Oxydative Aryl-Aryl-Verknüpfung von 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisochinolin-Derivaten

Oxidative Aryl-Aryl-Coupling of 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisoquinoline Derivatives We describe the synthesis of 2 by intramolecular oxidative coupling of 1, 1′-biisoquinoline derivatives 1 (Scheme 1). This heterocyclic system can be considered as a union of two apomorphine molecules and may thus exhibit dopaminergic activity. - The readily available tetrahydrobiisoquinoline 6 was methylated to 11 (Scheme 4) and reduced (with NaBH₃CN) to rac- 7 and (catalytically) to meso- 7 (Scheme 3). Reduction of 11 with NaBH₄ and of the biurethane rac- 9 with LiAlH₄/AlCl₃ afforded meso- and rac- 10 , respectively (Scheme 4). Demethylation of 6 , meso- 10 , meso- and rac- 7 led to 12 , meso- 14 , meso- and rac- 13 , respectively (Scheme 5). The latter two phenols were converted with chloroformic ester to the hexaethoxycarbonyl derivatives meso- and rac- 15 and subsequently saponified to the biurethanes meso- and rac- 16 , respectively (Scheme 5). - In order to assure proximity of the two aromatic rings, the ethano-bridged derivatives meso- and rac- 18 were prepared by condensing meso- and rac- 7 with oxalic ester and reducing the oxalyl derivatives meso- and rac- 17 with LiAlH₄/AlCl₃, respectively (Scheme 6). The ¹H-NMR, spectra at different temperatures showed that rac- 18 populated two conformers but rac- 17 only one, all with C₂-symmetry, and that meso- 17 as well as meso- 18 populated two enantiomeric conformers with C₁-symmetry. Whereas both oxalyl derivatives 17 were fairly rigid due to the two amide groupings, the ethano derivatives 18 exhibited coalescence temperatures of -20 and 30°. - The intramolecular coupling of the two aromatic rings was successful under ‘non-phenolic oxidative’ conditions with the tetramethoxy derivatives 7, 10 and 18 , the rac-isomers leading to the desired dibenzophenanthrolines, the meso-isomers, however, mostly to dienones (Scheme 9): With VOF₃ and FSO₃H in CF₃COOH/CH₂Cl₂ rac- 7 was converted to rac- 19 , rac- 18 to rac- 21 and rac- 10 to a mixture of rac- 20 and the dienone 23b of the morphinane type. Under the same conditions meso- 10 was transformed to the dienone 23a of the morphinane type, whereas meso- 18 yielded the dienone 24 of the neospirine type, both in lower yields. The analysis of the spectral data of the six coupling products offers evidence for their structures. With the demethylation of rac- 20 and rac- 21 to rac- 25 and rac- 26 , respectively, the synthetic goal of the work was reached, but only in the rac-series (Scheme 10). - In the course of this work two cleavages of octahydro-1,1′-biisoquinolines at the C(1), C(1′)-bond were observed: (1) The biurethanes 9 and 16 in both the meso- and rac-series reacted with oxygen in CF₃COOH solution to give the 3,4-dihydroisoquinolinium salts 27 and 28 ; the latter was deprotonated to the quinomethide 30 (Scheme 11). (2) Under the Clarke-Eschweiler reductive-methylation conditions meso- and rac- 7 were cleaved to the tetrahydroisoquinoline derivative 32 .     

A convenient and diastereoselective route to homoallyl alcohols: Addition of (z)- or (e)-alkenyl-dimethoxyboranes to aldehydes

(Z)-2-Butenyl-dimethoxyborane adds smoothly to propanal and benzaldehyde to afford the homoallyl alcohols (R*,R*)- 1 and (R*,R*)- 2 , In contrast (E)-2-butenyl-dimethoxyborane leads to adducts having the (R*,S*)-configuration. Dimethoxy-(Z)-2-pentenylborane, dimethoxy-(Z)-(2-methyl-2-butenyl)borane and (2Z,4E)-or (2E,4Z)hexadienyl-dimethoxyborane, treated with propanal, give (R*,R*)- 3 , (R*,R*)- 4 , (E),(R*,S*)- 5 and (Z),(R*, R*)- 5 , respectively. A transition state model implying a pericyclic electron motion is in perfect agreement with the regio- and stereoselective outcome of these borane reactions.     

