Reactions with β-cyanoethylhydrazine,III. A new approach for the synthesis of substituted 3,5-diaminopyrazole and 1,2,4-triazoles

The reactivity of -cyanoethylhydrazine toward enaminonitrile and aroyl isothiocyanates is reported. A variety of 3,5-diaminopyrazole and ³-1,2,4-triazolin-5-thione derivatives could be prepared.

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Reaktionen mit -Canyethylhydrazin, 3. Mitt.: Ein neuer Weg zur Synthese von substituierten 3,5-Diaminopyrazolen und 1,2,4-Triazolen

Zusammenfassung Es wird über die Reaktivität von -Cyanethylhydrazin gegenüber Enaminonitril und Aroylisothiocyanaten berichtet. Es konnte eine Reihe von 3,5-Diaminopyrazol-und ³-1,2,4-Triazolin-Derivaten hergestellt werden.

     

α-Alkoxy-β-dicarbonylverbindungen durch Acylierung von Lithiumenolaten

A series of -alkoxy--dicarbonyl compounds2 were prepared by acylation of lithium enolates in good to excellent yields by a simple one-pot procedure.

     

Porphyrins. 38. Reaction of Porphyrins Containing Hydroxy(alkoxy)ethyl or Alkoxymethyl Substituents with Nucleophiles in the Presence of Zinc Acetate. A Novel, Promising Method for the Modification of Porphyrins on the Periphery of the Macrocycle

Porphyrins which contain 1-hydroxy(alkoxy)ethyl or alkoxymethyl substituents on the periphery of the macrocycle (i.e. formally able to yield benzyl type carbocations) react with nucleophiles (4-tert-butylphenol or the -diketones acetylacetone, benzoylacetone, dibenzoylmethane, or 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione) in the presence of excess zinc acetate. They give high yields of the corresponding addition products, which are the zinc complexes of porphyrins with a 1-(4-tert-butylphenoxy)ethyl substituent or with substituents containing -diketone residues.     

Reaction of β-Cyclodextrin with N-2,3-Epoxypropylphthalimide. Preparation, Characterisation and Study of a New Substituted Cycloheptaamylose. Effects on the Water Solubility of Drugs

The reaction of -cyclodextrinwith N-2,3-epoxypropylphthalimide yielded a set of newamorphous host compounds with high solubility whichwas transmitted to the corresponding host-guestcomplexes. The structure was determined by comparing the 1H- and 13C-NMR spectra with those of theparent compound, the degree of substitution by integration of the corresponding NMR signals, and C, H,and N elemental analysis.     

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.     

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.     

Synthesis of Substituted 1,2,4-Triazines Based on 1,2-Bis(2,5-dimethyl-3-thienyl)ethanedione

A novel, convenient method has been developed for the synthesis of 1,2-bis(2,5-dimethyl-3-thienyl)ethanedione, from which were prepared 5,6-bis(2,5-dimethyl-3-thienyl)-1,2,4-triazines (analogs of the photochromic 1,2-diarylethenes). The principial possibility of using 1,2,4-triazines obtained as photochromic agents was investigated.     

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.     

Photochemical addition of diethyl ether to β,β,β',β'-tetrakis(trifluoromethyl)divinyl ether

The 1:1 adducts of diethyl and ,,','-tetrakis(trifluoromethyl)divinyl ether (1),i.e., 3,5-(ee)-bis[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2,6-dimethyl-1,4-dioxane (2) (3 isomers) and 4-ethoxy-1,1,1-trifluoro-2-trifluoromethyl-3-[3,3,3-trifluoro-2(trifluoromethyl)propenyloxy]pentane (3), have been obtained by UV-irradiation of a solution of divinyl ether1 in diethyl ether. The X-ray structural investigation of the all-(e)-isomer of dioxane (2) has been carried out.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 85–88, January, 1994.     

