Formation of dioxospiroindene[1,3]thiazine and thioxoindeno[2,1-<Emphasis Type="Italic">d</Emphasis>]imidazolone derivatives from alkenylidene-hydrazinecarbothioamides

The reaction of (substituted) alkenylidene-hydrazinecarbothioamides with 2-(1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile led to the formation of 1,3-dioxospiroindene[1,3]-thiazine and thioxoindeno[2,1-d]imidazolone derivatives in modest yields. In addition, 1,3-dihydroxyindan-2-ylidenepropanedinitrile was found. Explanations of these conversions involving nucleophilic reactions and condensations are presented.     

Synthesis, spectroscopic, thermal characterization, and antimicrobial activity of miconazole drug and its metal complexes

Metal complexes having the general composition [MCl₂(H₂O)₂(L)₂]·yH₂O (where y?=?1?C3, M?=?Mn(II), Cu(II), Co(II), Ni(II), and Zn(II) and L?=?miconazole drug?=?MCNZ) and [MCl₂(H₂O)₂(L)₂]Cl·3H₂O (where M?=?Cr(III) and Fe(III)) have been synthesized. All the synthesized complexes were identified and confirmed by elemental analyses, IR, diffused reflectance, and thermal analyses (TG and DTA) techniques as well as molar conductivity and magnetic moment measurements. The molar conductance data reveals that bivalent metal complexes are non-electrolytes while Cr(III) and Fe(III) complexes are electrolytes and of 1:1 type. IR spectral studies reveal that MCNZ is coordinated to the metal ions in a neutral unidentate manner with N donor site of the imidazole-N. On the basis of magnetic and solid reflectance spectral studies, an octahedral geometry has been assigned for the complexes. Detailed studies of the thermal properties of the complexes were investigated by thermogravimetry (TG) and differential thermal analyses (DTA) techniques and the activation thermodynamic parameters are calculated using Coats?CRedfern method. The free MCNZ drug and its complexes were also evaluated against bacterial species (P. aeruginosa, S. aureus, B. subtilis, E. Coli) and fungi (A. fumigatus, P. italicum, and C. albicans) in vitro. The activity data show that the metal complexes have higher biological activity than the parent MCNZ drug.     

Spectrofluorimetric and Spectrophotometric Stability‐Indicating Methods for the Analysis of Veralipride in Presence of Its Degradants and in Spiked Human Plasma

Spectrofluorimetric and spectrophotometric stability‐indicating methods were developed and validated for analysis of veralipride (Ver) in presence of its hydrolytic and oxidative degradants. The spectrofluorimetric method was based on direct measurement of the intrinsic fluorescence of Ver at 366 nm after excitation at 299 nm using sodium lauryl sulfate (SLS) as micelle enhancer. The fluorescence intensity plot was linear over the concentration range 1.0–10.0 µg·mL^?1. The high sensitivity of the method allowed its successful application to the analysis of Ver in spiked human plasma. Two other methods were developed. They are based on the oxidative coupling reaction of Ver with 3‐methyl benzothiazolin‐2‐one hydrazone (MBTH) hydrochloride in presence of ceric ammonium sulphate in an acidic medium. The first method depends on spectrophotometric measurement of the stable green colored oxidative coupling product at 660 nm. The different experimental parameters affecting the reaction were optimized. Linearity range is 10.0–100.0 µg·mL^?1. The second method depends on a fluorescence quenching effect of Ver on the fluorescence of Ce³⁺. The difference in fluorescence intensity was measured at 380 nm after excitation at 300 nm. This method is applicable over the concentration ranges 0.25–2.50 µg·mL^?1. The methods were validated according to the ICH guidelines. They were successfully applied for the analysis of Ver in drug substance, drug product and in laboratory prepared mixtures containing different percentages of hydrolytic and oxidative degradants.     

Synthesis and Spectroscopic Structural Elucidation of New Quinoxaline Derivatives

A quinoxaline‐2,3‐dione derivative was synthesized, and its chemical structure was determined through spectral analysis. Alkylation of this compound under phase transfer catalysis (PTC) conditions yielded monoalkylated and diakylated adducts. The monolalkylation process was shown to be regioselective occurring on the quinoxalic nitrogen atom rather than on its pyrazolic analogue. The full characterization of the synthesized compounds was studied by concerted use of NMR and MS techniques. Assignments of proton and carbon atoms were achieved through analysis of the 1D ¹H and ¹³C NMR spectra combined with homo‐ and hetero-nuclear 2D NMR experiments. Determination of the alkylation site was achieved through long‐range proton–carbon coupling correlations spectroscopy.     

