Stereochemistry of retro-diel-salder fragmentation in gas-phase ions formed by chemical ionization

Retro Diels Alder fragmentation is highly stereospecific in the diones 1 under chemical ionization conditions, both with methane and isobutane as the reagent gases. Only the cis-isomers yield abundant protonated diene and quinone ions. The isotope effect indicates preferential protonation on a CO oxygen, and a subsequent H-migration prior to the formation of the protonated diene cations in the cis isomers.     

Energetics of retro-Diels–Alder fragmentation in limonene as characterized by surface-induced dissociation,and energy- and angle-resolved mass spectrometry

Ionized limonene and related isomeric compounds have been examined by collisional activation at both gaseous and solid targets. The gas-phase collision-induced dissociation (CID) experiments were performed as a function of collision energy and scattering angle and the surface-induced dissociation (SID) experiments as a function of collision energy, in order to vary systematically the internal energy deposited in the molecular ion. The virtual absence of retro-Diels–Alder (RDA) fragmentation upon conventional CID, as compared to its importance in the electron impact (EI) mass spectrum, the subject of a study by Boyd and coworkers, was confirmed. However, as the ion internal energy was increased by raising the collision energy or the scattering angle, RDA fragmentation was observed and it became a dominant mode of fragmentation for SID at collision energies in the range of 25–50 eV. The energy deposited into the colliding ion in the SID technique is compared with that deposited upon CID in the eV and keV energy ranges and upon EI. The order obtained is: SID > EI > low-energy, multiple-collision CID > high-energy, single-collision CID > low-energy, single-collision CID. The distribution of energies in SID is narrower than in the other techniques. High internal energies are accessible by increasing the scattering angle in CID; however, this is accompanied by an increase in the width of the internal energy distribution, and it is therefore not possible to channel fragmentation predominantly into RDA by this method. It is concluded that RDA fragmentation of limonene is a high-energy process and that this is the explanation for its behavior. Isomerization, occurring through 1,3-hydrogen migrations of the molecular ions of limonene, isolimonene, terpinolene and α-terpinene, was investigated and long-lived molecular ions of the first three compounds were found to maintain distinct structures.     

Hydrogen transfer in the retro-Diels–Alder fragmentation of trans-4-amino-, isopropyl-amino-, piperidino- and pyrrolidino-2H-1-benzopyran-3-ols

The electron impact mass spectra of trans-4-amino-, isopropylamino-, pyrrolidino- and piperidino-2H-1-benzopyran-3-ols show intense peaks corresponding to the retro-Diels–Alder reaction. In addition significant ions due to hydrogen transfer to and from the retro-Diels–Alder fragment ion are observed. The transfer of hydrogen to this retro-Diels–Alder fragment ion is influenced by the nature and location of the aromatic substituents, and the amino group at C(4). The loss of hydrogen from the retro-Diels–Alder ion is subject only to the nature of the amino group at C(4). Hydrogen transfer to the retro-Diels–Alder ion is shown to arise from the gem-dimethyl group at C(2), as it is attenuated by successive removal of the methyl groups.     

Dehydration‐fragmentation mechanism of cathinones and their metabolites in ESI‐CID