Studied Directed toward the Synthesis of Phomenoic Acid. Part 2. Stereocontrolled Synthesis of the C(7)-to-C(14) Segment

Starting from the esters (2E,4S)- 6 and (2E,4R)- 6 , bromo aldehydes (S)- 9 and (R)- 9 as well as bromo alcohols (S)- 10 and (R)- 10 , respectively, were prepared. Bromo alcohol (R)- 8 was converted to the diol (2E,4R)- 16 . Ozonolysis of the latter led to aldehyde (R)- 17 , which was transformed, by a Wittig reaction, to (2R,4E,6R)- 18 , corresponding to the C(7)-to-C(14) segment of phomenoic acid ( 1 ). Attempts to improve the yields by applying a Julia coupling of (R)- 23 , which was prepared from (2E,4R)- 7 , with (R)- 24 were unsuccessful. Finally, the coupling of the iodo derivative (2E,4S)- 28 with the lithiated derivative of 1,3-dithiane 30 by the Corey-Seebach ‘Umpolung’ led to (3S,4E)- 32 which is a derivative of the C(7)-to-C(14) segment of 1 , suitable for further transformations.     

Über die Stereospezifität der α-Alkylierung von β-Hydroxycarbonsäureestern. Vorläufige Mitteilung

About the Stereospecific α-Alkylation of β-Hydroxyesters It was found, that dianions derived from β-hydroxyesters with lithium diisopropylamide (LDA) at ?50 to ?20° were alkylated stereospecifically (Scheme 1). The stereospecificity was 95–98%, the threo-compound (threo -2, -3 and -4) being the main product. This was proved for threo -2 and -3 by preparing the β-lactones 7 and 8 , respectively, which were pyrolyzed to trans-1, 4-hexadiene (9) and trans-1-phenyl-2-butene (10) , respectively (Scheme 2). Moreover, the acid threo -6 from threo -3 was converted by dimethylformamide-dimethylacetal to cis-1-phenyl-2-butene (11) (s. footnote 6). The alkylation of α-monosubstituted β-hydroxyesters also turned out to be stereospecific. Reduction of 16 and 18 with actively fermenting yeast furnished (+) -17 and (+) -2. respectively (Scheme 4), which were each mixtures of the (2R, 3S)- and the (2S, 3S)-isomers. Alkylation of (+) -17 with allyl bromide yielded after chromatography (2S, 3S) -19 and of (+) -2 with methyl iodide (2R, 3S) -19 , the oxidation of which finally gave (S)-(?) -20 and (R)-(+) -20 , respectively.     

Synthesis, X-Ray Diffraction Data, and 1H and 13C NMR Spectra of N-(N-Arylsulfonylimidoyl)-1,4-benzoquinonimines Derived from N-Aroyl(acetyl)-1,4-benzoquinonimines

Oxidation of N-(N-arylsulfonylimidoyl)-4-aminophenols gave the corresponding N-[N-arylsulfonylimidoyl)-1,4-benzoquinonimines, derivatives of N-aroyl- and N-acetyl-1,4-benzoquinonimines. The structure of the products was studied by the X-ray diffraction method and ¹H and ¹³C NMR spectroscopy. N-(N-Arylsulfonylimidoyl)-1,4-benzoquinonimines were found to undergo fast (on the NMR time scale) Z E isomerization about the CÍN bond in the quinonimine fragment. N-(N-Arylsulfonylacetimidoyl)-1,4-benzoquinonimines in solution give rise to dynamic Z E-isomerization with respect to the CÍN bond in the N-arylsulfonylacetimidoyl fragment.     

Asymmetric Phase-Transfer Catalysis by Quaternary Ammonium Ions Derived from Cinchona-Alkaloid Analogs Containing 1,1′-Binaphthalene Moieties

