The modern mass spectrometer—a complete chemical laboratory

Using nitrobenzene as an example, various ways in which a contemporary mass spectrometer can be utilized to yield a wealth of information about the compound studied are reviewed. Applying a variety of different techniques and procedures, in addition to the conventional low resolution mass spectrum, the following nitrobenzene spectra have been obtained: collision induced dissociation mass spectrum, mass analysed ion kinetic energy spectra, collision induced dissociation mass analysed ion kinetic energy spectra, spectra obtained at constant B/E, spectra obtained at constant B²/E, high voltage scans of metastable ion fragmentation processes, consecutive fragmentations in different field free regions, charge exchange mass spectra, charge stripping mass spectra, doubly charged ion mass spectra, chemical ionization mass spectra, negative ion mass spectra, negative ion mass analysed ion kinetic energy spectra, negative ion mass analysed ion kinetic energy collision induced dissociation spectra, charge inversion spectra, etc. The complementary types of information available from the above studies are discussed to show the unique versatility of mass spectrometry as a technique for the examination of organic compounds.     

Mass spectral behavior of n-alkynes

The 70 e V-electron impact mass spectra of the C₇–C₁₀ n-alkynes have been determined as well as the metastable ion spectra of the molecular ions and the [CS₂]⁺ and [N₂O]⁺ charge exchange mass spectra of the C₇-C₉ n-alkynes. The metastable ion mass spectra provide only a limited opportunity to distinguish between isomers; however, the 70-eV EI mass spectra of isomeric compounds permit a ready distinction between isomers. The [CS₂]⁺ charge exchange mass spectra of isomeric compounds also show substantial differences. The [N₂O]⁺ charge exchange mass spectra do not show the enhancement of β-fission fragments observed in field ionization experiments, despite representing ions of similar internal energy, and it is concluded that field dissociation is responsible for the β-fission fragments in the field ionization experiments.     

Chemical ionization and electron impact mass spectra of alicyclic substituted 2-aryl-1,3-dithianes

The methane and isobutane chemical ionization mass spectra of alicyclic substituted 2-aryl-1,3-dithianes were examined by gas chromatography mass spectrometry. The protonated molecular ion was found to be of low abundance in the methane spectra, while a protonated cyclic sulfide cation (m/z 107) appeared as the base peak. A protonated molecular ion was the base peak when isobutane was used as the reagent gas. Electron impact mass spectra displayed weak molecular ions and were characterized by the m/z 106 fragment.     

Electron-impact fragmentation of N-substituted 2-aminobenzoxazoles and 2-aminobenzothiazoles

The mass spectra of twenty-eight N-substituted 2-aminobenzoxazoles and 2-aminobenzothiazoles have been recorded and the identity of various ions in the mass spectra have been established by high resolution measurement. The molecular compound of series, benzoxazole, undergoes loss of hydrogen cyanide and carbon monoxide from the molecular ion as the most important decomposition pathways. The mass spectra of N-substituted benzothiazoles showed a similar fragmentation as that of N-substituted benzoxazoles.     

Stereochemical effects in the electron impact mass spectra of cis-trans isomeric 1,2,3,4-tetramethylcyclohexanes

The mass spectra of six cis-trans isomeric 1,2,3,4-tetramethylcyclohexanes are discussed. The intensity ratio of [M? CH₃]⁺/[M? C₂H₅]⁺ correlates with the strain energies of the stereoisomers. Therefore, the identification of cis-trans isomers is possible by means of their mass spectra. The mass spectra of deuterium labelled compounds demonstrate favoured fragmentation of the axial methyl groups and ring opening between the cis substituted carbon atoms of the cyclohexane.     

Structural characterization of flavonoid glycosides from leaves of wheat (Triticum aestivum L.) using LC/MS/MS profiling of the target compounds

The aim of this study was to present integrated mass spectrometric methods for the structural characterization and identification of flavonoid glycoconjugates. During the liquid chromatography/mass spectrometry analyses, TriVersa NanoMate chip‐based system with nanoelectrospray ionization and fraction collection was combined to a quadrupole time‐of‐flight mass spectrometer. In the extract samples prepared from green leaves of wheat plantlets, 41 flavonoid derivatives were recognized. Part of the target natural products had the full structure being characterized after the registration of mass spectra, where m/z values for protonated [M + H]⁺ and deprotonated molecules [M ? H]^? were annotated. MS² and pseudo‐MS³ experiments were performed for [M + H]⁺ or [M ? H]^? and aglycone ions (Y₀^+/?‐type), respectively. It should be underlined that pseudo‐MS³ mass spectra were registered for aglycone product ions in the mass spectra of O‐glycosides present in the extract samples. In many cases, only tentative structural identification of aglycones was possible, mainly because of the presence of numerous C‐monoglycoside or C‐diglycoside in the samples. Acylation of the sugar moiety and/or methylation of the aglycone in the flavonoid glycosides under study was observed. The existence of isobaric and/or isomeric compounds was demonstrated in the extract studied. The collision‐induced dissociation mass spectra registered for C,O‐diglycosides and C,C‐diglycosides did not permit to draw complete structural conclusions about the compounds studied. For the investigated class of natural products, unambiguous classification of sugar moieties linked to the aglycones from the recorded mass spectra was not possible. Registration of the positive and negative ion mass spectra did not lead to the precise conclusion about the glycosylation position at C‐6 or C‐8, and O‐4′ or O‐7 atoms. It was possible, on the basis of the collected MS² spectra, to differentiate between O‐glycosides and C‐glycosides present in the samples analyzed. Copyright © 2013 John Wiley & Sons, Ltd.     

