Intrinsic gas-phase electrophilic reactivity of cyclic N-alkyl- and N-acyliminium ions

The intrinsic gas-phase reactivity of cyclic N-alkyl- and N-acyliminium ions toward addition of allyltrimethylsilane (ATMS) has been compared using MS(2) and MS(3) pentaquadrupole mass spectrometric experiments. An order of electrophilic reactivity has been derived and found to agree with orders of overall reactivity in solution. The prototype five-membered ring N-alkyliminium ion 1a and its N-CH(3) analogue 1b, as well as their six-membered ring analogues 1c and 1d, lack N-acyl activation and they are, accordingly, inert toward ATMS addition. The five- and six-membered ring N-acyliminium ions with N-COCH(3) exocycclic groups, 3a and 3b, respectively, are also not very reactive. The N-acyliminium ions 2a and 2c, with s-trans locked endocyclic N-carbonyl groups, are the most reactive followed closely by 3c and 3d with exocyclic (and unlocked) N-CO(2)CH(3) groups. The five-membered ring N-acyliminium ions are more reactive than their six-membered ring analogues, that is: 2a > 2c and 3c > 3d. In contrast with the high reactivity of 2a, its N-CH(3) analogue 2b is inert toward ATMS addition. For the first time, the transient intermediates of a Mannich-type condensation reaction were isolated-the beta-silyl cations formed by ATMS addition to N-acyliminium ions-and their intrinsic gas-phase behavior toward dissociation and reaction with a nucleophile investigated. When collisionally activated, the beta-silyl cations dissociate preferentially by Grob fragmentation, that is, by retro-addition. With pyridine, they react competitively and to variable extents by proton transfer and by trimethylsilylium ion abstraction-the final and key step postulated for alpha-amidoalkylation. Becke3LYP/6-311G(d,p) reaction energetics, charge densities on the electrophilic C-2 site, and AM1 LUMO energies have been used to rationalize the order of intrinsic gas-phase electrophilic reactivity of cyclic iminium and N-acyliminium ions.     

Coordination of sodium cation to an oxygen function and olefinic double bond to form molecular adduct ion in fast atom bombardment mass spectrometry

Steroidal allylic alcohols formed Na+ adduct ion peaks [M+Na]+ by the addition of NaCl in FAB mass spectrometry. A comparison of the intensities of the adduct ion peaks of allylic alcohols with those of the corresponding saturated alcohols and olefin suggested that the olefinic double bond and the proximal hydroxyl group had coordinated to Na+. The adduct ion was stable and did not undergo dehydroxylation. We suggest that the Na+ adduction will be useful for the molecular weight determination of allylic alcohols which are susceptible to dehydroxylation under FAB mass spectrometric conditions. Na+ adduct ions of alpha,beta-unsaturated carbonyl compounds were also investigated.     

Structurally diagnostic ion-molecule reactions: acylium ions with alpha-, beta- and gamma-hydroxy ketones

Gas-phase reactions of four acylium ions and a thioacylium ion with three isomeric alpha-, beta- and gamma-hydroxy ketones are performed by pentaquadrupole mass spectrometric experiments. Novel structurally diagnostic reactions are observed, and found to correlate directly with interfunctional group separation. All five ions tested (CH(3)CO(+), CH(2)(double bond)CHCO(+), PhCO(+), (CH(3))(2)NCO(+) and (CH(3))(2)NCS(+)) react with the gamma-hydroxy ketone (5-hydroxy-2-pentanone) to form nearly exclusively a cyclic oxonium ion of m/z 85 that formally arises from hydroxy anion abstraction. With the beta-hydroxy ketone (4-hydroxy-2-pentanone), CH(2)(double bond)CHCO(+), PhCO(+) and (CH(3))(2)NCO(+) form adducts that undergo fast cyclization via intramolecular water displacement, yielding resonance-stabilized cyclic dioxinylium ions. With the alpha-hydroxy ketone (3-hydroxy-3-methyl-2-butanone), PhCO(+), (CH(3))(2)NCO(+) and (CH(3))(2)NCS(+) form stable adducts. Evidence that these adducts display cyclic structures is provided by the triple-stage mass spectra of the (CH(3))(2)NCS(+) adduct; it dissociates to (CH(3))(2)NCO(+) via a characteristic reaction-dissociation pathway that promotes sulfur-by-oxygen replacement. If cyclizations are assumed to occur with intramolecular anchimeric assistance, relationships between structure and reactivity are easily recognized.     

