Nucleosides and Nucleotides. 151. Conversion of (Z)-2'-(Cyanomethylene)-2'-deoxyuridines into Their (E)-Isomers via Addition of Thiophenol to the Cyanomethylene Moiety Followed by Oxidative Syn-elimination Reactions(1)

The Wittig reaction of 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-beta-D-erythro-pentofuranos-2-ulosyl]uracil (6) with Ph(3)P=CHCN afforded (Z)-2'-cyanomethylene derivative 7 exclusively. The (E)-isomer was accessed from its (Z)-isomer through a sequence of addition of thiophenol to the 2'-cyanomethylene moiety of the (Z)-isomer from the alpha-face, selectively, and stereoselective oxidative syn-elimination of the resulting adduct. The diastereofacial selectivity of the benzenethiolate addition to the cyanomethylene moiety was found to be influenced by participation of the 2-carbonyl group at the base moiety and steric hindrance of the sugar protecting groups. Although nucleophilic addition reactions at the 2'-position of 6 have been well-known to occur from the alpha-face selectively, treatment of 7 with LiSPh in THF unexpectedly afforded a mixture of alpha- and beta-phenylthio derivatives 8 and 9 in almost equal ratio. Furthermore, an unusual beta-facial selective addition was observed on treatments of 7 with PhSAlMe(2) in CH(2)Cl(2) or with LiSPh in the presence of Mg(ClO(4))(2) in THF. On the other hand, when (Z)-2'-(cyanomethylene)-5'-O-triisopropylsilyl derivative 10 was treated with LiSPh, the alpha-phenylthio derivative 13 was obtained predominantly (89:11). Oxidation of 8 with m-chloroperbenzoic acid (m-CPBA) in CH(2)Cl(2) and pyrolysis of the resulting sulfoxides afforded the (Z)-isomer 7 exclusively. Treatment of 13 with m-CPBA under the same conditions afforded the desired (E)-cyanomethylene derivatives 18 as a major product (E:Z = 14:1) in good yield. Deprotection of 18 by the standard procedures furnished (E)-2'-(cyanomethylene)-2'-deoxyuridine (5).     

UV-vis, IR and (1)H NMR spectroscopic studies of some Schiff bases derivatives of 4-aminoantipyrine

Five Schiff bases derived from 4-aminoantipyrine and benzaldehyde derivatives (I) are prepared and their UV-vis, IR, (1)H NMR and fluorescence spectra are investigated and discussed. The electronic absorption spectra of the hydroxy 4-aminoantipyrine Schiff bases Ib and Ie as well as the fluorescence spectra of Ie are studied in the organic solvents of different polarity. The UV-vis absorption spectra of 4-aminoantipyrine Schiff bases Ib, Id and Ie are investigated in aqueous buffer solutions of varying pH and utilized for the determination of pK(a) and DeltaG of the ionization process. The reactions of the hydroxy compounds Ib and Ie with Ni(II) and Cu(II) ions are also studied. The results of spectral studies are supported by some molecular orbital calculations using an atom superposition and electron delocalization molecular orbital theory for a compound Ib.     

Coordination of Y(III), Ce(III), La(III) and Zr(IV) with Some Salicylidene Aromatic Schiff Bases

Coordination compounds formed by the interaction of some salicylidene aromatic Schiff bases with Y(III), Ce(III), La(III), and Zr(IV) are prepared and characterized by elemental analysis, electronic and i.r. spectra as well as conductometric methods. The i.r. spectra indicate that coordination takes place through the azomethine nitrogen atoms and OH groups. The structure of such products depend mainly on the type of Schiff base used. Also, the formation constant of the complexes are evaluated.     

Determination of ethambutol in pharmaceutical preparations by atomic absorption spectrometry,spectrophotometry and potentiometry

Simple methods are described for the determination of ethambutol in pharmaceutical preparations. They are based on the reaction of the drug with copper phosphate suspension in a borate buffer of pH 9.2, whereby a blue 11 water-soluble copper-ethambutol complex is quantitatively formed. Four portions of the reaction solution are used for (i) measurement of copper by atomic-absorption spectrometry at 324.7 nm; (ii) potentiometric titration with EDTA with use of a solid-state copper ion-selective electrode; (iii) visual titration with EDTA (copper-PAN indicator); and (iv) spectrophotometric measurement of the copper-ethambutol complex at 640 nm. The results obtained are in good agreement and are better than those of the British Pharmacopoeia (BP) method.     

New colorimetric methods for the determination of trazodone HCl,famotidine, and diltiazem HCl in their pharmaceutical dosage forms

Two sensitive and simple spectrophotometric methods are developed for the determination of trazodone HCl, famotidine, and diltiazem HCl in pure and pharmaceutical preparations. The methods are based on the oxidation of the cited drugs with iron(III) in acidic medium. The liberated iron(II) reacts with 1,10-phenanthroline (method A) and the ferroin complex is colorimetrically measured at 510 nm against reagent blank. Method B is based on the reaction of the liberated Fe(II) with 2,2-bipyridyl to form a stable colored complex with lambda(max )at 520 nm. Optimization of the experimental conditions was described. Beer's law was obeyed in the concentration range of 1-5, 2-12, and 12-32 microg mL(-1) for trazodone, famotidine, and diltiazem with method A, and 1-10 and 8-16 microg mL(-1) for trazodone and famotidine with method B. The apparent molar absorptivity for method A is 1.06x10(5), 2.9x10(4), 1.2x10(4) and for method B is 9.4x10(4 )and 1.6x10(4), respectively. The suggested procedures could be used for the determination of trazodone, famotidine, and diltiazem, both in pure and dosage forms without interference from common excipients.     