Application of NMR Spectroscopy and Mass Spectrometry to the Structural Elucidation of Modified Flavan‐3‐ols and Their Coupling Reaction Products*

NMR and MS techniques were used for the unambiguous structural elucidation of synthesized modified monomeric and dimeric flavan‐3‐ols presenting different substituents on the A‐ring C8 position. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI‐MS techniques. Assignments of proton and carbon atoms was achieved through analysis of the 1D ¹H and ¹³C NMR spectra combined with homo‐ and heteronuclear 2D NMR experiments. In each case, HMBC correlation between proton H2 and carbon C8a was observed allowing assignment of this carbon, which represents the key for attribution of the A‐ring carbon atoms. The synthesis and structural characterization of activated monomeric and dimeric flavanols were also achieved and used as precursors for preparation of natural and modified dimeric procyanidin derivatives. The preparation of various dimeric species involving modified flavanols was explored through different coupling reactions. The structures of the compounds formed were characterized on the basis of their MS and NMR spectral analysis. Dimeric species were characterized through proton–proton and proton–carbon correlations, which distinguished between the different flavanol moieties and established their sequences.     

Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and DL-phenylalanine and some transition metals

The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as glycine (Gly) or dl-phenylalanine (PhA) were prepared and characterized with different physicochemical methods. IR spectra confirm that Pir and Ten behave as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its deprotonated carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its deprotonated carboxylic and amino groups. The solid reflectance spectra and magnetic moment measurements confirm that all the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. Thermal behaviour of the complexes is extensively studied using TG and DTA techniques. TG results show that water molecules (hydrated and coordinated) and anions are removed in the first and second steps while Gly, PhA, Pir and Ten are decomposed in the next and subsequent steps. The pyrolyses of the chelates into different gases are observed in the DTA curves as exo- or endothermic peaks. Also, phase transition states are observed in some chelates. Different thermodynamic parameters are calculated using Coats-Redfern method and the results are interpreted.     

A general route to α-alkyl (E)-α,β-unsaturated aldehydes

Bis(trimethylsilyl)-tert-butylaldimines 3 react with aldehydes in the presence of zinc bromide at room temperature to give, after hydrolysis, the desired α-alkyl α,β-ethylenic aldehydes in good yield and with very high E stereoselectivity. The reaction was believed to proceed via the α-silyl β-siloxyimines 4.     

Synthesis of (E)-2,5-disubstituted 1,3,4-thiadiazolyl-2,3-diphenylpropenones from alkenylidene-hydrazinecarbothioamides

Conjugated alkenylidene-hydrazinecarbothioamides react in high yield with 2,3-diphenylcyclopropenone to give a series of (E)-2,5-disubstituted 1,3,4-thiadiazolyl-2,3-diphenylpropenones.     

Construction and performance characteristics of new ion selective electrodes based on carbon nanotubes for determination of meclofenoxate hydrochloride

This work offers construction and comparative evaluation the performance characteristics of conventional polymer (I), carbon paste (II) and carbon nanotubes chemically modified carbon paste ion selective electrodes (III) for meclofenoxate hydrochloride are described. These electrodes depend mainly on the incorporation of the ion pair of meclofenoxate hydrochloride with phosphomolybdic acid (PMA) or phosphotungestic acid (PTA). They showed near Nernestian responses over usable concentration range 1.0 × 10⁻⁵ to 1.0 × 10⁻² M with slopes in the range 55.15–59.74 mV (concentration decade)⁻¹. These developed electrodes were fully characterized in terms of their composition, response time, working concentration range, life span, usable pH and temperature range. The electrodes showed a very good selectivity for Meclo with respect to a large number of inorganic cations, sugars and in the presence of the degradation product of the drug (p-chloro phenoxy acetic acid). The standard additions method was applied to the determination of MecloCl in pure solution, pharmaceutical preparations and biological samples. Dissolution testing was also applied using the proposed sensors.