Ion–molecule reactions of methoxymethyl cations with some organic substrates studied by ion cyclotron resonance spectrometry

The reactions of methoxymethyl cations generated from dimethyl ether with propene, butene-2, vinyl methyl ether, acetaldehyde and acetone have been studied. The collision complexes, generated with the olefines, may eliminate an olefine, a methanol and a formaldehyde molecule as shown by double resonance experiments. From deuterium labelling it is found, that in the cases of propene and butene-2 the elimination of an olefine is accompanied by an extensive H/D interchange in the collision complexes, which has been shown not to occur in the long-lived reactant methoxymethyl cations if the internal energy of the methoxymethyl cations is less than 2.3 eV. The H/D interchange in these collision complexes is reduced in the elimination of methanol and is almost completely suppressed in the elimination of formaldehyde. In reactions with vinyl methyl ether, however, the eliminations of methanol and formaldehyde from the corresponding collision complexes appear to proceed with extensive H/D interchange. These observations point to acyclic collision complexes rather than 4-membered ring complexes. The collision complexes generated with acetaldehyde and acetone decompose by elimination of formaldehyde only. Deuterium labelling has shown that the formaldehyde molecule contains the original methylene group of the reactant methoxymethyl cations. In addition, ¹⁸O labelling in acetone has shown that the original oxygen atom of the methoxymethyl cations is retained completely in the eliminated formaldehyde. These observations exclude any formation of 4-membered ring collision complexes and can only be explained by acyclic complexes. Possible mechanisms of all reactions mentioned are discussed in the light of these results.     

Gas phase anionic ipso substitution reactions of some alkyl phenyl ethers

It is shown by ¹⁸O labelling that phenoxide anions are formed both by an S_N2 and a nucleophilic aromatic substitution mechanism in the reaction of OH^? with methyl phenyl ether. These mechanisms are of minor importance in the ethyl phenyl ether system where phenoxide anions are generated almost exclusively by an E₂ mechanism.     

The mechanism of CO loss in the electron impact-induced fragmentation of benzoin and its methyl ether

The electron impact-induced fragmentation of benzoin methyl ether gives rise to the formation of an m/e 91 fragment ion which is not present in the mass spectrum of benzoin. Deuterium and ¹³C labelling, as well as low energy experiments, revealed that this ion is formed from [M – benzoyl]⁺ by transfer of both the ether methyl group and the hydrogen atom from the α-position to the adjacent phenyl ring followed by loss of CO and hydrogen.     

High resolution mass spectrometry—I. Some substituted δ-lactones

The mass spectra of some δ-lactones substituted in various positions by methyl groups have been studied both by accurate mass measurements at high resulution and by deuterium labelling. The loss of carbon dioxide has been shown to be important only for a mono-substituted lactone. A fragmentation mode common to all the lactones studied is the elimination of the ring oxygen atom, plus the adjacent carbon atom with its substituents, as a neutral carbonyl molecule such as formaldehyde, acetaldehyde or acetone. Deuterium labelling has uncovered the existence of a rearrangement involving hydrogen transfer in an even-electron ion, and a mechanism involving a six-membered transition state is proposed for this. The bond fissions, common to all the lactones, by which the principal ions in the mass spectra arise, are summarised.     

Ion-molecule reactions of oxygenated chemical ionization reagents with vincamine

The ion-molecule reactions of ions from acetone, dimethyl ether, 2-methoxyethanol, and vinyl methyl ether with vincamine were investigated. Reactions with dimethyl ether result in [M+13]⁺ and [M+45]⁺ products, reactions with 2-methoxyethanol produce [M+13]⁺ and [M+89]⁺ ions, and reactions with acetone or vinyl methyl ether ions generate predominantly [M+43]⁺ ions. Collision-activated dissociation and deuterium labeling experiments allowed speculation about the product structures and mechanisms of dissociation. The methylene substitution process was shown to occur at the hydroxyl oxygen and the phenyl ring of vincamine for dimethyl ether reactions, but the methylene substitution process was not favored at the hydroxyl oxygen for the 2-methoxyethanol reactions, instead favored at the 12 phenyl position. The reaction site is likely different for the 2-methoxyethanol ion due to its capability for secondary hydrogen-bonding interactions. For the [M+45]⁺ and [M+89]⁺ ions, evidence suggests that charge-remote fragmentation processes occur from these products. In general, the use of dimethyl ether ions or 2-methoxyethanol ions for ionmolecule reactions prove highly diagnostic for the characterization of vincamine; both molecular weight and structural information are obtained. Limits of detection for vincamine with dimethyl ether chemical ionization via this technique on a benchtop ion trap gas chromatography-tandem mass spectrometer are in the upper parts per trillion range.     