In Situ Crystallization of Bacterial Cellulose III. Influences of Different Polymeric Additives on the Formation of Microfibrils as Revealed by Transmission Electron Microscopy

Effects of polymer additives on the formation of microfibrils of bacterial cellulose have been examined by transmission electron microscopy. Among additives with different degrees of polymerization (DP) or substitution (DS), carboxymethyl cellulose sodium salt (CMC) with DP = 80 and DS = 0.57 is the most effective in producing separate, smaller-size microfibrils. By increasing the concentration of this CMC from 0.1 to 1.5%, the percentage of microfibrils measuring 3–7 nm wide is increased and levels off at around 1.0%. Other polymer additives such as xyloglucan are less effective than CMC in producing microfibrils with smaller sizes and the resulting microfibrils still tend to aggregate. The number of charged substituents and the molecular weight seem to be important factors in the production of highly separate smaller-size microfibrils. The reduction in average microfibril size is well correlated to the decrease in mass fraction of cellulose I in bacterial cellulose crystals. On the basis of these results, the mechanism of the crystallization of celluloses I and I is discussed. The effect of colony types, smooth and rough, on the formation of microfibrils in the presence of CMC is also described.     

Sila-Riechstoffe und Riechstoffe-Isostere, 10. Mitt. Ein neuer Weg zu Sila-β-Jonon

Preparation of sila--ionone (14) was possible by a novel route with yields nearly 5 times higher than before¹, with the formerly unknown 1,1,3-trimethyl-1-silacyclohexanone-2 (6) as a key substance. The nine reaction steps may be seen from Scheme 1. 2-Ethinyl-1,1,3-trimethyl-1-silacyclohexan-2-ol (7) could not be dehydrated to give the analogous silacyclohexene derivative9. But dehydration was successful in the case of 2-(1-butin-3-ol) substituents; here only the ring but not the chain hydroxyl group was eliminated.

     

Analytical relationships between the ionization of 1,3-dicarbonylic ligands and stability of their Cr(III), Ni(II), Co(II) and Cu(II) 1∶1 chelates

It has been demonstrated that the logarithm of the stability constant of some monochelated chromium(III) compounds, with structurally similar 1,3-dicarbonylic species, is linearly related to the negative logarithm of the acid ionization constant of the ligand. Graphical and analytical correlations which could be useful in predicting equilibrium constants of chromium(III)--diketonates, as well as other first-row transition metal derivatives, have been developed. A quantitative evaluation of the complexes stability has been carried out, providing information about the effects of ligand substituents on the equilibrium constants.     

Charge-transfer complexes betweenp-toluidine and iodine in solution: A kinetic study

The kinetics of charge-transfer interaction betweenp-toluidine and iodine in methylene chloride was investigated in depth. Thethermal process of formation of theinner complex was found to proceed to an equilibrium. Thephotochemical process follows a different reaction coordinate, going through the formation of an exciplex between the excitedouter complex and the amine ground state. In both cases the same ionic complex (Am ₂I⁺I ₃ ^– , whereAm stands forp-toluidine) was detected as the final product.

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Kinetische Untersuchung der Charge-Transfer-Komplexe zwischenp-Toluidin und Jod

Zusammenfassung Die Kinetik der Charge-Transfer-Wechselwirkung zwischenp-Toluidin und Jod in Methylenchlorid wurde ausführlich untersucht. Derthermische Prozeß, der zur Bildung desinner-Komplexes führt, geht bis zu einem Gleichgewicht. Derphotochemische Prozeß folgt einer unterschiedlichen Reaktionskoordinate und verläuft über die Bildung eines Exziplexes zwischen dem angeregtenouter-Komplex und dem Amin im Grundzustand. In beiden Fällen wurde derselbe ionische Komplex (Am ₂I⁺I ₃ ^– , wobeiAm fürp-Toluidin steht) als Endprodukt festgestellt.

     

In vitro Release Study of Tretinoin from Tretinoin/Cyclodextrin Derivative Complexes

The effects of -cyclodextrin, hydroxypropyl -cyclodextrin and dimethyl -cyclodextrin complexes on the in vitro release of tretinoin gels were investigated. The experiments were carried out in a Franz cell using a silicone membrane as a barrier for the diffusion of the vehicle. Two types of vehicle were compared: a hydroalcoholic gel in which both tretinoin and the inclusion complexes are soluble, and an aqueous gel in which only the complexes are soluble but tretinoin is dispersed. As expected, the release rate of free tretinoin in the hydroalcoholic gel is much faster than in the aqueous gel. However, with the aqueous gel, the cyclodextrin complexation enhances the diffusion rate of the active drug through the membrane, especially with the hydroxypropyl cyclodextrin inclusion compound. The release of tretinoin is related not only to the stability constant of the inclusion, but also to the binding properties of the inclusion compounds to the vehicle.     

