Electron Impact Ionization Conditions Research Articles

N-Aryl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido-[3,2,1-ij]quinoline-6-carboxamides. The Synthesis and Effects on Urinary Output.

Continuing a targeted search for new leading structures with diuretic action among tricyclic derivatives of hydroxyquinolines, which are of interest as potential inhibitors of aldosterone synthase, the synthesis of a series of the corresponding pyrido[3,2,1-ij]quinoline-6-carboxanilides was carried out by amidation of ethyl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylate with aniline, aminophenols and O-alkylsubstituted analogs with high yields and purity. The optimal conditions of this reaction are proposed; they make it possible to prevent partial destruction of the original heterocyclic ester and thereby avoid formation of specific impurities of 7-hydroxy-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinolin-5-one. To confirm the structure of all substances obtained, elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry were used. Moreover, the peculiarities of their 1H and 13C-NMR spectra, as well as their mass spectrometric behavior under conditions of electron impact ionization, were discussed. The effect of pyrido[3,2,1-ij]quinoline-6-carboxanilides on the urinary function of the kidneys was studied in white rats of both genders by the standard method of oral administration at a dose of 10 mg/kg. Testing was conducted in comparison with hydrochlorothiazide, as well as with structurally close pyrrolo[3,2,1-ij] quinoline-5-carboxanilides studied earlier with the same substituents in the anilide fragments. It was found that addition of one methylene unit to the heterocycle partially hydrogenated and annelated with the quinolone core has a positive impact on biological properties—most of the substances studied exhibit a statistically significant diuretic effect exceeding the activity of not only hydrochlorothiazide, in some cases, but also the action of the structural analogs. The important structural and biological regularities, which are common with pyrroloquinolines and introduced by a chemical modification, were revealed. The importance of the presence in the structure of terminal amide fragments of tricyclic quinoline-3-carboxamides of a 4-methoxy-substituted aromatic ring was particularly marked. The expediency of further study of pyridoquinolines as promising diuretic agents has been shown.

Mass Spectrometric Fragmentation of 1, 8-Bis[4-substituted-(oxazolin-2-yl)] anthracenes: Ring-contraction Rearrangement of Oxazoline Ring under Electron-Impact Ionization Conditions

The mass spectrometric fragmentation of 1, 8-bis[4-substituted(oxazolin-2-yl)] anthracenes (AnBOXes) was investigated by using mass-analyzed ion kinetic energy spectrometry under electron-impact ionization conditions. All the compounds could undergo a ring contraction by the loss of an RCH == CH 2 molecule to form 1-oxazirinyl-8-(oxazolin-2-yl) anthracene ions, which could further lose an R radical, followed by the loss of oxazoline. These ions could also eliminate an R radical and subsequently undergo ring-contraction rearrangements to lose a CHCH 2O fragment and an epoxide molecule, respectively. The ions that are formed could further lose CHCH 2O and CH 2 ==CH fragments. Several ring-contraction rearrangements of the oxazoline ring were observed under electron-impact ionization conditions.

Mass Spectral Fragmentation of ( S, S)- N, N′-Bis [1-(hydroxymethyl) alkyl] anthracene/Naphthalene-1, 8-dicarboxamides under Electron Impact Ionization Conditions

The mass spectrometric fragmentation of ( S, S)- N, N′-bis[1-(hydroxymethyl) alkyl] anthracene/naphthalene-1, 8-dicarboxamides was investigated with the aid of mass-analyzed ion kinetic energy spectrometry and the elemental compositions of important fragment ions were determined by accurate mass measurement under electron impact ionization conditions. All the compounds could eliminate formaldehyde. The [M-CH 2O] ions could also eliminate imine, aziridine, aziridinone, 2-amonoalkan-1-ol, water, and other fragments. Several cyclizations were observed under electron impact ionization.

Mass Spectrometric Fragmentation of 2a,4-Disubstituted 2,2a,3,4-Tetrahydro-2-phenyl-1H-azeto[2,1-d]- [1,5]benzothiazepin-1-ones Under Electron Impact Ionization Conditions and Comparison with their 2-Heteroatom Substituted Analogues

The mass spectrometric behavior of seven 2a,4-disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][1,5]benzothiazepin-1-ones has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate a phenylketene molecule, an ethyl or benzyl radical, or a phenylketene molecule plus an SH radical. The mass spectrometric behavior of the title compounds was compared to those of 2-heteroatom-substituted analogues.