The synthesis and catalytic properties of a new type of enantioselective phase-transfer catalysts, incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1′-binaphthalene moiety, are described. Catalyst (+)-(aS,3R,4S,8R,9S)- 4 with the quinuclidine fragment attached to C(7′) in the major groove of the 1,1′-binaphthalene residue was predicted by computer modeling to be an efficient enantioselective catalyst for the unsymmetric alkylation of 6,7-dichloro-5-methoxy-2-phenylindanone ( 1 ; Scheme 1, Fig. 1). Its synthesis involved the selective oxidative cross-coupling of two differently substituted naphthalen-2-ols to afford the asymmetrically substituted 1,1′-binaphthalene derivative (±)- 17 in high yield (Scheme 3). Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and functional-group manipulation gave access to the 7-bromo-1,1′-binaphthalene derivative (−)-(aS)- 11 (Scheme 4). Nucleophilic addition of lithiated (−)-(aS)- 11 to the quinuclidine Weinreb amide (+)-(3R,4S,8R)- 8 afforded the two ketones (aS,3R,4S,8R)- 27 and (aS,3R,4S,8S)- 28 as an inseparable mixture of diastereoisomers (Scheme 6). Stereoselective reduction of this mixture with DIBAL-H (diisobutylaluminum hydride; preferred formation of the C(8)−C(9) erythro-pair of diastereoisomers with 18% de) or with NaBH₄ (preferred formation of the threo-pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)-(aS,3R,4S,8S,9S)- 29 , (+)-(aS,3R,4S,8R,9R)- 30 , (−)-(aS,3R,4S,8S,9R)- 31 , and (+)-(aS,3R,4S,8R,9S)- 32 (Scheme 6). A detailed conformational analysis, combining ¹H-NMR spectroscopy and molecular-mechanics computations, revealed that the four diastereoisomers displayed distinctly different conformational preferences (Figs. 2 and 3). These novel Cinchona-alkaloid analogs were quaternized to give (+)-(aS,3R,4S,8R,9S)- 4 , (+)-(aS,3R,4S,8S,9S)- 5 , (+)-(aS,3R,4S,8R,9R)- 6 , and (−)-(aS,3R,4S,8S,9R)- 7 (Scheme 7) which were tested as phase-transfer agents in the asymmetric allylation of phenylindanone 1 . Without any optimization work, (+)-(aS,3R,4S,8R,9S)- 4 was found to catalyze the allylation of 1 yielding the predicted enantiomer (+)-(S)- 3b in 32% ee. The three diastereoisomeric catalysts (+)- 5 , (+)- 6 , and (−)- 7 gave access to lower enantioselectivities (6 to 22% ee's), which could be rationalized by computer modeling (Fig. 4).     

Multiple Enantioselection by an Enzyme-Catalyzed Transacylation Reaction

Multiply enantioselective enzyme-catalyzed transacylation reactions are described. Two instances of triply enantioselective enzyme-catalyzed transacylations are 1) the reaction of rac-1-indanol with rac-1,1′-bi-2-naphthy]-2,2′-dibutyrate to afford (S)-1-indanoL (R)-1-indanylacetate, (S)-1,1′-bi-2-naphthyl-2,2′-diol, and (R)-1,1′-bi-2-naphthyl-2,2′-dibutyrate and 2) the reaction of rac-1-indanol with rac-2,2′-bis(butyroxymethyl)biphenyl to afford (S)-1-indanol, (R)-1-indanylbutyrate, (S)-2,2′-biphenyldimethanol, and (R)-2,2′-bis(butyroxy-methyl)biphenyl. Doubly enantioselective enzyme-catalyzed transacylations are described according to two instances: 1) the reaction of rac-1-indanol with rac-1,1′-bi-2-naphthyl-2-ol-2′-butyrate afforded (S)-1-indanol, (R)-1-indanylacetate, (S)-1,1′-bi-2-naphthyl-2,2′-diol, and (R)-1,1′-bi-2-naphthyl-2-ol-2′-butyrate, and 2) the reaction of rac-1-indanol with 1,3,5-O-methylidne-2,4,6-tri-O-butyrate-myo-inositol to afford (S)-1 -indanol, (R)-l-indanylbutyrate, and 1,3,5-O-methylidne-2,6-di-O-butyrate-myo-inositol. Multiply enantioselective enzyme-catalyzed reactions have a merit of the enhancement of enantiomeric excess over singly enantioselective ones.     

Circular Dichroism of Tricarbonyl(diene)iron Complexes. The Octant Rule Applied to Ketones Perturbed by Remote Fe(CO)3 Groups. Crystal Structure of (±)-Tricarbonyl[(1RS,4RS,5RS,6SR)-C5,6,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron

The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)- 7 ) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)- 8 ), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)- 11 ) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)- 12 ) are reported. The chirality in (+)- 7 and (+)- 8 is due to the Fe(CO)₃ moieties uniquely. The signs of the Cotton effects observed for (+)- 7 and (+)- 8 obey the octant rule (ketone n→π*_CO transition). Optically pure (?)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((?)- 10 ) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*_CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (?)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((?)- 2 ) and (?)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((?)- 3 ) and of the 3-denterated derivatives (?)- 5 and (?)- 6 are also reported. The CD spectra of the complexes (?)- 2 , (?)- 3 , (+)- 7 , and (+)- 8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)₃ moiety in (±)- 8 was established by single-crystal X-ray diffraction.     

