Reactions Of Radical Cations Research Articles

Gas-Phase Intercluster Thiyl-Radical Induced C-H Bond Homolysis Selectively Forms Sugar C2-Radical Cations of Methyl D-Glucopyranoside: Isotopic Labeling Studies and Cleavage Reactions.

A suite of isotopologues of methyl D-glucopyranosides is used in conjunction with multistage mass spectrometry experiments to determine the radical site and cleavage reactions of sugar radical cations formed via a recently developed 'bio-inspired' method. In the first stage of CID (MS2), collision-induced dissociation (CID) of a protonated noncovalent complex between the sugar and S-nitrosocysteamine, [H3NCH2CH2SNO + M]+, unleashes a thiyl radical via bond homolysis to give the noncovalent radical cation, [H3NCH2CH2S• + M]+. CID (MS3) of this radical cation complex results in dissociation of the noncovalent complex to generate the sugar radical cation. Replacement of all exchangeable OH and NH protons with deuterons reveals that the sugar radical cation is formed in a process involving abstraction of a hydrogen atom from a C-H bond of the sugar coupled with proton transfer to the sugar, to form [M - H• + D+]. Investigation of this process using individual C-D labeled sugars reveals that the main site of H/D abstraction is the C2 position, since only the C2-deuterium labeled sugar yields a dominant [M - D• + H+] product ion. The fragmentation reactions of the distonic sugar radical cation, [M - H•+ H+], were studied by another stage of CID (MS4). 13C-labeling studies revealed that a series of three related fragment ions each contain the C1-C3 atoms; these arise from cross-ring cleavage reactions of the sugar. Graphical Abstract ᅟ.

Highly Stable Hydroquinone Ether-Based Catholyte for Non-Aqueous Redox Flow Batteries

Hydroquinone ethers are a key class of catholyte materials for non-aqueous redox flow batteries, showing high open-circuit potential, electrochemical reversibility and chemical tunability. However, the instability of many hydroquinone ethers, particular to electrochemical oxidation, limits their applicability. 2,5-dialkylation of the benzene core has been by far the only effective chemical approach to suppress the side reactions of the corresponding radical cations, restricting the chemical space of structures from which to choose. This talk will describe a bicyclo-alkyl substitution strategy that yields a hydroquinone ether with unprecedentedly high electrochemical stability. The influences of different substituents on the electrochemical properties are investigated. The electrochemical stability is determined via a full flow cell using a benzothiadiazole-based anolyte. In addition, the low impedance shown in the single electrolyte flow cell indicates its great promises as catholyte for high-performance non-aqueous redox flow batteries.

ChemInform Abstract: Visible‐Light‐Driven Photocatalytic Activation of Inert Sulfur Ylides for 3‐Acyl Oxindole Synthesis.

Bicarbonyl-substituted sulfur ylide is a useful, but inert reagent in organic synthesis. Usually, harsh reaction conditions are required for its transformation. For the first time, it was demonstrated that a new, visible-light photoredox catalytic annulation of sulfur ylides under extremely mild conditions, permits the synthesis of oxindole derivatives in high selectivities and efficiencies. The key to its success is the photocatalytic single-electron-transfer (SET) oxidation of the inert amide and acyl-stabilized sulfur ylides to reactive radical cations, which easily proceeds with intramolecular C-H functionalization to give the final products.

Competition Studies and the Use of Mechanistic Insight to Overcome Synthetic Barriers