Double transacetalization of diacylium ions

A novel gas-phase reaction of diacylium ions of the O=C=X(+)=C=O type (X = N, CH) is reported: double transacetalization with cyclic acetals or ketals. The reaction is exothermic and highly efficient, and forms members of a new class of highly charged-delocalized ions: cyclic ionic diketals. Pentaquadrupole double- and triple-stage mass spectrometric (MS(2) and MS(3)) experiments reveal the high double transacetalization reactivity of O=C=N(+)=C=O and O=C=CH(+)=C=O, whereas the synthesis of differently substituted cyclic ionic diketals is performed in MS(3) experiments via sequential mono- and double transacetalization of O=C=N(+)=C=O and O=C=CH(+)=C=O with different acetals. With cyclic acetals, the acylium-thioacylium ion O=C=N(+)=C=S reacts promptly and selectively by mono-transacetalization at its acylium site, but the free thiacylium site of its cyclic ionic ketal is nearly unreactive by double transacetalization. Therefore, only the acylium site of O=C=N(+)=C=S can be efficiently protected by transacetalization. Low-energy MS(3) collision-induced dissociation of the cyclic ionic diketals of O=C=N(+)=C=O and O=C=CH(+)=C=O sequentially frees each of the protected acylium site to form the mono-derivatized ion, and then the fully deprotected diacylium ion.     

Gas-phase oxirane addition to acylium ions on reaction with 1,3-dioxolanes elucidated by tandem and triple stage mass spectrometric experiments

Acylium ions containing a variety of substituents all undergo an unprecedented reaction with 1,3-dioxolanes which gives rise to a cyclic, resonance-stabilized oxonium ion, formally the product of oxirane (C₂H₄O) addition to the reagent ion. The structure for the ion–molecule product is supported by multiple-stage mass spectrometric experiments, performed in a pentaquadrupole mass spectrometer, which show the expected fragmentation by C₂H₄O loss to yield the original reactant acylium ions. The oxonium ions are formed in relatively high abundance in many cases and are observed even when proton-transfer reactions would be expected to occur competitively owing to the acidity of some of the acylium ions studied. This ion–molecule reaction is proposed to serve as a general method for identification and/or trapping of ions of the whole acylium ion class and also for the gas-phase generation of the oxonium ions. The reaction with 1,3-dioxolane is also useful in distinguishing the most stable C₂H₃O⁺ ion, the acetyl cation, from its two stable isomers, O-protonated ketene and the oxiranyl cation. The thioacetyl cation, the only sulfur analog investigated, also reacts with dioxolane to form the corresponding oxirane addition product, indicating that the C₂H₄O addition reaction occurs and that it may be useful for identification of the thioacylium class and for the gas-phase generation of sulfur analogs of oxonium ions.     

Ion/molecule reaction inside the collision cell of a tandem quadrupole mass spectrometric system. 2. Energy dependence of ammonium ion formation

The dependence of the protonation of neutral ammonia on the axial kinetic energy of protonated reactant ions has been studied in the gas phase, using various protonated carbonyl compounds, inside the collision cell of a tandem quadrupole mass spectrometric system. The hypothesis of two different and non-competitive reaction channels has been proposed. The first is characterized by a very low (peaked at ±0.05 eV_cm) and well-defined axial kinetic energy of the reactant ion, while the second is more energy demanding (estimated threshold at ±0.2 eV_cm) and expressed by a collisionally induced dissociation-like energy curve. Fourier transform mass spectrometric experiments have shown that ammonium ion can be generated by direct proton exchange and fragmentation of the adduct ion obtained.     

