Unimolecular and collision-induced fragmentation of protonated nitroarenes

The unimolecular fragmentation reactions of 28 protonated nitroarenes, occurring on the metastable ion time-scale, are reported. In addition, the collision-induced fragmentation of the same species have been studied at 10 eV and at 50 eV collision energy. When an OH, COOH or NH₂ substituent is ortho to the nitro function, the dominant fragmentation involves loss of H₂O, for both unimolecular and collision-induced reactions. When there is an electron-releasing substituent ortho or para to the litro group, loss of OH is the dominant fragmentation reaction both on the metastable ion time-scale and for ions activated by collision. When the electron-releasing substituent is meta to the nitro group, loss of NO₂ is the dominant low-energy unimolecular fragmentation reaction while loss of HNO₂ is the most important fragmentation for ions activated by 50 eV collisions. Elimination of NO from [MH]⁺ occurs to a significant extent in the unimolecular fragmentation of protonated nitrobenzene and those protenated nitrobenzenes containing electron- attracting substituents. In the collision-induced dissociation of these species loss of HNO₂ occurs at the expense of loss of NO. The results are consistent with protonation predominantly at the nitro group. The results are discussed in terms of the use of neutral loss scans in tandem mass spectrometry to monitor complex mixtures for nitroarenes.     

Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.     

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.     

Protonation susceptibility and fragmentation capability of functional groups in chemical ionization mass spectrometry of simple bifunctional compounds. Semi-quantitative interpretation of spectra

Positive-ion, methane-mediated chemical ionization mass spectra were measured for simple bifunctional aromatic compounds of the type m-XCH₂C₆H₄CH₂Y, where X = NH₂ and N(CH₃)₂, and Y = OH and OCH₃. Essentially only three peaks of ions, [MH]⁺, [MH – XH]⁺ and [MH – YH]⁺, have appeared for each compound. Since the two functional groups XCH₂– and YCH₂– do not interact with each other after protonation or after fragmentation, they are assumed to be protonated and to undergo fragmentations independently. The relative protonation susceptibility and fraction of fragmenting [MH]⁺ can be estimated for each functional group in these compounds. A semi-quantitative interpretation of the observed spectra is presented.     

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.     

Site of protonation in the chemical ionization mass spectra of olefinic methyl esters

The H₂ and CH₄ chemical ionization mass spectra of the olefinic esters methyl acrylate, methyl methacrylate, methyl crotonate, methyl 3-butenoate, methyl 2-methyl-2-butenoate, methyl 3-methyl-2-butenoate and methyl cinnamate have been determined. In addition to the expected loss of CH₃OH from [MH]⁺, in many cases the protonated molecules also show loss of CO or CH₂CO with methoxy group migration to the positive ion centre, indicative of protonation at the double bond. These rearrangement reactions, which have analogies in electron impact mass spectra, result in chemical ionization mass spectra of isomeric molecules which show more substantial differences than the electron impact mass spectra. In the case of methyl cinnamate, isotopic labelling experiments show considerable interchange of the added proton with the ortho and meta phenyl hydrogens prior to CH₃OH or CH₂CO loss, although the extent of interchange is not the same for both cases.     

Studies in chemical ionization mass spectrometry: 17-hydroxy steroids

The chemical ionization mass spectra of several hydroxy steroids were obtained using methane as the reactant gas. The spectra are much less complex than the electron ionization spectra and little fragmentation of the steroid nucleus is observed. The major fragment ions involve the loss of water from [M + H]⁺. A 3-keto group in the steroids was characterized by an abundant [M + C₂H₅]⁺ ion. 5α- and 5β-Dihydrotestosterone could be distinguished by their spectra, with H₂ as the reactant gas by marked differences in amounts of [M + H]⁺, [M + H ? H₂O]⁺ and [M + H ? 2H₂O]⁺. Substituted 3α-X-, 17 β-ol compounds, (X = Cl, Br) were also studied to obtain relative amounts of protonation at these sites.     

Ionisation Chimique de Composés Aromatiques Nitrés

The collision induced dissociations of [MH – 30]⁺ ions observed in the chemical ionization (methane) mass spectra of some nitro aromatic compounds show that these ions are formed by reduction in the ion source with subsequent protonation and not by the previously reported losses of NO^· from the protonated molecular ions.     

Electron impact,electron capture negative ionization and positive chemical ionization mass spectra of organophosphorus flame retardants and plasticizers

Phosphate esters are important commercial products that have been used both as flame retardants and as plasticizers. To analyze these compounds by gas chromatographic mass spectrometry, it is important to understand the mass spectra of these compounds using various ionization modes. This paper is a systematic overview of the electron impact (EI), electron capture negative ionization (ECNI) and positive chemical ionization (PCI) mass spectra of 13 organophosphate esters. These data are useful for developing and optimizing analytical measurements. The EI spectra of these 13 compounds are dominated by ions such as H₄PO₄⁺, (M ? Cl)⁺, (M ? CH₂Cl)⁺ or (M)⁺ depending on specific chemical structures. The ECNI spectra are generally dominated by (M ? R)^?. The PCI spectra are mainly dominated by the protonated molecular ion (M + H)⁺. The branching of the alkyl substituents, the halogenation of the substituents and, for aromatic phosphate esters, ortho alkylation of the ring are all significant factors controlling the details of the fragmentation processes. EI provides the best sensitivity for the quantitative measurement of these compounds, but PCI and ECNI both have considerable qualitative selectivity. Copyright © 2013 John Wiley & Sons, Ltd.     

