Crystal and Molecular Structure of Cu(II) Bis-(2-methoxy-2,6-dimethyl-3-imino-5-heptanonate)

A new compound from the series of alkoxyketoiminates, Cu(II) bis-(2-methoxy-2,6-dimethyl-3-imino-5-heptanonate), has been synthesized and studied by X-ray crystallography. Crystal data for CuO₄N₂C₂₀H₃₆: a=10.154(1), b=9.921(1), c=11.684(2) , =96.17(1)°, space group P2₁/c, Z=2, dcalc =1.226 g/cm³, R=0.037. The structure is molecular and built from isolated trans-complexes. The copper atom has a plane square environment of two oxygen atoms (Cu–O 1.93 ) and two nitrogen atoms (Cu–N 1.90 ). The O–Cu–N chelate angle is 91.7°. The complex has an intramolecular hydrogen bond, N–H...O 2.16 , involving the alkoxy oxygen atom. The molecular packing in the crystal is close to that of copper(II) dipivaloylmethanate. The calculated van der Waals intermolecular interaction energies and thermogravimetric characteristics of the complexes are compared.     

Nitrosation of mefenorex in the presence of cyclodextrins

- and -Cyclodextrin (CD) and heptakis-2,6-di-O-methyl--cyclodextrin (DIMEB) form soluble inclusion compounds with mefenorex (MEF); with -CD a partial inclusion occurs. No solid inclusion compound could be obtained with the four CDs. -, -CD and DIMEB, but not -CD, enhance the nitrosation rate of MEF if the nitrosation assay procedure (NAP test) is applied. During this reaction with - and -CD, solid inclusion compounds of the CDs and nitrosomefenorex (NMEF) precipitate.Part of the Ph.D. thesis of V. Wedelich, Freie Universität Berlin, 1985.     

Spectroscopic detection of theendo-enol form of 2-acetylcyclopentane-1,3-dione

According to vibrational spectroscopic data, in the gas phase at 280 °C and in crystals prepared by sublimation, 2-acetylcyclopentane-1,3-dione was established to exist not as trione 1 but as the enol-form 2 with an exo-cyclic C=C bond (v(C=C) = 1593 cm^–1) and an intramolecular hydrogen bond. The enol 3 prepared by crystallization from CCl₄ is also stabilized by an intramolecular H-bond but has anendo-cyclic C=C bond (v(C=C) = 1545 cm^–1). In a trichloroethylene solution, both theexo- andendo-enol forms co-exist, and the percentage of the latter is 11 %. The frequencies in the vibrational spectra have been assigned using the normal coordinate calculation of2, 3, and their OD-analogs. The mechanism of tautomer transfer is discussed in terms of PMO theory.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 57–62, January, 1994.The authors are grateful to professor J. G. Ramos (Madrid Institute of Optics) for making it possible to record the far IR and Raman spectra in his laboratory, to Dr. V. Z. Kurbako for the registration of spectra and its discussion, and to Dr. N. A. Kubasova for recording the Raman spectra with a Coderg Ar-300 instrument.     

Glykosylazide als Ausgangsbasis zur Gewinnung von Nucleosidanalogen, 3. Mitt. Synthese von Alkylaminotetrazol- und Uretidinonnucleosiden

The -ribofuranosylazide1 is transformed after usual derivatization by suitable protecting groups into the P–N-ylid2, which gives the corresponding N-Glykosyl-N-alkylcarbodiimides4 and a small amount of the glykosylisocyanatde-rivative3 by reaction with alkylisocyanates. The carbodiimides4 were reacted with hydrazoic acid to give the alkylaminotetrazolnucleosides5 and finally the free nucleosidanalogs6. In the case of5 c the 5-aziridinyltetrazolnucleosid5 h was formed by an usual neighbouring group reaction. In addition the compound1 is transformed into the 3,5-diprotected anchor derivative7 by reaction withTIPSCl₂. The latter could be transformed by usual steps into the alkylaminotetra-zolnucleosides8 with a free 2-OH group. In the next step the 2-p-tolylthiocarbo-nates9 were prepared followed by transformation to the 2-desoxynucleosides10 by means of tributyltinhydride. Finally the free 2-desoxynucleosides11 were prepared. By reacting the carbodiimides4 with phenylisocyanate a mixture of the two possible regiouretidinonnucleosidderivatives12 and13 are formed. In the case of the N-glykosyl-N-allylcarbodiimide4 d only the one isomer13 d arises.