Meerwein reaction of phosphonium ions with epoxides and thioepoxides in the gas phase

Phosphonium ions are shown to undergo a gas-phase Meerwein reaction in which epoxides (or thioepoxides) undergo three-to-five-membered ring expansion to yield dioxaphospholanium (or oxathiophospholanium) ion products. When the association reaction is followed by collision-induced dissociation (CID), the oxirane (or thiirane) is eliminated, making this ion molecule reaction/CID sequence a good method of net oxygen-by-sulfur replacement in the phosphonium ions. This replacement results in a characteristic mass shift of 16 units and provides evidence for the cyclic nature of the gas-phase Meerwein product ions, while improving selectivity for phosphonium ion detection. This reaction sequence also constitutes a gas-phase route to convert phosphonium ions into their sulfur analogs. Phosphonium and related ions are important targets since they are commonly and readily formed in mass spectrometric analysis upon dissociative electron ionization of organophosphorous esters. The Meerwein reaction should provide a new and very useful method of recognizing compounds that yield these ions, which includes a number of chemical warfare agents. The Meerwein reaction proceeds by phosphonium ion addition to the sulfur or oxygen center, followed by intramolecular nucleophilic attack with ring expansion to yield the 1,3,2-dioxaphospholanium or 1,3,2-oxathiophospholanium ion. Product ion structures were investigated by CID tandem mass spectrometry (MS(2)) experiments and corroborated by DFT/HF calculations.     

气相中双取代苯在丙酮离子体系中的加合反应研究

研究了11双取代苯在丙酮离子体系中的离子－分子反应特性及加合离子的碎裂反应特性,发现推电子基有利于加合反应的发生而吸电子基不利于加合反应的发生。双取代异构体的加合产物相对强度可以反映出它们取代基的位置及其性质的差异。邻苯二胺与乙酰基离子形成的加合离子在碎裂反应过程中可以发生与液相中胺的还原烷基化反应相类似的碎裂反应。     

Identification of the aromatic tertiary N-oxide functionality in protonated analytes via ion/molecule reactions in mass spectrometers

A mass spectrometric method is presented for the rapid identification of compounds that contain the aromatic N-oxide functional group. This method utilizes a gas-phase ion/molecule reaction with 2-methoxypropene that yields a stable adduct for protonated aromatic tertiary N-oxides (and with one protonated nitrone) in different mass spectrometers. A variety of protonated analytes with O- or N-containing functional groups were examined to probe the selectivity of the reaction. Besides protonated aromatic tertiary N-oxides and one nitrone, only three protonated amines were found to form a stable adduct but very slowly. All the other protonated analytes, including aliphatic tertiary N-oxides, primary N-oxides, and secondary N-oxides, are unreactive toward or react predominantly by proton transfer with 2-methoxypropene.     

Gas-phase polar [4+ + 2] cycloaddition with ethyl vinyl ether: a structurally diagnostic ion-molecule reaction for 2-azabutadienyl cations

The intrinsic reactivity of eight gaseous, mass-selected 2-azabutadienyl cations toward polar [4(+) + 2] cycloaddition with ethyl vinyl ether has been investigated by pentaquadrupole mass spectrometric experiments. Cycloaddition occurs readily for all the ions and, with the only exception of those from the N-acyl 2-azabutadienyl cations (N-acyliminium ions), the cycloadducts are found to dissociate readily upon collision activation (CID) both by retro-Diels-Alder reaction and by a characteristic loss of an ethanol (46u) neutral molecule. Ethanol loss from the intact polar [4(+) + 2] cycloadduct functions therefore as a structurally diagnostic test: 72 u neutral gain followed by 46 u neutral loss, i.e., as a combined ion-molecule reaction plus CID 'signature' for N-H, N-alkyl and N-aryl 2-azabutadienyl cations. The two N-acyliminium ions tested are exceptional as they form intact cycloadducts with ethyl vinyl ether which dissociate exclusively by the retro-Diels-Alder pathway.     

