Action of HCl on 3-hydroxypyrazolo(iso)quinolines to give 1-chloropyrazoles: evidence for an addition–elimination mechanism by ab initio calculations in gas phase and water

 Addition–elimination reactions involving a nucleophile and a remote leaving group [S^H _N(AE)^tele] are well-known under basic conditions, especially amongst electron-poor six-membered heterocycles, but are less commonly encountered for five-membered heterocycles and are rare under acidic conditions. Concentrated HCl converts 1-hydroxy-1H-pyrazolo[3,4-c] isoquinoline and 1-hydroxy-1H-pyrazolo[3,4-c]quinoline into 3-chloro-1H-pyrazolo[3,4-c]isoquinoline and 3-chloro-1H-pyrazolo[3,4-c]quinoline, respectively. However, apparently neither the isomeric 1-hydroxy-1H-pyrazolo[4,3-c](iso)-quinolines nor the parent 1-hydroxypyrazole undergo this reaction. Additionally, all these systems are refractory under basic conditions. We present a plausible mechanism for the reaction, involving the 3-addition of Cl^- to the diprotonated heterocycle, followed by the elimination of water. Calculations of the initial transition states and intermediates, using optimisation at B3LYP/6-311+G(d,p), including thermochemistry [HF/6-31+G(d)], and single-point Poisson–Boltzmann self-consistent reaction field determination of the free energy of solvation (Jaguar Poisson–Boltzmann self-consistent reaction field), support this mechanism and reproduce the observed order of reactivity, the addition step being 2–4 kcal less favourable for the isomeric 1-hydroxy-1H-pyrazolo[4,3-c](iso)quinolines and provide a rationalisation for the role of strong acid. Received: 27 June 2002 / Accepted: 6 September 2002 / Published online: 14 February 2003     

Quantification of monohydroxy-PAH metabolites in urine by solid-phase extraction with isotope dilution-GC–MS

For measurement of biomarkers from polycyclic aromatic hydrocarbon (PAH) exposure, an analytical method is described quantifying hydroxylated PAH (OH-PAH) in urine samples. This method determined monohydroxy metabolites of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The sample preparation consisted of enzymatic hydrolysis, solid-phase extraction and derivatization with a silylating reagent. Five carbon-13 labeled standards were used for isotope dilution. Analytes were separated by gas chromatography (GC) and quantified with high-resolution mass spectrometry (HRMS). This method produced good recoveries (41-70%), linearity, and specificity. Data were corrected for blank levels from the naphthalene, fluorene, and phenanthrene metabolites. Method detection limits ranged from 2 ng L(-1) for 1-hydroxypyrene to 43.5 ng L(-1) for 1-hydroxynaphthalene. Using quality control charts from two urine pools, the method can be readily applied to biomonitoring PAH exposure.     

Lanthanum chromites partially substituted by calcium,strontium and barium synthesized by urea combustion

Because of their electrical, magnetic and catalytic properties rare earth and transition metal mixed oxides are important compounds. Lanthanum chromites have been extensively used as solid oxide fuel cell (SOFC) interconnect materials. In this work, lanthanum chromites partially substituted by alkaline earth metals were synthesized by the urea combustion process. TG and DSC techniques were used to evaluate the presence of the organic material in the powder after reaction on the hot plate. The powders were calcinated at 900°C and characterized by XRD and SEM. The results show that the particles have nanometric dimensions and the perovskite structure was formed.     

Stereoselective synthesis of cis- and trans-2,3-disubstituted eight-membered medium-ring ethers based on Ireland-Claisen rearrangement of 3-alkoxy-2-propenyl glycolate esters and ring-closing olefin metathesis

A simple stereoselective synthesis of cis- and trans-2,3-disubstituted medium-sized cyclic ethers has been developed based on geometry-selective synthesis of 3-alkoxy-2-propenyl glycolate esters, Ireland-Claisen rearrangement of the glycolate esters, and ring-closing olefin metathesis.     

Novel method for bulk resistance evaluation in conductivity measurement for high-purity water

A major issue with the electrolytic conductivity measurement for pure water is the lack of standard or reference methods. A primary method traceable to SI and suitable for pure-water conductivity measurement was developed at the Physikalisch-Technische Bundesanstalt (PTB), Germany, as the base for the calibration method for the conductivity measuring devices at the low conductivity level. This paper provides a novel method to calculate the bulk resistance of pure water using impedance measured at a single frequency, which is one of the key procedures for the primary methods.     

Formal total synthesis of hemibrevetoxin B by a convergent strategy

Concise construction of the trans-fused 7/7/6/6 tetracyclic ether part of hemibrevetoxin B (1) was achieved by a convergent strategy based on coupling reaction of an acyl anion equivalent, reductive cyclization of an α,ε-dihydroxyketone, and introduction of a methyl group at the central ring junction by the Nicolaou method. The resultant tetracyclic ether was transformed into the known intermediate, which was already converted to 1 by the Yamamoto group, thereby completing the formal total synthesis of 1.     