Because intramolecular anodic olefin coupling reactions involve a reversal in polarity of a normally nucleophilic olefin, they can be used to develop entirely new pathways to a variety of molecules. The reactions are compatible with a wide variety of functional groups, the generation of fused, bridged, and spirocyclic ring skeletons, and the formation of quaternary carbons. However, not all anodic olefin coupling reactions work. The reactions are triggered by the formation of a highly reactive radical cation intermediate. If the desired reaction pathway is not fast enough, then the radical cation will initiate undesirable reaction pathways, often involving elimination, fragmentation, or solvent trapping. When this occurs, the question quickly becomes what can be done to solve the problem and channel the reaction down a more productive pathway? The best way to address this question has been to carefully probe the mechanism of the reactions, identify the nature of the undesirable reactions, and then manipulate the relative rates of the reactions available to the radical cation to favor the process that is wanted. Several steps in the reaction can be important, but two play an especially important role (Scheme 1). First, the rate of the cyclization is important. If the cyclization is too slow, then side reactions involving the reactive radical cation will begin to dominate. The rate of the second oxidation (k2) is also critical for the success of the reaction. Many radical cyclizations are reversible and in those cases the loss of the second electron helps to drive the product to completion. Understanding these principles is essential for the design of more complex reactions, and in the talk to be presented, a series of new anodic cyclization reactions (Scheme 2) will be used to highlight the important interplay between mechanistic considerations and synthetic design. Each of the reactions discussed will involve a transformation that was originally a failure but is now a cornerstone of ongoing synthetic efforts. Figure 1

The anodic reactivity of 4,4′-dimethoxychalcone: a synthetic and mechanistic investigation

The anodic oxidation of the 4,4′-dimethoxychalcone (DMC) was investigated by different electrochemical methods at a platinum working electrode and in acetonitrile as a solvent. The DMC exhibited a single irreversible anodic peak around 1.6 V versus Ag/AgCl. On the time scale of cyclic voltammetry experiments, the highly reactive radical cation issued from the first electron transfer underwent a second order rate-limiting reaction. The potential imposed electrolyses of DMC led to the formation of a semi-conducting oligomer with 40 % yield. Using different physico-chemicals methods, the structural study confirmed the formation of an o-phenylenevinylene oligomer. The values of the corresponding optical and electrochemical band gaps were calculated to be 3.15 and 2.86 eV, respectively. Finally, a mechanism for the DMC electro-oligomerization was proposed on the basis of the obtained results.

Visible-Light-Driven Photocatalytic Activation of Inert Sulfur Ylides for 3-Acyl Oxindole Synthesis.

Bicarbonyl-substituted sulfur ylide is a useful, but inert reagent in organic synthesis. Usually, harsh reaction conditions are required for its transformation. For the first time, it was demonstrated that a new, visible-light photoredox catalytic annulation of sulfur ylides under extremely mild conditions, permits the synthesis of oxindole derivatives in high selectivities and efficiencies. The key to its success is the photocatalytic single-electron-transfer (SET) oxidation of the inert amide and acyl-stabilized sulfur ylides to reactive radical cations, which easily proceeds with intramolecular C-H functionalization to give the final products.

(Organic and Biological Electrochemistry Division Manuel M. Baizer Award) Following the Lead of R. B. Woodward and M. M. Baizer: Using Concepts in Physical Organic Chemistry to Shape the Course of Electrochemical Reactions

One of R. B. Woodward’s many contributions to organic chemistry was the way in which he used physical organic chemistry and an understanding of mechanism to shape the development of new synthetic methods. From the use of temporary, conformational constraints to dictate the stereochemistry of a complex target to the interception of a key intermediate to bring about a cis-hydroxylation reaction from the most hindered face of a molecule, the Woodward group beautifully demonstrated that the outcome of a reaction could be predetermined by considering and then controlling its mechanistic features. In a similar manner, Manuel M. Baizer taught us much about how to think about electrochemical reactions. His work helped take the “magic” out of electroorganic processes and demonstrated that electroorganic reactions were indeed organic reactions. They were triggered by electron-transfer processes and had additional parameters that needed to be considered, but to a great extent they could be understood and optimized as synthetic transformations by considering their chemical mechanism. This perspective served to make organic electrochemistry accessible to the larger synthetic community. The combination of lessons learned from these two pioneers laid the foundation for our own studies concerning electrochemical reactions and their use in synthesis. From the oxidation of amides used in the synthesis of peptidomimetics, to the use of oxidative cyclization reactions in synthesis, to the site-selective generation of chemical reagents for the functionalization of microelectrode array surfaces, we have continually relied on the fact that electroorganic reactions are simply organic reactions and can thus be optimized as such. The overall approach has fueled not only our own work, but also that of so many others, far too many to name here. In the talk to be presented, an overview of electrochemical synthetic methods will be presented against a backdrop of the mechanistic insights and findings that enabled and enhanced their development. An emphasis will be placed on the synthetic utility of reactions that take advantage of reactive radical cation intermediates,1 site-selective reactions on conducted on microelectrode arrays,2 and a look toward the future use of paired electrochemical reactions for the on-site generation of chemical reagents.3