Intermolecular Phenolic Hydroxy Methylation Occurring between Chiral N,N′‐Bis(2‐hydroxyphenyl)‐2,2‐dimethyl‐1,3‐dioxolane‐4,5‐dicarbamide and Co‐crystallized Methanol under Electron Impact Ionization Conditions

AbstractAn intermolecular phenolic hydroxy methylation occurring between chiral N,N′‐bis(2‐hydroxyphenyl)‐2,2‐dimethyl‐1,3‐dioxolane‐4,5dicarbamide and co‐crystallized methanol under electron impact ionization conditions was observed. The result was confirmed by X‐ray diffraction structural analysis of a co‐crystalline of (R,R)‐enantiomer and methanol.

Mass spectral fragmentation of (S,S)-2-substituted 4,4-diphenyl-3,1-oxazabicyclo[3.3.0]octanes: ring contraction of pyrrolidine and 1,3-oxazolidine in mass spectrometry.

The mass spectral behaviour of (S,S)-2-substituted 4,4-diphenyl-3,1-oxazabicyclo[3.3.0]octanes has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under fast atom bombardment (FAB) and electron impact (EI) ionization conditions. Under FAB ionization, all compounds show a tendency to form protonated aldehyde or benzophenone ions and to form protonated 1-azabicyclo[3.1.0]hexane ions, which can further lose an ethylene or cyclopropane from the pyrrolidine ring to produce protonated 1-azabicyclo[1.1.0]butane ions and 3H-azirine ions, respectively. Under EI ionization, a similar fragmentation to that under FAB ionization was observed. The title compounds also show a tendency to yield oxirane ions and oxirenium ions by loss of pyrrolidine and pyrrolidine plus H. Ring contractions of 1,3-oxazolidine by loss of an aldehyde or ketone and of pyrrolidine by loss of an ethylene or cyclopropane were observed under both FAB and EI ionization conditions.

Mass Spectrometry Study of Acylthioureas and Acylthiocarbamates

A variety of acylthiocarbamates and acylthioureas have been investigated under electron impact ionization (EI), chemical ionization (CI) and electrospray ionization (ESI) conditions. Sequential product-ion fragmentation (MSn) was performed to elucidate the degradation pathways for these compounds. Comparisons are made between positive and negative even-electron ions from ESI and CI and the odd-electron ions obtained under EI conditions. The data collected in this paper provide information on the strong differences found in the fragmentation process of these compounds.

Electron impact mass spectral fragmentation of chiral bisbenzoxazole, bisbenzothiazole and biscarbamide derivatives of 2,2-dimethyl-1,3-dioxolane.

The mass spectrometric fragmentation behaviour of five pairs of (R,R)- and (S,S)-4,5-bis(benzoxazol-2-yl)-2,2-dimethyl-1,3-dioxolane derivatives, one pair of (R,R)- and (S,S)-4,5-bis(benzothiazol-2-yl)-2,2-dimethyl-1,3-dioxolanes, and three pairs of (R,R)- and (S,S)-N,N'-bis(2-hydroxyaryl)-2,2-dimethyl-1,3-dioxolane-4,5-dicarbamides, all important compounds for asymmetric catalysis (P. Jiao et al., Tetrahedron Asymmetry 2001; 12: 3081), has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization conditions. The spectral observations have been rationalized in terms of fragment ion structures and fragmentation mechanisms that will provide an aid to spectral interpretation for new compounds of this type.

Structural elucidation by electrospray mass spectrometry: an approach to the in vitro metabolism of the macrolide immunosuppressant SDZ RAD

SDZ RAD [40-O-(2-hydroxyethyl)rapamycin] is a macrolide immunosuppressant that is currently under clinical investigation after organ transplantation. The elucidation of its metabolic pathway is essential to improve the understanding of its therapeutic potentials and safety. In this article we describe investigations on the structural identification of some major metabolites of the drug produced by human liver microsomes in vitro. The principles described may be generally applicable for the structural elucidation of complex compound mixtures in biological matrices. Under the conditions of electron impact ionization, SDZ RAD undergoes extensive fragmentation and no information sufficient for structural elucidation is obtained. Therefore, mass spectrometry based on soft electrospray ionization (ESI) in conjunction with collision-induced fragmentation was the method of choice. High-performance liquid chromatography coupled to an ESI mass spectrometer resulted in separation and identification of 16-O-demethyl-SDZ RAD, the ring-opened form of SDZ RAD, and its dehydrate. Additionally, we characterized several demethylated and hydroxylated metabolites.

Determination of 15N isotopic enrichment and concentrations of allantoin and uric acid in urine by gas chromatography/mass spectrometry.

