Stereochemical Analysis of Monodeuterated Isomers By GC/MS/MS

Abstract

GC/MS/MS techniques to quantitate mixtures of acyclic stereoisomers are explored for a set of secondary n-alkyl phenyl ethers vicinally substituted with deuterium. Examination of a set of test compounds using a commercial quadrupole ion trap instrument (GC/QIT) reveals large differences between threo and erythro diastereomers when trapped molecular ions expel neutral alkene as a result of collisionally activated dissociation (CAD). All of the monodeuterated compounds give PhOH•+ (m/z 94) and PhOD•+ (m/z 95) as the principal fragments under GC/QIT/CAD conditions. The threo isomers give consistently larger values of the ion intensity ratio r = m/z 95/m/z 94 than do the corresponding erythro, with a ratio of ratios r t /r e as high as 3. A nonlinear calibration curve shows that the threo decomposes to a lesser extent than the erythro in mixtures of the two stereoisomers; hence, the precision of quantitation is sensitive to experimental error. Sustained off-resonance irradiation experiments in an FT-ICR give virtually complete dissociation, which results in a linear calibration curve. Ion−molecule reactions of the fragment ions indicate that alkene expulsion does not take place via a six-member cyclic transition state, while the stereochemical selectivity appears to rule out the intermediacy of ion−neutral complexes. Threo- and erythro-2-phenoxy-3-deuterio-n-octane (and their mixtures) are proposed as test compounds for evaluating the capability of GC/MS/MS instrumentation to perform stereochemical analyses on subnanomole samples of isotopically labeled molecules.

Parallels between decompositions of even- and odd-electron ions: structures from dissociation of 3-chloro-n-propyl phenyl ether

“…•+ , 9 we conclude that the m/z 95 ions from 3-5 also have the ionized phenol structure, with even smaller contributions from ionized cyclohexadienone than the ions from CH 3 CH(OPh)CD 2 H.…”

“…We conceive of three general mechanisms for expulsion of neutral C 3 H 5 Cl: (i) via a concerted elimination (as is thought to occur in ionized isopropyl phenyl ether and other sec-alkyl phenyl ethers [9][10][11][12] ); (ii) via ion-neutral complexes (as occurs in ionized n-propyl phenyl ether [9][10][11][12][13][14][15] ); and (iii) via distonic ions. The first of these options can be ruled out as an exclusive pathway.…”

“…A more gentle method of deciding whether two ions have the same structure consists of examining the bimolecular reactions of deuterated analogues with a gaseous base, in order to assess which sites are acidic. 9 As an example, consider the m/z 99 ion in the source mass spectrum 2, whose CAD spectrum (vide supra) suggests that it consists of ionized C 6 D 5 OH mixed with an isomer (other than C 6 D 4 HOD). The relative proportions of the isomeric ions cannot be measured from the CAD spectrum, since the relative cross-sections are unknown.…”

Stereospecificity of the Hofmann elimination in the gas phase

“…a assessing specificity. [21][22][23] For all three systems 3-5 in Table 1, this figure of merit has a value r ¼ 1.9 at 8 V, slightly less than the value for ESI-CAD of a different pair of 4-d 1 -3-hexyl diastereomers 23 The results suggest a simple mechanism. Heterolysis of the C-N bond either expels neutral amine to yield a free alkyl cation or else forms an ion-neutral complex.…”

Isotopic Labelling in Mass Spectrometry

“…The unlabelled ion is an even-electron species. Reproduced a from Nguyen V, Bennett JS andMorton TH (1997) Journal of the American Chemical Society 119: 8342 with permission of the American Chemical Society with modifications.…”