Mechanism of homogeneously and heterogeneously catalysed Meerwein-Ponndorf-Verley-Oppenauer reactions for the racemisation of secondary alcohols

The mechanism of hydrogen transfer from alcohols to ketones, catalysed by lanthanide(III) isopropoxides or zeolite Beta has been studied. For the lanthanide catalysed reactions, (S)-1-phenyl-(1-(2)H(1))ethanol and acetophenone were used as case studies to determine the reaction pathway for the hydrogen transfer. Upon complete racemisation all deuterium was present at the 1-position, indicating that the reaction exclusively takes place via a carbon-to-carbon hydrogen transfer. Zeolite Beta with different Si/Al ratios was applied in the racemisation of (S)-1-phenylethanol. In this case the racemisation does not proceed via an oxidation/reduction pathway but via elimination of the hydroxy group and its re-addition. This mechanism, however, is not characteristic for all racemisation reactions with zeolite Beta. When 4-tert-butyl cyclohexanone is reduced with this catalyst, a classical MPV reaction takes place exclusively. This demonstrates that zeolite Beta has a substrate dependent reaction pathway.     

Application of iridium pincer complexes in hydrogen isotope exchange reactions

Iridium pincer complex catalyzed hydrogen to deuterium exchange could be achieved using aromatic and heteroaromatic substrates. The reactions proceed under mild conditions and with high regioselectivity. The efficiency of the hydrogen isotope exchange reaction depends on the electronic properties of the pincer complex catalyst.     

Oxygen-atom transfer from carbon dioxide to a Fischer carbene at (PNP)Ir

Dehydrogenation of the dihydride (PNP)IrH2 with norbornylene in the presence of t-butyl methyl ether leads to formation of an iridium(I) Fischer carbene complex, (PNP)Ir C(H)OtBu, by double C-H activation and loss of H2. The square planar pincer-type carbene effects quantitative oxygen-atom transfer from CO2 (1 atm) at ambient temperature to generate t-butyl formate and (PNP)Ir-CO. The iridium carbene reacts similarly with carbonyl sulfide and phenyl isocyanate, causing sulfur-atom and nitrene-group transfer, respectively. In the absence of a hydrogen acceptor, thermolysis of (PNP)IrH2 in t-butyl methyl ether under an atmosphere of CO2 also results in the formation of (PNP)Ir-CO and oxidation of t-butyl methyl ether to t-butyl formate via an iridium carbene. Preliminary mechanistic studies indicate that these reactions proceed through an intermediate four-membered metallalactone.     

Mass spectrometric investigation of benzyliderieaniline

The mass spectral fragmentation of benzylideneaniline has been studied by deuterium labelling. Under electron impact, molecular ions undergo simple fission at the phenyl–N, phenyl–C and C?N bonds, hydrogen migration reactions, and skeletal rearrangement fragmentations. Except in the skeletal rearrangement reactions, hydrogen scrambling does not feature in benzylideneaniline upon electron impact.     

Photocatalytic Dehalogenative Deuteration of Halides over a Robust Metal–Organic Framework

Deuterium labelling of organic compounds is an important process in chemistry. We report the first example of photocatalytic dehalogenative deuteration of both arylhalides and alkylhalides (40 substrates) over a metal–organic framework, MFM-300(Cr), using CD₃CN as the deuterium source at room temperature. MFM-300(Cr) catalyses high deuterium incorporation and shows excellent tolerance to various functional groups. Synchrotron X-ray powder diffraction reveals the activation of halogenated substrates via confined binding within MFM-300(Cr). In situ electron paramagnetic resonance spectroscopy confirms the formation of carbon-based radicals as intermediates and reveals the reaction pathway. This protocol removes the use of precious-metal catalysts from state-of-the-art processes based upon direct hydrogen isotope exchange and shows high photocatalytic stability, thus enabling multiple catalytic cycles.     

