Mass spectra of dihydroxy stereoisomers of 3-methoxy-1,3,5(10)-estratrienes

Electron impact mass spectral data for each of the four isomeric 16,17-, 15,17- and 14,17-diols of 3-methoxy-1,3,5(10)-estratriene and the 15,17-diols of 3-methoxy-14β-1,3,5(10)-estratriene are reported. The mass spectra of the diols show very similar fragmentation patterns except for differences in the relative abundances of particular ions. The different [M ? H₂O]⁺˙/[M] ⁺˙ and [M ? 2H₂O] ⁺˙ [M] ⁺˙ ratios can be used for distinguishing between the four isomeric 3-methoxy-1,3,5(10)-estratriene-14,17-diols as well as between the four isomeric 3-methoxy-14β-1,3,5(10)-estratriene-15,17-diols. No significant differences could be detected in the spectra of the epimeric 16,17-and 15,17-diols of 3-methoxy-1,3,5(10)-estratriene.     

Destabilized carbenium ions: α-carbomethoxy-α,α-dimethyl-methyl cations

Tertiary α-carbomethoxy-α,α-dimethyl-methyl cations a have been generated by electron impact induced fragmentation from the appropriately α-substituted methyl isobutyrates 1–4. The destabilized carbenium ions a can be distinguished from their more stable isomers protonated methyl methacrylate c and protonated methyl crotonate d by MIKE and CA spectra. The loss of I^— and Br˙ from the molecular ions of 1 and 2, respectively, predominantly gives rise to the destabilized ions a, whereas loss of Cl˙ from [3]^{+ ˙} results in a mixture of ions a and c. The loss of CH₃˙ from [4]⁺˙ favours skeletal rearrangement leading to ions d. The characteristic reactions of the destabilized ions a are the loss of CO and elimination of methanol. The loss of CO is associated by a very large KER and non-statistical kinetic energy release (T₅₀ = 920 meV). Specific deuterium labelling experiments indicate that the α-carbomethoxy-α,α-dimethyl-methyl cations a rearrange via a 1,4-H shift into the carbonyl protonated methyl methacrylate c and eventually into the alkyl-O protonated methyl methacrylate before the loss of methanol. The hydrogen rearrangements exhibit a deuterium isotope effect indicating substantial energy barriers between the [C₅H₉O₂]⁺ isomers. Thus the destabilized carbenium ion a exists as a kinetically stable species within a potential energy well.     

Unusual neutral and radical losses in 2′-substituted N-phenylanthranilic acids on electron impact

Unusual expulsions of [H₂O + CO₂] from the M⁺˙ of N-(o-carboxyphenyl)anthranilic acid, [H₂O + CH₂O] from the M⁺˙ of N-(o-methoxyphenyl)anthranilic acid and [H₂O + ˙NO₂] from the M⁺˙ of N-(o-nitrophenyl) anthranilic acid were observed under electron impact conditions. These processes are stepwise in the corresponding para-substituted N-phenylanthranilic acids. The proposed fragmentation pathways and their mechanisms are supported by B/E linked-scan spectra, collision-activated decomposition (CAD)–mass-analysed ion kinetic energy (MIKE) spectra, high-resolution data, deuterium labelling and chemical substitution.     

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.     

Loss of methyl from ionized 2-hydroxy-1,3-butadiene

The loss of methyl from unstable, metastable and collisionally activated [CH₂?CH? C(OH)?CH₂]⁺˙ ions (1⁺˙) was examined by means of deuterium and ¹³C labelling, appearance energy measurements and product identification. High-energy, short-lived 1⁺˙ lose methyl groups incorporating the original enolic methene (C(1)) and the hydroxyl hydrogen atom (H(0)). The eliminations of C(1)H(1)H(1)H(4) and C(4)H(4)H(4)H(0) are less frequent in high-energy ions. Metastable 1⁺˙ eliminate mainly C(1)H(1)H(1)H(4), the elimination being accompanied by incomplete randomization of the five carbon-bound hydrogen atoms. The resulting [C₃H₃O]⁺ ions have been identified as the most stable CH₂?CH? CO⁺ species. The appearance energy for the loss of methyl from 1 was measured as AE[C₃H₃O]⁺ = 10.47 ± 0.05 eV. The critical energy for 1⁺˙ → [C₃H₃O]⁺ + CH₃˙ is assessed as E_c ? 173 kJ mol^?1. Reaction mechanisms are proposed and discussed.     

