Solvent effects on methyl transfer reactions. 2. The reaction of amines with trimethylsulfonium salts.

The reaction of ammonia and pyridine with trimethylsulfonium ion has been studied in gas phase and solution. Density functional theory at the B3LYP/6-31+G level was used to describe the energy changes along the reaction coordinate in the gas phase, and the self-consistent isodensity polarizable continuum model (SCI-PCM) was used to calculate the effect of cyclohexane and dimethyl sulfoxide as the solvent on the energy changes. The effect of water as the solvent was studied using the Monte Carlo free energy perturbation method. The reaction with both ammonia and pyridine follows a similar rather convoluted path in gas phase, with the formation of several reaction complexes before and after the formation of the transition state. All the species found in gas phase persist in cyclohexane, yielding a reaction path very similar to that in gas phase but with significant differences in the relative energy of the critical points. In DMSO, the energy profile is greatly simplified by the disappearance of several of the species found in gas phase and in cyclohexane. The activation free energy increases with the polarity of the solvent in both reactions. Increasing the polarity of the solvent also increases the exothermicity of the reaction of trimethylsulfonium ion with ammonia and reduces it in the reaction with pyridine. In water, the free energy profile follows the same trend as found for DMSO, and free energy of activation is calculated to be larger by about 2-3 kcal/mol. This is in good agreement with an experimental measurement of the effect of solvent on the rate of reaction.     

Electrospray ionization mass spectrometry studies of rhenium(I) bipyridyl complexes

Electrospray ionization mass spectrometry (ESMS) has been employed to study the formation of fragment ions of a series of rhenium(I) bipyridyl complexes [(4,4'-di-(COOEt)2-bpy) Re(CO)3XPyPF6], where bpy is 2,2'-bipyridine, Py is pyridine, and X is H, 4-methyl, 3-methyl, 4-hydroxyl, 3-hydroxyl, 4-amino, or 3-amino of the pyridine ligand. The effects of substituents (X) on the stabilities of the complexes have been investigated with the increase of fragmentor voltages. For different X, the stabilities of the complexes increase as X become more electron-donating from H to CH3, OH, and NH2. For the same substituent, the p-substituted pyridines have stronger stabilizing effect than the corresponding m-substituted ones. Ligand exchange reaction was found in acetonitrile, where the pyridine ligand has been replaced by the solvent indicated by the formation of [M-PF6- XPy+MeCN]+ in the fragmentation.     

Combination of ultrasound‐assisted ethyl chloroformate derivatization and switchable solvent liquid‐phase microextraction for the sensitive determination of l‐methionine in human plasma by GC–MS

A green and fast analytical method for the determination of l ‐methionine in human plasma is presented in this study. Preconcentration of the analyte was carried out by switchable solvent liquid phase microextraction after ethyl chloroformate derivatization reaction. Instrumental detection of the analyte was performed by means of gas chromatography–mass spectrometry. N,N‐Dimethyl benzylamine was used in the synthesis of switchable solvent. Protonated N,N‐dimethyl benzylamine volume, volume/concentration of sodium hydroxide, and vortex period were meticulously fixed to their optimum values. Besides, ethyl chloroformate, pyridine, and ethanol volumes were optimized in order to get high derivatization yield. After the optimization studies, limit of detection and quantitation values were attained as 3.30 and 11.0 ng/g, respectively, by the developed switchable solvent liquid phase microextraction gas chromatography–mass spectrometry method that corresponding to 76.7‐folds enhancement in detection power of the gas chromatography–mass spectrometry system. Applicability and accuracy of the switchable solvent liquid phase microextraction–gas chromatography–mass spectrometry method were also checked by spiking experiments. Percent recovery results were ranged from 97.8 to 100.5% showing that human plasma samples could be analyzed for its l ‐methionine level by the proposed method.     

