Baclofen impurities: Facile synthesis and novel environmentally benign chromatographic method for their simultaneous determination in baclofen

An efficient, economic and high yielding method was described for the synthesis of baclofen (BAC) pharmacopoeial impurities (impurity A and impurity B) which can be used for gram‐scale synthesis. Furthermore, a novel ecofriendly thin‐layer chromatographic TLC–densitometric method was established and validated for the determination of BAC and its synthesized impurities. The developed TLC–densitometric method is based on the chromatographic separation using TLC plates (60 F₂₅₄) using a green mobile phase of ethyl acetate–methanol–ammonia solution, 33% (8:2:0.1, by volume) with UV scanning at 220 nm. The proposed method was validated with respect to International Conference on Harmonization guidelines. The validated method was successfully applied for determination of BAC in pure form and in its commercial dosage form. Additionally, the greenness profile of the developed method was evaluated and compared with those of the reported chromatographic methods. The developed method was found to be superior to the published methods, being environmentally benign.     

Highly Enantioselective Catalytic Kinetic Resolution of α-Branched Aldehydes through Formal Cycloaddition with Homophthalic Anhydrides

A new catalytic methodology was developed to promote an efficient one-pot kinetic resolution of racemic aldehydes with selectivity (s*) of up to 91 (99:1 d.r., >99 % ee) in a cycloaddition reaction with enolizable anhydrides to afford dihydroisocoumarin products (a core prevalent in natural products and molecules of medicinal interest) containing three contiguous stereocentres.     

Validated ecofriendly chromatographic method for quantitative determination of anti‐migraine quaternary mixture

A novel ecofriendly, cost and time saving high‐performance thin‐layer chromatographic method was developed and validated for simultaneous determination of metoclopramide, ergotamine, caffeine, and paracetamol in bulk and pharmaceutical formulation. The separation was carried out on silica gel plates, using ethyl acetate:ethanol:ammonia (9:1:0.1, v/v/v) as a developing system. Ultraviolet detection was carried out at 272 nm. The resulting retention times were 0.15, 0.36, 0.49, and 0.74 min for metoclopramide, ergotamine, caffeine, and paracetamol, respectively. The greenness profile assessment was achieved to the proposed method to evaluate its greenness characters to the environment with acceptable results. Validation parameters were checked according to International Conference of Harmonization guidelines to achieve the international requirements for quality control analysis of the proposed drugs.     

THE PREPARATION AND SOME REACTIONS OF 3-THIETANONES

Abstract

3-Thietanones have been prepared by treating certain ketones with thionyl chloride or sulphur dichloride. In the case of ketones containing a tertiary alpha proton the initial product obtained on treatment with thionyl chloride is the sulphinyl chloride which then cyclises to the thietanone.     

A Simple and Convenient Synthesis of Glycosyl Azides

Treatment of glycosyl halides with NaN₃ in aqueous acetone or acetonitrile is a convenient method for the stereoselective synthesis of 1,2-trans-per-O-acetyl-glycosyl azides.     

Spectral and Thermal Studies of Some New Metal Complexes Derived from N-[(Phenylamino)Thioxomethyl] Hydrazinocarbonyl Methyl Pyridinium Chloride (PTHMPC)

New metal complexes derived from the reaction of N-[(phenylamino)thioxomethyl] hydrazino carbonyl methyl pyridinium chloride (H₂L; PTHMPC) with some metal salts of the general formula MX₂ [(X = Cl^? and/or CH₃COO^?; M = Cd(II), UO₂(II), Mn(II) and Zr(IV)] were synthesized and characterized by elemental analyses, spectral analyses (IR, UV-vis., ¹H NMR), thermal analyses (TGA, DTG), and conductance and magnetic measurements. The results showed that the ligand exists in metal complexes either in the keto form or in the enol form. Moreover, the IR spectral data suggest that the acetate ion behaves in a monodentate manner. Semi-empirical calculations ZINDO/1, PM3, and AM1 have been used to study the molecular geometry and the harmonic vibrational spectra of the ligand and its metal complexes with the purpose of assisting the experimental assignment of the complexes. Generally, there is an agreement between the observed and the calculated spectra. Finally, the thermodynamic parameters (ΔE*, ΔH, ΔG, and ΔS) have been calculated from the data of thermal analyses (TGA and DTG).

