Substitution reactions under NH3 chemical ionization conditions in cis-/trans-1,2-dihydroxybenzosuberans

The nucleophilic substitution reaction under NH₃ chemical ionization (CI) conditions in cis- and trans-1,2-dihydroxybenzosuberans (1–4) has been studied with the help of ND₃ CI and metastable data. The results indicate that in the parent diols 1 (cis) and 2 (trans), the substitution ion [M_sH]⁺, is produced mainly by the loss of H₂O from the [MNH₄]⁺ ion (S_Ni reaction) while in their 7-methoxy derivatives 3 and 4, the ion-molecule reaction between [M? OH]⁺ and NH₃ seems to be the major pathway for the formation of [M_sH]⁺. The substitution ion from 1 and 2 and the [MH]⁺ ion from trans-1-amino-2-hydroxybenzosuberan give similar collision-induced dissociation mass-analysed ion kinetic energy spectra. Interestingly, their diacetates do not undergo the substitution reaction.     

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.     

Provitamin D and vitamin D isomerizations in the mass spectrometer. Translational energy release and collision-induced dissociation studies

Collision-induced dissociation mass-analysed ion kinetic energy spectrometry and translational energy release studies have established that provitamin D₃ (7-dehydrocholesterol), provitamin D₂ (ergosterol), vitamin D₃ and vitamin D₂ isomerizations in the mass spectrometer occur at the fragment ion level leading to [M? H₂O? CH₃]⁺ ions of identical structure. It was found that the reaction, [M]⁺˙→[M? H₂O]⁺˙, plays a central role in these isomerizations.     

Why Are B ions stable species in peptide spectra?

Protonated amino acids and derivatives RCH(NH₂)C(+O)X · H⁺ (X = OH, NH₂, OCH₃) do not form stable acylium ions on loss of HX, but rather the acylium ion eliminates CO to form the immonium ion RCH = NH ₂ ⁺ . By contrast, protonated dipeptide derivatives H₂NCH(R)C(+O)NHCH(R′)C(+O)X · H⁺ [X = OH, OCH₃, NH₂, NHCH(R″)COOH] form stable B₂ ions by elimination of HX. These B₂ ions fragment on the metastable ion time scale by elimination of CO with substantial kinetic energy release (T _1/2 = 0.3–0.5 eV). Similarly, protonated N-acetyl amino acid derivatives CH₃C(+O)NHCH(R′)C(+O)X · H⁺ [X = OH, OCH₃, NH₂, NHCH(R″)COOH] form stable B ions by loss of HX. These B ions also fragment unimolecularly by loss of CO with T _1/2 values of ～ 0.5 eV. These large kinetic energy releases indicate that a stable configuration of the B ions fragments by way of activation to a reacting configuration that is higher in energy than the products, and some of the fragmentation exothermicity of the final step is partitioned into kinetic energy of the separating fragments. We conclude that the stable configuration is a protonated oxazolone, which is formed by interaction of the developing charge (as HX is lost) with the N-terminus carbonyl group and that the reacting configuration is the acyclic acylium ion. This conclusion is supported by the similar fragmentation behavior of protonated 2-phenyl-5-oxazolone and the B ion derived by loss of H-Gly-OH from protonated C₆H₅C(+O)-Gly-Gly-OH. In addition, ab initio calculations on the simplest B ion, nominally HC(+O)NHCH₂CO⁺, show that the lowest energy structure is the protonated oxazolone. The acyclic acylium isomer is 1.49 eV higher in energy than the protonated oxazolone and 0.88 eV higher in energy than the fragmentation products, HC(+O)N⁺H = CH₂ + CO, which is consistent with the kinetic energy releases measured.     

Fragmentation of selected C6H10O isomers: Evidence for a common [C5H7O]+ ion generated by methyl loss from cyclohexene oxide and 5,6-dihydro-4-methyl-2H-pyran

The loss of CH₃˙ from the molecular ions of cyclohexene oxide and 5,6-dihydro-4-methyl-2H-pyran has been investigated. On the basis of metastable peak shape analysis, collision-induced dissociation/mass-analysed ion kinetic energy spectra and thermochemical data it is concluded that the same [C₅H₇O]⁺ ion is formed in both cases.     