Approaches for on-line coupling of extraction and chromatography

This review provides an overview of the approaches available in order to perform on-line coupling of various extraction techniques with liquid and gas chromatography, for the analysis of semivolatile and nonvolatile analytes in liquid and solid samples. The main focus is on the instrumental set-up of these techniques. Selected real applications are described by way of illustration. The extraction methods suitable for on-line coupling covered in this review are: liquid-liquid extraction, solid-phase extraction, membrane-based techniques, pressurised liquid extraction, supercritical fluid extraction, and microwave- and sonication-assisted extractions. The following systems are not covered in this review: on-line coupled solid-phase extraction-liquid chromatography, purge-and-trap-GC, and membrane extraction with a sorbent interface-GC.Abbreviations DMAE Dynamic microwave-assisted extraction - DSAE Dynamic sonication-assisted extraction - FIA Flow injection analysis - FID Flame ionisation detection - GC Gas chromatography - HGAAS Hydride generation atomic absorption spectroscopy - IC Ion chromatography - IPLC Ion pair liquid chromatography - LC Column liquid chromatography - LLE Liquid-liquid extraction - LVI Large-volume injection - MAE Microwave-assisted extraction - MESI Membrane extraction with a sorbent interface - MMLLE Microporous membrane liquid-liquid extraction - MS Mass spectrometry - NP Normal-phase - OTT Open-tubular trapping - OTTTD Open-tubular trapping with thermal desorption - PAH Polycyclic aromatic hydrocarbon - PHWE Pressurised hot water extraction - PCB Polychlorinated biphenyl - PLE Pressurised liquid extraction - PTV Programmed-temperature vaporizer - RP Reversed-phase - RSD Relative standard deviation - SAE Sonication-assisted extraction - SFE Supercritical fluid extraction - SIM Selective ion monitoring - SLM Supported liquid membrane - SPE Solid-phase extraction - SPE-TD Solid-phase extraction-thermal desorption - SVE Solvent vapour exit - TD Thermal desorption     

Stereoselective Double Functionalization of Iron-Carbonyl Complexes of 5,6,7,8-Tetramethylidenebicyclo[2.2.2]oct-2-ene. Crystal Structure and Absolute Configuration of (–)-trans-μ-[(2S,5R,7S)-C,5,6,C-η:C,7,8,C-η-(6,7,8-trimethylidene-5-((Z)-2-oxopropylidene)-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron)

The Friedel-Crafts monoacylation of trans-η-[(1RS,2RS,4SR,5SR,6RS,7SR,8SR)-C,5,6,C-η:C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron) ((±)- 5 ) is highly stereoselective and yields trans-η-[(1RS,2RS,4RS,5SR,6RS,7RS,8SR)-C,6-η,oxo-σ:C,7,8,C-η-(6,7,8-trimethylidene-5-((Z)-2-oxopropylidene)-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron) ((±)- 8 ) which equilibrates with the trans-η-[(1RS,2RS,4RS,5SR,6RS,7RS,8SR)-C,5,6,C-η:C,7,8,C-η-(6,7,8-trimethylidene-5-((Z)-2-oxopropylidene)-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron) ((±)- 9 ) on heating. Optically pure (–)- 9 has been prepared from the corresponding optically pure alcohol (+)- 4 . The structure and absolute configuration of (–)- 9 was established by single-crystal X-ray diffraction.     

Circular Dichroism of Planar,Exocyclic S-cis-Butadienes Remotely Perturbed

Optically pure 5,6-dimethylidenebicyclo[2.2.1]hept-2-yl derivatives have been prepared. The sign of the Cotton effects associated with lowest-energy transition of 2–(dicyanomethylidene)-((?)-(1S,4S)- 15 ), (E)-2-(methoxyimino)-((+)-(1S,4S)- 16 ), (Z)-2-(methoxyimino)-5,6-dimethylidenebicyclo[2.2.1]heptane ((?)(1S,4S)- 17 ), and 2,3,5-trimethylidenebicyclo[2.2.1]heptane ((?)-(1R,4S)- 18 ) is opposite to the chirality constituted by the coupling of the electric transition moments of the two homoconjugated π-chromophores (Kuhn-Kirkwood dipole-coupling mechanism). When the substituents at C(2) are not π-functions, no general rule can be retained for the chiroptical properties of the 5,6-dimethylidenebicyclo[2.2.1]hept-2-yl systems as shown for dimethyl acetal (?)-(1S,4S)- 19 , ethylene acetal (+)-(1R,4R)- 20 , exo and endo methyl ethers (+)-(1R,2S,4R)- 21 and (+)-(1R,2R,4R)- 22 , and for spirol[5,6-dimethylidenebicyclo[2.2.1]heptane-2.2'-oxiranes](?)-(1S,2S,4S)- 23 and (?)-(1S,2S,4S)- 24 .     