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Phosphorylation of Dienyl Diprenoid Alcohols

Abstract

The reactions of geraniol, nerol, and linalool with N,N-diethylamido O,O-propylenephosphite and diethyl chlorophosphite were studied. On the basis of these studies, new dienyl diprenoid phosphite esters were obtained.

GRAPHICAL ABSTRACT     

Trimethylphenylammonium Tribromide as a New and Efficient Oxidizing Agent for the Oxidative Coupling of Thiols into Disulfides and Chemoselective Oxidation of Sulfides into Sulfoxides

Abstract

Trimethylphenylammonium tribromide has been introduced as a versatile and new oxidizing agent for the preparation of disulfides and sulfoxides from thiols and sulfides, respectively. The reaction progress is simple, and proceeds under mild and homogenous conditions in ambient temperature.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT      

Identification tree based on fragmentation rules for structure elucidation of organophosphorus esters by electrospray mass spectrometry

Organophosphorus compounds have played important roles as pesticides, chemical warfare agents and extractors of radioactive material. Structural elucidation of phosphonates poses a particular challenge because their initial forms can be hydrolyzed, thus, degradation products may predominate in samples acquired in the field. The analysis of non‐volatile organophosphorus compounds and their degradation products is possible using electrospray tandem mass spectrometry ESI‐MS/MS. Here, we present a generic strategy that allows the unambiguous identification of substituents for two families of organophosphorus compounds: the phosphonates and phosphates. General fragmentation rules were deduced based on the study of decomposition pathways of 55 organophosphorus esters, including examples found in the literature. Multistage MS (MSⁿ) experiments at high resolution in a hybrid mass spectrometer provide accurate mass measurements, whereas collision‐induced dissociation experiments in a triple quadrupole give access to small fragment ions. The creation of a specific nomenclature for each possible structure of organophosphorus compound, depending on the alkyl side chain linked to the oxygen, was achieved by applying these fragmentation rules. This led to the creation of an ‘identification tree’ based upon the unique consecutive decomposition pathways uncovered for each individual compound. Hence, seven structural motifs were created that orient an unequivocal identification using the ‘identification tree’. Despite the similar structures of the ensemble of phosphate and phosphonate esters, distinct identifications based upon characteristic neutral losses and diagnostic fragment ions were possible in all cases. Copyright © 2013 John Wiley & Sons, Ltd.     

Collision cell pressure effect on CID spectra pattern using triple quadrupole instruments: a RRKM modeling

Control of the ion internal energy in mass spectrometry is needed to establish a workable mass spectral library. The purpose of this study is to understand and to compare the pressure effects on the collision‐induced dissociation (CID) spectrum pattern recorded using triple quadrupole instruments. The monoprotonated Leucine enkephalin [YGGFL, H⁺] was used as a thermometer molecule to calibrate the electrospray ionization (ESI) and the CID internal energies deposited on the molecular species and the time scale of ion decompositions. The survival yield and the ratio of a₄/b₄ fragment ions were mainly monitored. The energy uptake for the ESI source geometry used in our study has no impact on the CID spectrum fingerprint. The collision cell pressure for the [YGGFL, H⁺] has a major influence on the SY curves slope and on the experimental time scale. To demonstrate the pressure effect on internal energy distribution, three models (threshold, thermal and collisional) based on RRKM theory were built using the Masskinetics software. As a result, the limit of each model is discussed, and the investigation demonstrates that the thermal model, using truncated Maxwell‐Boltzmann internal energy distribution, is well‐suited for simulating the experimental data at high pressure widely used in the analytical conditions. Copyright © 2013 John Wiley & Sons, Ltd.