Construction and Evaluation of a Promazinium Cation-Selective Electrode

 The construction of a plasticised PVC matrix-type promazinium cation-selective membrane electrode and its use in the potentiometric determination of promazine hydrochloride in pharmaceutical preparations are described. It is based on the use of the ion-associate species, formed by promazinium cation and tetraphenylborate (TPB) counter ion. The basic electrode performance characteristics are evaluated according to IUPAC recommendations. It exhibited a linear response for 1 × 10⁻²−1 × 10⁻⁵ M of promazine hydrochloride solutions with a cationic Nernstian slope over the pH range 2–6. Common organic and inorganic cations showed negligible interference. Direct potentiometric determination of 1 × 10⁻²−1 × 10⁻⁵ M aqueous promazine hydrochloride using this membrane electrode system showed an average recovery of 99.5% with a mean standard deviation of 1.5%. This electrode was successfully used for monitoring the titration of promazine hydrochloride with sodium tetraphenyl borate and for determining promazine hydrochloride in ampoules. Received June 15, 2001 Revision November 6, 2001     

Entanglement Between a Single Two-Level Atom and Quantum Systems of <Emphasis Type="Italic">N</Emphasis>-Level Atoms in the Presence of an External Classical Field

We study a single two-level atom interacting with quantum systems of N-level atoms in the presence of an external classical field. We obtain an analytic solution under a specified condition. Then we determine the time-dependent wave function through the evolution operator and employ the wave function obtained for careful investigation of the temporal evolution of the atomic inversion and linear entropy, where the influence of the external classical field is examined. Our study of the linear entropy shows that the system is almost in a mixed state, and the maximum value of entanglement occurs through the linear entropy. Furthermore, we examine the variance squeezing and entropy squeezing for different values of the external classical field parameter, which leads to different observations of the squeezing in the quadratures. In particular, it leads to an increase in the amount of squeezing for all quadratures, as well as the squeezing period.     

A dansyl-based optical probe for detection of singly and doubly charged anions

This paper reports the synthesis of a new molecule, 5-(dimethylamino)naphthalene-1-sulfonic acid 2,3-bis(3-phenylureido)phenyl ester (1), as an optical probe for anions. The effect of the presence of various anions on the spectroscopic properties of 1 was examined using UV–vis absorption spectroscopy, fluorescence and ¹H NMR titration experiments. Strong binding of 1 to carboxylate, oxalate, cyanide and dihydrogen phosphate anions resulted in an increase in the emission of 1 and changes in its ¹H NMR chemical shifts. Binding constants of 1 to anions were also calculated based on the binding isotherms derived from the spectroscopic titrations.     

Synthesis,characterization and studies of new 3‐benzyl‐4H‐1,2,4‐triazole‐5‐thiol and thiazolo[3,2‐b][1,2,4]triazole‐5(6H)‐one heterocycles

3‐Benzyl‐4‐phenyl‐1,2,4‐triazole‐5‐thiol ( 1 ) was synthesized and used as starting material for preparation of 1,2,4‐triazole bearing substituted thiosemicarbazides moiety ( 4a‐d ) in high yields. The thiosemicarbazides 4a‐d were cyclized in basic medium to give two triazole rings linked by thiomethylene group ( 5a‐d ), while cyclization of thiosemicarbazides 4a‐d with chloroacetyl chloride in the presence of CHCl₃ and K₂CO₃ afforded the thiazolidinone derivatives 6a‐d . The reaction of thiosemicarbazides 4a‐c with phenacyl bromide in the presence of EtOH and fused CH₃COONa gave the corresponding thiazoline ring systems 7a‐c . Condensation of the 3‐benzyl‐1,2,4‐triazole‐5(1H)‐thiol ( 1 ) with chloroacetic acid and aromatic aldehydes ( 8a‐ g) in boiling acetic acid/acetic anhydride mixture in the presence of fused sodium acetate gave one single isomer only, which might be 9a‐g or 10a‐g . Upon application of Micheal addition reaction on compounds 9a‐e with cyclic secondary amines such as piperidine or morpholine the 2‐benzyl‐6‐(α‐amino‐aryl/methyl)‐1,3‐thiazolo[3,2‐ b][1,2,4]‐triazol‐5‐ols ( 11a‐j ) were obtained in good yields The structure of all new compounds were determined using both spectral and elemental analyses.     

Antianexiety activity of pyridine derivatives synthesized from 2-chloro-6-hydrazino-isonicotinic acid hydrazide

A series of oxadiazole pyridine derivatives were synthesized by using 2-chloro-6-hydrazinoisonicotinic acid hydrazide as starting material. Treatment of the hydrazide with carbon disulfide to afford the oxadiazole derivative, which was treated with 5-methyl-2-furancarbaldehyde, formic acid, acetic acid/acetic anhydride, or phthalic anhydride to yield the corresponding pyridinodiazoles and on imide. Condensation of the hydrazide with p-fluorobenzaldehyde in ethanol or acetic acid in the presence of sodium acetate afforded hydrazone and oxadiazole derivatives, which were acetylated and cyclized with acetic anhydride to N-acetyloxadiazole derivatives. The hydrazone was treated with acetic acid in the presence of sodium acetate, or bromine water/sodium acetate to give on oxadiazole, while it was cyclized with chloroacetyl chloride in the presence of TEA to oxoazetidinaminoisonicotinamide. Finally, condensation of the hydrazide with acid anhydrides in refluxing glacial acetic acid afforded the corresponding bisimide derivatives. The pharmacological screening showed that many of these obtained compounds have good antianexiety activity comparable to diazepam^® as positive control.