Herrn Prof. Dr.A. Neckel mit den besten Wünschen zum 60. Geburtstag gewidmet.     

Synthesis and biological activity of yuccagenin bisrhamnoside

The two hydroxyls of yuccagenin can be glycosylated by Koenigs-Knorr condensation with acetobromorhammose in dichloroethane in the presence of mercuric cyanide. The bisrhamnoside of yuccagenin markedly lowers the cholesterol and triglyceride content in blood serum of healthy animals and animals with experimental hyperlipidemia.Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 242–243, May–June, 2000.     

peri-Naphthylenediamines 18. 1,8-Bis(dimethylamino)-4-vinylnaphthalene

The 1-[1,8-bis(dimethylamino)-4-naphthyl[ethyl carbocation generated from the corresponding alcohol in benzene in the presence of Al₂O₃ undergoes elimination according to theE1 mechanism to give previously unknown 1,8-bis(dimethylami no)-4-vinyl naphthalene in a good yield. This compound was also synthesized from 1,8-bis(dimethylamino)-4-formylnaphthalene by the Wittig reaction. Polymerization of the vinylic derivative obtained was studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2297–2300, September, 1996.     

Schiff base derivatives of lanthanons-synthesis of La(III), Pr(III) and Nd(III) derivatives of β-ketoimines derived from 2,4-pentanedione

Reactions of the isopropoxides of some of the lighter lanthanons with bidentate -ketoimines, such asAAH-n-C₄H₉ andAAH-C₆H₅ (donor system: N,OH) and tridentate -ketoimines such asAA(CH₂CH₂)H₂ andAA(CH₂CHCH₃)H₂ (donor system: HO,N.OH) have led to products of the typesLn(O-i-C₃H₇)_3n (AA-R) _n ,Ln(Oi-C₃H₇) (AAR') andLn ₂(AAR')₃ [Ln=La(III), Pr(III) or Nd(III);n=1 or 2;R=-n-C₄H₉ or-C₆H₅ andR'=-CH₂CH₂-or-CH₂CHCH₃-]. Some undergo exchange reactions with an excess oftert-butanol, leading to the corresponding complexesLn(O-tert-C₄H₉)_3n (AA-n-C₄H₉) _n andLn(O-tert-C₄H₉) (AA-CH₂CH₂). All these have been characterised by elemental analysis, molecular weight determinations and their ir spectra. A thermogravimetric analysis of the diisopropoxy derivatives has also been carried out.

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Schiff-Basen Derivate von Lanthaniden-Synthese von La(III), Pr(III) und Nd(III) chelaten mit -Ketoiminen

Zusammenfassung Reaktionen von Lanthanid-Isopropoxiden mit zweizähnigen -Ketoiminen [AAH-n-C₄H₉ undAAH-C₆H₅; Donorsystem: N,OH] und dreizähnigen -Ketoiminen [AA(CH₂CH₂)H₂ undAA(CH₂CHCH₃)H₂; Donorsystem: OH, N,OH] führten zu Produkten vom, TypLn(O-i-C₃H₇)_3-n (AA-R) _n ,Ln(O-i-C₃H₇) (AAR') undLn ₂(AAR')₃ [Ln=La(III), Pr(III) oder Nd(III);n=1 oder 2;R=n-C₄H₉ oder C₆H₅ undR'=CH₂CH₂ oder CH₂CHCH₃]. Einige Komplexe unterliegen bei Behandlung mit einem Überschuß vontert-Butanol einer Austauschreaktion, die zu den entsprechenden Butoxid-Komplexen führt [Ln(O-tert-C₄H₉)_3-n , (AA-n-C₄H₉) _n undLn(O-tert-C₄H₉) (AACH₂CH₂)]. Alle Derivate wurden mittels Elementaranalyse, Molgewichtsbestimmung und IR-Spektroskopie charakterisiert. Eine thermogravimetrische Analyse der Diisopropoxi-Derivate wurde ebenfalls ausgeführt.