The Chemistry of Separations Ligand Degradation by Organic Radical Cations

Solvent based extractions of used nuclear fuel use designer ligands in an organic phase extracting ligand complexed metal ions from an acidic aqueous phase. These extractions will be performed in highly radioactive environments, and the radiation chemistry of all these complexants and their diluents will play a major role in determining extraction efficiency, separation factors, and solvent-recycle longevity. Although there has been considerable effort in investigating ligand damage occurring in acidic water radiolysis conditions, only minimal fundamental kinetic and mechanistic data has been reported for the degradation of extraction ligands in the organic phase. Extraction solvent phases typically use normal alkanes such as dodecane, TPH, and kerosene as diluents. The radiolysis of such diluents produce a mixture of radical cations (R•+), carbon-centered radicals (R•), solvated electrons, and molecular products such as hydrogen. Typically, the radical species will preferentially react with the dissolved oxygen present to produce relatively inert peroxyl radicals. This isolates the alkane radical cation species, R•+ as the major radiolytically-induced organic species that can react with, and degrade, extraction agents in this phase. Here we report on our recent studies of organic radical cation reactions with various ligands. Elucidating these parameters, and combining them with the known acidic aqueous phase chemistry, will allow a full, fundamental, understanding of the impact of radiation on solvent extraction based separation processes to be achieved.

The role of organic solvent radical cations in separations ligand degradation

The dodecane radical cation reaction rate constant with CMPO was measured using ps electron pulse radiolysis/absorption spectroscopy as k = (1.30 ± 0.11) × 1010 M−1s−1 in dodecane/0.10 M CH2Cl2 solution. No reactivity increase occurred when these solutions were pre-contacted with nitric acid, similar to the behavior observed for TODGA. To corroborate these kinetic data with steady-state radiolysis measurements, where acid pre-contacted CMPO showed significantly less degradation, it is proposed that the dodecane radical cation always reacts directly with TODGA, but for CMPO the charge-transfer occurs with the CMPO·HNO3 complex formed in the acid contacted solvent.

H-atom loss and migration in hydrogen-rich peptide cation radicals: The role of chemical environment

Hydrogen-atom loss and intramolecular hydrogen-atom migration in peptide radical and cation radical were investigated by quantum chemical calculations for models that include zero to three hydrogen bonds with the ammonium groups. Five different DFT functionals have been checked to study the geometry relaxation and fragmentation processes after electron attachment to peptide cations. The structural changes associated with the geometry relaxation are shown to be dependent on the level of calculation. Furthermore, comparison with CCSD(T) calculations indicates that an adequate description of the electronic state of the reduced protonated peptide is not a sufficient prerequisite to provide accurate energy barrier. Calculating fragmentation reactions of hydrogen-rich peptide cation radicals is pointed out to be a challenging task as none of the DFT functionals are fully effective to describe the whole process. M06-2X is an adequate choice if it provides the correct ground state, otherwise LC-BLYP should be chosen.The electron attachment site and the electron affinity value are highly sensitive to the number of hydrogen bonds with the ammonium group. An ammonium cation with zero, one, and, to a smaller extent, two hydrogen bonds easily captures an incoming electron and subsequently undergoes an H-atom loss process rather than a proton coupled electron transfer. This suggests an explanation for the low amount of c and z fragments observed upon ECD for small protonated peptides, where the ammonium groups cannot be highly intramolecularly “solvated”.