Mechanisms of mass spectrometric fragmentations: X–Interaction between remote or-groups in decalin-1,5-diols and their dimethyl ethers

The mass spectra of the five stereoisomers of decalin-1,5-diol and its dimethyl ether have been investigated. The differences in the mass spectra of stereoisomers I to III with a trans- decalin ting system are small. The differences are much larger in the mass spectra of the two isomers IV and V of the cis-decalin series and the elimination of CH₂O, formed by interaction between the two methoxy groups, from the molecular ion is only observed in the mass spectrum of Vb.     

Electron-impact mass spectrometry of Nuphar alkaloids

Principal peaks in the mass spectra of deoxynupharidine are accounted for on the basis of high resolution mass spectrometry and peak shifts in the mass spectra of deoxynupharidine-4-d₁ and deoxynupharidine-6β, 7β-d₂. Cleavage of the quinolizidine ring system of deoxynupharidine occurs predominantly in ring A, giving m/e 136, 107, 98, 94 and 81. The origins of the family of ions [M — alkyl]⁺ and m/e 178 are considered. A comparative survey is made of the occurrence of these ions, and others, in the mass spectra of piperidine, quinolizidine and thiospirane types of Nuphar alkaloids. Attention is directed toions useful in distinguishing structural types.     

The mass spectra and ionization potentials of the neutral fragments produced during the electron bombardment of aromatic compounds

A mass spectrometer equipped with a dual ionization chamber ion source has been used to characterize directly the neutral species produced in the dissociative ionization of gases by electron impact. Neutral fragment mass spectra have been obtained for the electron ionization and fragmentation of benzene, toluene, o-xylene, m-xylene, p-xylene, mesitylene and isotopically labeled toluene. The neutral fragment mass spectra correlate well with the structures of the molecules. The abundant species in the neutral fragment mass spectra also correlate reasonably well with the abundant complementary positive ions of the normal mass spectra. Ionization potentials have been determined for the abundant neutral species produced. Where comparisons with values reported elsewhere are possible, the agreement is usually within ±0.2 eV or less.     

Unexpected mass spectral skeletal rearrangements in aromatic thioamides

Interesting skeletal rearrangements, resulting in the formation of unexpected fragments, have been noticed in the mass spectra of aromatic thioamides of cyclic amines such as piperidine, morpholine and pyrrolidine. Suitable mechanisms, based on mass analysed ion kinetic energy spectra, high voltage scan spectra and high resolution data, have been proposed for the formation of [M? SH]⁺ ions and the fragment at m/z (103+R) in the mass spectra of these compounds. The mass spectra of the thioamides of non-cyclic amines and the thioamides of aliphatic acids contain peaks corresponding to a four-centred skeletal rearrangement followed by the elimination of either the thioalkoxy or the thiophenoxy radical from the molecular ions.     

Determination of ion structures in structurally related compounds using precursor ion fingerprinting

Structurally-related alkaloids were analyzed by electrospray ionization/multiple stage mass spectrometry (ESI/MS ⁿ ) at varying collision energies to demonstrate a conceptual algorithm, precursor ion fingerprinting (PIF). PIF is a new approach for interpreting and library-searching ESI mass spectra predicated on the precursor ions of structurally-related compounds and their matching product ion spectra. Multiple-stage mass spectra were compiled and constructed into “spectral trees” that illustrated the compounds’ product ion spectra in their respective mass spectral stages. The precursor ions of these alkaloids were characterized and their spectral trees incorporated into an MS ⁿ library. These data will be used to construct a universal, searchable, and transferable library of MS ⁿ spectra. In addition, PIF will generate a proposed structural arrangement utilizing previously characterized ion structures, which will assist in the identification of unknown compounds.     