     

Configuration interaction methods for improving unrestricted Hartree-Fock spin densities

Limited Configuration Interaction wave functions based on Unrestricted Hartree-Fock natural orbitals are found to be easy to compute and to give much more satisfactory spin densities than are provided by techniques currently in use.     

A new method for the synthesis of CF3-containing aminovinyl ketones

A new method for the synthesis of aminovinyl trifluoromethyl ketones was developed. The method is based on the reactions of 4-sulfonyl-1,1,1-trifluorobut-3-ene-2,2-diols with various alkyl-, aryl-, dialkyl-, and alkylarylamines. The stereochemistry of the compounds obtained was studied.     

Substituted 1,2-Thiazetidine 1,1-Dioxides. Synthesis of (<Emphasis Type="Italic">RS</Emphasis>)- and (<Emphasis Type="Italic">S</Emphasis>)-1,2-Thiazetidine-3-acetic Acid 1,1-Dioxide and its Reactions with Amino Acids and Dipeptides

Summary. (RS)-2-tert-Butyldimethylsilyl-1,2-thiazetidine-3-acetic acid 1,1-dioxide prepared from (RS)-S-benzyl--homocysteine was condensed via DCC/NHS with various L-amino acid esters or dipeptide esters yielding N-silylated -sultam peptides. A -sultam active ester was isolated as an intermediate. Desilylation with TBAF in THF yielded stable N-unsubstituted products, and deprotection of the benzyl esters was achieved by catalytic hydrogenation. (S)-S-Benzyl--homocysteine was obtained by fractional crystallization of the brucine salt of the racemate and transformed into benzyl (S)-1,2-thiazetidine-3-acetate, which was on the other hand synthesized by an enantiospecific route from -benzyl Boc-L-aspartate. Some -sultam peptides were prepared from the (S)-enantiomer, and finally some -sultam peptides containing D-Ala units were obtained.     

Synthesis of β-D-xylofuranosyl- and 2,2′-anhydro-1-β-D-lyxofuranosylpyrimidine nucleosides

-D-Xylofuranosylpyrimidines were obtained by condensation of silyl derivatives of pyrimidines with 1,2-di-O-acetyl-3,5-di-O-benzoyl-D-xylofuranose with subsequent deprotection of the sugar fragment. Refluxing 2-O-tosyl derivatives of nucleosides with NaI results in the formation of 2,2-anhydro-compounds.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1137–1141, June, 1993.     

Transformationen von β-Glycofuranosylisocyaniden in Tetrahydrofuranderivate

Summary Readily available -glycofuranosyl isocyanides1,2,4,5,6,18,19,20 are transformed into the corresponding protected tetrahydrofurans21,22,23,24,25,26 by means of tributyltin hydride andAIBN. The synthesis of18 and19 by dehydration of the formamide15 is described. Starting with 6-deoxy-1,2-O-isopropyliden--D-allofuranose (7) crystalline 1,2-O-diacetyl-3,5-dibenzoyl--D-allofuranose (9) is obtained.9 is first transformed into the anomeric azides11,12 and13,14 and subsequently into the formamide15.

     

Interaction of fluoroalkyl-containing β-diketones with amines

The composition of products of the interaction of asymmetric fluoroalkyl-containing -diketones with amines was studied. Mixtures of regioisomeric -aminovinylketones and products of cleavage and secondary condensation are formed, depending on the temperature, the solvent, the nature of the fluorinated and nonfluorinated substituents in the -diketone, and the basicity of the amine. The major product is a -aminovinylketone in which the NH₂ group is removed from the fluoroalkyl substituent. No -aminovinylimines, products of condensation involving two electrophilic centers, were observed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2278–2284, September, 1996.     

