Fragmentation of oxime and silyl oxime ether odd‐electron positive ions by the McLafferty rearrangement: new insights on structural factors that promote α,β fragmentation

The McLafferty rearrangement is an extensively studied fragmentation reaction for the odd‐electron positive ions from a diverse range of functional groups and molecules. Here, we present experimental and theoretical results of 12 model compounds that were synthesized and investigated by GC‐TOF MS and density functional theory calculations. These compounds consisted of three main groups: carbonyls, oximes and silyl oxime ethers. In all electron ionization mass spectra, the fragment ions that could be attributed to the occurrence of a McLafferty rearrangement were observed. For t‐butyldimethylsilyl oxime ethers with oxygen in a β‐position, the McLafferty rearrangement was accompanied by loss of the t‐butyl radical. The various mass spectra showed that the McLafferty rearrangement is relatively enhanced compared with other primary fragmentation reactions by the following factors: oxime versus carbonyl, oxygen versus methylene at the β‐position and ketone versus aldehyde. Calculations predict that the stepwise mechanism is favored over the concerted mechanism for all but one compound. For carbonyl compounds, C–C bond breaking was the rate‐determining step. However, for both the oximes and t‐butyldimethylsilyl oxime ethers with oxygen at the β‐position, the hydrogen transfer step was rate limiting, whereas with a CH₂ group at the β‐position, the C–C bond breaking was again rate determining. n‐Propoxy‐acetaldehyde, bearing an oxygen atom at the β‐position, is the only case that was predicted to proceed through a concerted mechanism. The synthesized oximes exist as both the (E)‐ and (Z)‐isomers, and these were separable by GC. In the mass spectra of the two isomers, fragment ions that were generated by the McLafferty rearrangement were observed. Finally, fragment ions corresponding to the McLafferty reverse charge rearrangement were observed for all compounds at varying relative ion intensities compared with the conventional McLafferty rearrangement. Copyright © 2012 John Wiley & Sons, Ltd.     

Spectrométrie de Masse—IV: Fragmentation des Dicétones—ϵ

The mass spectra of ten symmetrical ?-diketones are reported and a number of fragmentation patterns are documented by deuterium labelling experiments. The McLafferty rearrangement involving one of the carbonyl groups is not an important fragmentation pathway although such a double rearrangement is observed for long-chained ?-diketones. Special attention has been given to the ions resulting from the loss of either a molecule of water or the neutral species C₂H₄ which may involve an electron-impact induced formation of cyclobutanol-type ions analogous to the photochemical Yang's reaction.     

Massenspektrometrische Untersuchung Organischer Stickstoffverbindungen. XII—H-übertragungen Durch Nachbargruppen-Wechselwirkung bei αω′-bis-(N-Piperidyl)-Aromaten

The electron-impact-induced fragmentation of several dipiperidines, which are strongly influenced by neighbouring group participation, could be established by the investigation of ²H labelled compounds. In addition to a novel McLafferty rearrangement, specific as well as selective hydrogen transformations preceding the elimination of piperidine could be proven. The isomeric diamines can be clearly distinguished and identified by means of mass spectrometry.     

Spectroscopic investigation of H atom transfer in a gas-phase dissociation reaction: McLafferty rearrangement of model gas-phase peptide ions

Wavelength-selective infrared multiple-photon photodissociation (WS-IRMPD) was used to study isotopically-labeled ions generated by McLafferty rearrangement of nicotinyl-glycine-tert-butyl ester and betaine-glycine-tert-butyl ester. The tert-butyl esters were incubated in a mixture of D(2)O and CH(3)OD to induce solution-phase hydrogen-deuterium exchange and then converted to gas-phase ions using electrospray ionization. McLafferty rearrangement was used to generate the free-acid forms of the respective model peptides through transfer of an H atom and elimination of butene. The specific aim was to use vibrational spectra generated by WS-IRMPD to determine whether the H atom remains at the acid group, or migrates to one or more of the other exchangeable sites. Comparison of the IRMPD results in the region from 1200-1900 cm(-1) to theoretical spectra for different isotopically-labeled isomers clearly shows that the H atom is situated at the C-terminal acid group and migration to amide positions is negligible on the time scale of the experiment. The results of this study suggest that use of the McLafferty rearrangement for peptide esters could be an effective approach for generation of H-atom isotope tracers, in situ, for subsequent investigation of intramolecular proton migration during peptide fragmentation studies.     