Metastable ion study of organosilicon compounds. Part III—trimethoxyphenylsilane

The unimolecular decomposition of trimethoxyphenylsilane (1) was investigated by mass-analysed ion kinetic energy (MIKE) spectrometry, deuterium-labelling studies and from high resolution data. The characteristic fragmentations of metastable molecular ion of 1 were losses of C₆H₆ and C₇H₇^· with rearrangements. Almost complete H/D scrambling occurred in the molecular ion prior to these decompositions. The other important fragmentation routes corresponded to expulsions of CH₃O^· and C₆H₅^·. These fragmentations were followed by consecutive elimination of an H₂CO molecule, as commonly observed in the mass spectra of alkoxysilanes. In these fragmentation processes, H/D scrambling increased as the internal energy of the molecular ion was lowered. The fragmentations of 1 were compared with those of its carbon analogue, α,α,α-trimethoxytoluene.     

Differentiation of the isomeric 1,2-cyclopentanediols by ion-molecule reactions in a triple-quadrupole mass spectrometer

Collisionally activated decompositions and ion-molecule reactions in a triple-quadrupole mass spectrometer are used to distinguish between cis- and trans-1,2-cyclopentanediol isomers. For ion kinetic energies varying from 5 eV to 15 eV (laboratory frame of reference), qualitative differences in the daughter ion spectra of [MH]⁺ are seen when N₂ is employed as an inert collision gas. The cis ?1,2-cyclopentanediol isomer favors H₂O elimination to give predominantly [MH- H₂O]⁺. In the trans isomer, where H₂O elimination is less likely to occur, the rearrangement ion [HOCH₂CHOH]⁺ exists in significantly greater abundance. Ion-molecule reactions with NH₃ under single-collision conditions and low ion kinetic energies can provide thermochemical as well as stereochemical information. For trans ?1,2-cyclopentanediol, the formation of [NH₄]⁺ by proton transfer is an exothermic reaction with the maximum product ion intensity at ion kinetic energies approaching 0 eV. The ammonium adduct ion [M + NH₄]⁺ is of greater intensity for the trans isomer. In the proton transfer reaction with the cis isomer, the formation of [NH₄]⁺ is an endothermic process with a definite translational energy onset. From this measured threshold ion kinetic energy, the proton affinity of cis ?1,2-cyclopentanedioi was estimated to be 886 ± 10 kJ mol^?1.     

Translational energy release and stereochemistry of steroids. XI—Determination of the configuration of α,β-unsaturated 3-keto steroid alcohols with the hydroxyl group in rings C and D

The elimination of water from metastable molecular ions of epimeric hydroxy steroids of the Δ⁴-3-keto series containing a hydroxyl group in the conformationally rigid rings C and D has been studied. The measurement of translational energy released during the loss of water and collision-induced decomposition (CID) mass-analysed ion kinetic energy (MIKE) spectrometry were the techniques used. It was found that it is possible to determine the configuration of the hydroxy steroids of this series on the basis of the CID MIKE spectra of [M ? H₂O]^+˙ ions formed by dehydration of metastable molecular ions in the first field-free region of a reversed geometry double-focusing mass spectrometer.     

