Hydrogen migrations in mass spectrometry. V—loss of olefin from n-propyl esters following chemical ionization

The sources of the migrating hydrogen in the elimination of propylene from the protonated and ethylated n-propyl acetate and n-propyl benzoate molecules have been determined by studying the CH₄ and H₂ chemical ionization mass spectra of esters specifically deuterated in the propyl group. It is shown that the migrating hydrogen originates from C-1 ( ～ 27%), C-2 ( ～ 23%) and C-3 ( ～ 50%) of the propyl group, independent of ester and mode of ionization. It is argued that the observed reaction involves specific competing H-migration reactions from each propyl position to the ether oxygen in a keto-protonated (ethylated) ester molecule.     

Chemical ionization of phenyl n-propyl ether and methyl substituted analogs: Propene loss initiated by competing proton transfer to the oxygen atom and the aromatic ring

The mechanism of propene loss from protonated phenyl n-propyl ether and a series of mono-, di-, and trimethylphenyl n-propyl ethers has been examined by chemical ionization (CI) mass spectrometry in combination with tandem mass spectrometry experiments. The role of initial proton transfer to the oxygen atom and the aromatic ring, respectively, has been probed with the use of deuterated CI reagents, D₂O, CD₃OD, and CD₃CN (given in order of increasing proton affinity), in combination with deuterium labeling of the β position of the n-propyl group or the phenyl ring. The metastable [M + D]⁺ ions of phenyl n-propyl ether—formed with D₂O as the CI reagent—eliminate C₃H₅D and C₃H₆ in a ratio of 10:90, which indicates that the added deuteron is incorporated to a minor extent in the expelled neutral species. In the experiments with CD₃OD as the CI reagent, the ratio between the losses of C₃H₅D and C₃H₆ from the metastable [M + D]⁺ ions of phenyl n-propyl ether is 18:82, whereas the ratio becomes 27:73 with CD₃CN as the reagent. A similar trend in the tendency to expel a propene molecule that contains the added deuteron is observed for the metastable [M + D]⁺ ions of phenyl n-propyl ether labeled at the β position of the alkyl group. Incorporation of a hydrogen atom that originates from the aromatic ring in the expelled propene molecule is of negligible importance as revealed by the minor loss of C₃H₅D from the metastable [M + H]⁺ ions of C₆D₅OCH₂CH₂CH₃ irrespective of whether H₂O, CH₃OH, or CH₃CN is the CI reagent. The combined results for the [M + D]⁺ ions of phenyl n-propyl ether and deuterium-labeled analogs are suggested to be in line with a model that assumes that propene loss occurs not only from species formed by deuteron transfer to the oxygen atom, but also from ions generated by deuteron transfer to the ring. This is substantiated by the results for the methyl-substituted ethers, which reveal that the position as well as the number of methyl groups bonded to the ring exert a marked effect on the relative importances of the losses of C₃H₅D and C₃H₆ from the metastable [M + D]⁺ ions of the unlabeled methyl-substituted species.     

Selective reagents in chemical ionization mass spectrometry: Tetramethylsilane with ethers

Chemical ionization mass spectra of several ethers obtained with He/(CH₃)₄Si mixtures as the reagent gases contain abundant [M + 73]⁺ adduct ions which identify the relative molecular mass. For the di-n-alkyl ethers, these [M + 73]⁺ ions are formed by sample ion/sample molecule reactions of the fragment ions, [M + 73 ? C_nH_2n]⁺ and [M + 73 ? 2CnH_2n]⁺. Small amounts of [M + H]⁺ ions are also formed, predominantly by proton transfer reactions of the [M + 73 ? 2CnH_2n]⁺ or [(CH₃)₃SiOH₂]⁺ ions with the ethers. The di-s-alkyl ethers give no [M + 73] ⁺ ions, but do give [M + H]⁺ ions, which allow the determination of the relative molecular mass. These [M + H]⁺ ions result primarily from proton transfer reactions from the dominant fragment ion, [(CH₃)₃SiOH₂]⁺ with the ether. Methyl phenyl ether gives only [M + 73]⁺ adduct ions, by a bimolecular addition of the trimethylsilyl ion to the ether, not by the two-step process found for the di-n-alkyl ethers. Ethyl phenyl ether gives [M + 73]⁺ by both the two-step process and the bimolecular addition. Although the mass spectra of the alkyl etherr are temperature-dependent, the sensitivities of the di-alkyl ethers and ethyl phenyl ether are independent of temperature. However, the sensitivity for methyl phenyl ether decreases significantly with increasing temperature.     