Mass spectra of some thionocarbamates

The mass spectra of a number O-alkylthionocarbamates with two, one or no alkyl substituents on the nitrogen atom are presented and discussed. The main primary fragmentation pathways are McLafferty rearrangements, including the double so-called protonated McLafferty rearrangement. Generally, rearrangement products give charge delocalized ions, which release hydroxyl or sulphydryl radicals and water or hydrogen sulphide, to produce stable fragments. It has been found that the position of alkyl moieties may be deduced on the basis of mass spectral fragmentation patterns.     

The mass spectra of some α-lactams

The electron-impact induced fragmentation of eight aziridinones has been studied by conventional as well as by high resolution mass spectrometry. All α-lactams exhibit a molecular ion. The major primary step, in the fragmentation, is the ejection of carbon monoxide from the molecular ion. Ions of the general formula R₁? NC and R₂R₃C?O were found in the mass spectra of all α-lactams investigated. A skeletal rearrangement to rationalize these ions is proposed. The fragmentation of the molecular ion is affected by the N-substituent. Exact mass measurement and specific deuterium labeling indicate the absence of McLafferty rearrangement from either the N- or C-substituent.     

2-Aminothiazole derivatives. I. Mass spectra of 2-acetylacetamidothiazoles and N-(2-thiazolyl)-β-(2′-thiazolylamino)crotonamides

2-Acetylacetamidothiazoles ( 2 ) and N-(2-thiazolyl)-β-(2′-thiazolylamino)crotonamides ( 3 ) break down in a well-defined manner upon electron impact. In either of the two cases, the fragmentation pattern involves hydrogen transfer, similar to the McLafferty rearrangement. The principal ions formed are characterised and the most plausible mechanism of their formation is discussed.     

Fragmentation sous impact electronique de l'acetate de tertiobutyle

The mass spectral fragmentation of tert-butylacetate has been studied by means of high resolution studies, deuterium labelling and metastable transition determinations. Besides the McLafferty rearrangement, two less classical rearrangement mechanisms of oxygen-containing ions are observed and some isotope effects are reported.     

浅析质谱中的广义麦式重排

麦氏重排是对质谱分析中分子离子的重排反应提出的经验规则。对经典麦式重排的概念、裂解过程及其应用做进一步拓展,形成了广义麦式重排。在广义麦式重排中,γ-H的经典麦式重排是一步完成的六元环协同裂解,分子离子亦可通过六元环或五元环过渡态进行协同重排裂解,发生相应的γ-R、β-H (或R)的迁移,产生不同的碎片离子。这种广义麦氏重排在各种常见官能团化合物中均可发生,其在质谱解析和化合物结构研究中具有广泛应用。     

Zur Weiteren Kenntnis des Chlorophylls und des Hämins—XIX. Zur McLafferty-Umlagerung in gerad- und in Ungeradelektronischen Systemen

It is shown that in porphin derivatives the McLafferty rearrangement occurs preferentially in even electron systems, in fact with high relative abundance starting from M²⁺, but less favorably in ions formed by elimination of a radical. Starting from this observation the formulation of a general scheme for the McLafferty rearrangement is attempted.     