Dimethyl cuprate undergoes C-C bond coupling with methyliodide in the gas phase but dimethyl argenate does not

Multistage mass spectrometry experiments have been used to synthesize and study the reactions of (CH3)2M-(M = Cu and Ag) with methyl iodide in the gas phase. While the dimethylcuprate ion (M = Cu) reacts with CH3I via C-C bond cross coupling, its silver congener is unreactive. The experimental results are consistent with MP2/6-31++G** ab initio calculations, which reveal that the preferred mechanism for Cu involves the formation of a T-shaped Cu transition state. [reaction: see text]     

Comparison of the Reactivity of the Three Distonic Isomers of the Pyridine Radical Cation Toward Tetrahydrofuran in Solution and in the Gas Phase

The reactivity of the three distonic isomers of the pyridine radical cation toward tetrahydrofuran is compared in solution and in the gas phase. In solution, the distonic ions were generated by UV photolysis at 300 nm from iodo-precursors in acidic 50:50 tetrahydrofuran/water solutions. In the gas phase, the ions were generated by collisionally activated dissociation (CAD) of protonated iodo-precursors in an FT-ICR mass spectrometer, as described in the literature. The same major reaction, hydrogen atom abstraction, was observed in solution and in the gas phase. Attempts to cleave the iodine atom from the 2-iodopyridinium cation in the gas phase and in solution yielded the 2-pyridyl cation in addition to the desired 2-dehydropyridinium cation. In the gas phase, this ion was ejected prior to the examination of the desired ion’s chemical properties. This was not possible in solution. This study suggests that solvation effects are not significant for radical reactions of charged radicals. On the other hand, the even-electron ion studied, the 2-pyridyl cation, shows substantial solvation effects. For example, in solution, the 2-pyridyl cation forms a stable adduct with tetrahydrofuran, whereas in the gas phase, only addition/elimination reactions were observed.      

Experimental and theoretical study of the gas-phase interaction between ionized nitrile sulfides and pyridine

The gas-phase reactivity of ionized nitrile sulfides, R-C≡N⁺-S^·, towards neutral pyridine was studied both experimentally (six sector hybrid mass spectrometer) and theoretically (density functional theory and Møller-Plesset ab initio calculations). An ionized sulfur atom transfer and a cycloaddition process respectively yielding ionized pyridine N-thioxide and a thiazolopyridinium cation were observed. Whereas the very efficient S^·+ transfer reaction probably involves the intermediacy of several ion-molecule complexes, the thiazolopyridinium ion formation is likely to be initiated by an electrophilic attack of the R-C≡N⁺-S^· ion on the nitrogen atom of pyridine; the resulting intermediate then undergo an intramolecular substitution of an α-hydrogen atom by the sulfur atom.     

<Emphasis Type="Italic">AB initio</Emphasis> quantum chemical study of the reaction mechanism of ethynide ion formation in the C<Subscript>2</Subscript>H<Subscript>2</Subscript>/MOH/DMSO system (M = Li,Na, K)

The reaction mechanism of the formation of alkali metal ethynides C₂H₂ + MOH → C₂HM + H₂O (M = Li, Na, K) is studied for the gas phase (MP2/6-311++G**//RHF/6-31+G*) and also with regard to the solvent effect of dimethyl sulfoxide (DMSO) included within the continuum model. Among all acetylene complexes with alkali metal hydroxides considered (C₂H₂·MOH (M = Li, Na, K)), only the complex with KOH is thermodynamically stable in DMSO solution. The formation of this structure results in activation of the acetylene molecule towards electrophilic attack. The formation of alkali metal ethynide in solution is also thermodynamically favorable only in the system with potassium hydroxide of a whole series of metals considered. Further, the ethynide ion can interact in KCCK·HOH systems.     