Chemical ionization of fluorophenyl n-propyl ethers: Loss of propene from the metastable [M + D]+ ions

Chemical ionization (CI) mass spectrometry with the reagents D₂O, CD₃OD, and CD₃CN (given in order of increasing proton affinity) has been used to generate metastable [M + D]⁺ ions of a series of mono-, di-, and trifluorophenyl n-propyl ethers and analogs labeled with two deuterium atoms at the β position of the alkyl group. Loss of propene is the main reaction of the [M + D]⁺ ions, whereas dissociation with formation of propyl carbenium ions is of minor importance. The combined results reveal that the deuteron added in the CI process can be incorporated in the propene molecules as well as in the propyl carbenium ions. The extent to which the added deuteron is exchanged with the hydrogen atoms of the propyl group is markedly dependent on the position of the fluorine atom(s) on the ring and the exothermicity of the initial deuteron transfer. For 3-fluorophenyl n-propyl ether, exchange is not observed if D₂O is the CI reagent, and occurs only to a minor extent in the experiments with the CI reagents CD₃OD and CD₃CN. Similar results are obtained for the 3,5-difluoro- and 2,4,6-trifluorophenyl ethers, whereas significant exchange is observed prior to the dissociations of the [M + D]⁺ ions of the 4-fluoro- and 2,6-difluorophenyl n-propyl ethers, irrespective of the nature of the CI reagent. These results are discussed in terms of the occurrence of initial deuteron transfer either to the oxygen atom or the aromatic ring followed by formation of an ion/neutral complex of a fluorine-substituted molecule and a secondary propyl carbenium ion. Initial deuteron transfer to the oxygen atom is suggested to yield complexes that can react by exchange between the added deuteron and the hydrogen atoms of the original propyl group prior to dissociation. By contrast, initial deuteron transfer to the ring is suggested to lead to complexes that react further by loss of propene molecules containing only the hydrogen/deuterium atoms of the original propyl entity.     

Metastable ions in chemical ionization

The ion [C₃H₅]⁺ generated in a chemical ionization source by a variety of methods, including protonation and charge exchange, exhibits a metastable peak for H₂ loss which is two orders of magnitude weaker than that formed in an electron impact source. The stable [C₃H₅]⁺ ions generated by electron impact and chemical ionization undergo collision-induced dissociation to a comparable extent, both losing H₂ by only one of the two competitive mechanisms observed for metastable ions. In contrast to the behavior of [C₃H₅]⁺, the molecular ions of p-substituted nitrobenzene, generated by charge exchange at high source pressure, yield composite metastable peaks for NO loss which are very similar in shape and intensity to those generated by electron impact. The contrasting behavior of the metastable ions extracted from high pressure ion sources in the two systems may be due to differences in the efficiencies of quenching of the ionic states responsible for fragmentation as metastable ions. It is noteworthy that the NO loss reactions require considerably lower activation energies than does the H₂ loss reaction.     

Cationic polymerization of vinyl monomers initiated by 10-methylphenothiazine cation radicals

A small quantity of 10-methylphenothiazine cation radical (MPT^.+), electrochemically prepared and stocked in acetonitrile solution, initiated cationic polymerizations of n-butyl, t-butyl, and 2-methoxyethyl vinyl ethers and p-methoxystyrene, while no initiation occurred for phenyl vinyl ether, styrene, methyl methacrylate, and phenyl glycidyl ether. ¹H-NMR studies of oligomers and low molecular weight compounds isolated from the reaction mixture for the polymerization of t-butyl vinyl ether in the presence of a small amount of D₂O indicated that electron transfer from the monomer to MPT^.+ was involved in the initiation step. ¹H- and ¹³C-NMR and MO calculation implied that monomers with higher electron densities on the vinyl groups and with lower ionization potentials were more susceptible to the initiation of MPT^.+. © 1994 John Wiley & Sons, Inc.     

Chemical ionization mass spectrometry—XIX: n-hexane and n-octane as reactants

The suitability of n-hexane and n-octane as reactant gases in chemical ionization mass spectrometry has been investigated. The mass spectra of these substances have been investigated as a function of pressure up to 2·4 Torr for n-hexane and 1·7 Torr for n-octane. The major ion present in n-hexane at 0·8 Torr is [C₆H₁₃]⁺ (m/e 85) with a relative intensity of 0·65. In n-octane at 0·8 Torr the major ions are [C₈H₁₇]⁺ (m/e 113), [C₆H₁₃]⁺ (m/e 85) and [C₅H₁₁]⁺ (m/e 71). The relative intensities of these ions are 0·38, 0·12 and 0·19, respectively. These alkyl ions in both n-hexane and n-octane are thought to have tertiary structures. Rate constants for the rates of reaction of the primary ions in the two compounds have been determined. The n-hexane chemical ionization spectra of 26 compounds were determined. The spectra of polar compounds are dominated by proton transfer, whereas those of nonpolar compounds exhibit proton transfer and in addition often surprisingly large amounts of electron transfer. The n-octane chemical ionization spectra of 15 compounds were determined and the spectra in general are quite similar to those obtained with n-hexane. n-Hexane and n-octane can be used as reagents in analytical chemical ionization mass spectrometry, but except in certain specialized uses they would probably have no advantage over i-butane.     