The effects of intramolecular hydrogen bonding on the reactivity of phenoxyl radicals in model systems

The effects of hydrogen bonding and spin density at the oxygen atom on the gas-phase reactivity of phenoxyl radicals were investigated experimentally and theoretically in model systems and the dipeptide LysTyr. Gas-phase ion-molecule reactions were carried out between radical cations of several aromatic nitrogen bases with the neutrals nitric oxide and n-propyl thiol. Reactivity of radical cations 4–6 correlated with the spin density. The possibility of hydrogen bonding was explored in compounds which allowed four-, five-, and six-membered rings to be formed between the protonated nitrogen and the phenoxyl oxygen, while possessing similar spin density at the oxygen atom. The N+-H⋯O bond length was calculated to decrease in the series (1–3), consistent with the theoretical calculations finding weak hydrogen bonding in 2 and strong hydrogen bonding in 3. This coincided with the decrease in reaction rates of 1–3 with both nitric oxide and n-propyl thiol. DFT calculations found that the lowest energy structure of the distonic radical cation of the dipeptide [LysTyr(O)]+ has a short hydrogen bond between the protonated Lys side chain and the phenoxyl oxygen, 1.70Å, which is consistent with its low reactivity.

Reactive radical cation transfer in the cages of icy clathrate hydrates

Clathrate hydrates are crystalline compounds consisting of hydrogen-bonded host water frameworks that eventually structure polyhedral cages. We suggest for the first time their potential as nano-reactors in which target reactions can occur. The energetics of one-dimensional CO radical cation (CO·+) transfers through the hexagonal faces of sI large cages are closely examined to verify the reaction concept in an icy confined space. The barrier energies for migrating a CO radical cation from the cage center to the edge of the hexagonal face are estimated to be 87 and 311 kJ/mol according to calculations with the B3LYP 6−311+G (d, p) basis set, significantly depending on the orientation of the radical. These results indicate that the barrier energy increases sharply when the CO radical cations are oriented parallel to the cage’s hexagonal face. In the parallel migration mode, the hydrogen-bonded water networks are repulsed by electron clouds of CO·+ located on the same plane; thus, the repulsion forces induce a significant increase in the barrier energies. Further, we used separate basis sets of high and low levels processed by the ONIOM scheme for the effective calculation of the entire cage structure of the clathrate hydrates with guest molecules. The calculation run time was significantly shortened when the ONIOM scheme was adopted, while a difference in the barrier energy of approximately 5% was observed compared to the full-scale calculation with a high-level basis set.

Formation and properties of a bicyclic silylated digermene.

In the presence of PMe3 or N-heterocyclic carbenes, the reaction of oligosilanylene dianions with GeCl2⋅dioxane gives germylene–base adducts. After base abstraction, the free germylenes can dimerize by formation of a digermene. An electrochemical and theoretical study of a bicyclic tetrasilylated digermene revealed formation of a comparably stable radical anion and a more reactive radical cation, which were characterized further by UV/Vis and ESR spectroscopy.

Isomerization of Oxygen-Containing Radical Cations

Isomerization is an important reaction mode of organic transformations. Although extensive works have been carried out for isomerization reactions of carbocations and free radicals, few studies have been reported on isomerization reactions of radical cations. In the present work, we would like to report full computational studies of structures and reactivity of peroxy radical cations, which are formed by reactions of molecular oxygen with various aliphatic and aromatic alkenes, and the corresponding carbonyl oxide radical cations that may be formed by a hydrogen, a methyl, or a phenyl migration in the peroxy radical cations.

Transformation of polycyclic aromatic hydrocarbons (PAHs) on Fe(III)-modified clay minerals: Role of molecular chemistry and clay surface properties

Clay-driven transformation of polycyclic aromatic hydrocarbons (PAHs) is critically influenced by their molecular structure and clay surface properties. In the present study, several PAHs were selected as model molecules to investigate their potential transformation on Fe(III)-saturated clay minerals under various mineralogical and environmental conditions. Results suggest that the reactivity of PAHs is highly correlated with their ionization potential (IP) values. PAHs with IP lower than a threshold between 7.5 and 7.6 prefer undergoing a one-electron transfer reaction. Otherwise, Fe(III)-smectite is unable to degrade PAHs with IP above it. The electron-transfer process leads to the reduction of Fe(III) to Fe(II) and formation of organic radical cations, which are more stable in clay interlayers than at other clay sites. Subsequent reactions of radical cations with oxygenic species (such as H2O) result in formation of oxygenated products. The surface chemical properties, i.e., the hydration of cations, fraction of Fe(III), layer charge location, and type of ligands, strongly affect the interaction between PAHs and Fe(III), thus modulate the reactivity of surface Fe(III)-species on the clay minerals. This study provides the first direct evidence for clay-catalyzed transformation of PAHs supporting the plausibility of their in situ degradation in soils, and demonstrates that abiotic reactions with surface-bound Fe(III) may affect or even dominate the long-term behavior of PAHs in soils, particularly in the presence of swelling clay minerals.