Improvement of Solubility and Dissolution of 19-Norprogesterone via Inclusion Complexation

In an effort to modify the solubility and dissolution rate of the contraceptive steroid, 19-norprogesterone in order to improve its bioavailability, the cyclodextrin complexation approach was chosen. In solution, the complex formation with -cyclodextrin (-CD), hydroxyethyl -cyclodextrin (HE--CD) and hydroxypropyl -cyclodextrin (HP--CD) was confirmed by using solubility, UV, IR and ¹H-NMR spectrophotometric techniques. The phase solubility diagrams were categorized as A_L-type. The complexing affinity of the CDs investigated were ranked as follows: -CD > HP--CD > HE--CD. The complexation thermodynamic parameters were obtained from the temperature dependence of the dissociation constants. In the solid state, differential scanning calorimetery (DSC) and optical microscopy methods were utilized to characterize the complexes. Dissolution studies showed that such molecularly encapsulated forms offered a marked improvement in the dissolution rate compared to the parent drug.     

Ring opening of fluoroalkyl-containing α,β-epoxyketones by aromatic amines

Aromatic amines cause ,-epoxyketones containing a -fluoroalkyl group to undergo ring opening at the -position to give -amino--hydroxyketones.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 882–883, May, 1994.     

Elucidation of a common structure of selective fibrinogen receptor antagonists

In this paper, we investigate the common structural and electrostatic parameters of a series of specific inhibitors of the IIb3 integrin. Molecular dynamics simulations with an explicit aqueous environment led to an original theoretical pattern. Our results may suggest that the studied non-peptide IIb3 antagonists developed upon the Arg-Gly-Asp ubiquitous recognition sequence, in fact, should mimic the C-terminus part of the fibrinogen chain. This assumption could, therefore, explain their specificity with respect to other Arg-Gly-Asp-dependent integrins.     

Substituted 1,2-Thiazetidine 1,1-Dioxides. Synthesis and Properties of N-Alkylated and N-Acylated Derivatives of 1,2-Thiazetidine-3-acetic Acid 1,1-Dioxide

Summary. 1,2-Thiazetidine-3-acetic acid 1,1-dioxide was N-alkylated using bromoacetates, and N-acylated using either acyl chlorides, protected amino acid fluorides, or N-protected amino acid NCA, which seemed to be the most universal method. Most of the obtained -sultam peptides were sensitive against humidity, they hydrolyzed forming sulfonic acids, and reactions with amines resulted in sulfonamides. Reactions of N-acylated products showed that the sulfonyl group was faster attacked than the imide structure.     

Asymmetrical synthesis of organometallic analogs of natural compounds. 8. Reactions of pentafluorobenzaldehyde with the Ni(II) complex of a schiff base of glycine and (S)-2-[N-(benzylprolyl)amino]benzophenone

Reaction of pentafluorobenzaldehyde with a Ni(II) complex of a Schiff base formed from glycine and (S)-2-[N-(benzylprolyl)amino]benzophenone yields, depending on the reaction conditions, the hitherto unknown, diastereo-and enantiomerically pure amino acids 2R,3S--(4-methoxytetrafluorophenyl)serine, 2S,3R--(4-methoxytetrafluorophenyl)serine, 2S,3S--(pentafluorophenyl)serine, and 2S,3R--(pentafluorophenyl)serine.A. N. Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, 117813 Moscow. Institute of Bioorganic Chemistry and Petroleum Chemistry, Ukrainian Academy of Sciences, 252028 Kiev. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 687–693, March, 1992.     

Pyrazolopyrimidines Based on 5-Aminopyrazoles Unsubstituted at the Position 1

By condensation of various symmetric -diketones with a series of 5-aminopyrazoles that are unsubstituted at the position 1, we have obtained a series of pyrazolo[1,5-a]pyrimidines that are of interest as physiologically active compounds. Hexafluoroacetylacetone reacts in another direction, forming pyrazolo[4,5-b]pyridine.