Allylumlagerung beiS N -Reaktionen von 4-(α-Chloralkyl)pyridazinen

The preparation of 4-(-chloroalkyl)pyridazines (4, 7b, 7c, 10) is reported. Compounds4, 7a, 7b, and7c were found to be attacked by methoxide ions mainly at the heteroaromatic ring, thus forming 5-methoxy-4-alkylpyridazines.10 on reaction with sodium methanolate yields exclusively 4-benzyl-5-methoxymethyl-pyridazine (12). In addition, starting from4, the amines5a, 5b, 6a, and6b were prepared.

Herrn Univ.-Prof. Dr.Karl Schlögl mit den herzlichsten Wünschen zum 60. Geburtstag gewidmet.     

Crystal and Molecular Structure of (BzlMe3N) 2 + [Fe2OCl6]2-

The crystal and molecular structure of (BzlMe₃N) ₂ ⁺ [Fe₂OCl₆]^2- has been determined. The asymmetric unit contains two benzyltrimethylammonium cations and two half -oxo-bis(trichloro-iron(III)) anions. The bridging -oxygen atoms of these anions are located over crystallographic symmetry elements. Therefore, the two anions resulting from the symmetry operations correspond to two different conformers presenting angular and linear dispositions of the Fe-O-Fe bond angle. Mössbauer spectrum consists of two asymmetric lines that are adequately simulated by two equally populated quadrupole doublets associated with the two iron sites.     

Use of ethyl oxamate for syntheses of oxamato(-1) and novel μ-oxamato(-2) complexes

Summary The use of ethyl oxamate for the synthesis of inorganic oxamato complexes is reported. A reaction system leading to the preparation of the novel polymeric -oxamato(-2) complexes [M(oxm)(H₂O)₂] _x (M=Cu, Zn, Cd), [Co(oxm)(H₂O)₂] _x ·0.5xH₂O and [Ni(oxm)(H₂O)₂] _x ·xH₂O is described (H₂ oxm = oxamic acid). Ethyl oxamate can also be used for the preparation of monomeric oxamato(-1) complexes.

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Der Einsatz von Ethyloxamat für die Synthese von Oxamato(-1) und neuen -Oxamato(-2)-Komplexen (Kurze Mitt.)

Zusammenfassung Es wird der Einsatz von Ethyloxamat für die Synthese von anorganischen Oxamato-Komplexen beschrieben. Ein Reaktions-System für die Herstellung von neuen -Oxamato(-2)-Komplexpolymeren: [M(oxm)(H₂O)₂] _x ; (M = Cu, Zn, Cd), [Co(oxm)(H₂O)₂] _x ·0.5xH₂O und [Ni(oxm)(H₂O)₂] _x ·xH₂O, wird vorgestellt. Ethyloxamat kann auch für die Herstellung von monomeren Oxamato(-1)-Komplexen verwendet werden.

     

Reactivity of pyrrole pigments,XXI: Structure and reactivity of Cu(II) and Zn(II) bilindione chelates

Summary Several Mn, Cu, and Zn chelates of etiobiliverdin-IV-, mesobiliverdin-IX, and its dimethyl ester are studied. The results show that the chemical constitution of the Cu biliverdin chelate corresponds to a formal metal oxidation state of (II) coordinated to a neutral radical of the NH trideprotonated biliverdin. The reactivity of the Cu(II) bilindione chelates in nucleophilic solvents agrees with that expected for a neutral radical structure of the ligand; in CH₃OH, they undergo oxidation towards dimethoxybilipurpurins. The magnetic behaviour of Cu(II) etiobiliverdinate-IV- in the solid state shows an intramolecular weak antiferromagnetic coupling d⁹Cu-to--radical (J=–23 cm^–1) and an intermolecular weak antiferromagnetic coupling -radical-to--radical (J=–45 cm^–1). The analogy of this magnetic behaviour to that of the cation radical of metalloporphyrins is discussed.