Reactions of 5-methylcytosine cation radicals in DNA and model systems: Thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar

Purpose: To study the formation and subsequent reactions of the 5-methyl-2′-deoxycytidine cation radical (5-Me-2′-dC•+) in nucleosides and DNA-oligomers and compare to one-electron oxidized thymidine.Materials and methods: Employing electron spin resonance (ESR), cation radical formation and its reactions were investigated in 5-Me-2′-dC, thymidine (Thd) and their derivatives, in fully double-stranded (ds) d[GC*GC*GC*GC*]2 and in the 5-Me-C/A mismatched, d[GGAC*AAGC:CCTAATCG], where C* = 5-Me-C.Results: We report 5-Me-2′-dC•+ production by one-electron oxidation of 5-Me-2′-dC by Cl2•− via annealing in the dark at 155 K. Progressive annealing of 5-Me-2′-dC•+ at 155 K produces the allylic radical (C-CH2•). However, photoexcitation of 5-Me-2′-dC•+ by 405 nm laser or by photoflood lamp leads to only C3′• formation. Photoexcitation of N3-deprotonated thyminyl radical in Thd and its 5′-nucleotides leads to C3′• formation but not in 3′-TMP which resulted in the allylic radical (U-CH2•) and C5′• production. For excited 5-Me-2′,3′-ddC•+, absence of the 3′-OH group does not prevent C3′• formation. For d[GC*GC*GC*GC*]2 and d[GGAC*AAGC:CCTAATCG], intra-base paired proton transferred form of G cation radical (G(N1-H)•: C(+ H+)) is found with no observable 5-Me-2′-dC•+ formation. Photoexcitation of (G(N1-H)•:C(+ H+)) in d[GC*GC*GC*GC*]2 produced only C1′• and not the expected photoproducts from 5-Me-2′-dC•+. However, photoexcitation of (G(N1-H)•:C(+ H+)) in d[GGAC*AAGC:CCTAATCG] led to C5′• and C1′• formation.Conclusions: C-CH2• formation from 5-Me-2′-dC•+ occurs via ground state deprotonation from C5-methyl group on the base. In the excited 5-Me-2′-dC•+ and 5-Me-2′,3′-ddC•+, spin and charge localization at C3′ followed by deprotonation leads to C3′• formation. Thus, deprotonation from C3′ in the excited cation radical is kinetically controlled and sugar C-H bond energies are not the only controlling factors in these deprotonations.

ChemInform Abstract: Mass Spectrometry of Hydroxylamines, Oximes and Hydroxamic Acids

AbstractReview: 192 refs.

Photophysical and Electrochemical Investigations of the Fluorescent Probe, 4,4′-Bis(2-benzoxazolyl)stilbene

In solution, 4,4'-bis(2-benzoxazolyl)stilbene (BBS) was found to exhibit consistently high absolute fluorescence quantum yields (Φ(fl) ≥ 0.88) and a monoexponential lifetime, both independent of BBS concentration. The BBS steady-state and time-resolved photophysics were investigated by different techniques to understand the various deactivation pathways. Nonradiative deactivation of BBS singlet excited state by intersystem crossing was found to be negligible. Other than fluorescence, the excited state of BBS was found to be deactivated by trans-cis photoisomerization. At low concentrations (≈5 μg/mL), UV spectroscopy and laser flash photolysis showed concordant results that the photoinduced cis isomer gradually replaced the original absorption spectrum of the pure trans isomer. However, at high concentrations (≈0.2 mg/mL), (1)H NMR and DOSY measurements confirmed that irradiating BBS at 350 nm induced a conversion from the trans-BBS into its cis isomer by photoisomerization. It was further found that the stilbene moiety of both isomers was photocleaved. The resulting photoproduct was an aldehyde that was oxidized under ambient conditions to its corresponding carboxylic acid, i.e., 4-(1,3-benzoxazol-2-yl)benzoic acid. The structure of the photoproduct was unequivocally confirmed by X-ray diffraction. Spectroscopic investigation of BBS showed a limited photoisomerization after irradiation at 350 nm of a trans solution. The BBS electrochemistry showed irreversible oxidation, resulting in an unstable and highly reactive radical cation. Similarly, the cathodic process was also found to be irreversible, giving rise to a radical anion and showing its n-doping character.

