A New Entry for Short and Regioselective Synthesis of [1,2,4]Triazolo[4,3‐b][1,2,4]‐triazin‐7(1H)‐ones

Reaction of benzenediazonium chloride with active [1,2,4]triazin‐3‐ylthio‐methylene compounds 3 afforded the azo coupling products 5 , which yielded [1,2,4]triazolo[4,3‐b][1,2,4]triazin‐7(1H)‐ones 8 upon treatment with sodium ethoxide in ethanol. The latter products 8 were characterized on the basis of alternate synthesis and spectral data. The mechanism of formation of 8 and the regiochemistry of the studied reactions are discussed.     

Darstellung und Atropisomerie von 1‐(2‐Aryl)‐piperidin‐2‐onen

Preparation and Atropisomerism of 1‐(2‐Aryl)‐piperidin‐2‐ones Course and rate of the dehydrogenation of N‐tertiary piperidines dependent on their substitution in 4‐position and on the hydroxy bearing neighbor group were examined, using mercury(II)‐EDTA and the model amino alcohols 1a 1e, 3a 3f, 8a 8f and 10a 10f . The results showed that increasing size of 4‐substituents and neighbor groups too decreased the rate of reaction. The products from the 2‐substituted benzylic alcohols, the 2‐piperidones 7a 7g, 9a 9g and 11a 11g demonstrated atropisomerism. In the case of chiral neighbor groups diastereomeric mixtures were formed.     

Beziehungen zwischen algistatischer Aktivität und physikalisch‐chemischen Eigenschaften von 5‐Amino‐1‐aryl‐1H‐tetrazolen

A series of 20 5‐amino‐1‐aryl‐1H‐tetrazoles was synthesized by diazotation of corresponding 1‐amino‐3‐aryl‐guanidines and tested for growth‐inhibiting activity against autotrophic Chlorella vulgaris cultures. In the used tests the different algae growth was quantified by photometric measurements at 680 nm. From obtained dosage‐effectivity relationships the reciprocal values of isoeffective concentrations c ₅₀ were derived and defined as activity parameters A in QSAR (quantitative structure‐activity relationship) studies. It could be shown that the algistatitic activity (log A) of the tested heterocycles strongly depends on hydrophobicity described by their octan‐1‐ol/water partition coefficients (log P). The calculated linear relationships between log A and log P can be significantly improved by separate treatment of meta‐/para‐ and ortho‐substituted compounds or using an indicator variable to describe the lower activity of ortho‐substituted 5‐ami‐no‐1‐aryl‐1H‐tetrazoles in common regression equations. The results are discussed and compared with analogous QSAR found for earlier tested series of N‐heterocycles and compounds with urea structure.     

Nucleophile Substitution in der 1,3,5-Triazinreihe. IX. Kinetik und Mechanismus der Reaktion von Cyanurchlorid mit 4′-substituierten 4-Aminoazobenzenen

Nucleophilic Substitutions in 1,3,5-Triazines. VII. The Kinetic and ¦ Mechanism of Cyanuric Chloride with 4′-Substituted 4-Aminoazobenzens The kinetic and mechanism of cyanuric chloride reaction with 4′-substituted 4-aminoazobenzens in dioxan-water was studied by conductometry. An addition-elimination mechanism with a monomolecular elimination of chlorine ion at low water concentrations or a nucleophilic attack of 4-aminoazobenzens at high water concentration as low step has been supported by experimental data.     

Nucleophile Substitutionen an Kohlensäurederivaten. XII. Kinetik und Mechanismus der Reaktion von N-Nitro-N-alkylurethanen mit primären aliphatischen Aminen

Nucleophilic Substitutions to Carbonic Acid Derivates. XII. Kinetics and Mechanism of the Reaction of N-Nitro-N-alkyl-urethanes with Primary Aliphatic Amines The aminolysis of N-alkyl-N-nitrourethanes takes place, as the kinetical studies demonstrate, by means of several consecutive steps. The nucleophilic attack of the amine (first step; reaction B), as well as the proton-transfere (second step; reaction C), are quick pre-equilibres, followed by the slow, rate-determining elimination of the nitramino-group (reaction D). During the deprotonation, an intermediate with two to the nitramino-group antiperiplanar orbitals is formed, providing the necessary mesomeric assistance of the elimination.     

Ring Transformations of Bicyclic Cycloalka[d]‐ to the Isomeric Cycloalka[c]isothiazolium Salts and their Oxidation to ω‐(2‐Aryl‐1,1,3‐trioxo‐2,3‐dihydro‐1H‐isothiazol‐4‐yl)‐alkanoic Acids

The synthesis of tetrahydro‐2,1‐benzisothiazolium salts 8 and cyclohepta[c] isothiazolium salts 11 by ring transformation of bicyclic isothiazolium perchlorates 2 , 3 is described and the by‐products 9 , 10 and 12 are characterized. Oxidation of the bicyclic salts 8 and 11 results in a new route to obtain ω‐(2‐aryl‐1,1,3‐trioxo‐2,3‐dihydro‐1H‐isothiazol‐4‐yl)‐alkanoic acids 17 and 18 by Criegee‐type‐rearrangement.     