Heat transfer to a particle under plasma conditions with vapor contamination from the particle

Heat transfer to a copper particle immersed into an argon plasma is considered in this paper, including the effects of contamination of the plasma (transport coefficients) by copper vapor from the particle. Except for cases of high plasma temperatures, the vapor content in the plasma is shown to have a considerable influence on heat transfer to a nonevaporating particle, and, to a lesser extent, on heat transfer to an evaporating particle. Evaporation itself reduces heat transfer to a particle substantially as shown in a previous paper [Xi Chen and E. Pfender, Plasma Chem. Plasma Process.,2, 185 (1982)]. Comparisons of the calculated results with those based on a method suggested in the above reference show that the simplified assumptions employed, i.e., that the surface temperature is equal to the boiling point and that plasma properties based on a fixed composition are applicable, can be employed to simplify calculations for many cases. This study reveals that a considerable portion of a particle must be vaporized before a steady concentration distribution is established around the particle.Nomenclature C _p specific heat at constant pressure - D diffusion coefficient of copper in the mixture - D _a diffusion coefficient of copper atoms in the mixture - D _i ambipolar diffusion coefficient of copper ions in the mixture - f mass fraction of copper in the mixture - f _a mass fraction of copper atoms in the mixture - f _i mass fraction of copper ions in the mixture - f mass fraction of copper in the plasma far away from the particle - f _s mass fraction of copper at the particle surface - G total mass flow rate due to evaporation - G _a mass flow rate of copper atoms - G _i mass flow rate of copper ions - H function defined in Eq. (19) - h specific enthalpy - h _s specify enthalpy at the particle surface - h specific enthalpy corresponding toT andf - k thermal conductivity - L latent heat of evaporation - M ₁ molecular weight of argon (M ₁=39.99) - M ₂ molecular weight of copper (M ₂=63.55) - p ₀ pressure of the gas mixture - p _s partial pressure of copper vapor at the particle surface - Q ₀ heat flux to a particle without evaporation - Q ₁ heat flux to a particle with evaporation - R gas constant - r radical coordinate - r _s particle radius - S heat conduction potential defined in Eq. (4) - S _s surface value ofS, corresponding toT _s andf _s - S free-stream value ofS, corresponding toT andf - T temperature - T _b boiling temperature of particle material - T _s particle surface temperature - T plasma temperature - density - T temperature step for numerical integration     

Thermische (E), (Z)-Isomerisierungen bei substituierten Propenylbenzolen

Thermal (E), (Z)-Isomerizations of Substituted Propenylbenzenes The thermal isomerizations of (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)phenol ((E)- and (Z)- 3 ), (E)- and (Z)-N-methyl-2-(1′-propenyl)anilin ((E)- and (Z)- 4 ), (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)anilin ((E)- and (Z)- 5 , (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z- 6 ), (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z)- 7 ), (E)- and (Z)-2-(1′-propenyl)toluene ((E)- and (Z)- 8 ), (E)- and (Z)-4-(1′-propenyl)toulene ((E)- and (Z)- 9 ) as well as of (E)- and (Z)-2-(2′-butenyl)-mesitylene ((E)- and (Z)- 10 ) in decane solution were studied (Scheme 2). Whereas the isomerization of the 2-propenylphenols (E)- and (Z)- 3 occurs already between 130 and 150° (cf. Table 1), the isomerization of the 2-propenylanilins 4 and 5 takes place only at temperatures between 220 and 250° (cf. Tables 2 and 3). The activation values and the experiments using N-deuterated 4 (cf. Scheme 4) show that 2-propenylphenols and -anilins isomerize via sigmatropic [1,5]-hydrogen-shifts. For the isomerization of the methyl-substituted propenylbenzenes temperatures > 360° are required (cf. Tables 4 and 5). The activation values of the isomerization of (E)- and (Z)- 6 and (E)- and (Z)- 9 are in accord with those of other (E), (Z)-isomerizations which occur via vibrationally excited singlet biradicals (cf. Table 7). Nevertheless, thermal isomerization of 2′-d-(Z)- 8 (cf. Scheme 6) demonstrates that during the reaction deuterium is partially transfered into the ortho-methyl group, i.e. 1,5-hydrogen-shifts must have participated in isomerization of (E)- and (Z)- 8 (cf. Scheme 8). Under the equilibrium conditions 2,4,6-trimethylindan ( 17 ) is formed slowly at 368° from (E)- and (Z)- 6 , very probably via a radical 1,4-hydrogen-shift (cf. Scheme 9). In a similar way 2-ethyl-4,6-dimethylindan ( 19 ; cf. Table 6) arises from (E)- and (Z)- 7 . Thermolysis of (E)- and (Z)- 10 in decane solution at 367° results in almost no (E),(Z)-isomerization. At prolonged heating 19 and 2,5,7-trimethyl-1,2,3,4-tetrahydronaphthalene ( 20 ) are formed; these two products arise very likely from an intermolecular radical process (cf. Scheme 10).     