Single-step synthesis of polypyrrole nanowires by cathodic electropolymerization

Polypyrrole nanowires are successfully fabricated with a one-step process by cathodic electropolymerization from an aqueous solution without templates and chemical additives. The method utilizes electrochemically generated NO+ to oxidize the neutral pyrrole monomers, making it possible to use oxidizable metal substrates, such as Cu and Ni. The synthesized nanowires are directly deposited on the substrate in the form of a thin film consisting of fine polypyrrole nanowires with a nanoporous and interconnected network structure. The growth kinetics of the polypyrrole nanowires was investigated by analyzing the effects of the chemical composition of the electrolyte and the synthesis time on the formation of polypyrrole nanowires. It was found that the polymerization process of pyrrole is very sensitive to the reactivity of radical cations. For a radical cation with high reactivity, the polypyrrole nanospheres are synthesized near the electrode in the solution. In contrast, for a radical cation with sufficiently low reactivity, the polypyrrole nanowires are grown on the priorly deposited polypyrrole nanospheres.

Unimolecular reactions of gaseous picoline radical cations. A new experimental and computational study

The fragmentation reactions of the molecular ion of the three isomeric methylpyridines (2-picoline 1, 3-picoline 2, and 4-picoline 3) were studied using methods of tandem mass spectrometry and quantum chemical calculations with Gaussian-3 (G3) theory using the B3LYP density functional method (G3//B3LYP). Additionally RRKM calculations of the microcanonical rate constants of selected reaction pathways were performed. Derivatives of 2- and 4-picoline which bear an isotopically labeled methyl substituent (CD3: 1-d3 and 3-d3, 13CH3: 1-13C and 3-13C) were also analyzed. Of the four primary dissociation reactions of the picoline radical cations 1+–3+, the loss of a hydrogen atom, the elimination of an ethyne molecule and the elimination of a hydrogen cyanide molecule are observed in the MIKE spectra, while the loss of a methyl radical is only found in the collisional activation (CA) mass spectra of the molecular ions. The CA mass spectra of the labeled picoline radical ions reveal that some positional hydrogen exchange and carbon exchange takes place before the loss of the methyl radical. According to the G3 and RRKM calculations, the direct cleavage of the methyl substituent competes effectively with increasing internal energy of the ion with the loss of a methyl radical after rearrangements. The other three pathways found for metastable molecular ions are accompanied by efficient or complete hydrogen scrambling. The theoretical calculations prove that this scrambling occurs mainly by initial H-transfer from the methyl group to the pyridine ring and a subsequent H-ring walk. The calculations show further, that loss of H may occur from many of the intermediate ions after the rearrangements but that the direct loss of H from the methyl substituent competes successfully even at low energies, contrary to the behavior of the toluene radical ion. The elimination of an ethyne molecule gives rise to a broad flat-topped signal in the mass-analyzed ion kinetic energy (MIKE) spectra, and the MIKE spectra of 1-13C and 3-13C exhibit a 1:1 sharing of the 13C-label between ionic and neutral products. These particular features are explained by the theoretical calculations by a first rearrangement of the picoline radical cations to a seven-membered aza-cycloheptatriene radical cation 4+ followed by a rearrangement to a more rigid bicyclo-[3.2.0] isomer before the elimination of ethyne. Finally, the elimination of a hydrogen cyanide molecule exhibits only minor loss of 13C-label in the case of 1-13C and 3-13C. This observation does not agree with any mechanism including a rearrangement to 4+. The theoretical calculations suggest that instead the loss of the hydrogen cyanide molecule proceeds by a cleavage of the pyridine ring after the initial H-transfer from the methyl substituent. Although this pathway needs more energy than a rearrangement to 4+, its rate coefficients are superior owing to its loose transition states.