Mass spectrometry of stable free radicals—II: pyrrolidine nitroxides

3-Substituted-2,2,5,5-tetramethylpyrrolidine nitroxides are stable free radicals used extensively in the synthesis of ‘spin labels’. The high resolution mass spectra of these nitroxides substituted with ? CH₂OH, ? OH, ? NH₂ and ?o have been recorded on magnetic tape and the elemental compositions of the ions calculated by computer. Ionisation by electron bombardment(70eV), gives rise to an even-electron molecular ion species. [M+1]⁺. ions are observed in the spectra of all compounds examined, except in the case of the 3-carbonyl compound, 2,2,5,5-tetramethylpyrrolid-3-one-1-oxyl. Loss of a methyl radical from these ions leads to the appearance of ions at [M -14]⁺. The predominant fragmentation for those compounds in which the substituents can supply electrons to the ring, is the sequential elimination of isobutene, nitric oxide and a hydrogen radical. In the case of the 3-hydroxy compound, these ions account for 23 percent of the total ion current. 2,2,5,5-Tetramethylpyrrolid-3-one-1-oxyl, which bears an electron-withdrawing substituent gives rise to a fragmentation pattern somewhat different from those of the other compounds. The main features are the absence of a peak at [M + 1]⁺˙ and the general phenomenon of fewer peaks but with higher intensities.     

Mass spectra of alkylferrocenes and biferrocenyls

Mass spectra of alkylferrocenes and biferrocenyls have molecular ion peaks which are also base peaks. The predominant fragment ions are formed by beta-cleavage of the alkyl group. Gamma-and alpha-cleavages are the only other significant modes of alkyl side-chain fragmentation. The cleavage of the alkyl group is often accompanied or followed by the cleavage of either one or both of the cyclopentadienyl-iron bonds. Weak m/e 121 ([C₅H₅]⁺) mass peaks are found in the spectra of 1,1′-dialkyl- and 1,1′-disilyl-ferrocenes. Therefore, the m/e 121 peak may not be used as a sensitive criterion to determine the presence of unsubstituted cyclopentadienyl rings. The relative intensity of the peak may, however, serve as an indicator. Expansion of the cyclopentadienyl ring to six- and seven-carbon rings in the fragmentation of alkylferrocenes, diethylbiferrocenyl and deuterated ethylferrocenes is indicated. The spectra of benzylferrocene and benzylferrocene-alpha-d₂ do not show a beta-cleavage but suggest a pentalene ring formation. Methyl and phenyl groups in the beta-position of substituted ferrocenes were found to migrate to the iron atom.     

Investigation of azoles and azines. 76. Mass spectra of 5- and 6-substituted uracils

Peaks of molecular ions that generally have the maximum intensity are observed in the mass spectra of most of the investigated 5- and 6-substituted uracils and 5-substituted orotic acids and their deutero analogs and methylated derivatives. The principal pathway of the fragmentation of the molecular ions is retrodiene fragmentation with the formation of [O=C₍₄₎C₍₅₎R⁵C₍₆₎R₍₆₎N₍₁₎R¹]⁺ (F₁) ions. The stabilities of the latter depend on the nature and position of the substituents attached to the C₍₅₎ and C₍₆₎ atoms. The fragmentation of the F₁ ions can be realized via four principal pathways (B-E) with the detachment of N-CR⁶ (B), O=C=CR⁵ (C), CO (D), and R⁶ (E) fragments. The most general pathway for the fragmentation of 5-substituted uracils is pathway C, whereas the most general pathway for 6-substituted uracils is pathway E. In the spectra of 5-substituted orotic acids the intensities of the molecular-ion peaks are high (100%) only in the case of electron-donor R⁵ and decrease sharply with an increase in the electron-acceptor strength of the substituent. The principal pathways of fragmentation of the molecular ions are decarboxylation (F) and retrodiene fragmentation (A), the contribution of which is appreciably smaller. The M-CO₂ ions formed after decarboxylation undergo fragmentation via a scheme similar to that observed for 5-substituted uracils.See [1] for Communication 75.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 520–531, April, 1990.     