Evidence suggesting the occurrence of [2+3] cycloaddition products in the ion/molecule reactions of suitably substituted allyl cations and olefins

The ion/molecule reactions of allyl cations and 2-methoxyallyl cations with vinyl methyl ether, 1-chloro-2-ethoxyethene and 1,2-dimethoxyethene are discussed in terms of [2+3] cycloaddition reactions. Deuterium labelling of the cations has been used for the study of the reaction mechanisms. The appearance of various product ions in these ion/molecule reactions lead to the suggestion that in reactions of allyl cations with alkenes non-cyclic [C₅H₅]⁺ product ions are formed preferentially, but that in reactions of 2-methoxyallyl cations with alkenes a significant part of the product ions are methoxycyclopentadienyl cations. These observations are ascribed to the stabilizing effect of the methoxy group with regard to the positive charge in the product ions.     

Allylic halogenation of unsaturated amino acids

A range of dehydro amino acid derivatives has been prepared and subjected to halogenation using either molecular bromine or chlorine, or NBS. Allylic halogenation of the unsaturated amino acid side chains occurs through radical bromination with NBS. The procedure is complementary to treatment with chlorine, which also affords allyl halides. This latter and unusual reaction is shown through a deuterium labelling study to proceed via an ionic mechanism. The choice of NBS or chlorine for allyl halide synthesis is shown to depend on the potential to avoid competing reactions, such as halolactonization of leucine derivatives with chlorine, and hydrogen abstraction and bromine incorporation at multiple sites on treatment of isoleucine derivatives with NBS. The synthetic utility of the allyl halides prepared in this study is indicated through the synthesis of a cyclopropyl amino acid derivative and the extension of the carbon skeleton of an amino acid side chain.     

Skeletal rearrangements on chemical ionization of dibenzyl ether and derivatives

Protonated molecular ions of dibenzyl ether, formed by chemical ionization using hydrogen and isobutane as reagent gases, undergo skeletal rearrangements to lose water and formaldehyde, both in the ion source and the flight path. The rearrangements have been elucidated by deuterium labelling and chemical substitution. The water lost contains the reagent proton and an aromatic hydrogen atom, and the aromatic hydrogen atoms have been shown to be mobile prior to the reaction. It is proposed that the skeletal rearrangement for water loss is initiated by protonation on the ether oxygen atom, followed by benzyl migration. The formaldehyde lost contains benzylic hydrogen atoms exclusively, and it is proposed that the skeletal rearrangement is preceded by hydrogen rearrangement of an oxygen protonated molecular ion to a ring protonated molecular ion. Daughter ion structures are supported by comparisons of their collision induced dissociation spectra with those of isomeric ions prepared by alternative routes.     

Density functional theory gas- and solution-phase study of nucleophilic substitution at di- and trisulfides

 Density functional calculations indicate that nucleophilic substitution in the thiolate–disulfide and thiolate–trisulfide exchange reactions proceeds by an addition–elimination pathway. Solution calculations were performed using B3LYP/6-31+G* and the polarized continuum method. These solution-phase calculations indicate that for the reactions where the sulfur under attack bears a hydrogen atom, the substitution proceeds via an addition–elimination mechanism; however, when a methyl group is attached to the sulfur under attack, the S_N2 mechanism is predicted. Received: 12 October 2001 / Accepted: 28 November 2001 / Published online: 8 April 2002     

Mass spectrometric study of hexamethyldisilazane and some of its N-substituted derivatives

The electron-impact-induced decomposition of the title compounds has been investigated in detail. Deuterium labelling was used to study the mechanisms of fragmentation and the structures of ions generated. Hydrogen, methyl and phenyl group migrations to one of the silicon atoms were observed as significant secondary processes. These processes are usually γ-transitions, from which it is inferred that these rearrangements occur via 4-membered cyclic transition complexes.     

A solid-phase iridium-based ortho-exchange catalyst for the one-step labelling of aromatic substrates with deuterium

A wide range of aromatic compounds containing suitable directing groups can be labelled efficiently with deuterium using isotopic exchange catalysed by an easily prepared polystyrene based ortho-exchange catalyst. The labelling reactions can be carried out efficiently at ambient temperature by simple stirring of the substrate and catalyst under a deuterium atmosphere for a few hours. Isolation consists of a simple filtration and evaporation of the solvent. Deuterium is incorporated with ortho-regiospecificity.     