Reactivity in the gas phase. Behaviour of isoxazoles under negative ion chemical ionization conditions

[M ? H⁺]^? ions of isoxazole (la), 3-methylisoxazole (1b), 5-methylisoxazole (1c), 5-phenylisoxazole (1d) and benzoylacetonitrile (2a) are generated using NICI/OH^? or NICI/NH₂^? techniques. Their fragmentation pathways are rationalized on the basis of collision-induced dissociation and mass-analysed ion kinetic energy spectra and by deuterium labelling studies. 5-Substituted isoxazoles 1c and 1d, after selective deprotonation at position 3, mainly undergo N ? O bond cleavage to the stable α-cyanoenolate NC ? CH ? CR ? O^? (R = Me, Ph) that fragments by loss of R? CN, or R? H, or H₂O. The same α-cyanoenolate anion (R = Ph) is obtained from 2a with OH^?, or NH₂^?, confirming the structure assigned to the [M ? H⁺]^? ion of 1d, On the contrary, 1b is deprotonated mainly at position 5 leading, via N? O and C(3)? C(4) bond cleavages, to H? C ≡ C? O ^? and CH₃CN. Isoxazole (1a) undergoes deprotonation at either position and subsequent fragmentations. Deuterium labelling revealed an extensive exchange between the hydrogen atoms in the ortho position of the phenyl group and the deuterium atom in the α-cyanenolate NC ? CD = CPh ? O^?.     

Isomerization and fragmentation of methylfuran ions and pyran ions in the gas phase

The mutual interconversion of the molecular ions [C₅H₆O]⁺ of 2-methylfuran (1), 3-methylfuran (2) and 4H-pyran (3) before fragmentation to [C₅H₅O]⁺ ions has been studied by collisional activation spectrometry, by deuterium labelling, by the kinetic energy release during the fragmentation, by appearance energles and by a MNDO calculation of the minimum energy reaction path. The electron impact and collisional activation mass spectra show clearly that the molecular ions of 1–3 do not equilibrate prior to fragmentation, but that mostly pyrylium ions [C₅H₅O]⁺ arise by the loss of a H atom. This implies an irreversible isomerization of methylfuran ions 1 and 2 into pyran ions before fragmentation, in contrast to the isomerization of the related systems toluene ions/cycloheptatriene ions. Complete H/D scrambling is observed in deuterated methylfuran ions prior to the H/D loss that is associated with an iostope effect k_H/k_D = 1.67–2.16 for metastable ions. In contrast, no H/D scrambling has been observed in deuterated 4H-pyran ions. However, the loss of a H atom from all metastable [C₅H₅O]⁺ ions gives rise to a flat-topped peak in the mass-analysed ion kinetic energy spectrum and a kinetic energy release (T₅₀) of 26 ± 1.5 kJ mol^?1. The MNDO calculation of the minimum energy reaction path reveals that methylfuran ions 1 and 2 favour a rearrangement into pyran ions before fragmentation into furfuryl ions, but that the energy barrier of the first rearrangement step is at least of the same height as the barrier for the dissociation of pyran ions into pyrylium ions. This agrees with the experimental results.     

Differentiation of isomeric 5- and 7-oxo derivatives of tetrahydrothiazolo[3,2-a]pyrimidine by electron impact mass spectrometry

The electron impact mass spectra of two series of 5-oxo-tetrahydro-5H-thiazolo [3,2-a]pyrimidine-6-ethylcarboxylates and 7-oxo-tetrahydro-7H-thiazolo [3,2-a]pyrimidine-6-ethylcarboxylates were measured and fragmentation patterns examined. Structures were assigned from analysis of oxo molecular ion fragmentations. Compounds of the 5-oxo series gave an [M – CO₂C₂H₅]⁺ fragmentation whereas compounds of the 7-oxo series gave three characteristic cleavages. This decomposition was confirmed for one pair of isomers by high-resolution mass spectrometry and unimolecular mass-analysed ion kinetic energy spectrometry. Electron impact mass spectrometry is a convenient method for assigning structures of 5- and 7-oxo regioisomers of tetrahydrothiazolo[3,2-a]pyrimidine-6-carboxylates.     