A method for the determination of 15N enrichment and concentration of allantoin and uric acid simultaneously in urine using gas chromatography/mass spectrometry (GC/MS) is described. The urine samples contained [1,3-15N2] uric acid and its oxidation product allantoin. The uric acid and allantoin were isolated using an AG1-X8 (Cl-form) anion-exchange column and heated with a mixture containing 1:1 dimethylformamide and N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA). The tert-butyldimethylsilyl (TBDMS) derivatives of allantoin and uric acid formed were injected into a gas chromatograph interfaced with a mass spectrometer operated under electron impact ionization conditions. Isotope ratio measurements were made from the abundance of the M-57 ions at m/z 398, 399 and 400 for allantoin and at m/z 567 and 569 for uric acid. 15N2 allantoin (99 at.%) was produced from [1,3-15N2] uric acid by treatment with uricase and used as a standard. Quantitation of allantoin and uric acid was based on isotopic dilution by spiking the urine sample with known quantities of 99 at.% [15N] uric acid and allantoin internal standards. The observed isotope ratio measurements from the prepared standards matched the theoretical values. Coefficients of variation in measurements of isotope ratio and concentration were 0.2 and 0.5%, respectively. The method was applied in a study to measure the urinary recovery of [1,3-15N2] uric acid continuously infused for 8-10 h into the blood of four sheep each on two occasions. Within 24 h, 65.9 +/- 9.1% of the tracer was excreted in the urine unchanged. Little was converted into allantoin (approximately 7% of the dose). The total recovery (5 days) of the infused tracer averaged 69.5 +/- 7.6% as uric acid and 76.8 +/- 9.3% as the sum of uric acid and allantoin. Uricase activities in plasma, liver and kidney of sheep were also measured using [1,3-15N2] uric acid as a substrate. Uricase activity was estimated to be 0.6 mU g-1 wet tissue in the liver and there appeared to be none in plasma and kidney. The low uricase activities in sheep tissues appeared to explain the limited conversion of the intravenously administered [15N] uric acid to allantoin but did not explain the large quantities of allantoin excreted in urine (8.96 +/- 0.86 and 1.36 +/- 0.25 mmol d-1 for allantoin and uric acid, respectively). The GC/MS method for the determination of 15N enrichment and concentration of allantoin and uric acid in urine is accurate and precise and provides a useful tool for studies on uric acid and allantoin metabolism.

Decomposition of 3,5-diaryloxathiolane-2-oxides under electron impact

1,2-diarylcyclopropanes are known to form the corresponding 3,5-diaryl-1,2-oxathiolane-oxides upon reaction with sulfur dioxide in the presence of trifluoroacetic acid. The reverse reaction, the elimination of sulfur dioxide from 3,5-diaryl-1,2-oxathiolane-2-oxides to form the corresponding 1,2-diarylcyclopropanes, is also known in organic chemistry. In the present work, the loss of sulfur dioxide from the molecular ion of 3,5-diphenyl-1,2-oxathiolane-2-oxide ( 1), 3-phenyl-5-(p-methoxyphenyl)-1,2-oxathiolane-2-oxide ( 2), and 3,5-di-(p-methoxy phenyl)-1,2-oxathiolane-2-oxide ( 3) was observed in the ion source of a mass spectrometer under electron impact ionization conditions (EI). The resulting (M-SO 2) + ions had the same collisional activation mass spectra as the cation-radicals of the authentic 1,2-diphenylcyclopropane ( 4), 1-(p-methoxyphenyl)-2-phenylcyclopropane ( 5), and 1,2-(p-methoxyphenyl) cyclopropane ( 6), respectively, indicating their common structure. Therefore, the molecular ions of 1,2-oxathiolane-2-oxides 1–3 lose SO 2 to give rise to pseudomolecular ions of diarylcyclopropanes 4–6. The fragmentation reactions of 1,2-diphenylcyclopropane (compound 4) under EI were studied in detail using tandem mass spectrometry and high resolution mass spectrometry in order to establish their ion structure and fragmentation mechanisms. Our data suggests that the cation radicals of diphenylcyclopropane isomerize giving primarily cation-radicals of a methyldihydrophenanthrene structure. The latter undergoes dissociation to give rise to protonated phenanthrene ( m / z = 179), fluorenyl-cation ( m / z = 165) and indenyl-cation ( m / z = 115). Since SO 2 elimination from 3,5-diaryl-1,2-oxathiolane-2-oxides to form diarylcyclopropanes takes place both in solution and in the gas phase under EI, the compounds under study can serve as examples of a system in which a condensed phase reactions parallel cation radical reactions within the ion source of a mass spectrometer.