Mass Spectra of New Heterocycles. XVII. Main Fragmentation Routes of Molecular Ions of 4-Alkoxy-5-amino-3-methylthiophene-2-carbonitriles under Electron and Chemical Ionization

For the first time decomposition was investigated of 4-alkoxy-5-amino-3-methylthiophene-2-carbonitriles under the conditions of electronic (70 eV) and chemical (reagent gas methane) ionization. At the electronic ionization the compounds under study [except for 4-(1-ethoxyethoxy) and 4-(ferrocenylmethoxy) derivatives] form stable molecular ions that decompose mainly by the cleavage of an alkyl radical from the alkoxy-substituent. Further fragmentation of the arising ion [M–Alk]⁺ depends on the substituent nature in the amino group. In the mass spectrum of 4-(ferrocenylmethoxy)-substituted thiophene peaks of the ion [FcCH₂]⁺ and its fragmentation products prevail. In the mass spectra of chemical ionization predominant peaks belong to ions M^+·, [M + H]⁺ and [M + C₂H₅]⁺, and fragment ions are absent.     

Fragmentation reactions of some aliphatic esters in the NCl(F−) and NCl(NH2−) mass spectra

The NCI(F^?) and NCI(NH₂^?) mass spectra of a series of aliphatic acetates and of methyl and ethyl trimethylacetate have been obtained. The formation of fluoroenolate ions CH₂COF^? and of carboxamide anions RCONH^? (R ? CH₃))CH₃C). respectively, is observed besides formation of [M ? H]^? ions and carboxylate ions RCOO^? (R ? CH₃, (CH₃)₃C). The relative intensities of the different anions depend on the structure of the ester molecules and on the primary reactant anions. Usually, the NCI(NH₂^?) spectra of the acetates are dominated by [M ? H]^? ions ([M? D]^? ions in the case of trideuteroacetates) fragmenting unimolecularly by elimination of an alcohol. The carboxylate ions are important fragments, too, but carboxamide ions are only observed with large intensities in the NCI(NH₂^? spectra of the trimethylacetates. The NCI(F^?) spectra show much larger intensities of carboxylate ions and fluoroenolate ions. The mechanisms of the fragmentation reactions are discussed. The results indicate that most or even all of the fragment ions in the NCI(F^? mass spectra of aliphatic esters are formed by addition-elimination reactions via a tetrahedral intermediate, while competition between direct proton abstraction and addition-elimination reactions occurs in the NCI(NH₂^?) mass spectra because of the higher basicity of NH₂^? resulting in an early transition state for direct proton abstraction.     

Mass-spectrometric differentiation of diexo- and diendo-fused isomers of norbornane/ene-condensed 2-thiouracil and 1,3-thiazino[3,2-a]-pyrimidine derivatives: Stereoselectivity of retro-Diels-Alder fragmentations under EI and CI conditions

The stereoisomers of the title compounds produce nearly identical electron ionization (EI) mass spectra, which are dominated in the case of the norbornene-condensed derivatives by retro-Diels-Alder (RDA) fragmentation of the hydrocarbon ring. The RDA fragmentation mainly occurs with H transfer and gives rise to [M-C₅H₅]⁺. For the norbornane-condensed derivatives, the main fragmentation routes include the formation of [M-C₅H₇]⁺ (protonated thiouracil) and [M-C₇H₉]⁺ (only from thiazinopyrimidines). The latter species are formed via RDA decomposition of the pyrimidone subunit of the heterocyclic system, a process previously observed for cyclohexane-condensed analogs of these compounds. Only minor differences could be detected between the EI spectra of the diexo and diendo isomers. Under chemical ionization (CI) conditions, the norbornane-condensed compounds produced no significant fragment peaks with either isobutane or methane as reagent gas. In contrast, the isobutane and methane CI spectra of the norbornene-condensed compounds exhibited prominent peaks of [MH-C₅H₆]⁺ and [(M+C_xH_y)-C₅H₆]⁺ originating from moderately stereoselective RDA fragmentations. The relative abundances of the RDA ions obtained from the respective stereoisomers with the same reagent gas were consistently different over a range of experimental conditions. The non-occurrence of RDA fragmentation of the thiazinopyrimidine ring under CI conditions suggested that its energy of activation is higher than that for either of the norbornene-ring RDA fragmentations (with or without H transfer) observed under EI and CI conditions.     

