Detection Of Radical Intermediates Research Articles

Enhanced Mechanistic Understanding Through the Detection of Radical Intermediates in Organic Reactions.

Two applications of a radical trap based on a homolytic substitution reaction (SH2') are presented for the trapping of short-lived radical intermediates in organic reactions. The first example is a photochemical cyanomethylation catalyzed by a Ru complex. Two intermediate radicals in the radical chain propagation have been trapped and detected using mass spectrometry (MS), along with the starting materials, products and catalyst degradation fragments. Although qualitative, these results helped to elucidate the reaction mechanism. In the second example, the trapping method was applied to study the radical initiation catalyzed by a triethylboronoxygen mixture. In this case, the concentration of trapped radicals was sufficiently high to enable their detection by nuclear magnetic resonance (NMR). Quantitative measurements made it possible to characterize the radical flux in the system under different reaction conditions (including variations of solvent, temperature and concentration) where modelling was complicated by chain reactions and heterogeneous mass transfer.

Regioselective Rearrangement of Nitrogen- and Carbon-Centered Radical Intermediates in the Hofmann-Löffler-Freytag Reaction.

The Hofmann-Löffler-Freytag (HLF) reaction serves as a late-stage functionalization technique for generating pyrrolidine heterocyclic ring systems. Contemporary HLF protocols utilize in situ halogenated sulfonamides as precursors in the radical-mediated rearrangement cycle. Despite its well-established reaction mechanism, experiments toward the detection of radical intermediates using EPR techniques have only recently been attempted. However, the obtained spectra lack the distinct features of the N-centered radicals expected for the employed reactants. This paper presents phenylbutylnitrone spin-trapped C-centered and N-centered radicals, generated via light irradiation from N-halogen-tosyl-sulfonamide derivatives and detected using EPR spectroscopy. NMR spectroscopy and DFT calculations are used to explain the observed regioselectivity of the HLF reaction.

Photoinduced and Thermal Single-Electron Transfer to Generate Radicals from Frustrated Lewis Pairs.

Archetypal phosphine/borane frustrated Lewis pairs (FLPs) are famed for their ability to activate small molecules. The mechanism is generally believed to involve two‐electron processes. However, the detection of radical intermediates indicates that single‐electron transfer (SET) generating frustrated radical pairs could also play an important role. These highly reactive radical species typically have significantly higher energy than the FLP, which prompted this investigation into their formation. Herein, we provide evidence that the classical phosphine/borane combinations PMes3/B(C6F5)3 and PtBu3/B(C6F5)3 both form an electron donor–acceptor (charge‐transfer) complex that undergoes visible‐light‐induced SET to form the corresponding highly reactive radical‐ion pairs. Subsequently, we show that by tuning the properties of the Lewis acid/base pair, the energy required for SET can be reduced to become thermally accessible.

Development of an indicator for the direct visualization of radical intermediates in organic reactions.

A color-indicator based on a derivative of rhodamine amide was developed for the detection of radical intermediates in organic reactions. This derivative showed sensitive color changes for various radical intermediates initiated by chemical reagents or UV light.

Probing Conformational Change During Radical Propagation in the E.coli Class 1a RNR Using 3‐aminotyrosine as a Radical “Sink”

The E. coli class Ia ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxynucleoside 5ʹ‐diphosphates (dNDPs) using nucleoside 5ʹ‐diphosphates (NDPs) as substrates. The catalytic mechanism of RNR requires an active site thiyl radical, which is generated via reversible oxidation by a tyrosyl radical cofactor located over 35 Å away. The model for the long range oxidation involves multiple proton‐coupled electron transfer (PCET) steps through aromatic amino acid residues. Efforts to study the radical hopping mechanism have been challenging due to kinetic masking of the chemistry by a conformational gate. Lowering the midpoint potentials of pathway residues by using the amber stop codon suppression method to site‐specifically incorporate the unnatural amino acid (UAA) 3‐aminotyrosine (NH2Y) acts as a radical “sink” on pathway and changes the rate limiting step of the radical propagation mechanism from a conformational change to a PCET step. NH2Y‐incorporated RNR (NH2Y‐RNRs) have allowed the detection of radical intermediates on this PCET pathway and have established the role of three tyrosines, Y356, Y730 and Y731, in the PCET pathway. Despite the large perturbation in midpoint potential, NH2Y‐RNRs can also do multiple turnovers and produce dNDPs. The study of the rapid kinetics of NH2Y● and dNDP formation demonstrates the kinetic and chemical competence of the NH2Y● intermediates. Additionally, insight into the kinetic model of the NH2Y‐RNRs give rise to further details of multiple, more subtle conformational changes within the PCET pathway mechanism. Specifically, the NH2Y● populations exist in two distinct conformations, with one less competent in nucleotide reduction.