Synthèse des (−)-(6R)-et(+)-(6S)-tétrahydro-6-[(Z)-pent-2-ényl]-2H-pyran-2-one,lactones de Jasminum grandiflorum L. et de Polianthes tuberosa L.

Synthesis of (?)-(6R)- and (+)-(6S)-Tetrahydro-6-[(Z)-pent-2-enyl]-2H-Pyran-2-one, lactones from Jasminum grandiflorum L. and from Polianthes tuberosa L. (?)-(2S)-Ethyl 2-hydroxyhexanedioate ((2S)- 2 ) was obtained by kinetic resolution of racemic ethyl 2-hydroxy-hexanedioate with baker's yeast. The key intermediates (+)-(5R)- and (?)-(5S)-ethyl 5,6-epoxyhexanoate ((5R)- and (5S)- 6 , resp.) are proved to be useful synthons for the total synthesis of chiral 6-alkyl-δ-lactones, as exemplified by the preparation of both enantiomers of jasmine lactone ((6R)- and (6S)- 10 , resp.).     

Raspailynes,Novel Long-Chain Acetylenic Enol Ethers of Glycerol from the Marine Sponges Raspailia pumila and Raspailia ramosa

The sponges Raspailia pumila and ramosa (Demospongiae, Tetractinomorpha, Axinellida) from the North-East Atlantic are shown to contain a series of novel long-chain enol ethers of glycerol where the enol ether C?C bond is conjugated, in sequence, to both an acetylenic and an olefinic bond. Polar extracts give raspailynes hydroxylated at their (1Z5Z)-1,5-alkadien-3-ynyl chain, like raspailyne Al ( = (+)-(S)-3-[((1Z,5Z)-16-hydroxy-hexadeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; (+ 2 ) and isoraspailyne A ( = (+)-3-[((1Z,5Z)-17-hydroxyocta-deca-1,5-dien-3-ynyl)oxy]-1,2-[propanediol; (+)- 3 ). Less polar extracts give 3 different types of raspailynes not hydroxylated at the chain. Raspailynes of the first type have either the (1Z,5Z)-configuration in a linear chain such as raspailyne B2 (( = (?)-(s)-3-[((1Z,5Z)-trideca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; (?)-4), raspailyne Bl ( = (?)-3-[((1Z,5Z)-tetradeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol;(?)- 5 ), and raspailyne B ( = 3-[((1Z,5Z)-pentadeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; 6 ) or the (1Z,5Z)-pentadeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; 6 )or the (1Z,5Z)-configuration in a chain ending with an isopropyl group, like isoraspailyne Bl ( = 3-[((1Z,5Z)-12-methyltrideca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; 7 ) and isoraspailyne B ( = 3-[((1Z,5Z)-13-methyltetradeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; 8 ). Raspailynes of the second type have the (1Z,5E)-configuration, like isoraspailyne Bla ( =3-[((1Z,5E)-tetradeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; 9 ) and isoraspailyne Ba ( = 3-[((1Z,5E)-13-methyltetradeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol; 10 ). Raspailynes of the third type have the (1E,5Z)-configuration, like isoraspailyne Blb ( = 3-[((1E,5Z)-tetradeca-1,5-dien-3-ynyl)oxy]-1,2,-propanediol; 11 ). The (S)-configuration for (+)- 1 ,((+)- 2 , and (?)- 4 is derived from chemical correlations.     