Theoretical investigation of formation mechanism of bipyridyl molecule on Ni(111) surface: implication for synthesis of N-doped graphene from pyridine

The formation mechanism of bipyridyl molecule catalyzed by nickel catalyst with pyridine precursor has been studied using density functional theory calculations. The formation of bipyridyl on Ni(111) surface from two pyridine molecules is considered as the initial process of N-doped graphene growth, and the minimum energy pathway for the formation has been investigated in detail. The whole formation processes mainly includes three steps, i.e., the dehydrogenation of the first pyridine, adsorption and dehydrogenation of the second pyridine, and formation of the bipyridyl molecule. It is found that the C-H bond of pyridine could be selectively dissociated while the C-C and C-N bond connections are retained during the catalytic processes. The N-doped graphene formed by pyridine only contains pyridine-like nitrogen atoms, suggesting a possible way to produce N-doped graphene with pure pyridine-like nitrogen atoms. The comparison of formation mechanisms between bipyridyl and biphenyl molecules was carried out, and the results imply a lower temperature process for synthesis of N-doped graphene from pyridine than that for graphene from benzene.     

Application of electrospray ionization mass spectrometry for studies of anionic σ-adducts of aromatic nitrocompounds

It has been found that anionic σ-adducts formed in the reactions of highly electrophilic nitroarenes with selected carbanions, alkoxide anions and amines can be transferred to the gas phase using an electrospray ion source and the resulting ions can be studied using various mass spectrometry techniques in the solvent-free environment. This method can also be used for estimating the relative equilibrium constants of the σ-adduct formation reactions in a liquid phase.     

Mechanism of the oxidation of organic sulphides by permanganate ion

The kinetics of the oxidation of number of aryl methyl, alkyl phenyl, dialkyl and diphenyl sulphides by permanganate ion to yield the sulphoxides, have been studied. The reaction is first order with respect to the sulphide and permanganate and is independent of hydrogen ion concentration. The reaction exhibited negative polar reaction constants and a small degree of steric hindrance. The lack of solvent isotope effect and the observed solvent effect ( m = 0.39 for McSPh) are explained by an electrophilic attack of permanganate-oxygen on the sulphide yielding a polar transition state. A moderate anchimeric assistance was observed in the oxidation ofo-C00Me ando-C00H substituted methyl phenyl sulphide. A mechanism involving a one-step electrophilic oxygen transfer from permanganate ion to the sulphide and a polar product-like transition state, has been proposed.     

Dimerization of ionized 4‐(methyl mercapto)‐phenol during ESI,APCI and APPI mass spectrometry

A novel ion/molecule reaction was observed to occur under electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo ionization (APPI) conditions, leading to dimerization of ionized 4‐(methyl mercapto)‐phenol followed by fast H^· loss. The reaction is particularly favored during ESI, which suggests that this ion/molecule reaction can occur both in the solution inside the ESI‐charged droplets and in the gas‐phase environment of most other atmospheric pressure ionization techniques. The dimerization reaction is inherent to the electrolytic process during ESI, whereas it is more by ion/molecule chemistry in nature during APCI and APPI. From the tandem mass spectrometry (MS/MS) data, accurate mass measurements, hydrogen/deuterium (H/D) exchange experiments and density functional theory (DFT) calculations, two methyl sulfonium ions appear to be the most likely products of this electrophilic aromatic substitution reaction. The possible occurrence of this unexpected reaction complicates mass spectral data interpretation and can be misleading in terms of structural assignment as reported herein for 4‐(methyl mercapto)‐phenol. Copyright © 2009 John Wiley & Sons, Ltd.     

A theoretical study on nitration mechanism of benzene and solvent effects

Aromatic nitration is an important and canonical example of electrophilic substitution in organic chemistry. The research on nitration mechanism is also very important for synthesis of explosives since benzene molecule is a basic unit to build up into the energetic material. Besides the electrophilic substitution mechanism, there is an electron transfer mechanism[1,2]. The nitronium ion (NO+ 2), however, is a generally accepted active nitrating agent in the aromatic nitration. Therefore, the …     

Formation of [M + 15](+) ions from aromatic aldehydes by use of methanol: in-source aldolization reaction in electrospray ionization mass spectrometry