Various cathinone‐derived designer drugs (CATs) have recently appeared on the drug market. This study examined the mechanism for the generation of dehydrated ions for CATs during electrospray ionization collision‐induced dissociation (ESI‐CID). The generation mechanism of dehydrated ions is dependent on the amine classification in the cathinone skeleton, which is used in the identification of CATs. The two hydrogen atoms eliminated during the dehydration of cathinone (primary amine) and methcathinone (secondary amine) were determined, and the reaction mechanism was elucidated through the deuterium labeling experiments. The hydrogen atom bonded to the amine nitrogen was eliminated with the proton added during ESI, in both of the tested compounds. This provided evidence that CATs with tertiary amine structures (such as dimethylcathinone and α‐pyrrolidinophenones [α‐PPs]) do not undergo dehydration. However, it was shown that the two major tertiary amine metabolites (1‐OH and 2″‐oxo) of CATs generate dehydrated ions in ESI‐CID. The dehydration mechanisms of the metabolites of α‐pyrrolidinobutiophenone (α‐PBP) belongs to α‐PPs were also investigated. Stable‐isotope labeling showed the dehydration of the 1‐OH metabolite following a simple mechanism where the hydroxy group was eliminated together with the proton added during ESI. In contrast, the dehydration mechanism of the 2″‐oxo metabolite involved hydrogen atoms in three or more locations along with the carbonyl group oxygen, indicating that dehydration occurred via multiple mechanisms likely including the rearrangement reaction of hydrogen atoms. These findings presented herein indicate that the dehydrated ions in ESI‐CID can be used for the structural identification of CATs.     

Chain transfer by addition–substitution–fragmentation mechanism. I. End–functional polymers by a single-step free radical transfer reaction: Use of a new allylic linear peroxyketal

A new chain transfer agent, ethyl 2-[1-(1-n-butoxyethylperoxy) ethyl] propenoate (EBEPEP) was used in the free radical polymerization of methyl methacrylate (MMA), styrene (St), and butyl acrylate (BA) to produce end-functional polymers by a radical addition–substitution–fragmentation mechanism. The chain transfer constants (C_tr) for EBEPEP in the three monomers polymerization at 60°C were determined from measurements of the degrees of polymerization. The C_tr were determined to be 0.086, 0.91, and 0.63 in MMA, St, and BA, respectively. EBEPEP behaves nearly as an “azeotropic” transfer agent for styrene at 60°C. The activation energy, E_atr, for the chain transfer reaction of EBEPEP with PMMA radicals was determined to be 29.5 kJ/mol. Thermal stability of peroxyketal EBEPEP in the polymerization medium was estimated from the DSC measurements of the activation energy, E_ath = 133.5 kJ/mol, and the rate constants, k_th, of the thermolysis to various temperature. © 1994 John Wiley & Sons, Inc.     

Use of different microporous and mesoporous materials as catalyst in the Diels–Alder and retro-Diels–Alder reaction between cyclopentadiene and p-benzoquinone: Activity of Al-, Ti- and Sn-doped silica

Diels–Alder cycloaddition between cyclopentadiene and p-benzoquinone has been studied using amorphous silica and different ITQ-2 and MCM-41 pure silica and metal containing materials as catalysts. The reaction can afford different products depending on the molecular reacting site, and the possibility of consecutive additions. Structured solid catalysts increase the selectivity to the endo–endo isomer. Silanol groups have not enough Brönsted acidity to interact with the carbonyl groups present in the dienophile, to reduce LUMO's energy and provide a better overlap between HOMO and LUMO, according to the frontier molecular orbital theory.

The introduction of transition metal atoms in the framework increases the reaction rate for the Diels–Alder reaction while preserving the selectivity to the endo–endo isomer. The presence of more acidic OH groups enhance the retro-Diels–Alder reaction increasing the selectivity to the endo–exo isomer.     

Stereochemistry of organic sulphur compounds: 12—Configurational assignment of 2-methylsulphinyl-1-phenylethanol and some O-derivatives

The conformational analysis of the diastereomeric 2-methylsulphinyl-1-phenylethanol and its O-methyl and O-acetyl derivatives has been performed by ¹H NMR spectroscopy. The study of the influence of dilution and solvent polarity changes on the coupling constants has permitted the configurational assignment of each diastereoisomer. The role played by hydrogen bonding in the hydroxysulphoxides has also been studied by IR spectroscopy.     

