SOME REACTIONS OF 3-AMINO-2-CARBOETHOXY-4,6-DIMETHYLTHIENO[2,3-b]-PYRIDINE. SYNTHESIS OF SOME NEW THIENOPYRIDOPYRIMIDINES

Abstract

Thienopyridine oxazinone (1) has been prepared and explored as a precursor by its reaction with some reagents namely, ammonium acetate, aliphatic amines, aromatic amines, hydrazine hydrate, thiosemicarbazide, and ethyl glycinate to give pyridothienopyrimidines (11-VII). The pyrimidinone compound (11) was converted to the 4-chloro derivative (X) by its reaction with excess POCl₃ Interaction of the 4-chlorocompound (X) with some reagents namely, hydrazine hydrate, methyl amine, aniline, sodium thiophenolate, ethyl glycinate, thiosemicarbazide and thiourea, yielded pyridothieno-pyrimidine derivatives (XI-XVII) substituted at 4-position, respectively.     

Action of Hydrazines on 2‐(2‐Oxindolin‐3‐ylidene)malononitrile, (E,Z)‐Ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate and Isatin‐β‐thiosemicarbazone as a Source of Spiro Indoline‐pyrazole Systems

2‐(2‐Oxindolin‐3‐ylidene)malononitrile ( 1a ) or (E,Z)‐ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate ( 1b ) or isatin‐β‐thiosemicarbazone ( 1c ) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline‐2‐one moiety ( 2 ). The hydrazone derivatives ( 2 ) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives ( 3a , 3b ). Also, cinnoline derivative ( 9 ) is obtained by action of hydrazine hydrate on the N‐acetyl derivative of ( 6a ). The structures of the newly synthesized compounds were evaluated by IR, ¹H‐NMR spectroscopy, mass spectra and elemental analyses.     

Utility of 4‐Benzylidene‐2‐phenyl‐5(4H)‐oxazolone in Synthesis of Triazine,Oxadiazole and Imidazole Derivatives of Anticipated Biological Activity

Treatment of oxazolone 1 with hydrazine hydrate at room temperature gave the (Z)‐configurated isomer hydrazide (Z)‐ 3 (high yield). However, refluxing 1 with hydrazine hydrate yielded the (E)‐configurated isomer hydrazide (E)‐ 2 (low yield).The hydrazide derivative (Z)‐ 3 has been utilized as synthon for the synthesis of 1,2,4‐triazinone, imidazolone, and oxadiazole derivatives through appropriate routes. The thiosemicarbazide and semicarbazide derivatives are synthesized by different routes. The structures of the new compounds were established on the basis of IR, ¹H‐NMR, mass spectral data, and elemental analysis.     

Synthesis and characterization of copper(II), cobalt(II), nickel(II), and iron(III) complexes with two diamine Schiff bases and catalytic reactivity of a chiral diamine cobalt(II) complex

New transition metal complexes of Co(II), Cu(II), Ni(II), and Fe(III) of the ligands 6,6′-(1E,1′E)-(4,5-dimethyl-1,2-phenylene)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(7-hydroxy-5-methoxy-2-methyl-4H-chromen-4-one) H₂L¹ and 6,6’-(1E,1′E)-cyclohexane-1,2-diylbis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(7-hydroxy-5-methoxy-2-methyl-4H-chromen-4-one) H₂L² have been prepared and characterized using physio-chemical and spectroscopic methods. The results obtained for the complexes indicated that the geometries of the metal centres are either square planar or octahedral. Cyclopropanation reactions of unactivated olefins by ethyldiazoacetate (EDA) in the presence of [L¹Cu]·H₂O, [L²Cu]·2H₂O and [L²*Co]·2H₂O as catalysts were examined. The results showed that only [L²*Co]·2H₂O can act as a catalyst for the cyclopropanation reaction of unactivated olefins with very high selectivity (up to 99% based on EDA).     

Development and Validation of HPLC,TLC and Derivative Spectrophotometric Methods for the Analysis of Ezetimibe in the Presence of Alkaline Induced Degradation Products

Reversed phase‐high performance liquid chromatography (RP‐HPLC), thin layer chromatography (TLC) densitometry and first derivative spectrophotometry (1D) techniques are developed and validated as a stability‐indicating assay of ezetimibe in the presence of alkaline induced degradation products. RP‐HPLC method involves an isocratic elution on a Phenomenex Luna 5μ C₁₈ column using acetonitrile: water: glacial acetic acid (50:50:0.1 v/v/v) as a mobile phase at a flow rate of 1.5 mL/min. and a UV detector at 235 nm. TLC densitometric method is based on the difference in Rf‐values between the intact drug and its degradation products on aluminum‐packed silica gel 60 F₂₅₄ TLC plates as stationary phase with isopropanol: ammonia 33% (9:1 v/v) as a developing mobile phase. On the fluorescent plates, the spots were located by fluorescence quenching and the densitometric analysis was carried out at 250 nm. Derivative spectrophotometry, the zero‐crossing method, ezetimibe was determined using first derivative at 261 nm in the presence of its degradation products. Calibration graphs of the three suggested methods are linear in the concentration ranges 1–10 mcg/mL, 0.1–1 mg/mL and 1–16 mcg/mL with a mean percentage accuracy of 99.05 ± 0.54%, 99.46 ± 0.63% and 99.24 ± 0.82% of bulk powder, respectively. The three proposed methods were successfully applied for the determination of ezetimibe in raw material and pharmaceutical dosage form; the results were statistically analyzed and compared with those obtained by the reported method. Validation parameters were determined for linearity, accuracy and precision; selectivity and robustness and were assessed by applying the standard addition technique.     