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Reaktivität von Pyrrolpigmenten, 21. Mitt.: Struktur und Reaktivität von Cu(II)- und Zn(II)-Chelaten von Bilindionen

Zusammenfassung Einige Mn, Cu and Zn Chelate von Etiobiliverdin-IV-, Mesobiliverdin-IX und seinem Dimethylester werden untersucht. Im Komplex koordiniert ein Metallatom (mit der Formalladung II) mit einem Neutralradikal des dreifach NH-deprotonierten Bilindions. Die Reaktivität des Komplexes gegenüber nukleophilen Lösungmitteln entspricht erwartungsgemäß dem eines neutralen -Radikals; in CH₃OH wird er zu Dimethoxybilipurpurin oxidiert. Bei Cu(II)-Etiobiliverdinat-IV beobachtet man im festen Zustand neben schwacher, antiferromagnetischer Kupplung zwischen d⁹Cu und -Radikal (J=–23 cm^–1) auch eine schwache, intermolekulare, antiferromagnetische Wechselwirkung zwischen zwei -Radikalen (J=–45 cm^–1). Dieses magnetische Verhalten wird dem des -Kationradikals von Metalloporphyrinen gegenübergestellt.

     

Synthesis and thermal decomposition of 3-aroyl-4-aryl-2-pyrazolines

Summary 3-Aroyl-4-aryl-2-pyrazolines (21–40) have been synthesized by the reaction of ,-unsaturated ketones (1–20) with diazomethane. These 2-pyrazolines gave -methyl-,-unsaturated ketones (41–46) on thermal denitrogenation.Dedicated to Prof. Dr.F. Sauter on the occasion of his 65^th birthday     

Reactions of 2-ethoxycarbonyl(carboxy)-5,6,7,8-tetrafluorochromones with N-nucleophiles

The direction of reactions of 2-ethoxycarbonyl-5,6,7,8-tetrafluoro- and 2-carboxy-5,6,7,8-tetrafluorochromones with ammonia, methylamine, hexylamine, and aniline depends on the inductive effect of the substituent at position C-2 of the chromone and on the basicity of the amine. Nucleophilic aromatic substitution of a fluorine atom takes place in the interaction of 2-ethoxycarbonyl-5,6,7,8-tetrafluorochromone with secondary amines (morpholine,N-methylpiperazine) and ethylenediamine.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 904–907, May, 1994.     

A Novel Cyclodextrin-containing Glass Thermoplastic System (GTS) for Formulating Poorly Water Soluble Drug Candidates: Preclinical and Clinical Results

We present a novel solid solution/dispersion technology with glass thermoplastic properties that provide good dissolution rates and oral bioavailabilities for poorly water-soluble weak bases. In this process, a thermoplastic gum was prepared by mixing a polyhydroxy acid such as citric acid or tartaric acid with a weakly basic drug, hydroxypropyl--cyclodextrin (HP--CD) and a cellulose polymer such as hydroxypropylmethylcellulose (HPMC) in a protic solvent. Removal of the solvent gave a material which could be loaded into hard gelatin capsules. Several model compounds were processed in this manner including methylene blue and itraconazole. The resulting data indicated that dissolution properties of GTS's based on methylene blue was pH independent and rapid with 80% dissolved within 30 min. Three GTS formulations of itraconazole containing 100 mg of the drug and 500 mg of citric acid as well as various concentrations of HP--CD and HMPC were found to dissolve rapidly (100% in 45 min). One of these formulations was selected for human pharmacokinetic evaluation and demonstrated significant oral bioavailability relative to unmanipulated drug.The studies suggest that the components of the GTS provide for solubilization through complexation and reduced pH and that the cellulose polymer acts to inhibit recrystallization of the supersaturated solution formed. The rationaldevelopment of the GTS dosage form can be useful for generating acceptable formulations for poorly water-soluble drug candidates.