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

Abstract

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.

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

“…A McLafferty rearrangement (Scheme ) was also observed, the product of which was depicted as a cyclic structure, op , after elimination of the tert ‐butyl group (Laulhé et al, ). The ion at m/z 117 in the spectrum shown in Figure is the silyl cation C 4 H 9 (CH 3 )Si‐OH, oq .…”

Electron ionization-induced release of coded isotopic reporter ions in an m/z zone of minimal interference for quantifiable, multiplexed GC-MS analyses

“…MS analysis of the eluted compounds revealed each derivatized carbonyl substrate generated characteristic fragment ions that enabled its structural assignment and designation of either E - or Z -oxime ether stereochemistry. 16 The isotopic MSTs at m/z 32–34 were abundant and clearly measurable in the ZMI of each spectrum. Relative ratios for the carbonyl substrates that gave diastereomeric oxime ethers were determined readily using MST measurements from either the Z - or E -isomer.…”

“…With the profile of carbonyls in hand, we next sought to identify the subset of aliphatic methyl ketones. Given that ketoxime ethers undergo characteristic EI-MS fragmentations (Figure 5), 16 a targeted m/z mass spectral analysis of the EIC revealed the presence of several AEP-methyl ketone adducts (Figure 4C, Table 1). The AEP-adducts were present as both E- and Z -isomers, and assignment of stereochemistry followed from analysis of the relative abundance of McLafferty fragment ionversus nitrilium ion formation.…”

“…The AEP-adducts were present as both E- and Z -isomers, and assignment of stereochemistry followed from analysis of the relative abundance of McLafferty fragment ionversus nitrilium ion formation. 16 …”

Aminooxy reagents for synthesis and analysis : expanding the role of oximation.

“…58 Thus, the fragmentation properties of oxime ethers could be applied to identify carbonyl metabolites. Results from this fundamental study led us to develop a new class of derivatizing reagents, and this work is described in Chapter 4.…”