A new charge-associated mechanism to account for the production of fragment ions in the high-energy CID spectra of fatty acids

A new mechanism, termed a charge-assisted process, is proposed as an additional mechanism to the charge-remote process to account for ions of the [M - CnH2n+2] series found in the positive and negative high energy CID spectra of fatty acids and related compounds when ionized as closed-shell ([M - H]- or [M + X]+) species. The new mechanism is based on that commonly invoked to account for similar ions in the electron-impact spectra of derivatized fatty acids whereby the positive charge on the derivative abstracts a hydrogen atom from various positions of the alkyl chain to leave a radical that initiates a radical-induced cleavage of the chain. It is proposed that in the high energy CID spectra of closed-shell ions, similar hydrogen migrations occur but unpairing of electrons is avoided by charge transfer to the alkyl chain. This charge then initiates a concerted cleavage of the chain to give an allylic carbonium (positive ion spectrum) or carbanion (negative ion spectrum). The mechanism avoids the need to involve radicals or loss of hydrogen atoms from even-electron (closed shell) ions and provides a driving force for the reaction, namely, the formation of ions with a stabilized charge. An extension of the mechanism is also proposed to account for the formation of odd-electron ions from these compounds. The charge-assisted mechanism does not rule out the occurrence of other mechanisms that have been accepted for many years but provides an alternative process that can account for some spectral features which were difficult to explain earlier.     

Stereochemistry of addition of carbanion reagents to `diacetone fructose aldehyde'. Configurational assignment of a 1-deoxyheptulose derivative by X-ray crystallography and NMR studies directed to the assignment of isomeric adducts

The addition of carbanionic reagents to `diacetone fructose aldehyde' (6) was investigated with a focus on the stereocontrol. The Grignard reagents, MeMgBr, EtMgBr, i-PrMgBr, and MeMgI, gave a high bias (≥90%) for one diastereomer, assigned as the R-isomer, in ether at −78 to 0°C. The reaction of PhMgBr showed diminished diastereoselectivity under these conditions, with a significant dependence of the isomer ratio on temperature and solvent. PhCH<sub>2</sub>MgBr only afforded the adduct of `allylic rearrangement', namely 13, with poor diastereocontrol (ca. 60:40). MeLi, t-BuLi, PhLi, and LiCH₂CO₂-t-Bu provided adducts of 6 enriched in the R-isomer in the range of 80–89%, whereas 2-lithio-2-ethyl-1,3-dithiane gave a 94:6 ratio of R:S adducts (15a:15b). The R absolute stereochemistry at the carbinol C1 center of 4a was established through X-ray analysis of sulfamate derivative 2a. Carbon-13 NMR chemical shift criteria (the chemical shifts for C1 and C3) were identified to facilitate the stereochemical assignment of C1 adducts of 6.     

Stereochemistry of organic sulphur compounds. part 13. Configurational assignment of diastereoisomers of 2-methylsulphinyl-1,2-diphenylethanol and of their O-methyl and O-acetyl derivatives

The synthesis, isolation and conformational analysis of the diastereomeric 2-methylsulphinyl-1,2-diphenylethanol and of its $\text{O}$-methyl and $\text{O}$-acetyl derivatives are reported. Chemical correlations and the study of the influence of solvent polarity changes on the coupling constants have permitted the configurational assignment. Lanthanide shift reagents have been used also. to this effect. The role of hydrogen bonding in the hydroxysulphoxides has been evaluated in diluted solutions by IR and NMR spectroscopy. A donor-acceptor interaction between oxygen and sulphur has been invoked to explain the differences in conformational behaviour between epimeric sulphoxides at sulphur atom.     

Fragmentation and charge transfer in gas-phase complexes of divalent metal ions with acetonitrile

The development of electrospray has enabled generation of gas-phase multiply charged metal ion complexes with various solvent molecules. These species exhibit rich fragmentation chemistry, involving competition among neutral ligand loss, ligand cleavage, and dissociative electron and proton transfer. Acetonitrile is a common aprotic solvent. Here we present a comprehensive MS/MS study on acetonitrile complexes of divalent metal cations. We measured the critical sizes below which dissociation channels other than the trivial neutral evaporation become operative and minimum sizes at which dications remain stable against charge reduction. For all sizes between the two, low-energy fragmentation patterns have been elucidated in detail.     