Unexpected [M + 15]⁺ ions were formed during the analysis of aromatic aldehydes by use of methanol in positive‐ion electrospray ionization mass spectrometry. Aromatic aldehydes with electron‐withdrawing groups or electron‐donating groups were all tested to make sure the universality. All the aromatic aldehydes studied with methanol as the solvent could generate [M + 15]⁺ ion, and for most of them, the [M + 15]⁺ ion was more intense than the [M + H]⁺ ion. Deuterium‐labeling experiment, high‐performance liquid chromatography–MS experiment, collision‐induced dissociation experiment, and theoretical calculations were performed to identify the formation of [M + 15]⁺ ion. The proposed reaction mechanism is a gas‐phase aldol reaction between protonated aromatic aldehydes and methanol occurring in electrospray source. Understanding and using this unique gas‐phase ion/molecule reaction can indeed offer a novel and fast approach for the direct identification of aromatic aldehydes. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of liquid phase composition on salt cluster formation in positive ion mode electrospray mass spectrometry: implications for clustering mechanism in electrospray

Potassium bromate salt clusters, [KBrO3]nKx(x+), formed by electrospray ionization were studied as a function of solution properties. Clusters with up to 4 positive charges were observed. Their abundance, charge state and distribution were shown to vary with the organic solvent in solution. The effects of 7 solvents, including methanol, ethanol, isopropanol, acetonitrile, acetone, pyridine, and 1,4-dioxane, were thoroughly investigated. Solvents with a low dielectric constant and a high viscosity seem to favor clustering in solution but do not systematically allow high charge state ion formation. On the other hand, cluster charge reduction during desolvation was not correlated with solvent cation affinity over the range of solvents examined. However, ion distribution in mass spectra could be rationalized as a combination of these two competing phenomena. Charge state increases with the cluster size but may be reduced during ion desolvation when high cation affinity solvent molecules are actually involved in the ion solvation shell. This assumption could be envisaged in either Iribarne or Dole mechanisms of ion release in the gas phase. However, intensity profiles of multiply charged clusters could only be understood in terms of the ion evaporation mechanism.     

Ion/molecule reactions in a miniature RIT mass spectrometer

Ion/molecule reactions were explored in a newly developed miniature mass spectrometer fitted with a rectilinear ion trap (RIT) mass analyzer. The tandem mass spectrometry performance of this instrument is demonstrated using collision induced dissociation (CID) and ion/molecule reactions. The latter includes Eberlin transacetalization reactions and electrophilic additions. Selective detection of the chemical warfare simulant dimethyl methyl phosphonate (DMMP) was achieved through selective Eberlin reactions of its characteristic phosphonium fragment ion CH3OP(+)(O)CH3 (m/z 93), with 1,4-dioxane or 1,3-dioxolane. Efficient adduct formation as a result of electrophilic attack by the phosphonium ion on various nucleophilic reagents, including 1,1,3,3-tetramethyl urea, methanesulfonic acid methyl ester, dimethyl sulfoxide and methyl salicylate, was also observed using the RIT device. The product ions of these reactions were analyzed using CID and the characteristic fragmentation patterns of the ionic addition products were recorded using multiple-stage experiments in the miniature RIT instrument. This study clearly demonstrates that a small, home-built, miniature RIT mass spectrometer can be used to perform analytically useful ion/molecule reactions and also that instruments like this have the potential to provide a portable platform for in situ detection of organophosphorus esters and related compounds with high specificity using tandem mass spectrometry.     

Using a nanoelectrospray-differential mobility spectrometer-mass spectrometer system for the analysis of oligosaccharides with solvent selected control over ESI aggregate ion formation