Mass spectrometric evidence for the formation of silaethene accompanying the fragmentation of a non‐ester silicon‐containing pyrethroid insecticide

AbstractThe non‐ester silicon‐containing pyrethroid SSI‐116 and its carbon analogue (ethofenprox, MTI‐500) were investigated using a tandem quadrupole mass spectrometer incorporating a hexapole collision cell under positive‐ion electron impact ionization conditions. Conventional mass spectrometry using the first quadrupole analyser only and tandem mass spectrometry on selected precursor ions and product ions, and also constant neutral loss scan experiments, were used. Accurate mass measurements on key ions were made using a high‐resolution double‐focusing mass spectrometer. Based on the experimental observations, mechanisms have been proposed to explain the major fragmentation pathways of SSI‐116 and ethofenprox. The novel expulsion of silaethene, CH2SiH2, as a neutral species from the silicon‐containing insecticide and the formation of an ion at m/z 135, isomeric with the fragment ion, [C9H11O]+, observed in the spectrum of its carbon analogue, have also been rationalized. Minor fragmentation pathways, found only in the silicon‐containing analogue, are also discussed.

Negative ion mass spectrometry of organotin compounds—an aid to environmental monitoring?

AbstractPositive‐ion mass spectra of organotin compounds include a large number of different ions and therefore the absolute detection level is reduced. Negative‐ion mass spectra are usually less complex and detection levels may therefore be improved. The negative‐ion mass spectra of selected organotin compounds of the type R4Sn, R3SnCI, R2SnCI2 and RSnCl3 were investigated using conventional electron impact ionization conditions. Simplified mass spectra, suitable for compound speciation, were obtained for R3SnCI2 and R2SnCI2 materials but the same fragmentation product SnCI was obtained from all the RSnCI3 samples. R4Sn compounds produced no negative‐ion data in these studies. No significant gains in detection levels were noted but some interesting re‐arrangement reactions leading to the formation of compounds consisting of substituents from the original tin atom were identified. These reactions may be of synthetic importance.

Thermal degradation of O‐acyl oximes under electron impact ionization conditions

AbstractThermal degradation of O‐acyl oximes under electron impact ionization (EI) conditions has been examined. The EI mass spectra gave fragment ions originating from thermal degradation, as well as molecular ions M+· and normal fragment ions due to unimolecular decomposition of the M+· ions. The fragment ions due to thermal degradation of O‐acyl oximes were identified by using fast‐atom bombardment (FAB) mass spectrometry with a liquid matrix together with the collision‐induced dissociation (CID) technique. While the FAB mass spectra of O‐acyl oximes gave, preferentially, M+· ions together with some characteristic fragment ions, as well as the molecular related ions [M+H]+ and [M−H]+, the spectra showed little evidence of the fragment ions which may originate from thermal degradation, under EI conditions. The CID spectra of selected M+· ions formed by electron impact also showed little of such fragment ions. The thermal degradation was directly confirmed by measuring the FAB mass spectra of O‐acyl oximes that had been heated in a sealed sample tube.

Mass spectrometry of lepidopterous insect sex pheromones containing a diene system

AbstractThe mass spectrometric behavior of some diene‐based sex pheromones of lepidopterous insects, under electron impact ionization conditions, was studied with the aid of mass‐analyzed ion kinetic energy spectroscopy and high‐resolution data. The similarity of the mass spectra of these dienes and their ability to distinguish double bond positional isomers and geometrical isomers was examined by a ‘minimum‐maximum’ similarity analysis.

Study of the major fragmentation pathways of cypermethrin and related synthetic insecticides using tandem mass spectrometry

AbstractFragmentation pathways of the synthetic pyrethroid cypermethrin and four structurally related insecticides were investigated using a tandem quadrupole mass spectrometer incorporating a hexapole collision cell under positive‐ion electron impact ionization conditions. Conventional mass spectrometry using the first quadrupole analyser only and tandem mass spectrometry on selected precursor ions and product ions, and also constant neutral loss scan experiments, were used. Mechanisms and fragmentation pathways are proposed to explain the inherent stability of ions associated with the benzylphenoxy portion of this class of insecticide.

Replacement of bromine by hydrogen in bromo derivatives of tetrahydropyrimido[4,5-b][1,4]benzthiazine under conditions of electron-impact ionization

Replacement of bromine by hydrogen in bromo derivatives of tetrahydropyrimido[4,5-b][1,4]benzthiazine under conditions of electron-impact ionization

Some Aspects of Intra- and Inter-Molecular Reactions of Siliconium Ions in the Vapor Phase

Abstract Intramolecular rearrangement processes in the mass spectra of trimethylsilyl derivatives of hydroxy steroids are discussed in terms of the reaction of a siliconium center and a heteroatom. The reaction is shown to be stereospecific. The reactivity of siliconium cations also results in the occurrence of intermolecular reactions under electron impact ionization conditions. Tetramethylsilane is used as a precursor for the production of siliconium ions and examples of chemical ionization mass spectra employing this reagent are shown.