Pi-aromatic and sulfur nucleophilic partners in cationic pi-cyclizations: intramolecular amidoalkylation and thioamidoalkylation cyclization via omega-carbinol lactams(1, 2).

NaBH(4) reduction of imides 1 and 6a,b,c followed by a pi-cyclization of the resultant N-acyliminium ions, generated in trifluoroacetic acid conditions, afforded two positional isomers, isoindolobenzothiazolinones 4 and 8, respectively. These ring closures proceeded via an intramolecular alpha-amidoalkylation with the classical pi-aromatic or the atypical sulfur atom as an internal nucleophile. A ready access to the related six-membered N,S-heterocyclic compounds such as isoindolobenzothiazinones 20a and 21a is also described. During this reaction, we have shown that omega-carbinol lactam precursor 14a led to endocyclic and exocyclic N-acyliminium ions 18a and 19a in equilibrium via the cyclic aza-sulfonium ion A. The latter furnished the expected products 20a and 21a in good yields. Similarly, different omega-carbinol lactams 14b-e substituted at C-angular position afforded the corresponding isoindolobenzothiazinones 20b-e and 21b-e bearing an angular alkyl, aralkyl, or aryl group. In the case of methyl 14b and benzyl 14e groups, an additional amount of the dehydration products 16b and 31 was isolated. These results indicate that the isomerization-pi-cyclization takes place via the cleavage of the thioether linkage in acidic medium.     

Decomposition of protonated formic acid: One transition state—Two product channels

The unimolecular chemistry of protonated formic acid, [HCOOH]H(+), has been investigated by analyzing the fragmentation of metastable ions (MI) during flight in a sector mass spectrometer, and by proton transfer to formic acid in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. High level ab initio calculations have been used to model the relevant parts of the potential energy surface (PES). In addition, ab initio direct dynamics calculations have been conducted, tracing out 60 different reaction trajectories. The only stable isomer in the mass spectrometric experiments is HC(OH)(2)(+), which is the precursor to both observed ionic products, HCO(+) and H(3)O(+), via the same saddle point of the potential energy surface. The detailed motion of the dissociating molecule during passage of the post-transition state region of the PES therefore determines which product ion is formed. After passing the TS a transient HC(O)OH(2)(+) molecule is first formed. High total energy increases the probability that the nascent water molecule will have sufficient speed to escape the HCO(+) moiety. Otherwise, typically at low energies, the two units recombine, upon which intra-complex proton transfer is very likely. Eventually, this will give the more stable H(3)O(+).     

Acyclic stereoselection in the reaction of nucleophilic reagents with chiral N-acyliminium ions generated from N-

Optically active N-[1-(phenylsulfonyl)alkyl]imidazolidin-2-ones react at low temperature in the presence of tin tetrachloride to give acyclic N-acyliminium ions. These electrophilic substrates give addition products upon reaction with pi-nucleophiles. Allyltrimethylsilane affords the corresponding allylated products in good yields and high diastereoselectivity. The stereochemical outcome of this process can be rationalized by taking into account the preference of the intermediate N-acyliminium ion for an E configuration that favors the attack of the nucleophile from the si-si face. Disappointing results are obtained using silyl ketene acetals; conversely trimethylsilyl enol ether of acetophenone gives the corresponding adducts in high diastereoselectivity. The utilization of trimethylsilyl enol ether of 2-acetylfuran is particularly interesting since the corresponding adducts are obtained with good diastereoselectivity and the furan ring could be amenable of further synthetic transformations.     