Differential mobility spectrometry (DMS), also commonly referred to as high field asymmetric waveform ion mobility spectrometry (FAIMS) is a rapidly advancing technology for gas-phase ion separation. The interfacing of DMS with mass spectrometry (MS) offers potential advantages over the use of mass spectrometry alone. Such advantages include improvements to mass spectral signal/noise, orthogonal/complementary ion separation to mass spectrometry, enhanced ion and complexation structural analysis, and the potential for rapid analyte quantitation. In this report, we demonstrate the successful use of our nanoESI-DMS-MS system, with a methanol drift gas modifier, for the separation of oligosaccharides. The tendency for ESI to form oligosaccharide aggregate ions and the negative impact this has on nanoESI-DMS-MS oligosaccharide analysis is described. In addition, we demonstrate the importance of sample solvent selection for controlling nanoESI oligosaccharide aggregate ion formation and its effect on glycan ionization and DMS separation. The successful use of a tetrachloroethane/methanol solvent solution to reduce ESI oligosaccharide aggregate ion formation while efficiently forming a dominant MH(+) molecular ion is presented. By reducing aggregate ion formation in favor of a dominant MH(+) ion, DMS selectivity and specificity is improved. In addition to DMS, we would expect the reduction in aggregate ion complexity to be beneficial to the analysis of oligosaccharides for other post-ESI separation techniques such as mass spectrometry and ion mobility. The solvent selected control over MH(+) molecular ion formation, offered by the use of the tetrachloroethane/methanol solvent, also holds promise for enhancing MS/MS structural characterization analysis of glycans.     

Bromine formation in solid NaBr/KNO<Subscript>3</Subscript> mixture and assay of this reaction via bromination of activated aromatics

Bromine formation in the mixture of solid NaBr and KNO₃ was observed and the process was studied in different acidified organic solvent–water mixtures by monitoring the bromination of acetanilide and other compounds, containing activated aromatic substituents. This assay is based on fast bromination reaction of these aromatic compounds, as differently from the assay of Br₂, the brominated aromatics can be easily determined by conventional gas chromatography–mass spectrometry (GC–MS) methods. It was found that bromine was generated autocatalytically on the surface of salt crystals and the reaction was characterized by a lag period, the duration of which depended on reaction conditions, and importantly on the type of the organic solvent in the reaction mixture. As the bromine formation could be easily controlled by reaction conditions, it was suggested that the studied reaction might have practical applications as an environmentally friendly and economically feasible bromination method. It was also shown that the bromination of aromatics followed the mechanism of classical electrophilic aromatic substitution reaction.     

The 1,3-dipolar cycloaddition of 1H-pyridinium-3-olate and 1-methylpyridinium-3-olate with methyl acrylate: a density functional theory study

The 1,3-dipolar cycloaddition reaction of 1-substituted pyridinium 3-olates with methyl acrylate is studied using density functional theory (DFT) method at the B3LYP/6-31G(d) level. The molecular mechanisms of the possible stereo- and regio-chemical pathways are characterized and explored. Solvent effects are also evaluated by the polarizable continuum model (PCM). Analysis of the results shows that there are relevant differences in the reaction pathways between the gas phase and with solvent. Only results in solvent phase are in accord with literature experimental results where 6-substituted 8-azabicyclo[3.2.1]oct-3-en-2-ones are formed preferentially. These polar cycloaddition reactions take place through highly asynchronous transition states in which nucleophilic attack by C2/C6 of the pyridinium-3-olates on the more electrophilic centre of the methyl acrylate initiates the process. Analysis of global and local indexes of the reactants is evaluated in order to explain the observed regioselectivity. Rate constants are calculated at room temperature using conventional transition state theory.     

Electrospray ionization mass spectrometry: a major tool to investigate reaction mechanisms in both solution and the gas phase

Electrospray ionization mass spectrometry (ESI-MS), in conjunction with its tandem version ESI-MS/MS, is now established as a major tool to study reaction mechanisms in solution. This suitability results mainly from the ability of ESI to "fish" ions directly from solution to the gas phase environment of mass spectrometers. In this review, we summarize recent studies from our laboratory on the use of on-line monitoring by ESI-MS ion fishing of several types of reactions that permitted us to follow how these reactions progress as a function of both time and conditions using the ultra-high sensitivity and speed of ESI-MS to detect and even characterize transient reaction intermediates. We also show that the intrinsic reactivity of each key gaseous species fished by ESI can be further investigated via ESI-tandem mass spectrometry experiments, searching for the most active species via gas-phase ion/molecule reactions. In the gas-phase, solvent and counter-ion effects are absent. These studies often permit a detailed overview of major steps via the interception, characterization and reactivity investigation of key reaction players.