Ion–molecule reactions in the gas phase. XVIII.—nucleophilic substitution of diastereomeric norborneols,norbornyl acetates and benzoates under ammonia chemical ionization

The comparative behaviour of the endo- and exo-norborneols and diastereomeric derivatives (acetates and benzoates) towards the NH₃/NH₄⁺ system was investigated. It appears that the proton affinity (PA) of the substrate relative to Pa(NH₃) strongly influences competition between the protonation and nucleophilic substitution processes yielding the MH⁺ and [M + NH₄ ? H₂O]⁺ ions, respectively. Tandem mass spectrometry was used to compare collision-activated dissociation spectra of [M + NH₄ ? H₂O]⁺ with those of analogous endo- and exo-norbornylamines protonated in the source. This demonstrates that an S_Nimechanism occurs specifically for the isomeric norborneols; in contrast, for acetates and benzoates, stereospecific S_Ni and S_N2 pathways take place for exo and endo derivatives, respectively. This particular behaviour is explained by considering the steric effect induced by the endo-H at C(6). In addition, the competitive decompositions of [M + NH₄ – H₂O]⁺ into NH₄⁺ and [C₇H₁₁]⁺ daughter ions are consistent with the formation of a proton-bound complex intermediate. The observed stereochemical effects for these dauther ions are rationalized by means of arguments based on the estimated heats of formation of the transition states, which is lower for the exo-norbonyl protonated amine, consistent with anchimeric assistance, rather than a stepwise pathway which is proposed for the endoisomer.     

Electron impact mass spectrometry of ethyl esters of halogenated acetic acids

The behaviour of a series of differently halogenated acetic acid ethyl esters was studied using electron impact and metastable ion techniques. The presence of different halogens strongly influences the fragmentation pathways and also the kinetic energy release values associated with some decomposition routes. By mass-analysed ion kinetic energy spectrometry, a composite metastable peak was detected for the transition CF₂BrCO⁺ → CF₂Br⁺, and rationalized on the basis of two different structures for the precursor ion.     

Metastable ion study of organosilicon compounds. Part V—tetramethoxysilane and trimethoxymethylsilane

The fragmentations of tetramethoxysilane ((CH₃O)₄Si (1)) and trimethoxymethylsilane ((CH₃O)₃SiCH₃ (3)) induced by electron impact were investigated by mass-analysed ion kinetic energy (MIKE) spectrometry and a deuterium-labelling study. These molecular ions begin to fragment by the loss of CH₃ or CH₃O. These fragmentations are followed by the loss of an aldehyde molecule (H₂CO), as commonly observed in the mass spectra of alkoxysilanes. Almost complete scrambling of the methoxy hydrogens takes place in the metastable molecular ion, [1]⁺˙, prior to the decomposition. On the other hand, a moderate extent of scrambling of the hydrogens takes place in [3]⁺˙. The fragmentations of [1]⁺˙ and [3]⁺˙ were compared with those of the corresponding carbon analogues, tetramethoxymethane ((CH₃O)₄C (2)) and 1,1,1-trimethoxyethane ((CH₃O)₃CCH₃ (4)), respectively.     

Study of selected ions in the ammonia desorption chemical ionization mass spectra of peracetylated gentiobiose and two isotopically labelled peracetylated gentiobioses

The ammonia desorption chemical ionization (NH₃-DCI) mass spectra of peracetylated gentiobiose (1) and two isotopically labelled gentiobioses (2 and 3) were examined. Compound 2 is labelled with trideuteroacetyl groups in the non-reducing moiety and 3 with trideuteroacetyl groups in the reducing moiety. It is shown that the [M + NH₄ – 42]⁺ ion is not formed direct from [M + NH₄]⁺ by loss of ketene but appears to be formed by way of a nucleophilic acyl substitution reaction resulting in a neutral species which complexes with NH₄⁺. The disaccharides undergo cleavage at either side of the glycosidic oxygen joining the two sugar residues, a process which is accompanied by addition of H or CH₃CO to afford neutral species which complex with NH₄⁺. The structures of the ions resulting from H transfer have been inferred by comparison of their mass-analysed ion kinetic energy (MIKE) spectra with MIKE spectra of the [M + NH₄]⁺ ions of compounds of established structure. A ring fragmentation reaction of 1, 2 and 3 is reported.     