Candidate reference method: Determination of valproic acid in serum by isotope-dilution mass spectrometry

Summary A method has been developed for the determination of valproic acid, without derivatization, in human serum by isotope-dilution mass spectrometry using labelled 2-propyl[3,3,3-d₃] valeric[5,5,5-d₃] acid as internal standard for accurate quantification of the concentration of valproic acid in the sample. After acidification, the analyte and internal standard are extracted withn-hexane. The amounts of valproic acid in the serum are calculated from the isotope ratio of valproic acid to labelled valproic acid, which is measured by electron impact (EI) and chemical ionization (CI) selected ion monitoring (SIM). The concentrations of valproic acid in sera measured using isotope-dilution mass spectrometry are compared with results from gas-liquid chromatography (GLC) and fluorescence polarization immunoassay (FPIA). The accuracy, precision and recovery of the GC-MS methods are discussed. The coefficient of variation determined from duplicate samples was less than 1.5%. The detection limit was 10 ng mL⁻¹ at a signal-to-noise ratio of 3:1. Part of this work was presented at the Kongre? der Deutschen Gesellschaft für Laboratoriumsmedizin, Berlin, 1994.     

Candidate reference method: Determination of valproic acid in serum by isotope-dilution mass spectrometry

Summary A method has been developed for the determination of valproic acid, without derivatization, in human serum by isotope-dilution mass spectrometry using labelled 2-propyl[3,3,3-d₃]valeric[5,5,5-d₃] acid as internal standard for accurate quantification of the concentration of valproic acid in the sample. After acidification, the analyte and internal standard are extracted withn-hexane. The amounts of valproic acid in the serum are calculated from the isotope ratio of valproic acid to labelled valproic acid, which is measured by electron impact (EI) and chemical ionization (CI) selected ion monitoring (SIM). The concentrations of valproic acid in sera measured using isotope-dilution mass spectrometry are compared with results from gas-liquid chromatography (GLC) and fluorescence polarization immunoassay (FPIA). The accuracy, precision and recovery of the GC-MS methods are discussed. The coefficient of variation determined from duplicate samples was less than 1.5%. The detection limit was 10 ng mL⁻¹ at a signal-to-noise ratio of 3∶1. Part of this work was presented at the Kongre? der Deutschen Gesellschaft für Laboratoriumsmedizin, Berlin, 1994.     

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. 2–i-C4H10 and NO spectra of alkynes

The position of the triple bond of n-alkynes can be determined by the analysis of the relative abundance of the C_nH_2n?1 ions in the chemical ionization (i-butane) spectra. However, chemical ionization (NO) spectra where both hydrocarbon and NO-containing ions are formed in a characteristic manner are more reliable for this purpose. The limitations of the fragmentation rules established earlier for electron impact spectra of alkynes were investigated by examination of additional examples.     

The study of C1?C3 monosubstituted alkyl benzenes by the inverse convolution of first differential ionization efficiency curves

The electron impact ionization efficiency curves for the parent ions and the [C₇H₇]⁺ fragment ion formed from monosubstituted alkyl benzenes (R?CH₃? n-C₃H₇) have been studied by applying the inverse convolution technique of Vogt and Pascual to the first derivative ionization efficiency curves of the ions. Ionization and appearance energies measured for the ions at threshold are in good agreement with recently published photoionization values. Structures in the ionization efficiency curves (higher energy processes) are also reported for about 4 e V above threshold. The heats of formation calculated for [C₇H₇]⁺ fragment ions obtained from toluene and ethyl benzene at threshold are equal to 864 and 865 kJ mol^?1 respectively, and are consistent with the tropylium structure. However, for the [C₇H₇]⁺ fragment ion obtained from n-propyl benzene at threshold the calculated heat of formation is equal to 923 kJ mol^?1 and probably corresponds to a benzyl structure.     

Mass spectrometry of substituted 1,3-dihydro-2H-imidazole-2-thiones

The electron impact mass spectra of the 4-formyl-1, 3-dihydro-2H-imidazole-2-thione, its six 1-methyl(n-propyl, n-hexyl)-3-methyl(phenyl)-disubstptuted derivatives, and the 1,3-dihydro-1-phenyl-2H-imidazole-2-thiome are discussed. The fragmentation pattern is strongly influenced by the alkyl or phenyl N-substituents, as well as by the length of the alkyl chain. The odd-electron ions containing an N-phenyl substituent, but not a propyl or hexyl group, eject a hydrogen atom from the phenyl ring, while the presence of a long alkyl chain greatly enhances the loss of the sulphyhydryl radical and facilitates the expulsion of several alkenes, and alkyl and alkenyl radicals.     