Origin of adduct ions in the electron-capture mass spectrum of tetracyanoethylene

The high-pressure electron-capture (HPEC) mass spectrum of tetracyanoethylene (TCNE) is dominated by unexpected hydrogen atom and hydrocarbon radical adduct ions when methane is used as the buffer gas. The origin of these unexpected ions was investigated by three separate mass spectrometric experiments: the electron-capture (EC) rate constant of TCNE was determined and integrated into a previously developed kinetic model of HPEC ion source events; electron impact mass spectra of TCNE were obtained following exposure of the ion source surfaces to irradiated methane and irradiated carbon dioxide; and TCNE was determined by gas chromatographic introduction into the HPEC ion source with multiple ion monitoring. All of these experiments suggest that the reactions leading to the major adduct ions observed in the HPEC mass spectrum of TCNE are initiated by alteration of TCNE on the walls of the ion source rather than in the gas phase.     

Identification and counting of carbonyl and hydroxyl functionalities in protonated bifunctional analytes by using solution derivatization prior to mass spectrometric analysis via ion-molecule reactions

A mass spectrometric method has been developed for the identification of carbonyl and hydroxyl functional groups, as well as for counting the functional groups, in previously unknown protonated bifunctional oxygen-containing analytes. This method utilizes solution reduction before mass spectrometric analysis to convert the carbonyl groups to hydroxyl groups. Gas-phase ion-molecule reactions of the protonated reduced analytes with neutral trimethylborate (TMB) in a FT-ICR mass spectrometer give diagnostic product ions. The reaction sequence likely involves three consecutive steps, proton abstraction from the protonated analyte by TMB, addition of the neutral analyte to the boron reagent, and elimination of a neutral methanol molecule. The number of methanol molecules eliminated upon reactions with TMB reveals the number of hydroxyl groups in the analyte. Comparison of the reactions of the original and reduced analytes reveals the presence and number of carbonyl and hydroxyl groups in the analyte.     

Metastable and collision-induced fragmentation studies and thermochemistry of isomeric C(4)H(11)Si(+) ions and their adducts with C(4)H(12)Si silanes

Metastable Ion (MI) and collision-induced dissociation (CID) mass spectra for all isomeric even-electron [C(4)H(12)Si - H](+) ions were recorded and compared. Deuterium labeling experiments indicated that most precursors give rise to silylium ions. Silylium ions with two or more methyl groups are found to lose C(2)H(4) after isomerization via a straightforward hydrogen transfer to the appropriate ethylsilylium ion. Similarly, all isomeric propyl- and butyl-containing silylium ions are found to lose C(2)H(4) by rearrangement preceding dissociation. In the CI source of the mass spectrometer many of the silylium ions are found to cluster with the parent neutral silane present in the source to give stable [M - H](+)+M adduct ions. The MI and CID spectra of these adduct ions were also obtained. In the MI spectra of all adducts, except i-BuSiH(3), only the starting silylium ion is observed. Under CID conditions generation of silylium ions dominates. Deuterium labeling studies show that this dissociation may be accompanied by some rearrangement, in particular for the adducts from i-BuSiH(3). High-pressure mass spectrometric clustering equilibrium measurements were also carried out to determine the enthalpies and entropies of binding of the silylium ions to the neutral silanes. These measurements yield insight into the effects of various alkyl group substitutions on the association thermochemistry in these adducts. Copyright 2000 John Wiley & Sons, Ltd.     

Chemical ionization of substituted naphthalenes using tetrahydrofuran as a reagent in gas chromatography with ion trap mass spectrometry

The ion/molecule reactions of nine monosubstituted naphthalene compounds in chemical ionization mass spectrometry (CI-MS) were studied using tetrahydrofuran (THF) as CI reagent. Proton affinity factors, substituent effects and the preferred site of adduct ion attachment were examined. Good correlation was observed between proton affinity and the formation of [M](+*) and [M+H](+) ions. The influence of substituents on protonation and site-specific adduct [M+13](+) and [M+41](+) ion formation is also observed, with the cyano substituent showing the most stable [M+41](+) ion. Collision-activated dissociation experiments were used to characterize the variety of adducts formed under CI conditions, and provided insight into product ion structures and mechanisms of dissociation and condensation during CI-MS/MS.     