Photocatalytic Oxygenation of Pivalic Acid with Molecular Oxygen via Photoinduced Electron Transfer using 10-Methylacridinium Ions

Photoirradiation of the absorption band of the 10-methylacridinium ion (AcrH+) with visible light in deaerated CH3CN/H2O (1:1 v/v) containing pivalic acid (Bu(t)COOH) and less than 1 equiv of NaOH results in the selective formation of 9-tert-butyl-9,10-dihydro-10-methylacridine (AcrHBu(t)). The same product is obtained in O2-saturated CH3CN/H2O under visible light irradiation. Photoirradiation of the absorption band of AcrHBu(t) with UV light in deaerated CH3CN/H2O (1:1 v/v) results in the formation of tert-butyl hydroperoxide (Bu(t)OOH), accompanied by regeneration of AcrH+. This cycle can be repeated several times. When AcrH+ is replaced by the 9-phenyl derivative (AcrPh+), AcrPh+ acts as an effective photocatalyst for the one-pot photooxygenation of Bu(t)COOH in the presence of less than 1 equiv of NaOH relative to Bu(t)COOH with O2 to yield Bu(t)OOH and Bu(t)H. The photocatalytic oxygenation mechanism is discussed based on the detection of radical intermediates by laser flash photolysis and ESR measurements as well as quantum yield determination.

Oxygenation of α-Methylstyrene with Molecular Oxygen, Catalyzed by 10-Methylacridinium Ion via Photoinduced Electron Transfer

Photooxygenation of α-methylstyrene with oxygen occurs efficiently in the presence of 10-methylacridinium perchlorate (AcrH+ClO4-) under visible light irradiation in oxygen-saturated acetonitrile (MeCN) to yield acetophenone as the main oxygenated product. No photoinduced oxygenation of α-methylstyrene occurs in the absence of AcrH+ under otherwise the same experimental conditions. Little photodegradation of AcrH+ occurs in the present photocatalytic system, which provides a clean method of photoinduced oxygenation reaction with molecular oxygen, alternate to the ene reaction of singlet oxygen. The photocatalytic oxygenation of α-methylstyrene with oxygen is shown to proceed via photoinduced electron transfer from α-methylstyrene to the singlet excited state of AcrH+ (1AcrH+*) on the basis of the fluorescence quenching of 1AcrH+* by α-methylstyrene, the quantum yield determination, and the detection of radical intermediates by laser flash photolysis and ESR measurements.

Galactose oxidase: Probing radical mechanism with ultrafast radical probe

The detection of radical intermediates in reaction mechanisms can be difficult. Many radicals are highly reactive species and have very short lifetimes. Many well established methods exist to detect radical intermediates, including direct electron spin resonance (ESR) detection and spin-trapping methods. Still, there are many problems in enzyme reaction mechanisms where such methods are not effective in addressing mechanistic questions. A radical at an enzyme active site will be short-lived if it is generated in the active site in close proximity to other radicals. This is not an uncommon situation. One selected example that illustrates this is in the reaction mechanism of flavin-containing monoamine oxidase enzymes. Electron transfer from the amine substrate to the flavin coenzyme generates a transient amine radical cation and flavin semiquinone radical. Further reactions can then lead to nonradical products and a normal catalytic turnover. This mechanism was determined through the use of radical clock radical-probing substrates to detect radical intermediates in the radical reaction mechanism. Ultrafast, hypersensitive radical-probing radical rearrangements represent the ultimate in the detection of radical intermediates in enzyme-catalyzed reactions. Such probes can detect radical intermediates that cannot be detected by any other expelfmental technique. The ultrafast, hypersensitive trans -2-phenylcyclopropylcarbinyl radical rearrangement, 5 to 6, has been applied to the study of several enzymes including galactose oxidase, the chloroperoxidase from Caldariomyces fumago , an alkane monooxygenase from Pseudomonas oleovorans , and cytochromes P450.

Stepwise Bond Formation in Photochemical and Thermal Diels−Alder Reactions of C60with Danishefsky's Dienes

Mechanisms of both the photochemical and thermal Diels−Alder reactions of C60 with Danishefsky's dienes are studied on the basis of product stereochemistry, kinetics, and the detection of radical intermediates. A stereochemically defined (1E,3Z)-1-methoxy-2-methyl-3-[(trimethylsilyl)oxy]-penta-1,3-diene (1a) is used as a stereochemical probe in the Diels−Alder reactions with C60. The major Diels−Alder product is trans-adduct (3) rather than cis-adduct (4) in both the photochemical and thermal Diels−Alder reactions. Such stereochemistry indicates that the Diels−Alder reactions proceed by a stepwise mechanism rather than a concerted mechanism. The transient spectra of C60•- formed in photoinduced electron transfer from 1a to the triplet excited state of C60 (3C60*) have been detected successfully in laser flash photolysis of the 1a-C60 system. The observed rate constants determined from the dependence of the quantum yields on the concentrations of Danishefsky's dienes agree well with those for the photoindu...