Reversible addition–fragmentation chain transfer polymerization of methyl methacrylate in suspension

The reversible addition–fragmentation chain transfer polymerization of methyl methacrylate mediated by 2‐cyanoprop‐2‐yl dithiobenzoate (CPDB) in bulk (60 and 70 °C) and suspension (70 °C) was studied, and in both polymerization systems, a good control of the molecular weight and polydispersity was observed. Stable suspension polymerizations were carried out over a range of CPDB concentrations, and with increasing CPDB concentration, the particle size and polydispersity index of the produced polymer decreased. The former was ascribed to the lower viscosities of the monomer and polymer droplets at low conversions, which caused easier breakup with the applied shear stresses. Lower polydispersity indices at higher CPDB concentrations were probably caused by a diminished gel effect, which was observed at lower CPDB concentrations at high conversions, causing a broadening of the molecular weight distribution. The livingness of the polymers formed in suspension was proven by successful chain extensions with methyl methacrylate, styrene, and 2‐hydroxyethyl methacrylate. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2001–2012, 2005     

Reversible addition–fragmentation chain transfer polymerization of methyl methacrylate in emulsion

Theoretical simulations showed that for controlled/living radical polymerization in an emulsion system, some of the earliest born particles could be superswollen to a size close to 1 μm. We hypothesized that the superswelling of these particles would lead to colloidal instability. Under the guidance of the simulation results, reversible addition–fragmentation chain transfer (RAFT) emulsion polymerization of methyl methacrylate (MMA) was carried out. Experimental results showed that increasing the initiation rate, surfactant level, and targeted molecular weight could improve the colloidal stability of the RAFT polymerization of MMA in an emulsion. The experimental results were in full accord with the theoretical predictions. The poor control of the molecular weight and polydispersity index was found to have a close relationship with the colloidal instability. For the first time, we demonstrated that RAFT polymerization could successfully be implemented with little coagulum, good control of the molecular weight, and a low polydispersity index with the same process used for traditional emulsion polymerization but with higher surfactant levels and initiation rates. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44:2837–2847, 2006     

Polymeric temperature and pH fluorescent sensor synthesized by reversible addition–fragmentation chain transfer polymerization

Simple‐structured copolymer, poly(NIPMAM‐co‐CPMA), consisting of N‐isopropylmethacrylamide (NIPMAM) and (Z)‐4‐(1‐cyano‐2‐(4‐(dimethylamino) phenyl)vinyl)phenylmethylacrylate (CPMA) units as thermo‐ and pH‐responsive fluorescent signaling parts, respectively, has been synthesized by reversible addition–fragmentation chain transfer polymerization. The copolymer PCN250 (m/n = 250) shows absorbance enhancement or decrease at different pH value. However, the fluorescence intensity of this copolymer shows enhancement with a rise in temperature regardless of pH value in the range of pH = 4–10. In addition, fluorescence suppression of copolymer (PCN250) was observed with high proton concentration. Moreover, the lower critical solution temperature of the copolymers, poly‐(NIPMAM‐co‐CPMA), with different component was also investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

GC–MS analysis and reaction mechanism of the gas-phase amination of 2,6-diisopropylphenol

The liquid product of the gas-phase amination of 2,6-diisopropylphenol (2,6-DIPP) to prepare 2,6-diisopropylaniline (2,6-DIPA) was analyzed using gas chromatography-mass spectrometry. Besides 2,6-DIPP and 2,6-DIPA, there are by-products such as water, 1,3-diisopropylbenzene, 2,6-diisopropylcyclohexamine in the liquid product, in which 2,6-diisopropylcyclohexamine is a major constitute by-product. The ratio of 2,6-diisopropylcyclohexamine to 2,6-DIPA is low when the reaction proceeds more completely at lower reaction space velocity, but this ratio increases when the reaction proceeds incompletely at higher space velocity. So that 2,6-diisopropylcyclohexamine is suggested to be the intermediate product of gas-phase amination of 2,6-DIPP. The reaction mechanism of gas-phase amination of 2,6-DIPP on the bifunctional palladium-lanthanum supported catalyst was proposed. This reaction was synergistically catalyzed by the Pd metal active sites that facilitated hydrogenation and dehydrogenation reactions and the acid sites on the catalyst support that accelerated isomerization and amination reactions.     