Reactions of 4-(2-aminothiazole-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline. Synthesis of thiazolo[3,2- a ]pyrimidine and imidazo[2,1- b ]thiazole derivatives

4-(2-Aminothiazol-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline was synthesized via the reaction of 4-bromoacetyl-3-methyl-5-oxo-1-phenyl-2-pyrazoline with thiourea [7] and was transformed to related fused heterocyclic systems. The antifungal and antibacterial studies revealed in some cases excellent biocidal properties.     

Validated stability-indicating methods for the determination of nizatidine in the presence of its sulfoxide derivative

Four new selective, precise, and accurate methods are described for the determination of nizatidine (NIZ) in the presence of its sulfoxide derivative in both the raw material and pharmaceutical preparations. Method A is based on zero-order (0D), first-derivative (1D), and second-derivative (2D) spectrophotometric measurement of NIZ in aqueous solution at the zero-crossing point of its sulfoxide derivative (at 314, 295-334, and 318-348 nm, respectively). Method B is a 1DD spectrophotometric method based on the simultaneous use of the first derivative of the ratio spectra and the measurement of peak amplitude at 297 nm. Method C uses a solvent-induced derivative-difference spectrophotometry with deltaD1 measurement from peak to peak at 315-345 nm. Method D involves quantitative densitometric evaluation of a mixture of the drug and its sulfoxide derivative after separation by high-performance thin-layer chromatography on silica gel plates with chloroform-methanol (9 + 1, v/v) as the mobile phase; Rf values for NIZ and its sulfoxide derivative were 0.4 and 0.2, respectively. The spot was scanned at 254 nm. The first-derivative spectrophotometric method was used to investigate the kinetics of the hydrogen peroxide degradation process at different temperatures. The apparent pseudo-first-order rate constant, half-life, and activation energy were calculated. The results obtained by the proposed methods were analyzed statistically and compared with those obtained by the official method. These methods are suitable as stability-indicating for the determination of NIZ in the presence of its oxidation-induced degradation product (sulfoxide derivative) either in the bulk powder or in pharmaceutical preparations.     

Kinetics of the crystallization of barium chromate

Summary The kinetics of the crystallization of barium chromate have been studied conductometrically at 298 K for both spontaneous and seeded growth systems. The rate of growth follows a quadratic dependence upon the relative supersaturation which suggests a surface-controlled growth mechanism. This rate equation holds fairly well for the various supersaturation and solid/solution ratios used. The presence of seeds in the solution appears to accelerate the growth rate. Analysis of the calculated induction times in unseeded systems corroborates the surface-controlled growth mechanism. The effect of some additives on the kinetics of growth has also been studied. The retarding effect of these inhibitors is interpreted in terms of adsorption of inhibitor ions at the active crystal growth sites.Dedicated to the memory of ProfessorE. N. Rizkalla who passed away on November 29, 1993     

The kinetics of the crystallization of barium chromate in presence of polyphosphate and phosphonates

Summary The inhibiting effect of polyphosphate and phosphonates on the crystallization of barium chromate for both seeded and unseeded systems has been investigated using the changes in ionic conductivity of the lattice ions in supersaturated solutions containing stoichiometric concentrations of barium and chromate at 298 K. The inhibitors studied are sodium tripolyphosphate (STP), ethylenediaminetetramethylenephosphonic acid (ENTMP), and 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP). The effect of these inhibitors on the growth of crystals has been studied at several inhibitor concentrations. The influence of these additives on barium chromate crystallization could be interpreted in terms of aLangmuir type adsorption isotherm. The crystallization retarding effect due to inhibitors is in the orderHEDP>STP>ENTMP. The inhibitors studied can be used as effective compounds for scale formation control.Deceased     

Two-dimensional problem of a two-temperature generalized thermoelastic half-space subjected to ramp-type heating

In this work, we will consider a half-space filled with an elastic material, which has constant elastic parameters. The governing equations are taken in the context of the theory of two-temperature generalized thermoelasticity. A linear temperature ramping function is used to more realistically model thermal loading of the half-space surface. The medium is assumed initially quiescent. Laplace and Fourier transform techniques are used to obtain the general solution for any set of boundary conditions. The general solution obtained is applied to a specific problem of a half-space subjected to ramp-type heating. The inverse Fourier transforms are obtained analytically while the inverse Laplace transforms are computed numerically using a method based on Fourier expansion techniques. Some comparisons have been shown in figures to estimate the effect of the ramping parameter of heating.