Synthesis and properties of polyamides based on 5,5′‐bis[4‐(4‐aminophenoxy)phenyl]‐hexahydro‐4,7‐methanoindan

A new diamine 5,5′‐bis[4‐(4‐aminophenoxy)phenyl]‐hexahydro‐4,7‐methanoindan ( 3 ) was prepared through the nucleophilic displacement of 5,5′‐bis(4‐hydroxylphenyl)‐hexahydro‐4,7‐methanoindan ( 1 ) with p‐halonitrobenzene in the presence of K₂CO₃ in N,N‐dimethylformamide (DMF), followed by catalytic reduction with hydrazine and Pd/C in ethanol. A series of new polyamides were synthesized by the direct polycondensation of diamine 3 with various aromatic dicarboxylic acids. The polymers were obtained in quantitative yields with inherent viscosities of 0.76–1.02 dl g⁻¹. All the polymers were soluble in aprotic dipolar solvents such as N,N‐dimethylacetamide (DMAc) and N‐methyl‐2‐pyrrolidone (NMP), and could be solution cast into transparent, flexible and tough films. The glass transition temperatures of the polyamides were in the range 245–282 °C; their 10% weight loss temperatures were above 468 °C in nitrogen and above 465 °C in air. © 2000 Society of Chemical Industry     

Zur physikalisch‐chemischen Charakterisierung von 5‐Amino‐1‐aryl‐1H‐tetrazolen: Charakterisierung von Wasserlöslichkeiten und ihre Beziehungen zu Octan‐1‐ol/Wasser‐Verteilungskoeffizienten

The aqueous solubilities (logS) of a set of 27 5‐amino‐1‐aryl‐1H‐tetrazoles with known biological activity were determined photometrically and correlated with their octan‐1‐ol/water partition coefficients (logP). The otained linear relationship between logS and logP can be significantly improved by a melting point term, an electronic term and several indicator variables describing the deviating solubility behaviour of compounds with hydrogen bonding groups and the dependence on substituent position. The calculated moreparameter equations allow the reliable prediction of aqueous solubilities for 5‐amino‐1‐aryl‐1H‐tetrazoles not yet synthesized or investigated.     

Zur physikalisch‐chemischen Charakterisierung von 5‐Amino‐1‐aryl‐1H‐tetrazolen: Kinetik der Verteilung im Zweiphasensystem Octan‐1‐ol/Wasser

The kinetics of distribution of 27 5‐amino‐1‐aryl‐1H‐tetrazoles in the two‐phase system octan‐1‐ol/water were investigated UV/Vis‐spectrophotometrically at various temperatures. Studies on relationships between the obtained firstorder rate constants (logk₁, logk₂) and the hydrophobicity of the tetrazoles described by their partition coefficients (logP) show a nearly constant rate of transport from the aqueous to the organic phase (k₁) above logP = 1,5 while the reverse rate (k₂) strongly depends on hydrophobicity. In the whole logP range investigated the kinetic behaviour can be described by bilinear relationships between logk and logP corresponding to known kinetic models for distribution processes in two‐layer systems.     

3,5‐Bis(benzylidene)‐4‐oxo‐1‐phosphonopiperidines and Related Diethyl Esters: Potent Cytotoxins with Multi‐Drug‐Resistance Reverting Properties

A series of 3,5‐bis(benzylidene)‐4‐piperidones 3 were converted into the corresponding 3,5‐bis(benzylidene)‐1‐phosphono‐4‐piperidones 5 via diethyl esters 4 . The analogues in series 4 and 5 displayed marked growth inhibitory properties toward human Molt 4/C8 and CEM T‐lymphocytes as well as murine leukemia L1210 cells. In general, the N‐phosphono compounds 5 , which are more hydrophilic than the analogues in series 3 and 4 , were the most potent cluster of cytotoxins, and, in particular, 3,5‐bis‐(2‐nitrobenzylidene)‐1‐phosphono‐4‐piperidone 5 g had an average IC₅₀ value of 34 nM toward the two T‐lymphocyte cell lines. Four of the compounds displayed potent cytotoxicity toward a panel of nearly 60 human tumor cell lines, and nanomolar IC₅₀ values were observed in a number of cases. The mode of action of 5 g includes the induction of apoptosis and inhibition of cellular respiration. Most of the members of series 4 as well as several analogues in series 5 are potent multi‐drug resistance (MDR) reverting compounds. Various correlations were noted between certain molecular features of series 4 and 5 and cytotoxic properties, affording some guidelines in expanding this study.     

Synthese von porösen Voll‐ und Core‐Shell‐Glaskugeln zur Trennung von chiralen Anästhetika

For the separation of chiral anesthetic gases suitable support materials for the selectors are necessary. Due to the controlled texture properties porous glass shows a high potential for such applications. In this study porous glass beads with particle diameters of 40 – 400 µm and 2 – 4 mm could be obtained via a special fluidized‐bed reactor and the method of ionotropic gelation. Furthermore, the first core‐shell beads on the basis of porous glasses could be synthesized via the combination of an ion‐exchange induced phase separation and a selective leaching step. The new materials are characterized by a defined mesoporous shell and a non‐porous glass core.