-based monomer polymerisations.     

Oxazoles XXI. Three Ester Ammonium Salts Resulting from the Rupture of an Oxazoline Ring

Abstract  

The synthesis and characterisation of three ammonium salts that are formed via a ring opening of a 2-oxazoline (i.e., a 4,5-dihydro-1,3-oxazole) are described. Compound 1, derived from 2-phenyl-2-oxazoline (Phox), was isolated as a major reaction product during an unrelated synthesis using Phox which was being carried out in the presence of NO₃ ⁻ ions. The isolated compound is identified as the nitrate salt of the terminal ammonium ester [H₃NCH₂CH₂OC(=O)Ph]⁺ (1). The X-ray crystal structure (C₉H₁₂N₂O₅) of 1 is revealed to be orthorhombic (space group Pna2₁) with a = 21.1304(8), b = 7.5975(2) and c = 6.8629(3)?. The analogous material 2a, obtained from the related oxazole 4,4-dimethyl-2-phenyl-2-oxazoline (MePhox) under identical conditions to that of 1, contains the [H₃NCMe₂CH₂OC(=O)Ph]⁺ cation. The X-ray crystal structure (C₁₁H₁₆N₂O₅) of 2a is monoclinic with a = 6.1270(3), b = 6.3603(3), c = 16.1632(8)? and β = 90.662(3)o and of space group P2₁. Chiral derivative 2b, was isolated from a wet CH₂Cl₂/THF solution upon treatment of MePhox with (S)-mandelic acid. This material was shown to also contain the [H₃NCMe₂CH₂OC(=O)Ph]⁺ cation, a lattice water molecule and an (S)-mandalate anion. The X-ray crystal structure of 2b (C₁₉H₂₃NO₅·H₂O) is orthorhombic (space group P2₁2₁2₁) with a = 6.4733(3), b = 11.4661(5) and c = 24.5791(11)?. One proposed mechanism by which all three materials are formed was first presented in seminal work by Deslongchamps. The compounds reported herein are representatives of a class of rarely isolated intermediates in heterocyclic ring opening reactions and they are also the first examples of (ω-ammoniumethyl)(aryl) esters to be structurally characterised.     

DYNGA: a general purpose QM-MM-MD program. I. Application to water

We present a general purpose QM-MM-MD engine (DYNGA) designed to test alternative hybrid Hamiltonians geared towards the treatment of problems of interest in structural biology including the use of experimental data constraints. In this first presentation we use DYNGA to explore the behaviour of a traditional QM-MM approach in the treatment of the water—water interaction. We find the potential energy hypersurface for the water dimer computed with the HF 4–31G*/TIP3P hybrid Hamiltonian tends to be too flat. We also explore the effect of using traditional QM-MM techniques on proton wires and conclude there is a need for improvement, possibly addressed by using polarizable force fields.     

PAST AND FUTURE MANAGEMENT OF A COLLAPSED FISHERY: THE BAY OF BISCAY ANCHOVY

Abstract We analyze the efficiency of the international management of the Bay of Biscay anchovy. While a sharing agreement between France and Spain has been in place since 1992, the fish stock collapsed in 2005 and the fishery closed from 2005 to spring 2010. We consider differences in production technologies between both countries and calibrate our model using data from 1987 to 2009. Our results suggest two sources of rent dissipation under the existing sharing agreement: inefficient quota allocation and production inefficiencies due to inflexible national regulations. We discuss several alternatives to improve management.     

In situ Observation of Evolving H2 and Solid Electrolyte Interphase Development at Potassium Insertion Materials within Highly Concentrated Aqueous Electrolytes

The solid-electrolyte interphase (SEI) is key to stable, high voltage lithium-ion batteries (LIBs) as a protective barrier that prevents electrolyte decomposition. The SEI is thought to play a similar role in highly concentrated water-in-salt electrolytes (WISEs) for emerging aqueous batteries, but its properties remain unknown. In this work, we utilized advanced scanning electrochemical microscopy (SECM) and operando electrochemical mass spectrometry (OEMS) techniques to gain deeper insight into the SEI that occurs within highly concentrated WISEs. As a model, we focus on a 55 mol/kg K(FSA)_0.6(OTf)_0.4 electrolyte and a 3,4,9,10-perylenetetracarboxylic diimide negative electrode. For the first time, our work showed distinctly passivating structures with slow apparent electron transfer rates alike to the SEI found in LIBs. In situ analyses indicated stable passivating structures when PTCDI was stepped to low potentials (≈−1.3 V vs. Ag/AgCl). However, the observed SEI was discontinuous at the surface and H₂ evolution occurred as the electrode reached more extreme potentials. OEMS measurements further confirmed a shift in the evolution of detectable H₂ from −0.9 V to <−1.4 V vs. Ag/AgCl when changing from dilute to concentrated electrolytes. In all, our work shows a combined approach of traditional battery measurements with in situ analyses for improving characterization of other unknown SEI structures.     

Mathematical Model for Vinyl‐Divinyl Polymerization

A mathematical model for the crosslinking copolymerization of a vinyl and divinyl monomer was developed and applied to the case of methyl methacrylate and ethylene glycol dimethacrylate batch polymerization. Model results compare favorably to the experimental findings of Li and Hamielec 23 for the system investigated. The model presented utilizes the numerical fractionation technique 15 and is capable of predicting a broad range of distributional properties both for pre‐ and post‐gel operating conditions as well as polymer properties that were not experimentally determined from the experimental findings of Li and Hamielec, such as crosslink density and branching frequency. The effects of divinyl monomer fraction and chain transfer agent level on the polymer properties and the dynamics of gelation were also investigated.

     

ConFlo III - an interface for high precision delta(13)C and delta(15)N analysis with an extended dynamic range

A newly developed interface coupling a CHN combustion device (elemental analyser 'EA') to an isotope ratio mass spectrometer is described and evaluated. The purpose of the device is to extend the dynamic range of delta(13)C and delta(15)N analysis from less than 2 orders of magnitude to more than 3 orders of magnitude. Carbon isotope ratio measurements of atropine as a model compound have been performed analysing between 1 μg to 5 mg C with acceptable to excellent precision (0.6 to 0.06 per thousand, delta-notation). The correction due to the blank signal is critical for sample amounts smaller than 4 μg C. The maximum sample weight is determined by the combustion capacity of the EA. Larger sample amounts are measured using dilution of a small part of the EA effluent with helium. The dilution mechanism works virtually free of isotope fractionation. Copyright 1999 John Wiley & Sons, Ltd.