Gas phase substitution under ammonia chemical ionization

Evidence for the isomerization of the [M + NH₄]⁺ adducts of nitrobenzene and triphenylnitrocyclohexenes to the isonitroso derivatives in the first field free region has been obtained. The isomerized adducts undergo successive loss of ?O and ?H or NH₃ to give ions corresponding to the substitution products. Mass analysed ion kinetic energy and collisionally activated dissociation/mass analysed ion kinetic energy data reveal that the adduct decomposes by similar pathways in the second field free region. In the ion source an addition elimination reaction and nucleophilic substitution contribute to the formation of the substituted product ion.     

Energy disposal in gas-phase nucleophilic displacement reactions

The partitioning of reaction exothermicity into relative translational energy of the products of gas-phase S_N2 (F^? + CH₃Cl) and nucleophilic aromatic substitution (F^? + C₆H₅Cl) reactions has been investigated using kinetic energy release Fourier transform ion cyclotron resonance spectroscopy. The chloride product ion is observed to be highly translationally excited for the S_N2 reaction, indicating a cold internal energy distribution for the products. For the chlorobenzene reaction the products are not generated with large translational energies. The results are compared with a statistical model. Ion-intensity profiles for the CH₃Cl reaction deviate significantly from the statistical model whereas the chlorobenzene results are consistent with this model. The kinetic energy release for the CH₃C1 reaction is compared with energy-disposal results for the photodissociation and dissociative electron-attachment processes of halomethanes. In all three cases a node in the molecular orbital between the carbon atom and the departing halogen results in a repulsive energy release. Ion-retention curves for the nucleophilic aromatic substitution reaction are consistent with the existence of a long-lived ion-dipole complex on the exit channel for this reaction.     

A mass spectrometric investigation on some 3-[2-(Nitroxy)alkyl]-2H-1,3-benzoxazin-4-(3H)-one derivatives

The electron ionization mass spectrometric behaviour of ten 3-[2-(nitroxy)alkyl]-2H-1,3-benzoxazin-4-(3H)-one derivatives has been studied by means of metastable ion studies. By mass-analysed ion kinetic energy spectrometry of the related molecular ions, clear differences have been evidenced between the 5-methyl derivative and the other compounds, consisting of a highly favoured loss of NO₂ radical. The same methodology has allowed easy characterization of isomeric compounds.     

Novel proximity effects and Ortho interactions in 2,2′-disubstituted diphenylamines on electron impact

Unexpected ejections of CH₃NO₂/[^˙CH₃ + ^˙NO₂], N₂O₄/[^˙NO₂ + ^˙NO₂] and CH₃OCH₃/[^˙CH₃ + ^˙OCH₃] were observed from the molecular ions of 2-methoxy-2′-nitrodiphenylamine, 2,2′-dinitrodiphenylamine and 2,2′-dimethoxydiphenylamine, respectively, under electron impact conditions owing to proximity effects. In other competing fragmentation pathways, novel proximity effects triggered by the ortho interactions leading to the unusual eliminations of [^˙CH₃ + H₂O] from M^+˙ of 2-methoxy-2′-nitrodiphenylamine and HNO₃/[^˙NO₂ + ^˙OH] from M^+˙ of 2,2′-dinitrodiphenylamine were observed. Evidence for the interpretation of the main fragmentation pathways was obtained from the metastable ion spectra and high-resolution mass spectrometry. Confirmation of the structures assigned to the ions was provided by collision-activated dissociation mass-analysed ion kinetic energy spectra.     

Oxidation reactions in triterpenes under chemical ionization conditions

From a collisional activation spectral study it has been found that certain triterpene alcohols with an ursane or oleanane skeleton undergo oxidation to the corresponding ketones under chemical ionization (NH₃) conditions giving rise to abundant [M + NH₄ ? 2]⁺ ions. Mass-analysed ion kinetic energy and B²/E scan results indicate that both [M + NH₄]⁺ and [M + N₂H₇ ? 2]⁺ ions contribute to the formation of the [M + NH₄ ? 2]⁺ ion.