Spectres de masse des anomeres pyranniques et furanniques de la thymidine,de leurs acetates et des bromohydrines correspondantes

The mass spectra of furanic and pyranic anomers of thymidine as well as those of acetates and bromohydrines of these four molecules are studied and compared. The stability of molecular ions is correlated with the chemical stability of these copmpounds. Molecular ions of β forms are more stable than those of α forms. The instability of the bromohydrines molecular ions is such that they are only observed for β furanic anomers. The eliminmation of the ·CH₂OH or ·CH₂OAc radical is noterd only for the furanic compound. The cleavage of CH₂O in the β furanic substances is correleated with the steric vicinity of the base and the sugar 5′ hydroxide. The ions[BH ? Ch?CH₂]⁺ and those resulting from this rearrangement and cleavage of sugar moiety, are enhanced in the case of furanic forms. After rupture of the N-glycosidic bon, the [B + H]⁺˙ and [B + 2H]⁺ ions resulting from the base and [S]⁺ are related to the molecular stereochemistry. The eliminationof one water molecular(or acetic acid) is easier in a sixs membered ring(pyranic). The concerted elimination of two water molecules (or acetic acid), more important in the furanic form, enables us to establish a ring cleavage mechanism which gives an ion with a conjugated aliphaticf structure; the pyranic form gives an aromatic cyclic ion in two steps.     

Mass spectrometric investigation of stereosomeric 1,2-dimethyl-4-substituted decahydroquinol-4-ol N-oxides. Concerning the configuration of the asymmetric nitrogen atom

The main fragmentation pathways of the N-1, C-2 and C-4 stereoisomers of the 1,2-dimethyl-4-R-transdecahydroquinoline-4-ol N-oxides (R=C?CH, CH?CH₂ and C₂H₅) under electron impact are discussed. The correlation between the mass spectrometric chromatographic behaviour and the configuration of polar groups in the N-oxides examined is discussed. The mass spectra of the N-1 stereoisomers may be subdivided into two groups, depending only on the orientation of N→O group and not of the 4-OH group. The spectra of N-oxides with the axial N-oxide group reveal less intense ions and much more intense [M? CH₃]⁺, [M? O]⁺, [M? OH]⁺ and ions, whereas in the spectra of their equatorial epimers the abundance of the ions exceeds the intensities of the latter ions.     

ToF‐SIMS and computation analysis: Fragmentation mechanisms of polystyrene,polystyrene‐d5, and polypentafluorostyrene

We studied the time‐of‐flight secondary ion mass spectrometry fragmentation mechanisms of polystyrenes—phenyl‐fluorinated polystyrene (5FPS), phenyl‐deuterated polystyrene (5DPS), and hydrogenated polystyrene (PS). From the positive ion spectra of 5FPS, we identified some characteristic molecular ion structures with isomeric geometries such as benzylic, benzocyclobutene, benzocyclopentene, cyclopentane, and tropylium systems. These structures were evaluated by the B3LYP‐D/jun‐cc‐pVDZ computation method. The intensities of the C₇H₂F₅⁺ (m/z = 181), CyPent‐C₉H₃F₄⁺ (m/z = 187), CyPent‐C₉H₄F₅⁺ (m/z = 207), and CyPent‐C₉H₂F₅⁺ (m/z = 205) ions were enhanced by resonance stabilization. The positive fluorinated ions from 5FPS tended to rearrange and produce fewer fluorine‐containing molecular ions through the loss of F (m/z = 19), CF (m/z = 31), and CF₂ (m/z = 50) ion fragments. Consequently, the fluorine‐containing polycyclic aromatic ions had much lower intensities than their hydrocarbon counterparts. We propose the fragmentation mechanisms for the formation of C₅H₅⁺, C₆H₅⁺, and C₇H₇⁺ ion fragments, substantiated with detailed analyses of the negative ion spectra. These ions were created through elimination of a pentafluoro‐phenyl anion (C₆F₅⁻) and H⁺, followed by a 1‐electron‐transfer process and then cyclization of the newly generated polyene with carbon‐carbon bond formation. The pendant groups with elements of different electronegativities exerted strong influences on the intensities and fragmentation processes of their corresponding ions.     