Characterization of different poly(2‐ethyl‐2‐oxazoline)s via matrix‐assisted laser desorption/ionization time‐of‐flight tandem mass spectrometry

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) coupled with CID (collision‐induced dissociation) has been used for the detailed characterization of two poly(2‐ethyl‐2‐oxazoline)s as part of a continuing study of synthetic polymers by MALDI‐TOF MS/MS. These experiments provided information about the variety of fragmentation pathways for poly(oxazoline)s. It was possible to show that, in addition to the eliminations of small molecules, like ethene and hydrogen, the McLafferty rearrangement is also a possible fragmentation route. A library of fragmentation pathways for synthetic polymers was also constructed and such a library should enable the fast and automated data analysis of polymers in the future. Copyright © 2009 John Wiley & Sons, Ltd.     

Massenspektrometrie und ihre anwendun auf strukturelle und stereochemische Probleme—CCVI: Beobachtungen bei der Fragmentierung Olefinischer Kohlenwasserstoffe

The molecular ions generated by electron-impact from olefins of the general structure I, II and III fragment mainly via the McLafferty rearrangement. Even under mild ionization conditions, however, they undergo isomerization before fragmentation takes place. The origin and mode of formation of an ion generated simultaneously by decay of the molecular ion and the McLafferty ion were investigated by means of 13C- and D-labelling. The influence of branching at the γ-, ω-, or ϵ-positions of the double bond in type I-olefins was studied.     

The structure of the product ion of a ‘McLafferty’ rearrangement

A series of alkylphenylketones has been examined. Whenever the alkyl chain is three or more carbon atoms long, the well-known McLafferty rearrangement occurs with elimination of the elements of a neutral olefin. The further fragmentation of the ion formed in this rearrangement reaction has been studied using the technique of ion kinetic energy (IKE) spectroscopy. The measured release of kinetic energy has been used to show that the rearrangement ion has an enolic type structure.     

Mass spectra of 1-(2′-hydroxy-5′-alkylphenyl)-1-alkanone (E)-oximes

The mass spectra of 1-(2′-hydroxy-5′-alkylphenyl)-1-ethanone (E)-oximes 1–6 and 1-(2′-hydroxy-5′-methylphenyl)-1-alkanone (E)-oximes 7–12 are given and the major fragmentation pathways discussed. The simultaneous loss of water and alkyl moieties from the molecular ion indicates that a skeletal rearrangement take place and a cycloheptatrienyloheterocyclic system is formed. The McLafferty rearrangement, γ-fission in the side aliphatic chain and oxygen expulsion are discussed with evidence being drawn from accurate mass measurements, metastable ions and comparison with mass spectral data of related compounds.     

Femtosecond Dynamics of Norrish Type-II Reactions: Nonconcerted Hydrogen-Transfer and Diradical Intermediacy

Norrish type-II and McLafferty rearrangements, which both involve an intramolecular transfer of a gamma H atom, can be differentiated on the femtosecond time scale. The McLafferty rearrangement results in ion fragmentation of the parent ketone, whereas the Norrish type-II reaction leads to a diradical species, which then either cyclizes or fragments (see scheme). For Norrish type-II reactions, the reaction time for the transfer of the hydrogen atom is within 70 - 90 fs, and the lifetime of the diradical intermediate is in the range of 400 - 700 ps at the total energy studied.     

Characterization of different poly(2‐oxazoline) block copolymers by MALDI‐TOF MS/MS and ESI‐Q‐TOF MS/MS

A complete library of poly(2‐oxazoline) block copolymers was synthesized via cationic ring opening polymerization for the characterization by two different soft ionization techniques, namely matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) and electrospray ionization quadrupole time‐of‐flight mass spectrometry (ESI‐Q‐TOF MS). In addition, a detailed characterization was performed by tandem MS to gain more structural information about the block copolymer composition and its fragmentation behavior. The fragmentation of the poly(2‐oxazoline) block copolymers revealed the desired polymer structure and possible side reactions, which could be explained by different mechanisms, like 1,4‐ethylene or hydrogen elimination and the McLafferty +1 rearrangement. Polymers with aryl side groups showed less fragmentation due to their higher stability compared to polymers with alkyl side groups. These insights represent a further step toward the construction of a library with fragments and their fragmentation pathways for synthetic polymers, following the successful examples in proteomics. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Mass spectrometric study of conjugated bifunctional acetylenes: 2—Ynals and ynones

