SYNTHESIS OF PYRIDAZOTHIENOTHIAZINE AND PYRIMIDOTHIENOPYRIDAZINES

Abstract

3-amino-4,5-diphenylthieno[2,3-c]pyridazine-2-arylcarboxamide 2 underwent cyclization with triethyl orthoformate and with nitrous acid to give the pyrimidothienopyridazines 3a-c, 4b respectively. 3-amino-4,5-diphenylthieno[2,3-c] pyridazine-2-carbohydrazide 6 reacted with aromatic aldehydes to give the corresponding carbohydrazones 7a-c. Compound 7 reacts with triethyl orthoformate, acetic anhydride or with CS₂/pyridine to produce pyrimidothienopyridazines 8,9 and pyridazothienothiazine 11.     

Efficient Routes for the Synthesis of Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines)

Bis(triazolo[3,4‐b]thiadiazine) 4 in which the fused system is linked directly to the benzene core can be synthesized in 75% yield by, firstly, preparation of bis(s‐triazole) 2 followed by reaction with phenacyl bromide 3 in refluxing EtOH/DMF mixture containing piperidine. Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 8 and 11 in which the triazolothiadiazines are linked to benzene core via alkyl or ether linkage were synthesized in 70 and 72% yields, respectively, starting from dicarboxylic acids 5 and 9 upon treatment with two moles of thiocarbohydrazide 6 to give the corresponding bis(4‐amino‐5‐mercapto‐s‐triazolo‐3‐y1) derivatives 7 and 10 and subsequent reaction with two equivalents of phenacyl bromide. Bis(6‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines) 15a , 15b , 15c , 15d , 15e , 15f , which are linked to arene cores via sulfanylmethylene spacers, were prepared by the reaction of 4‐amino‐4H‐1,2,4‐triazole‐3,5‐dithiol 12 with the appropriate bis(bromomethyl)benzenes 13a , 13b , 13c , 13d , 13e , 13f to give bis(4‐amino‐5‐mercapto‐4H‐3‐sulfanylmethyl)arenes 14a , 14b , 14c , 14d , 14e , 14f and subsequent reaction with phenacyl bromide. Compounds 15a , 15b , 15c , 15d , 15e , 15f were alternatively obtained in 60–70% yields by twofold substitution of 13a , 13b , 13c , 13d , 13e , 13f with two equivalents of 6‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine‐3‐thiol 16 in refluxing EtOH/DMF mixture containing KOH. Bis(triazolothiadiazine) 22 attached to the benzene core through the thiadiazine ring via an amine linkage was prepared in 70% yield starting from p‐phenylenediamine 19 by, firstly, acylation with chloroacetyl chloride 18 followed by bis‐alkylation with 1,2,4‐triazole 20 and subsequent intramolecular ring closure upon treatment with phosphorus oxychloride.     

The effect of magnetic fields on the stability of a cylindrical flow with mass and heat transfer

The effect of axial and radial magnetic fields on the Kelvin-Helmholtz stability of a cylindrical interface between the vapor and liquid phases of a fluid is studied when the vapor is hotter than the liquid and the two phases are enclosed between two cylindrical surfaces coaxial with the interface, and when there is mass and heat transfer across the interface. Both axisymmetric and asymmetric disturbances are considered. The linear dispersion relations are obtained and discussed. It is found that a uniform axial magnetic field has a stabilizing effect on the interface, while the effect of a radial magnetic field depends strongly on the choice of some physical parameters of the system. It is also found that the instability criterion is independent of heat and mass transfer coefficient, but it is different fromthat in the same problem without heat and mass transfer. Finally, the heat and mass transfer has a destabilizing influence on the system.     

Bestimmung der Homogenität von Legierungen mittels Autoradiographie and Aktivierungsanalyse

An für Konstruktionselemente verwendente verwendete Legierungen werden in Abhängigkeit von ihrer Verwendung folgende Anforderungen gestellt: hole Festigkeitskoeffizienten, erhöhte Temperaturbeständigkeit, erhöhte Korrosionbeständigketi gegen Chemikalien, erhöhte Verschleißbeständigkeit u. a. Chemische Heterogenität ist Ursache für Korrosionserscheinungen, Einleitung ungünstiger Reaktionen sowie Herabsetzung der örtlichen Reibfestigkeit und bewirkt damit eine Erniedrigung der Güteeigenschaften der Legierung. Einer der grundsätzlichen Wege, diesen Erscheinungen vorzubeugen, ist ein möglichst hoher Homogenitätsgrad der Legierung.     

Nonlinear bending inertia of a vibrating beam

Zusammenfassung Die bei Querschwingungen schlanker Stäbe mit zeitabhängiger Längsbelastung in der Bewegungsdifferentialgleichung auftretenden nichtlinearen Trägheitsterme, herrührend von der Longitudinalbewegung, werden hier im Gegensatz zu früheren Arbeiten mitberücksichtigt. Die sich daraus ergebenden nichtlinearen Korrekturen der Eigenfrequenzen des entsprechenden linearen Systems werden abgeschätzt.     

Determination of trace amounts of some elements in armco steel by the neutron activation method

The previously elaborated methods of the determination of As, Sc, La, Au, W, Mo, Ga and In have been adapted to the analysis of steel. Samples of Armco steel taken from three various points of a steel bar section were analysed. On the basis of the results obtained the distribution of the elements determined along the steel bar section is discussed.     

Synthesis and reactions of some 6-aryl and 2,6-diaryl-4-(4′-antipyrinyl)-2,3,4,5-tetrahydropyridazin-3-ones and screening for their antibacterial activities

Some new pyridazinone derivatives(3) were synthesized through addition of antipyrin to β-aroylacrylic acids (1) followed by cyclization of the adducts. Reactions of 3 with ethyl bromoacetate, benzenesulfonyl chloride, benzoyl chloride and POCl₃ give N-substituted products and monochlorosubstituted pyridazines (4), respectively. The reactions of the latter with thiourea give unexpected dithio-derivatives (5), which react with phenylhydrazine to give pyrazolopyridazino pyridazine derivatives (6). Reactions of 2 with NH₂OH in ethanol and pyridine afford oxime and oxazinone derivatives 7 and 8, respectively. The antibacterial activities of several compounds were screened.     

Synthesis and Molecular Docking Studies of Novel 2‐Phenyl‐4‐Substituted Oxazole Derivatives as Potential Anti‐cancer Agents

A novel series of 2,4‐disubstituted oxazole derivatives were synthesized, screened for their anti‐tumor activity against three cell lines MCF‐ 7 , TK‐10, and UACC‐62. Molecular docking study was carried out against epidermal growth factor receptor. A new series of 2‐phenyl‐4‐substituted oxazole derivatives were synthesized. A series of chiral α‐amino acid derivatives 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 were synthesized by coupling various l ‐acylated amino acid azide 3. The synthesized compounds were tested for their in vitro antitumor activity against MCF‐7, TK‐10, and UACC‐62 cell lines. Compound 6 exhibited the strongest inhibitory activity against TK cell lines, while compound 12 showed the highest activity against MCF‐7 cell lines. Compound 14 was the most active against UACC‐62 cell lines. Furthermore, a molecular docking study of the most active compounds was carried out using epidermal growth factor receptor X‐ray 3D structure (protein data bank ID 1 M17). Docking results revealed that compound 6 showed the highest binding energy of ΔG = ?78.17 Kcal/mol.