Stereo‐ and Regioselective Direct Multi‐Deuterium‐Labeling Methods for Sugars

Deuterium‐labeled sugars can be utilized as powerful tools for the architectural analyses of high‐sugar‐containing molecules represented by the nucleic acids and glycoproteins, and chiral building blocks for the syntheses of new drug candidates (heavy drugs) due to their potential characteristics, such as simplifying the ¹H NMR spectra and the stability of C? D bonds compared with C? H bonds. We have established a direct and efficient synthetic method of deuterated sugars from non‐labeled sugars by using the heterogeneous Ru/C‐catalyzed H–D exchange reaction in D₂O under a hydrogen atmosphere with perfect chemo‐ and stereoselectivities. The direct H–D exchange reaction can selectively proceed on carbons adjacent to the free hydroxyl groups, and the deuterium labeling of various pyranosides (such as glucose and disaccharides), as well as furanosides, represented by ribose and deoxyribose was realized. Furthermore, the desired number of deuterium atoms can be freely incorporated into selected positions by the site‐selective protection of the hydroxyl groups using acetal‐type protective groups because the deuterium exchange reaction never proceeds on positions adjacent to the protected hydroxyl groups.     

Fast Reactions of Atom Substitution from Polyatomic Molecules and Solid Salts by Thermally Equilibrated Atomic Reactants

A new class of fast thermal gas-phase reactions of the direct substitution of atoms in polyatomic molecules by atomic reactants is discovered. The Arrhenius parameters are determined for the reactions of atomic deuterium with a number of hydrogen-containing compounds, occurring via the direct substitution of hydrogen atoms and via the abstraction of hydrogen atoms. Fast substitution of alkali metal atoms from the crystals of their salts for the reaction chain carriers of hydrogen flames is found. The importance of reactions of these types in chain combustion is demonstrated. The kinetic isotope effects of hydrogen atom abstraction from hydrocarbon molecules by hydrogen and deuterium atoms are studied. A method for the kinetic studies of free atoms and radicals is developed, which takes into account the role of longitudinal diffusion in the jet and does not require the knowledge of the concentrations of atoms and radicals or the rate constants of other reactions.     

Studies on the preparation and exchange reactions of 5-deuterated uracils

The mechanism of base catalyzed proton exchange at the 5-position of uracil and its N-methylated derivatives has been studied. These reactions proceed by addition — elimination across the 5,6-double bond when the 1-nitrogen is substituted with a methyl group, or with anchimeric assistance of the N-1 anion if the 1-position is unsubstituted. The base catalyzed hydrolyses of 1,3-dimethyluracil and 3-methyluracil also appear to proceed through hydrated intermediates. A facile method for an acid catalyzed preparation of 5-deuterated uracils is described as well as a simple and accurate method for analysis of deuterium content.     

Gas-phase hydrogen/deuterium exchange of 5′- and 3′-mononucleotides in a quadrupole ion trap: Exploring the role of conformation and system energy

Gas-phase hydrogen/deuterium (H/D) exchange reactions for deprotonated 2'-deoxy-5'-monophosphate and 2'-deoxy-3'-monophosphate nucleotides with D(2)O were performed in a quadrupole ion trap mass spectrometer. To augment these experiments, molecular modeling was also conducted to identify likely deprotonation sites and potential gas-phase conformations of the anions. A majority of the 5'-monophosphates exchanged extensively with several of the compounds completely incorporating deuterium in place of their labile hydrogen atoms. In contrast, most of the 3'-monophosphate isomers exchanged relatively few hydrogen atoms, even though the rate of the first two exchanges was greater than observed for the 5'-monophosphates. Mononucleotides that failed to incorporate more than two deuterium atoms under default reaction conditions were often found to exchange more extensively when reactions were performed under higher energy conditions. Integration of the experimental and theoretical results supports the use of a relay exchange mechanism and suggests that the exchange behavior depends highly on the identity and orientation of the nucleobase and the position and flexibility of the deprotonated phosphate moiety. These observations also highlight the importance of the distance between the various participating groups in addition to their gas-phase acidity and basicity.