A further structural variation of product yield in collisional activation. Study of CH3S+ from dimethyl disulfide with high precursor ion resolution

The isobaric ions CH₃³²S⁺ and CH³⁴S⁺ from dimethyl disulfide were separated and collisionally activated in a four-sector mass spectrometer. The contributions of minor components to the collisional activation spectrum of the unresolved beam are not correctly predicted from consideration of isotope peak corrections using relative intensities of adjacent peaks in the mass spectrum of CH₃SSCH₃, because the isobaric components not only have different cross-sections for fragmentation but also different cross-sections for transmission of the unfragmented beam through the collision gas. Helium collision spectra of the two components are given.     

Mass-spectrometric behavior of isomeric nitro- and nitroaminoindolizines and indoles

Peaks of [M — NO]⁺ and [M — NO₂]⁺ ions are characteristic for the mass spectra of nitroindolizines, whereas peaks of ions of the indole type, viz., [M — HCN]⁺ and [M- H,- HCN]⁺ (for alkylindoles), are not characteristic. In the mass spectra of nitroindoles the latter ions give more intense peaks, while the loss of a nitro group or its rearrangement is a considerably less significant process. When a dialkylamino group is introduced in the nitroindolizine molecule, the primary processes in the fragmentation of such compounds are due to fragmentation of the alkylamino group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 765–768, June, 1982.     

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.     

Four-centred rearrangements in the mass spectra of aliphatic ethers

The [CH₃O?CHCH₃]⁺ ions observed in the mass spectra of ethers of formula CH₃OCH (CH₃)R(R = H or alkyl) undergo two rearrangement fragmentation reactions to form [C₂H₅]⁺ and [CH₂OH]⁺. The scope of the rearrangements has been investigated and it is shown that enlargement of the alkyl group on either side of the ether linkage leads to alternative fragmentation routes. From a study of metastable intensities it is concluded that the fragmentations probably occur directly from the [CH₃O?CHCH₃]⁺ structure through four centred rearrangements rather than through the intermediacy of the [C₂H₅O?CH₂]⁺ ion.     

Mass-spectrometric study of physiologically active β-thiosemicarbazones of N-alkylisatins

The molecular ions of isatin (I) and N-methyl- (II) and N-ethylisatin (III) -thiosemicarbazones undergo fragmentation via many pathways with the elimination of NH₃, H₂S, CO, CH₂N₂, CHN₃, CH₂N₂S, CH₂NS, and CHNS particles; this is due to primary localization of the charge on the heteroatoms of the thiosemicarbazone residue. A previously unknown rearrangement, which consists in migration of an HS group to the -carhon atom of the heteroring with subsequent ejection of a CHN₃ fragment. The [M — CO]⁺ ions undergo fragmentation with the elimination of CH₂N₂S; in the case of II and III fragmentation is preceded by detachment of a hydrogen atom (II) or a methyl group (III) from the substituent attached to the ring nitrogen atom. The [M — CO, -H, -CH₂NS]⁺ (II) and [M — CO, -CH₃, -CH₂N₂S]⁺ (III) ions undergo fragmentation with the ejection of HCN in two ways through both the ring nitrogen atom and the thiosemicarbazone residue. Schemes for the principal pathways of fragmentation and rearrangements are presented. The compositions of the ions were confirmed by the high-resolution mass spectra and the mass spectra of the N-deuteroalkyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 1979.     

Effect of the his residue on the cyclization of b ions

The MSⁿ spectra of the [M + H]⁺ and b ₅ peaks derived from the peptides HAAAAA, AHAAAA, AAHAAA, AAAHAA, and AAAAHA have been measured, as have the spectra of the b ₄ ions derived from the first four peptides. The MS² spectra of the [M + H]⁺ ions show a substantial series of b_n ions with enhanced cleavage at the amide bond C-terminal to His and substantial cleavage at the amide bond N-terminal to His (when there are at least two residues N-terminal to the His residue). There is compelling experimental and theoretical evidence for formation of nondirect sequence ions via cyclization/reopening chemistry in the CID spectra of the b tons when the His residue is near the C-terminus. The experimental evidence is less clear for ions when the His residue is near the N-terminus, although this may be due to the use of multiple alanine residues in the peptide making identifying scrambled peaks more difficult. The product ion mass spectra of the b ₄ and b ₅ ions from these isomeric peptides with cyclically permuted amino acid sequences are similar, but also show clear differences. This indicates less active cyclization/reopening followed by fragmentation of common structures for b _n ions containing His than for sequences of solely aliphatic residues. Despite more energetically favorable cyclization barriers for the b ₅ structures, the b ₄ ions experimental data show more clear evidence of cyclization and sequence scrambling before fragmentation. For both b ₄ and b ₅ the energetically most favored structure is a macrocyclic isomer protonated at the His side chain.     