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.     

Chemical ionization mass spectrometry of some crown ethers

Methane and isobutane chemical ionization mass spectrometry is superior to the classical electron impact technique for the analysis of aliphatic macrocyclic polyethers of the 4n-crown-n type. The latter reagent gas is particularly suited for molecular weight determinations.     

Alkene loss from metastable methyleneimmonium ions: Unusual inverse secondary isotope effect in ion-neutral complex intermediate fragmentations

The mechanism of propene elimination from metastable methyleneimmonium ions is discussed. The first field-free region fragmentations of complete sets of isotopically labelled methyleneimmonium ions (H₂C = $ \mathop {\rm N}\limits^{\rm +} $⁺R¹R²: R¹ = R² = n-C₃H₇; R¹ = R² = i-C₃H₇; R¹ = n -C₃H₇; R² = C₂H₅; R¹ = n-C₃H₇; R² = CH₃; R¹ = n-C₃H₇; R² = H) were used to support the mechanism presented. The relative amounts of H/D transferred are quantitatively correlated to two distinct mathematical concepts which allow information to be deduced about influences on reaction pathways that cannot be measured directly. Propene loss from the ions examined proceeds via ion-neutral complex intermediates. For the di-n-propyl species rate-determining and H/D distribution-determining steps are clearly distinct Whereas the former corresponds to a 1,2-hydride shift in a 1-propyl cation coordinated to an imine moiety, the latter is equivalent to a proton transfer to the imine occurring from the 2-propyl cation generated by the previous step. For the diisopropyl-substituted ions which directly form the 2-propyl cation-containing complex, the rate-determining hydride shift vanishes. The 2-propyl cation-containing complex can decompose directly or via an intermediate proton-bridged complex. Competition of these routes is not excluded by the experimental results. Assuming a 2:1:3 distribution, a preference for the α- and β-methylene of the initial n-propyl chain as the source of the hydrogen transferred is detected for n-propylimmonium ions containing a second alkyl chain R². This preference shows a clear dependence on the steric influence of R². During the transfer step isotopic substitution is found to affect the H/D distribution strongly. For the alternative route of McLafferty rearrangement leading to C₂H₄ loss, specific γ-H transfer is observed.     

Chemical ionization mass spectra of mononitroarenes

The H₂ and CH₄ chemical ionization mass spectra of a selection of substituted nitrobenzenes have been determined. It is shown that reduction of the nitro group to the amine is favoured by high source temperatures and the presence of water in the ion source. The H₂ chemical ionization mass spectra are much more useful for distinguishing between isomeric compounds than the CH₄ CI mass spectra because of the more extensive fragmentation. For ortho substituents bearing a labile hydrogen abundant [MH ? H₂O]⁺ fragments are observed. When the substituent is electron-releasing both ortho and para substituted nitrobenzenes show abundant [MH? OH]⁺ fragment ions while meta substituted compounds show abundant loss of NO and NO₂ from [MH]⁺. The latter fragmentation is interpreted in terms of protonation para to the substituent or ortho to the vitro function, while the first two fragmentation routes arise from protonation at the nitro group. When the substituent is electron-attracting the chemical ionization mass spectra of isomers are very similar except for the H₂O loss reaction for ortho compounds.     

Electron impact and single photon ionization cross sections of neutral silver clusters

Neutral silver atoms and small clusters Ag _n (n=1...4) were generated by sputtering, i.e. by bombarding a polycrystalline silver surface with Ar⁺ ions of 5 keV. The sputtered particles were ionized by a crossed electron beam and subsequently detected by a quadrupole mass spectrometer. In alternative to the electron impact ionization, the same neutral species were also ionized by single photon absorption from a pulsed VUV laser (photon energy 7.9 eV), and the photoionization cross sections were evaluated from the laser intensity dependence of the measured signals. By in situ combining both ionization mechanisms, absolute values of the ratio σ _e (Ag _n )/σ _e (Ag) between the electron impact ionization cross sections of silver clusters and atoms could be determined for a fixed electron energy of 46 eV. These values can then be used to calibrate previously measured relative ionization functions. By calibrating the results using literature data measured for silver atoms, we present absolute cross sections for electron impact ionization of neutral Ag₂, Ag₃ and Ag₄ as a function of the electron energy between threshold and 125 eV.     

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.     

Molecule/radical reactions prior to ionization under negative chemical ionization conditions

It is shown that alkyl radical species present in CH₄ or iso-C₄H₁₀ plasma can react with substrate molecules to give [M+C_nH_2n] species. These species become evident especially in negative chemical ionization as [M+C_nH_2n]^?˙ and, less obviously, in positive chemical ionization as [M+C_nH_2n+1]⁺ ions which, for example in natural products chemistry, may be mistaken for a series of homologous compounds present in the sample.