Über die «aus dem Ring»-Claisen-Umlagerung von Naphthalinderivaten

When a mixture of (E)- and (Z)-1-propenylnaphth-2-yl-allylether ((E/Z)- 5 ) is heated to 182° only the (E)-isomer rearranges to give the ‘out-of-ring’ product (E/Z)- 16 , (Z)- 5 remains unchanged. At higher temperature (Z)- 5 yields 2-methyl-naphtho[2,1-b]furane ( 15 ) as the main product. The mixture of β-chloro-allyl derivatives (E/Z)- 6 behaves in a similar way. These findings led us to suspect that the ‘out-of-ring’ products 16 and 18 are formed by direct [1, 5s] allyl migration from the starting ethers (E)- 5 and (E)- 6 . Kinetic' measurements made on (E)- and (Z)- 5 and the independently synthesized (E)- and (Z)-1-allyl-1-propenyl-1 H-naphthalen-2-ones ((E)- and (Z)- 17 ) show however, that the ethers (E)- 5 and (E)- 6 undergo a double [3s, 3s] rearrangement (i.e. Claisen followed by Cope rearrangement) and hydrogen migration to yield the ‘out-of-ring’ products (E/Z)- 16 and (E/Z)- 18 (Scheme 9). In the (Z)-series steric factors prevent the intermediate naphthalenones (Z)- 17 and (Z)-19 from undergoing the Cope rearrangement and instead, at higher temperature, cleavage of the allyl group occurs (Scheme 11). The isopropenyl derivative 7 behaves in a similar way (Scheme 5). Rearrangement of (E/Z)-1-propenylnaphth-2-yl benzyl ether ( 8 ) requires a higher temperature (214°). The nature of the products obtained (Scheme 4) makes the occurrence of a direct sigmatropic [1,5s] shift of the benzyl group very unprobable. In the case of (E/Z)-2-propenylnaphth-1-yl allyl ether ( 10 ) both isomers rearrange to yield the ‘out-of-ring’ product 30 and the para-Claisen product 32 (Scheme 7). This experiment also provides evidence against a sigmatropic [1,5s] shift of the allyl group. The same conclusion can be drawn from the thermal behaviour of (E/Z)-2-propenylphenyl allyl ether (11) and 6-t-butyl-2-propenylphenyl allyl ether ( 12 ) where only 11 yields traces of the ‘out-of-ring’ product 35 (Scheme 8). Up to this date there is no evidence whatsoever for the existence of a sigmatropic [1,5s] migration of an allyl group from oxygen to carbon. Thermal rearrangement of (E/Z)-1-propenylnaphth-2-yl propargyl ether ( 9 ) yields only (E/Z)-1-propenyl-benz[e]indan-2-one ( 27 ) (and its secondary product 28 ). The mechanism for this reaction is given in Scheme 12. Treatment of a mixture of (E/Z)- 18 with base yields the (Z)-cyclisation product 2,4-dimethylnaphth[2,1-b]oxepine ( 43 ) (Scheme 13).     

Syntheses of the Enantiomers of γ-Cyclogeranic Acid, γ-Cyclocitral,and γ-Damascone: Enantioselective protonation of enolates

(R)-and (S)-γ-cyclogeranic acid ((R)-and (S)- 9 , resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ-acids (R)-and (S)- 9 were converted into (R)-and (S)-methyl γ-cyclogeranate ((R)-and (S)- 6 , resp.), and (R)-and (S)-γ-damascone ((R)-and (S)- 5 , resp.). A more direct entry to (R)-and (S)- 9 consisted in the enantioselective protonation of a thiol ester enolate with (?)- or (γ)-N-isopropylephedrine((?)- or (γ)- 20 ) and subsequent hydrolysis of the (R)-and (S)-S-phenyl γ-thiocyclogeranate ((R)- and (S)- 24 , resp.; 97% ee). The esters (R)- and (S)- 24 were also used as precursors of (R)- and (S)-γ-damascone ((R)- and (S)- 5 , resp.). Alternatively, (S)- 5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (?)-N-isopropylephedrine ((?)- 20 ). Organoleptic evaluation demonstrated that the (S)-enantiomers of methyl γ-cyclogeranate and γ-damascone are markedly superior to their (R)-enantiomers.     

Spectroscopic and magnetic properties of Cu(II) complexes with selected biologically important ligands

The aim of this work was to study the spectroscopic and magnetic properties of copper(II) o-, m-, p-aminobenzoates, o-, m-, p-methoxybenzoates and o-, m- and p-nitrobenzoates. The complexes were synthesized and their compositions were evaluated by elementary analysis. The infrared and Raman spectra for Cu(II) aminobenzoates, methoxybenzoates and nitrobenzoates were recorded and assigned. The obtained data were compared with those previously published for aminobenzoic, methoxybenzoic and nitrobenzoic acids and their sodium salts. The structures of Cu(II) o-, m-, p-aminobenzoates, o-, m-, p-methoxybenzoates and o-, m- and p-nitrobenzoates as well as the change in the electronic charges distribution caused by Cu(II) complex formation were discussed.     