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.     

Controlled radical polymerization of a trialkylsilyl methacrylate by reversible addition–fragmentation chain transfer polymerization

The reversible addition–fragmentation chain transfer (RAFT) polymerization of a hydrolyzable monomer (tert‐butyldimethylsilyl methacrylate) with cumyl dithiobenzoate and 2‐cyanoprop‐2‐yl dithiobenzoate as chain‐transfer agents was studied in toluene solutions at 70 °C. The resulting homopolymers had low polydispersity (polydispersity index < 1.3) up to 96% monomer conversion with molecular weights at high conversions close to the theoretical prediction. The profiles of the number‐average molecular weight versus the conversion revealed controlled polymerization features with chain‐transfer constants expected between 1.0 and 10. A series of poly(tert‐butyldimethylsilyl methacrylate)s were synthesized over the molecular weight range of 1.0 × 10⁴ to 3.0 × 10⁴, as determined by size exclusion chromatography. As strong differences of hydrodynamic volumes in tetrahydrofuran between poly(methyl methacrylate), polystyrene standards, and poly(tert‐butyldimethylsilyl methacrylate) were observed, true molecular weights were obtained from a light scattering detector equipped in a triple‐detector size exclusion chromatograph. The Mark–Houwink–Sakurada parameters for poly(tert‐butyldimethylsilyl methacrylate) were assessed to obtain directly true molecular weight values from size exclusion chromatography with universal calibration. In addition, a RAFT agent efficiency above 94% was confirmed at high conversions by both light scattering detection and ¹H NMR spectroscopy. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5680–5689, 2005     

Stabilization and reactions of tetramethylurea radical cations in Freon matrices at 77 K: Intramolecular hydrogen transfer,ion-molecular reactions,and fragmentation by electron spin resonance study

ESR spectra for -irradiated at 77 K solutions /0.02–16%/ of tetramethylurea /TMU/ in CFCl₃ and Freon-113 have been studied. TMU^+. radical cations radiolytically produced in dilute solutions have been shown to undergo intramolecular hydrogen transfer upon photobleaching resulting in CH₂N= type radical. Evidence for intermolecular proton transfer in TMU^+. radical cations after annealing to phase transition temperature /110–120 K/ in Freon-113 was obtained. Primary radical cations of TMU^+. at their ground state take part in ion-molecular reaction via proton transfer. Molecular cations in their excited states may undergo fragmentation producing Me₂N radicals, which were trapped in liquid phase by t-BuNO as a spin trap.     

Mass spectrometry of transition–metal π-complexes. V—fragmentation and structure of chromium-coordinated ions

Mass spectrometric studies have been made of the [(C₇H₈)Cr]⁺ ions generated from (η⁶-PhCH₃)Cr(CO)₃ and (η⁶-c-C₇H₈)Cr(CO)₃. Fragmentation behaviour and appearance potential measurements have been used to show that the ions from the two precursors do not achieve a common structure. [(C₈H₁₀)Cr]⁺ generated from (η⁶-PhEt)Cr(CO)₃ and (η⁶-c-C₇H₇Me)Cr(CO)₃ behave similarly. A study of the α-d₃ toluene complex suggests the structure [CH₃C₆H₄–CrH]⁺ is appropriate for [C₇H₈Cr]⁺ ions generated from (η⁶-PhMe)Cr(CO)₃ and decomposing to [CrH]⁺.