Isomeric [C,H3,N,O]+˙ ions and their neutral counterparts

The isomeric ions [H₂NC(H)O]⁺˙, [H₂NCOH]⁺˙, [H₃CNO]⁺˙ and [H₂CNOH]⁺˙ were examined in the gas phase by mass spectrometry. Ab initio molecular orbital theory was used to calculate the relative stabilities of [H₂NC(H)O]⁺˙, [H₂NCOH]⁺˙, [H₃NCO]⁺˙ and their neutral counterparts. Theory predicted [H₂NC(H)O]⁺˙ to be the most stable ion. [H₂NCOH]⁺˙ ions were generated via a 1,4-hydrogen transfer in [H₂NC(O)OCH₃]⁺˙, [H₂NC(O)C(O)OH]⁺˙ and [H₂NC(O)CH₂CH₃]⁺˙. Its metastable dissociation takes place via [H₃NCO]⁺˙ with the isomerization as the rate-determining step. [H₂CNOH]⁺˙ undergoes a rate-determining isomerization into [H₃CNO]⁺˙ prior to metastable fragmentation. Neutralization-reionization mass spectrometry was used to identify the neutral counterparts of these [H₃,C,N,O]⁺˙ ions as stable species in the gas phase. The ion [H₃NCO]⁺˙ was not independently generated in these experiments; its neutral counterpart was predicted by theory to be only weakly bound.     

A study of the fragmentation of cyclopentane-1,3-diols and of cyclopentane-1,2,4-triols

The mass spectra of the two cyclopentane-1,3-diol and of the three cyclopentane-1,2,4-triol stereoisomers have been studied. Extensive deuterium labelling allows the detection of complex processes, especially for the elimination of water from the [M – H_2OO]⁺· and [M]⁺· ions.     

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.     

Mechanisms of mass spectrometric fragmentations: X–Interaction between remote or-groups in decalin-1,5-diols and their dimethyl ethers

The mass spectra of the five stereoisomers of decalin-1,5-diol and its dimethyl ether have been investigated. The differences in the mass spectra of stereoisomers I to III with a trans- decalin ting system are small. The differences are much larger in the mass spectra of the two isomers IV and V of the cis-decalin series and the elimination of CH₂O, formed by interaction between the two methoxy groups, from the molecular ion is only observed in the mass spectrum of Vb.     

The elusive methene ylides CH2CIH,CH2FH and CH2OH2

The possible existence of the ylides CH₂CIH, CH₂₅FH and CH₂OH₂ as stable neutral species in the gas phase has been investigated by the neutralization–reionization (NR) mass spectrometry of their radical cations using a double-focusing mass spectrometer of reversed geometry. The experiments were, for the most part, performed under single-collision conditions with Xe as the neutralization target gas and He and O₂ as reionization agents. For each ylidion a peak was observed in their NR mass spectrum which indicated that the neutral ylide had apparently been produced. However for CH₂FH⁺˙ and CH₂OH₂⁺˙ the m/z 34 and m/z 32 peaks, respectively, were attribut-able to interferences from the natural isotopic abundance of ions of lower mass. For CH₂CIH⁺˙, the NR recovery signal was found to arise from the presence of CH₃CI⁺˙ as an impurity in the ylidion flux. This was proved by examination of the collisional activation mass spectra of the [C, H₃, CI]⁺˙ ions produced in the NR mass spectra of the conventional ions and ylidions, an experiment performed using a triple-sector mass spectrometer.     

Stereochemical effects in the electron impact mass spectra of cis-trans isomeric 1,2,3,4-tetramethylcyclohexanes

The mass spectra of six cis-trans isomeric 1,2,3,4-tetramethylcyclohexanes are discussed. The intensity ratio of [M? CH₃]⁺/[M? C₂H₅]⁺ correlates with the strain energies of the stereoisomers. Therefore, the identification of cis-trans isomers is possible by means of their mass spectra. The mass spectra of deuterium labelled compounds demonstrate favoured fragmentation of the axial methyl groups and ring opening between the cis substituted carbon atoms of the cyclohexane.     