Characterization of cyclotrimethylenetrinitramine (RDX) by N,H isotope analyses with pyrolysis–atmospheric pressure ionization tandem mass spectrometry

Pyrolysis-atmospheric pressure chemical ionization was used to study the thermal decomposition of the energetic material cyclotrimethylenetrinitramine (RDX) and characterization of the individual molecular ion products was accomplished by tandem mass spectrometry. The analysis was aided with pyrolysis mass spectra of the (¹⁵N)- and perdeuterated RDX isotopes, and molecular formulae were derived for the m/z 46, 60, 74, 75, 85 and 98 molecular ions in the RDX pyrolysis mass spectrum. Equivalent fragments between the daughter ion mass spectra of the unlabeled and labeled RDX were determined in order to define a structure for each pyrolysis feature. Daughter ion mass spectra of pure reference compounds confirmed the identity of five of the six molecular ions. Perdeuterated RDX analyses provided evidence that m/z 74 and 75 are N,N-dimethylformamide and N-nitrosodimethylamine, respectively; m/z 46, 60 and 85 were identified as the protonated forms of formamide, N-methylformamide and dimethylaminoacetonitrile, respectively.     

Zum Mechanismus massenspektrometrischer Fragmentierungsreaktionen—IXSterische Effekte in den Massenspekten der Stereoisomeren von Decalin-2,3-diolen,Decalin-2,4-Diolen und Ihen Dimethyläthern

The mass spectra of all stereoisomers of decalin-2,3-diol, the corresponding dimethyl ethers and of some deuterated derivatives are discussed. The mass spectra of isomeric decalin-2,3-diols differ only slightly in ion intensities. The mass spectra of the stereoisomeric 2,3-dimethoxy-decalins are nearly identical within the series of transand cisderivatives. A mass spectrometric identification of the stereoisomers of these compounds is therefore diffucult. Stereoselective eliminations from the molecular ion are not observed. The mass spectra -of stereoisomeric decalin-1,4-diols show characteristic differences in the intensities of the[M ? H₂O]⁺˙-ions, which can be related to the geometry of the molecules in a similiar mode as was the case with cyclohexane-1,4-diols, The sterechemical control of the elimination of H₂O from the molecular ions has been confirmed by deuterium labelling. The mass spectra of stereoismeric 1,4-dimethoxy-decalins also differ characteristically in the intensities of the [M ? CH₃OH]⁺˙ ions. Furthermore peak due to the [M ? CH₂O]⁺˙ ions are only observed in the mass spectra of those stereoisomers, which have at least one conformation with a short distance between the two methoxy. The stereospecifity of the CH₃OH- and CH₂O-eliminationjs has also been determined by deuterium labelling.     

Dimethyl ketals of methylcyclohexanones as fragmentation-directing derivatives

The mass spectra of dimethyl ketal derivatives of cyclohexanone and the 2-, 3- and 4-methylcyclohexanones are discussed relative to their usefulness in indicating the point of alkyl substitution. Major fragments in the spectra (m/e 101 and m/e 115) arise by α-cleavage, hydrogen rearrangement and further cleavage to give even-electron species. The spectra yield structural information equivalent to that obtained from the corresponding ethylene ketals. The ease of preparation of dimethyl ketals and the mildness of reaction conditions relative to ethylene ketals warrant further exploitation of dimethyl ketals as fragmentation-directing derivatives in mass spectrometry.     

The mass spectra of carboxylic acids—V: Carboxyl-carboxyl interaction in the fragmentation of some cycloalkene-1,2-dicarboxylic acids

The fragmentation mechanisms of the six isomeric cyclohexene-1,2-dicarboxylic acids are discussed. Only the 1-cyclohexene acid, by virtue of the major sequential losses of H₂O and CO₂ from the molecular ion, is readily distinguishable from its isomers, all of whose mass spectra are closely similar. In contrast to cis and trans cyclohexane-1,2-dicarboxylic acids, whose mass spectra were markedly different, the cis and trans cyclohexene-1,2-dicarboxylic acids fragment in a similar fashion. The mass spectra of 1-cyclopentene-1,2-dicarboxylic acid and 1-cyclobutene-1,2-dicarboxylic acid also exhibit a strong carboxyl-carboxyl interaction; the fragmentation behaviour of the 1-cyclopenteneacid is, however, more complex than that of the 1-cyclohexene and 1-cyclobutene acids.     