This study is based on results obtained by new techniques for observing metastable ions which make it possible to determine the fragmentation paths of conjugated ynals and ynones. For the ynals, the most interesting fragment is the [M–28]⁺˙ ion. For the ynones, when a McLafferty rearrangement is feasible, the ion arising therefrom is more abundant than the [M? CO]^+. ion. However, this elimination of a neutral CO molecule is quite important for the true acetylene ketones.     

Massenspektrometrische Fragmentierungen β-Substituierter Adamantanone und Adamantandione

High resolution mass measurements and defocused metastable ion detection have been employed in an investigation of the electron-impact-induced fragmentation of a series of β-substituted adamantanones and adamantanediones. Whereas the isomeric bromo-, iodo- and thiocyanato-adamantanones give almost identical spectra, the fragmentation of the fluoro and chloro derivatives is dependent on whether the substituents are ‘axial’ or ‘equatorial’. Hydroxy- and acetoxy-adaman-tanones exhibit rather complex mass spectra. Adamantanediones, substituted in the β-position by various COR- and NR₁R₂-groups, exhibit characteristic ion peaks which are formed by McLafferty rearrangement and α-cleavage with subsequent elimination of carbon monoxide and allylic bond fission. The mass spectral behaviour of the isomeric hydroxy-carbomethoxy-adamantanones and dihydroxy-adamantanes is determined by the orientation of the functional groups.     

Elucidation of the double-bond position of long-chain unsaturated fatty acids by multiple-stage linear ion-trap mass spectrometry with electrospray ionization

Linear ion-trap (LIT) MS2 mass spectrometric approach toward locating the position of double bond(s) of unsaturated long-chain fatty acids and toward discerning among isomeric unsaturated fatty acids as dilithiated adduct ([M-H+2Li]+) ions are described in this report. Upon resonance excitation in a LIT instrument, charge-remote fragmentation that involves beta-cleavage with gamma-H shift (McLafferty rearrangement) is the predominant fragmentation pathway seen for the [M-H+2Li]+ ions of monoenoic long-chain fatty acids. The fragmentation process results in a dilithiated product ion of terminally unsaturated fatty acid, which undergoes consecutive McLafferty rearrangement to eliminate a propylene residue, and gives rise to another dilithiated adduct ion of terminally unsaturated fatty acid. In addition to the above-cited fragmentation process, the [M-H+2Li]+ ions of homoconjugated dienoic long-chain fatty acids also undergo alpha-cleavage(s) with shift of the allylic hydrogen situated between the homoconjugated double bonds to the unsaturated site. These fragmentation pathways lead to two types of CC bond cleavages that are allylic (alpha-cleavage) or vinylic, respectively, to the proximal CC double bond, resulting in two distinct sets of ion series, in which each ion series is separated by a CH2CHCH (40 Da) residue. These latter fragmentations are the predominant processes seen for the polyunsaturated long-chain fatty acids. The spectrum feature dependent on the position of unsaturated double bond(s) affords unambiguous assignment of the position of double bond(s) of long-chain unsaturated fatty acids.     

Letter: electron impact mass spectrometry study of a series of substituted 5- aminoalkylmethyl-cytosines and their 1-N-(o-, m- and p-)bromobenzyl-substituted derivatives

The electron-impact mass spectra of 5-aminoalkylmethyl-substituted cytosine and of their 1-N- o-(m- or p-)bromobenzyl-substituted derivatives are discussed. The influence of 5-aminoalkyl and 1-N-bromobenzyl substituents on the mode of mass fragmentation occurring upon electron impact ionization was demonstrated. The fragmentation pathways of all compounds and the characteristic ions in these spectra originating from the McLafferty rearrangement, RDA reactions and simple cleavages are presented.