The expulsion of OH˙ from the [M ? C2H4]+˙ ion from ethyl benzoate: Ring-deuterated compounds

Mass spectra and ion kinetic energy (IKE) spectra of o-, m- and p-d₁ ethyl benzoates have given further information on the loss of OH˙ and OD˙ from the [M ? C₂H₄]⁺˙ ions. The ‘metastable peaks’ in the mass spectra give information on fragmentations in the field-free region following the electric sector; the IKE spectra give information on fragmentations in the field-free region preceding this sector. Transfer of hydrogen and deuterium from the ortho-positions on the ring to the carboxyl group can occur, but scrambling of ring hydrogens does not take place. A sample of o-d₁ benzoic acid was also examined and confirmed that similar transfer reactions occur in this compound too.     

Steric effects in the mass spectra of the stereoisomers of decalin-1,3-diol and of 1,3-dimethoxy-decalin

The stereoisomers 1a–8a of decalin-1,3-diol have been synthesized by LAH-reduction of cis- and trans-decalin-1, 3-dione, respectively. With the exception of trans-decalin-1a,3e- and -1e,3a-diols, 7a and 8a, the stereoisomers have been isolated by column chromatography, and their configurations have been determined by ¹H-NMR, IR and chemical methods. It is shown by the aid of deuterated derivatives, that the elimination of H₂O, MeOH and CH₂O from the molecular ions of the stereoisomeric diols and di-O-methyl ethers, respectively, occurs predominantly by stereospecific reactions, if the ground state conformation of the molecule corresponds to the geometry of the transition state of the elimination reaction. The steric control of the fragmentations is greatly reduced, if conformational changes of the molecular ions have to occur prior to fragmentation. No clear steric effects are observed, if none of the conformations of the intact molecular ions corresponds to the transition state. These steric effects can be used to identify the various stereoisomers of decalin-1,3-diol and 1,3-dimethoxy-decalin by mass spectrometry.     

Charge stripping mass spectra: A method for identifying isomeric [C5H8]+˙ and [C3H6]+˙ ions

Charge stripping (collisional ionization) mass spectra are reported for isomeric [C₅H₈]⁺˙ and [C₃H₆]⁺˙ ions. The results provide the first method for adequately quantitatively determining the structures and abundances of these species when they are generated as daughter ions. Thus, loss of H₂O from the molecular ions of cyclopentanol and pentanal is shown to produce mixtures of ionized penta-1,3- and -1,4-dienes. Pent-1-en-3-ol generates [penta-1,3-diene]⁺˙. [C₃H₆]⁺˙ ions from ionized butane, methylpropane and 2-methylpropan-1-ol are shown to have the [propene]⁺˙ structure, whereas [cyclopropane]⁺˙ is produced from ionized tetrahydrofuran, penta-1,3-diene and pent-1-yne.     

Fingerprinting stereoisomers by survivor-ion mass spectrometry

Survivor-ion mass spectrometry is used to distinguish stereoisomeric cis- and trans-4-methylcyclohexanol. The method involves producing ions by electron impact ionization and submitting them without mass selection to collisional neutralization and reionization, followed by selective monitoring of non-dissociating ions. The differences in the electron impact mass spectra of the stereoisomers, due to the different fragment ion elemental compositions and structures, are highlighted by collisional neutralization with Xe, NO and CH₃SSCH₃, followed by reionization with oxygen. The differences in the survivor-ion spectra are due to different neutralization efficiencies of the isobaric and isomeric ions produced by electron impact ionization, different stabilities of the intermediate neutral species, different reionization efficiencies and reionized ion stabilities. Neutralization-reionization spectra of the C₇H₁₂^+., C₆H₉⁺, C₃H₆O^+. and C₃H₅O⁺ ions from stereoisomeric 4-methylcyclohexanols are also reported.     

Neutralization-reionization mass spectrometry (NRMS). Structural information from vertical neutralization and reionization efficiencies

The neutralization-reionization mass spectra of alkane radical ions indicate significant differences between the structures and geometries of alkane molecules and their molecular ions, confirming recent ab initio predictions. Ionic isomers that are indistinguishable by collisionally-activated dissociation because of easy interconversion can be characterized by neutralization-reionization if the corresponding neutrals show different reactivities, as is demonstrated for the [C₂H₅]⁺/C₂H₅˙ system and for [C₂H₄O₂]⁺˙ isomers. For identification of mixtures of more than one neutral species, the relative efficiency for reionizing each neutral must be determined; e.g. the O₂ reionization efficiency of ˙CH₂OH radicals is ～4 times greater than that of CH₃O˙. This information and reference reionization spectra of CH₃O˙ and ˙CH₂OH show that metastable or collisionally activated methyl acetate cations lose CH₃O˙, not ˙CH₂OH as previously reported; the newly-formed CH₃O˙ undergoes partial (～20%) isomerization to ˙CH₂OH in the ～10^?6s before reionization. Similar results are obtained for [B(OCH₃)₃]⁺˙.     