Charge-Reversal mass spectra of enolate ions of some open-chain and cyclic ketones for structure identification

The charge-reversal (CR) mass spectra of the enolate ions of heptanal and ten isomeric heptanones, of cyclohexanone, of cycloheptanone, of isomeric methylcyclohexanones, of isomeric ethylcyclohexanones and of the iso meric monoterpene ketones camphor, fenchone, pulegone and thujone were obtained by deprotonation using OH^? under chemical ionization conditions followed by collision of the [M ? H] ^? ions with helium in the second field-free region of a VG ZAB 2F mass spectrometer. The CR mass spectra were evaluated by similarity index (SI) values. Characteristic of the CR mass spectra of the open-chain enolates are fragment ions formed by α-cleavage. However, the CR mass spectra are dominated by peaks of small hydrocarbon ions, particularly in the case of cyclic and bicyclic enolates. The CR mass spectra of enolates of linear heptanones differing in the position of the carbonyl group can be easily correlated with the structure of the parent ketone. The CR mass spectra of enolates of isomeric heptan-2-ones differing only in the degree of branching of the alkyl group are similar, but can be distinguished by the SI values. The CR mass spectra of the enolates of the isomeric cyclic and bicyclic ketones studied are more or less identical and cannot be used for structural assignment.     

Rearrangement reactions in the positive and negative ion mass spectra of clausmarin A

The positive and negative ion mass spectra of clausmarin A, a naturally occurring tetracyclic coumarin, have been studied. The base peaks in the positive and negative ion spectra correspond to the complementary ions at m/z 143 and m/z 255, respectively, formed by a rearrangement reaction. The fragmentation pathways have been elucidated with the help of exact mass measurements and in situ deuterium labelling.     

Stereochemical applications of mass spectrometry. II—Chemical ionization mass spectra of isomeric dicarboxylic acids and derivatives

The H₂ and CH₄, chemical ionization mass spectra of the cis dicarboxylic acids, maleic and citraconic acid, show much more extensive loss of H₂O from [MH]⁺ than the trans isomers, fumaric acid and mesaconic acid. Similarly, esters of maleic acid show a much more facile loss of ROH (R=alkyl or phenyl) from [MH]⁺ than do esters of fumaric acid. Similar differences are observed in the chemical ionization mass spectra of the isomeric phthalic and isophthalic acids and derivatives, where the ortho isomers show more extensive fragmentation of [MH]⁺ than the meta isomers. The facile fragmentation of [MH]⁺ for the cis and ortho isomers is attributed to ROH elimination involving interaction between the two carboxylate functions and forming the stable cyclic anhydride structure for the fragment ion. By contrast ROH elimination from [MH]⁺ for the trans and metu isomers requires a symmetry-forbidden [1,3]-H migration in the carboxyl protonated species and cannot lead to the cyclic anhydride structure. The chemical ionization mass spectra of cis and trans cyclohexane-1,2-dicarboxylic acids are essentially identical and show extensive fragmentation of the [IMH]⁺ ion. Experiments using deuterium labelling show extensive carboxyl group interactions for both isomers. The chemical ionization mass spectra of maleanilic and phthalanilic acids and of the related anhydrides and imides also are reported, as are the electron impact mass spectra of diphenyl maleate, diphenyl fumarate, diphenyl phthalate, maleanilic acid and phthalanilic acid.     

Stereochemical applications of mass spectrometry: 1—The utility of electron impact and chemical ionization mass spectrometry in the differentiation of stereoisomeric benzoin oximes and phenylhydrazones

A study of the electron impact and chemical ionization (H₂, CH₄, and iso-C₄H₁₀) mass spectra of stereoisomeric benzoin oximes and phenylhydrazones indicates that while the former can be distinguished only by their chemical ionization mass spectra the latter are readily distinguishable by both their electron impact and chemical ionization mass spectra. The electron impact mass spectra of the isomeric oximes are practically identical; however, the chemical ionization spectra show that the E isomer forms more stable [MH]⁺ and [MH? H₂O]⁺ ions than the Z isomer for which both the [MH]⁺ and [MH? H₂O]⁺ ions are relatively unstable. In electron impact the Z-phenylhydrazone shows a lower [M]⁺˙ ion abundance and more facile loss of H₂O than does the E isomer. This more facile H₂O loss also is observed for the [MH]⁺ ion of the Z isomer under chemical ionization conditions.     

Doubly charged ion mass spectra: VI—Amines

Doubly charged ion mass spectra of 22 amines (2–10 carbon atoms) were determined using an Hitachi RMU-7L double focusing mass spectrometer. Molecular ions were not observed in the spectra of aliphatic amines. The most intense product ion peaks in the spectra of lower molecular weight amines resulted from hydrogen elimination from the molecular ion; however, as amine molecular weight increased the largest peaks resulted from both hydrogen and heavy atom elimination from the molecular ion. Dominant ions in the doubly charged ion spectra of lower molecular weight aliphatic amines were from reactions of [C_nH₃N]²⁺ (n:=2, 3, 4) type ions. The spectra of higher molecular weight aliphatic amines spanned a wide mass range. Appearance energies for some of the more prominent ions were measured in the range from 25 to 49 eV. A geometry optimized quantum mechanical self-consistent field molecular orbital treatment was used to compute the energies and structural parameters of prominent ions in the doubly charged ion mass spectra.