Ortho effects in organic molecules on electron impact. 14—Concerted and stepwise ejections of SO2 and N2 from N-arylidene 2-nitrobenzenesulphenamides

Unexpected ortho interaction of the nitro group has been noticed during the mass spectral fragmentations of N-arylidene 2-nitrobenzenesulphenamides, where the molecular ions expel SO₂ and N₂ both in concerted and stepwise processes. Loss of a hydrogen or the substituent from this fragment leads to a very abundant ion in all the compounds studied. Based on chemical evidence and linked-scan studies, a 1,2-phenylenetropylium cation structure has been postulated for the [M–SO₂–N₂–H/substituent]⁺ ion.     

Mass spectra of some isopropyl benzene derivatives. A study of the ortho effect

The mass spectra of a series of ortho, meta and para substituted isopropyl benzene derivatives have been determined where the second substituent is ? COOH, ? C(O)NH₂, ? C(O)C₆H₅, ? C(Ph)(=NPh) or ? CH(Ph)(NHPh). Two bis-isopropylbenzophenones have also been studied. The spectra are characterized by prominent ortho effects which distinguish the ortho derivatives from the meta and para.     

o-nitroaniline derivatives. IV—The mass spectra of o-nitroanils

The principal feature of the mass spectra of o-nitroanils, ArCH?NC₆H₄NO₂(o-), is an intense peak corresponding to the [ArCO]⁺ ion; this implies oxygen transfer from the nitro group to the azomethine carbon during the fragmentation process. In this series of anils, loss of OH from the molecular ion is not apparently an important fragmentation pathway, in contrast to the fragmentation of o-nitrobenzylideneanilines. Benzylideneaniline derivatives with an o-nitro substituent in both rings have mass spectra which indicate interaction of both nitro groups with the ? CH?N? group, but in this series of spectra the [M—17]⁺ ion is again of low intensity.     

Novel Ortho effects detected in the fast atom bombardment mass spectra of substituted bisaryl phosphate antagonists of platelet-activating factor

A series of substituted bisaryl phosphate compounds, (R¹CH₂)⁺ ArOP = O(O^?)(OArR²R₃), was analyzed and characterized by fast atom bombardment mass spectrometry. Abundant fragment ions were observed and correlated with the proposed structures. From fragmentation pattersn, ‘ortho effect’ reactions were demonstrated to have occurred when the phosphoryl oxygen reacted with the (CH₂R¹)⁺ and C?O(OCH₃) substituents in the ortho position, relative to the phosphate group, and displaced the R¹ and OCH₃ groups, respectively, to produce phosphorus containing six-membered rings fused to the aryl moiety. When the (CH₂R¹)⁺ substituents were in the meta position relative to the phosphate group, the ‘ortho effect’ reactions were not observed. However, when the C?O(OCH₃) substituent was in the meta position relative to the phosphate group, an abundant fragment ion containing a five-membered phosphate ring fused to the aryl ring was detected with the original phosphoryl oxygen ortho to both the phosphate oxygen and a formyl group, formed from the original C?O(OCH₃) substituent. All other fragmentations not involving the ‘ortho effect’ reactions were nearly identical for the different structural isomers of the substituted bisaryl phosphate compounds.     

An MNDO study of the electrophilic aromatic substitution on trifluorobenzenes

Summary MNDO calculations of trifluorosubstituted benzenes and their protonated intermediates [Ph-F₃]H⁺ were performed. The results are discussed with respect to changes in geometry, charge distribution and stabilities of the individual intermediates. It appears that the predominant influence which controls the protonation position is the ability of the substituent F to increase both the positive charge and polarities of the carbon bonds situated in themeta-position with respect to the substituent, thus directing protonation to theortho- andpara-positions.     

Mass spectrometric behaviour of 1-imino-substituted pyrazolo[1,2-a]-[1,2,4]triazoles under electron and chemical ionization

The spectra of five pharmacologically interesting substituted pyrazolo[1,2-a][1,2,4]triazole hydroiodides were measured under electron and chemical ionization. In the electron ionization spectra, in addition to the intense molecular ion peak of the free base (M⁺*), there was also a relatively intense molecular ion peak of the hydroiodide form, which is unusual since the hydroiodides are rarely so stable. The phenylimino and phenylamino substituents of the triazole ring affected the fragmentation behaviour of the compounds very much. The chemical ionization reagent gases used in this work were methane, isobutane, deuterated ammonia and acetone. In all the cases practically only [M+H]⁺ ions were observed, the only exception being acetone which also gave rise to intense [M+C₂H₃O]⁺ and [M⁺C₃H₇O]⁺ adduct ions. None of the reagent gases used was able to cause any fragmentation.     