Electron ionization mass spectrometry of systematically modified ligands in chromium(III) β-diketonates

The positive ion mass spectra of several chromium(III) β-diketonates with aliphatic α-substituents have been investigated. Metastable peaks in the spectra confirm that ions containing substituents with γ-H atoms undergo propene loss. This implies a McLafferty rearrangement of an open-chain ligand structure. Ethyl radicals are lost from n-butyl substituents; methyl groups are cleaved from the molecular ions of complexes formed from methyl-substituted ligands. The main fragment is, as expected, [ML₂]⁺; however, its further fragmentation is different from that of [ML₃]⁺. Electron donating substituents stabilize doubly charged molecular ions.     

Fragmentation Reactions of b<Subscript>5</Subscript> and a<Subscript>5</Subscript> Ions Containing Proline—The Structures of a<Subscript>5</Subscript> Ions

A detailed study has been made of the b₅ and a₅ ions derived from the amides H-Ala-Ala-Ala-Ala-Pro-NH₂, H-Ala-Ala-Ala-Pro-Ala-NH₂, and H-Ala-Ala-Pro-Ala-Ala-NH₂. From quasi-MS³ experiments it is shown that the product ion mass spectra of the three b₅ ions are essentially identical, indicating macrocyclization/reopening to produce a common mixture of intermediates prior to fragmentation. This is in agreement with numerous recent studies of sequence scrambling in b ions. By contrast, the product ion mass spectra for the a₅ ions show substantial differences, indicating significant differences in the mixture of structures undergoing fragmentation for these three species. The results are interpreted in terms of a mixture of classical substituted iminium ions as well as protonated C-terminal amides formed by cyclization/rearrangement as reported recently for a₄ ions (Bythell, Maître , Paizs, J . Am. Chem. Soc. 2010, 132, 14761–14779). Novel fragment ions observed upon fragmentation of the a₅ ions are protonated H-Pro-NH₂ and H-Pro-Ala-NH₂ which arise by fragmentation of the amides. The observation of these products provides strong experimental evidence for the cyclization/rearrangement reaction to form amides and shows that it also applies to a₅ ions.     

Charge reversal of three alkylamide ions: Free nitrenium ions

The methylnitrenium, ethylnitrenium and dimethylnitrenium ions are prepared by charge reversal collisional activation (CR CA) of the corresponding negative ions; their collisional activation mass spectra are shown to support the assigned structures. MINDO/3 energies are used to evaluate relative energies of [CH₄N]⁺ and [C₂H₆N]⁺ isomers, and to determine whether unstable forms rearrange spontaneously to stable ones. As in other examples, charge reversal here generates cations that do not exist in an energy well, but their transient existence is established because their fragmentation is more rapid than their rearrangement to a more stable form.     

Electron-impact induced fragmentation of thiirene and thiophene dioxides

The electron impact mass spectra of several substituted thiirene and thiophene oxides and dioxides have been investigated using both low and high resolution mass spectrometry. The predominant fragmentation process in the spectra of the thiirene compounds is the elimination of the hetero (SO or SO₂) function and formation of a substituted acetylene ion. The 5-membered ring thiophene dioxides exhibit mainly elimination of SO rather than SO₂. Plausible mechanisms leading to the formation of the principal ions are proposed on the basis of metastable transitions.     

Rearrangements and fragmentations of phenyl styryl sulfides: 1—Metastable ion spectra

The mass spectra of two isomeric phenyl styryl sulphides show abundant peaks for fragment ions formed after interesting and unusual rearrangements, e.g. loss of CHS^˙ and C₇H₇^˙. Information about these rearrangements was obtained by comparison of the metastable peak intensities and peak shapes with those of four isomers. It appears that isomerization reactions between the phenyl styryl sulfides and the isomers are possible and that most of the metastable ion fragmentations proceed via reacting configurations that are common to two or more of the compounds investigated. The results indicate that an earlier proposed mechanism for the fragmentation of phenyl vinyl sulfides is incomplete and only partly correct for the compounds studied. Metastable ion spectra were obtained using high voltage scans and constant B/E scans: a short comparison of the results obtained with the two methods is given.