Aromatic radical anions as possible intermediates in the nucleophilic aromatic substitution (SNAr): an EPR study

The reactions among halonitrobenzenes or polynitrobenzenes and alkoxides, thiolates or tertiary amines have provided the evidence that in a SNAr reaction type a single electron transfer from the nucleophile to the aromatic substrate, to generate two radical species within the solvent cage, can take place to some extent. The detection of radical intermediates by EPR spectroscopy, in several SNAr reactions, is reported.

The Kinetics and Mechanism of the Pyrolysis of Manganese and Manganese Silicide CVD Precursors

The gas-phase pyrolysis of methyl pentacarbonyl manganese and acetyl pentacarbonyl manganese, both alone and in the presence of trimethyl silane, has been investigated using stirred flow reactor kinetic measurements and IR laser powered pyrolysis, together with electron spin resonance (ESR) detection of radical intermediates. For methyl pentacarbonyl manganese alone, all observations support a mechanism initiated by methyl–manganese bond homolysis, whereas the initial step in the acetyl compound involves CO loss and methyl migration. The addition of trimethylsilane sensitizes decomposition of MeMn(CO)5, yielding methane and trimethylsilyl pentacarbonyl manganese; on the other hand, Me3SiH has little effect on the rate of decomposition of MeCOMn(CO)5. A mechanism based on methyl migration is proposed to account for these observations.

Detection of radical intermediates in the photo-oxidation of alkanols by ceric ammonium nitrate-CAN. an EPR study

The photolysis of acetonitrile solutions of alkanols in the presence of ceric ammonium nitrate-CAN, at different temperatures, leads to the formation of alkyl, peroxyl and nitroxyl radicals identified by EPR spectroscopy. The involvement of free alkoxy and alkylperoxy radicals as intermediates in the reaction path will be discussed.

Mechanisms of photo-oxidation of NADH model compounds by oxygen

When an oxygen-saturated acetonitrile (MeCN) solution containing the NADH model compound, 9,10-dihydro-l0-methylacridine (AcrH2), is irradiated with u.v. light firstly in the presence and secondly in the absence of perchloric acid (HClO4), AcrH2 is oxidized by oxygen to yield the 10-methylacridinium ion (AcrH+) and 10-methyl-9-acridone (AcrO) respectively, and reduction of oxygen yields hydrogen peroxide. The u.v. irradiation of a neutral aqueous solution containing 1-benzyl-1,4-dihydronicotinamide (BNAH) also results in the oxidation of BNAH by oxygen to yield BNA+ and H2O2. Kinetic studies and detection of radical intermediates by e.s.r. spectroscopy have revealed that the photo-oxidation of NADH model compounds by oxygen proceeds via radical-chain reactions, which are initiated by electron transfer from the singlet excited state of NADH model compounds to oxygen. The chain carrier for the photo-oxidation of AcrH2 in the presence of HClO4 in MeCN as well as for the photo-oxidation of BNAH in a neutral aqueous solution is hydroperoxy radical (HO2˙), while acridinylperoxy radical (AcrO2˙) acts as a chain carrier for the photo-oxidation of AcrH2 in the absence of HClO4, in MeCN.Although no photo-oxidation of AcrH2 by oxygen occurs under visible-light irradiation, AcrH2 is efficiently oxidized to AcrH+ in the presence of a flavin analogue used as a sensitizer, in MeCN under otherwise identical conditions. The flavin-sensitized photo-oxidation of AcrH2 by oxygen proceeds via one-electron reduction of a flavin analogue by AcrH2 followed by the efficient oxidation of the reduced flavin by oxygen without the appreciable contribution of radical-chain processes.

光化学反応気体中に生成するラジカル中間体検出へのスピントラップ‐ＥＳＲ法の応用

光化学反応気体中に生成するラジカル中間体検出へのスピントラップ‐ＥＳＲ法の応用

Detection of radical intermediates at a mercury electrode: Criteria of mechanism

Detection of radical intermediates at a mercury electrode: Criteria of mechanism

Detection of Radical Intermediates in the Radiolysis of Hydrocarbons with the Ethylene-C14 Scavenging Technique

<b>Detection of Radical Intermediates in the Radiolysis of Hydrocarbons with the Ethylene-C¹⁴ Scavenging Technique</b>