Absolute configuration assignment of ortho,meta, or para isomers by mass spectrometry

A general method based solely on mass spectrometric techniques for the absolute configuration assignment of ortho, meta, or para isomers of acyl nitrobenzenes and derivatives is described. Instead of comparing the mass spectra of the three intact molecules of each positional isomer and investigating each one of the many sets of positional isomers, the method generalizes the effort by performing structural analysis on configurationally diagnostic fragment ions that are common for a given class of compounds. These ions must therefore retain the positional information of the parent molecules and be unequivocally distinguished. Nitrobenzoyl cations are common and stable fragment ions of most acyl nitrobenzenes and derivatives retaining the respective ortho, meta, or para configuration of the precursor molecules. The different NO₂ and CO⁺ ring alignments profoundly influence their collision-induced dissociation and bimolecular reactivity, and the isomeric 2-, 3-, and 4-nitrobenzoyl cations are found to be unequivocally distinguished using both approaches. Absolute ortho, meta, or para positional assignment by tandem MS of every isomeric molecule of the acyl nitrobenzene class and derivatives forming detectable amounts of any of those diagnostic nitrobenzoyl cations is, therefore, possible. The ability to perform absolute (non-comparative) configuration assignment using such diagnostic ions is exemplified for a single test molecule of (2R)-(−)-2-methylglycidyl 4-nitrobenzoate. The general application of this absolute MS-only method for other classes of positional isomers is discussed.     

Mass spectra of a series of 2-p-substituted phenyl-1,3,2-dioxaborolanes

The mass spectra of a series of 2-p-substituted phenyl-1,3,2-dioxaborolanes have been examined and compared with the mass spectrum of 2-phenyl-1,3,2-dioxaborolane. Formation of the substituted ion [C₇H₆X]⁺ by electron impact induced rearrangement has been found to be influenced significantly by the presence and nature of the substituent at the para position of the phenyl ring.     

Electron impact ionization mass spectra of 2,4,5,5-tetrasubstituted 1,2,4-triazolidine-3-thiones. The effect of the ethoxycarbonyl group at position 4

The electron impact ionization mass spectra of 2,4,5,5-tetrasubstituted 1,2,4-triazolidine-3-thiones studied confirmed that the substituent at position 4 has the most dramatic influence on the fragmentation pattern. When the substituent is a methylallyl group the molecular ions exhibit four main routes of fragmentation, but when it is an ethoxycarbonyl/acetyl or a methyl group these direct decompositions of the molecular ion become less abundant. Interestingly all 4-ethoxycarbonyl derivatives and the 4-acetyl derivative exhibited the ions [M-R⁴-COOC₂H₄]⁺ and [M-R⁴-COCH₂]⁺, respectively, with the same composition.     

Collision-induced dissociation study of cyclization of α-diazo-ω-arylsulphonylaminoalkan-2-ones

The collision-induced dissociation mass-analysed ion kinetic energy (CID MIKE) spectra (electron impact and chemical ionization) of five α-diazo-ω-arylsulphonylaminoalkan-2-ones and corresponding N-arylsulphonylazetidin-3-ones and N-arylsulphonylpyrrolidin-3-ones were studied. The [M ? N₂]⁺˙ and [MH ? N₂]⁺ ions of two types of the diazo ketones provide CID MIKE spectra similar to those of the corresponding M⁺˙ and MH⁺ of the heterocyclic compounds, i.e. a cyclization analogous to that in solution takes place. For the other three types of diazo compounds the Wolff rearrangement prevails in both the gas and liquid phases. The effect of the substituents on the cyclization process was studied. The data obtained permit the results of acid-catalysed cyclization of similar diazo ketones to be predicted on the basis of their CID MIKE spectra. Chemical ionization provides a closer similarity with reactions in solution than electron impact ionization, which can be rationalized by the protonation of the diazo ketone molecule being the driving force of the cyclization reaction either in solution or in the ion source of a mass spectrometer.     

Positive electron impact and chemical ionization mass spectra of some nitramine nitrates

The positive electron impact (EI) and isobutane chemical ionization (CI) mass spectra of six nitramine nitrates were studied with the aid of some accurate mass measurements. In the EI spectra, β fission relative to both the nitramine and nitrate ester is important. In the CI spectra a major ion occurs at [MH – 45]⁺ and was found to be mainly due to [M + 2H ? NO₂]⁺. All of the compounds except N-(2 hydroxyethyl)-N-(2′,4′,6′-trinitrophenyl)nitramine nitrate gave an [MH]⁺ ion. The [MH – 45]⁺ ion in the isobutane CI mass spectra of tetryl is also due to [M + 2H ? NO₂]⁺.