Derivatization of protonated peptides via gas phase ion—molecule reactions with acetone

The protonated [M + H]+ ions of glycine, simple glycine containing peptides, and other simple di- and tripeptides react with acetone in the gas phase to yield [M + H + (CH3)2CO]+ adduct ion, some of which fragment via water loss to give [M + H + (CH3)2CO - H2O]+ Schiff's base adducts. Formation of the [M + H + (CH3)2CO]+ adduct ions is dependent on the difference in proton affinities between the peptide M and acetone, while formation of the [M + H + (CH3)2CO - H2O]+ Schiff's base adducts is dependent on the ability of the peptide to act as an intramolecular proton "shuttle." The structure and mechanisms for the formation of these Schiff's base adducts have been examined via the use of collision-induced dissociation tandem mass spectrometry (CID MS/MS), isotopic labeling [using (CD3)2CO] and by comparison with the reactions of Schiff's base adducts formed in solution. CID MS/MS of these adducts yield primarily N-terminally directed a- and b-type "sequence" ions. Potential structures of the b1 ion, not usually observed in the product ion spectra of protonated peptide ions, were examined using ab initio calculations. A cyclic 5 membered pyrrolinone, formed by a neighboring group participation reaction from an enamine precursor, was predicted to be the primary product.     

Unusual atmospheric pressure chemical ionization conditions for detection of organic peroxides

Organic peroxides such as the cumene hydroperoxide I (M(r) = 152 u), the di-tert-butyl peroxide II (M(r) = 146 u) and the tert-butyl peroxybenzoate III (M(r) = 194 u) were analyzed by atmospheric pressure chemical ionization mass spectrometry using a water-methanol mixture as solvent with a low flow-rate of mobile phase and unusual conditions of the source temperature (< or =50 degrees C) and probe temperature (70-200 degrees C). The mass spectra of these compounds show the formation of (i) an [M + H](+) ion (m/z 153) for the hydroperoxide I, (ii) a stable adduct [M + CH(3)OH(2)](+) ion (m/z 179) for the dialkyl peroxide II and (iii) several protonated adduct species such as protonated molecules (m/z 195) and different protonated adduct ions (m/z 227, 389 and 421) for the peroxyester III. Tandem mass spectrometric experiments, exact mass measurements and theoretical calculations were performed for characterize these gas-phase ionic species. Using the double-well energy potential model illustrating a gas-phase bimolecular reaction, three important factors are taken into account to propose a qualitative interpretation of peroxide behavior toward the CH(3)OH(2) (+), i.e. thermochemical parameters (DeltaHdegrees(reaction)) and two kinetic factors such as the capture constant of the initial stable ion-dipole and the magnitude of the rate constant of proton transfer reaction into the loose proton bond cluster.     

Discrimination of isomers by liquid ionization mass spectrometry with techniques of collisional activation and adduct ion formation

Liquid ionization mass spectrometry is a soft ionization technique used with liquid samples under atmospheric pressure. It facilitates the handling of reagents and the observation of ion–molecule reactions in the ion source. The differentiation of isomers by characteristic fragment ions, for example those resulting from asymmetrical cleavage of a cyclobutane ring, and by molecular adduct ion formation was studied. The samples studied were cyclobutane derivatives, alkyl 4-(3-oxo-3-pIienyl-l-aIkenyl)benzoate dimers, and reagents having two functional groups were used to produce adduct ions to clarify the difference between isomers. The reagents act on a sample molecule at two functional groups to form hydrogen bonds. Some correlations were observed between the structure of the sample and the relative abundances of molecular adduct ions and also fragment ions produced by collisionally activated dissociation.