Metastable [C4H8O]+˙ ions: Additional decompositions via the [2-butanone]+˙ ion

The losses of methyl and ethyl through the intermediacy of the [2-butanone]⁺˙ ion are shown to be the dominant metastable decomposition of 14 of 19 [C₄H₈O]⁺˙ ions examined. The ions that decompose via the [2-butanone]⁺˙ structure include ionized aldehydes, unsaturated and cyclic alcohols and enolic ions. [Cyclic ether]⁺˙ [cyclopropylmethanol]⁺˙ and [2-methyl-1-propen-1-ol]⁺˙ ions do not decompose through ionized 2-butanone. The rearrangements of various [C₄H₈O]⁺˙ ions the the 2-butanone ion were investigated by means of deuterium labeling. Those pathways involve up to eight steps. Ions with the oxygen on the end carbon rearrange to a common structure or mixture of structures. Those ions which ultimately rearrange to the [2-butanone]⁺˙ ion then undergo oxygen shifts from the terminal to the second and third carbons at about equal rates. However, this oxygen shift does not precede the losses of water and ethylene. Losses of water and ethylene were unimportant for ions with the oxygen initially on the second carbon. Ionized n-butanal and cyclobutanol, but not other [C₄H₈O]⁺˙ ions, undergo reversible hydrogen exchange between the oxygen and the terminal carbon. Rearrangement of ionized n-butanal to the [cyclobutanol]⁺˙ ion is postulated.     

Unimolecular reactions of ionized methyl acetate and its hydrogen-rearranged isomers

The proposed formation of [CH₃C(OH)OCH₂]⁺˙ (b) as the intermediate in the isomerization [CH₂?C(OH)OCH₃]⁺˙ (c)?b?[CH₃COOCH₃]⁺˙ (c has been confirmed by preparation of b from CH₃COOCH₂OCH₃. For the three isomers a–c the dominant metastable ion (MI) dissociation, CH₃O˙ loss, involves identical kinetic energy release values. The kinetic barriers for a?b and b?c must be nearly as high as that for CH₃O˙ loss from c, as shown by the insensitivity of the mass spectra from collisionally activated dissociation (CAD) of a–c to ionizing electron energy. The H/D scrambling of metastable [CH₂?C(OD)OCH₃]⁺˙ and c–D₃ ions confirm this, indicating that the barrier for a?b is slightly below that for b?c. Minor low-energy dissociations include losses of CH₄ and CH₃OH from a and losses of ˙CHO and CH₂O from b. Comparison of MI and CAD spectra of a–c with those from [CH₃(OH)CH₂O]⁺˙ (d) and [CH₃COCH₂OH]⁺˙ (e) give no evidence for skeletal rearrangement of a–c to d or e.     

Hydrogen transfer in the retro diels–alder fragmentation of oxygen-containing heterocyclic compounds. II—Chromones

Mass Spectra of unsubstituted, 2-methyl-, 3-methyl and 2,3-dimethylchromones were examined. These compounds showed [RDA]⁺˙ and [RDA + H]⁺ ions as characteristc ions, together with [M? H]⁺,[M? CO]⁺˙,[M? CHO]⁺ and [RDA? CO]⁺˙ ions. Based on deuterium labelling experiments and measurement of metastable peaks by the ion kinetic energy defocusing technique, the origin of transferred hydrogen in the [RDA + H]⁺ ion was clarified. The mechanism of the [RDA + H]⁺ ion formation is discussed.     

Losses of isobaric neutral species from molecular ions of isomeric nitroanisoles

Alternative losses of the isobaric neutral species CH₂O and NO˙ have been assessed for molecular ions of isomeric nitroanisoles fragmenting in the ion source and the first field free region of a double focusing mass spectrometer. Mass analyses of the primary fragment ions indicate that specific loss of CH₂O occurs from molecular ions of 2-nitroanisole, while specific loss of NO˙ occurs from molecular ions of 3-nitroanisole. Although the peak due to [M? NO]⁺ ions is negligible in the mass spectrum of 2-nitroanisole, evidence is presented to show that they are transient intermediates in the consecutive fragmentation for loss of the elements of CNO₂ from the molecular ions.