Effect of pore size distribution on the surface diffusivity in activated carbon: Hybrid Dubinin-Langmuir isotherm

The concentration dependence of the observed surface diffusivity for activated carbon due to the pore size distribution is theoretically investigated. The mathematical model is derived based on the assumption of a local hybrid adsorption isotherm (proposed recently by Shethna and Bhatia, 1994) and a local surface diffusive flux for a particular pore of half widthr. Using those local quantities and assuming a Gamma pore size distribution, the observed surface diffusivity is obtained. This observed surface diffusivity was found to increase rapidly with loading if the chemical potential is the driving force for surface flow. Furthermore, this observed surface diffusivity,D/D(0), was found to be the same as the Darken thermodynamic correction factor, using only the macroscopic isotherm information. This indicates that the thermodynamic correction factor contains information on the averaging of the surface heterogeneity.Nomenclature a coefficient for surface diffusivity - A adsorbate molecular area - c affinity parameter of the surface adsorption isotherm - C(P, T) concentration - C _max maximum adsorbed concentration - D _obs observed surface diffusivity - D _s intrinsic surface diffusivity - D _s0 coefficient of intrinsic surface diffusivity - E ₀ characteristic energy of Dubinin isotherm - F(r) pore size distribution - J local flux - J _obs observed flux - k empirical constant of Dubinin isotherm - K Langmuir affinity parameter - K _m Langmuir affinity parameter at maximum micropore half width - m structural parameter defined in Eq. (13) - n Dubinin variable exponent - q structural parameter defined in Eq. (13) - Q function ofr andT defined in Eq. (4) - Q _m function ofn defined in Eq. (8) - P pressure - P ⁰ vapour pressure - P _t threshold pressure defined in Eq. (3) - P ₀,P _L pressure at two end of the slab - P minimum pressure for Dubinin isotherm - P _m threshold pressure at maximum micropore half width - S ₁,S ₂ scaling factors defined in Eq. (15) - r pore half width - r ₀ smallest micropore half width - r _t threshold micropore half width demarcates Dubinin and Langmuir mechanisms - r _m maximum micropore half width - v _M liquid molar volume of adsorbate - V pore volume - R gas constant - T temperature - x axial variable - parameter defined in Eq. (A-7) - affinity factor of Dubinin isotherm - _L constant defined in Eq. (A-7) - small number - pore variance - non dimensional local isotherm - _D non dimensional Dubinin isotherm - _L non dimensional Langmuir isotherm - _S non dimensional surface isotherm - _obs non dimensional overall adsorption isotherm     

5a-Carba-β-D-, 5a-Carba-β-L- and 5-Thio-β-L-xylopyranosides as New Orally Active Venous Antithrombotic Agents

Mitsunobu displacement of (−)-(1S,4R,5S,6S)-4,5,6-tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-ol ((−)- 12 ; a (−)-conduritol-F derivative) with 4-ethyl-7-hydroxy-2H-1-benzopyran-2-one ( 16 ) provided a 5a-carba-β-D -pyranoside (+)- 17 that was converted into (+)-4-ethyl-7-[(1′R,4′R,5′S,6′R)-4′,5′,6′-trihydroxycyclohex-2′-en-1′-yloxy]-2H-1-benzopyran-2-one ((+)- 5 ) and (+)-4-ethyl-7-[(1′R,2′R,3′S,4′R)-2′,3′,4′-trihydroxycyclohexyloxy]-2H-1-benzopyran-2-one ((+)- 6 ). The 5a-carba-β-D -xyloside (+)- 6 was an orally active antithrombotic agent in the rat (venous Wessler's test), but less active than racemic carba-β-xylosides (±)- 5 and (±)- 6 . The 5a-carba-β-L -xyloside (−)- 6 was derived from the enantiomer (+)- 12 and found to be at least 4 times as active as (+)- 6 . (+)-4-Cyanophenyl 5-thio-β-L -xylopyranoside ((+)- 3 ) was synthesized from L -xylose and found to maintain ca. 50% of the antithrombotic activity of its D -enantiomer. Compounds (±)- 5 , (±)- 6 , and (−)- 6 are in vitro substrates for galactosyltransferase 1.