Syntheses and characterization of three hybrid materials based on polymeric copper complexes and saturated Keggin polyoxoanions

Three novel heteropolytungstates, [Cu(phen)₂]₄[α-SiW₁₂O₄₀] (1), [Cu₄(4,4′-bpy)₃(2,2′-bpy)₄][α-SiW₁₂O₄₀] · H₂O (2) and [Cu(4,4′-bpy)(4,4′-Hbpy)_0.5]₂[PW₁₂O₄₀] (3) (phen = 1,10-phenanthroline, 4,4′-bpy = 4,4′-bipyridine, 2,2′-bpy = 2,2′-bipyridine), have been synthesized and characterized by elemental analyses, IR, TG analyses and single-crystal X-ray diffraction. Compound (1) exhibits interesting chiral layer constructed from interperpendicular helical chains running along a crystallographic 2₁ axis in the c and a directions. Furthermore, the chiral layers are connected by the [α-SiW₁₂O₄₀]⁴⁻ anions via hydrogen bonding interactions to form a 3D superamolecular structure. The [Cu₄(4,4′-bpy)₃(2,2′-bpy)₄]⁴⁺ coordinated complexes in compound (2) are packed together via the aromatic π–π stacking interactions and exhibit an interesting 3D sandglasslike “host” network with 1D channels, in which [α-SiW₁₂O₄₀]⁴⁻ anions “guests” reside. Compound (3) has a unique 2D superamolecular network, which is composed of cationic Cu^I coordination polymer chains and discrete [PW₁₂O₄₀]³⁻ polyoxoanions as linkers. It is noteworthy that the monprotonated 4,4′-bpy ligands of (3) act as arms and connect the adjacent 2D network, generating a 3D interpenetrating superamolecular structure.     

Syntheses and properties of mixed dinuclear copper(II) complexes with heterocyclic dithiocarbamates and a cyclic octadentate tertiary amine

Five new Cu^II complexes of general formula [Cu₂(Rdtc)tpmc](ClO₄)₃, (1)–(5), where tpmc and Rdtc ^– refer to N,N,N,N-tetrakis(2-pyridylmethyl)-1,4,8,11-teraazacyclotetradecane and piperidine- (Pipdtc), 4-morpholine- (Morphdtc), 4-thiomorpholine- (Timdtc), piperazine- (Pzdtc) or N-methylpiperazine- (N-Mepzdtc) dithiocarbamates, respectively, have been prepared. Elemental analyses, conductometric and magnetic measurements, u.v./vis, i.r., e.p.r. and mass spectroscopy have been employed to characterize them. The complexes adopt an exo coordination of Cu^II ions and tpmc. The dithiocarbamate ion joins both the sulphur and the copper atoms acting as a bridging ligand The presence of different heteroatoms in the piperidine ring influences the (C=N) and (C=S) vibrations which decrease in the order of the complexes: Pipdtc>N-Mepipdtc>Pzdtc>Morphdtc>Timdtc ligands. Attention has been paid to the detailed mechanism of the mass spectral fragmentation of the complexes. The g _eff factors of the complexes have been also estimated by e.p.r. spectra. Finally, the complexes obtained demonstrate microbiologycal activity against some bacteria.     

Interaction between the antibacterial compound,oleuropein, and model membranes

Oleuropein, a secoiridoid glycoside extracted from the olive tree, Olea europaea L., has been described as showing antibacterial properties. However, the exact mechanism of these antimicrobial properties is not yet well understood. In the present study, we have studied the interaction of oleuropein with phosphatidylglycerol (PG) as a model membrane for Staphylococcus aureus (S. aureus) (Gram-positive bacteria) and phosphatidylethanolamine and Escherichia coli (E. coli) lipid extract as a model membrane for E. coli (Gram-negative bacteria). The study has been carried out using monolayers as model membranes and using kinetics at constant area and compression isotherms with Brewster angle microscopy (BAM) observations. The results show that oleuropein interacts in higher extent with PG monolayers, which is related with its stronger antibacterial effect against Gram-positive bacteria. The effects on the membrane are probably produced at the cell surface because oleuropein did not form stable mixed monolayers with the lipids assayed at the air/water interface.     

Investigation of Raman,FT-IR,EPR spectra and antimicrobial activity of 2-(5-H/Me/Cl-1<Emphasis Type="BoldItalic">H</Emphasis>-benzimidazol-2-yl)-phenol ligands and their Fe(NO<Subscript>3</Subscript>)<Subscript>3</Subscript> complexes

2-(5-H/Me/Cl-1H-benzimidazol-2-yl)-phenol ligands form 1:1 electrolytes, 5-coordinate monometallic complexes with iron(III) nitrate. The geometry of the [Fe(L)(OH)(H₂O)₂](NO₃) complexes was derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. In all of the complexes the ligands are bidentate, via one imine nitrogen atom and phenolate oxygen atom. The coordination is completed with a hydroxide ion, and two water molecules, adopting a distorted square pyramidal geometry. The structures of the compounds were confirmed on the basis of elemental analysis, molar conductivity, magnetic moment, FT-Raman, FT-IR (mid-IR, far-IR), EPR and u.v.–vis. The antimicrobial activities of the free ligands, their hydrochloride salts, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against nine bacteria and the results are compared with several known antibiotic agents. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram⁺ & Gram⁻ bacteria) activities that were either more active or as potent as the references.