Conformation and spectroscopy study of cycloheptoxy radical

Alkoxy radicals are important intermediates in the formation of tropospheric ozone. The spectroscopic identification and characterization of these species are important for understanding their chemistry in the atmosphere. In this work, we report the observation of the laser induced fluorescence (LIF) excitation spectrum of cycloheptoxy radical. The spectrum was assigned preliminary to the lowest energy twist-chair conformer (TC-i) of cycloheptoxy. The whole picture of the interconversions at ground state between different conformers of cycloheptoxy radicals was described by density functional theory calculations. The results revealed that despite the ring strain, the seven-membered ring alkoxy radical could exist in the supersonic jet-cooled condition. The decomposition and the low energy barrier pseudorotation between twist-chair conformers might be the reason of the much quieter spectrum of cycloheptoxy compared with the LIF spectrum of cyclohexoxy.     

Atmospheric reactions of alkoxy and β-hydroxyalkoxy radicals

Alkoxy and β-hydroxyalkoxy radicals are key intermediates formed in the atmospheric degradations of alkanes and alkenes, respectively. In the troposphere, these alkoxy radicals can decompose, isomerize, and react with O₂. The literature data concerning the rates of these reactions are evaluated, and predictive schemes allowing the calculation of rate constants for these alkoxy radical reactions for atmospheric purposes are proposed. Good agreement between calculated reaction rates and experimental data concerning the absolute and relative importance of these reaction pathways is obtained, and alkoxy and β-hydroxyalkoxy radical reaction rates for radicals for which experimental data are not presently available can now be calculated for use in atmospheric modeling. © 1997 John Wiley & Sons, Inc.     

The Effect of Alcohol and Carbonyl Functional Groups on the Competition between Unimolecular Decomposition and Isomerization in C4 and C5 Alkoxy Radicals

Presented here are computed rates for the thermal unimolecular decomposition of a variety of alkoxy radicals with four‐ and five‐carbon length backbones. Three classes of molecules are examined: alkoxy radicals with saturated hydrocarbon backbones, those with alcohol functional groups, and those with carbonyl functional groups. The chosen species represent many of those found during the combustion of fossil fuels as well as bio‐derived alternatives. Density functional theory calculations were benchmarked against higher level coupled cluster calculations and used to explore the potential energy surfaces of these systems. Transition state theory was used to calculate high‐pressure limit rate coefficients of all radical intermediates in the regimes relevant to atmospheric chemistry and combustion. We show that the assumption that alkoxy radicals quickly decompose via β‐scission to aldehydes and other radicals is not valid for some of the alkoxy radicals investigated in this work. We further illustrate how intra‐H migrations in larger alkoxy radicals with carbonyl and alcohol functional groups can dominate unimolecular decomposition under combustion and atmospheric relevant conditions. Finally, we discuss why carbonyl groups can increase or decrease intra‐H migration barriers depending on their location relative to the transferring H‐atom.     

Catalytic generation of alkoxy radicals from unfunctionalized alcohols

Alkoxy radicals have long been recognized as powerful synthetic intermediates with well-established reactivity patterns. Due to the high bond dissociation free energy of aliphatic alcohol O–H bonds, these radicals are difficult to access through direct homolysis, and conventional methods have instead relied on activation of O-functionalized precursors. Over the past decade, however, numerous catalytic methods for the direct generation of alkoxy radicals from simple alcohol starting materials have emerged and created opportunities for the development of new transformations. This minireview discusses recent advances in catalytic alkoxy radical generation, with particular emphasis on progress toward the direct activation of unfunctionalized alcohols enabled by transition metal and photoredox catalysis.     

Epoxide formation by ring closure of the cinnamyloxy radical

[formula: see text] The cinnamyloxy and oxiranyl benzyl radicals were generated by photolysis of alkyl 4-nitrobenzenesulfenates. The yet unprecedented epoxide ring formation from a primary alkoxy radical was observed. Experimental evidence supports the fact that the mode of ring opening of the oxiranyl carbinyl radical system is thermodynamically driven. B3LYP/6-31G* calculations indicate that the closed form of the radical is approximately 5 kcal/mol more stable than the open one.     

A DFT study of H-isomerisation in alkoxy-, alkylperoxy- and alkyl radicals: Some implications for radical chain reactions in polymer systems

Intramolecular 1-n H-shift (n = 2, 3… 7) reactions in alkoxy, alkyl and peroxy radicals were studied by density functional theory (DFT) at the B3LYP/6-311+G∗∗ level and compared with respective intermolecular H-transfers. It was found that starting from 1 to 3 H-shift the barrier heights stepwise decrease with increasing n reaching minimum for 1-5 and 1-6 H-shifts. This dependence can be ascribed to the decrease of the strain with increasing transition state (TS) ring size, which is minimal in six- and seven-member rings. The barrier heights of H-shifts in alkyl radicals are systematically larger than those in alkoxy radicals: the respective activation energies (E_a) of 1-5 and 1-6 H-shifts are about 59-67 kJ/mol for alkyl radical and 21-34 kJ/mol for alkoxy radicals. Further increase of the TS ring size in 1-7 H-shifts leads to the increase of the barrier to 44 kJ/mol in the hexyloxy radical and 84 kJ/mol for n-heptyl radical. We have also found that intermolecular H-transfer reactions in all three types of free radicals have smaller barriers than respective intramolecular 1-5 or 1-6 H-shifts by 4-25 kJ/mol. The mentioned difference can be explained in terms of enhanced nonbonding repulsion interaction in the cyclic TS structures compared to respective intermolecular TS. B3LYP/6-311+G∗∗ geometric parameters and imaginary frequencies for 1-n H-shifts TS are consistent with respective calculated barrier heights. Reactivity of some other radicals compared to alkoxy, peroxy and alkyl radicals as well as other factors influencing their reactivity (π-conjugation, steric effect and ring strain in cyclic TS, etc.) are also briefly discussed in relation to free radical reactions in polymer systems.     

Visible Light-Promoted Ring-Opening Alkenylation of Cyclic Hemiacetals through β-Scission of Alkoxy Radicals

The chemistry of alkoxy radicals was extensively explored during the period of 1960s to 1990s, but it has remained dormant for the past few decades. Recently, alkoxy radicals attract the attentions again, because new methods for generating alkoxy radical species have emerged. These newly developed methods are mainly based on the photolysis by visible light under mild conditions, thus allowing for new transformations of the carbon-centered radical species that are generated from the β-scission or hydrogen abstraction of the alkoxy radicals. Herein, we demonstrate that the alkoxy radicals derived from cyclic hemiacetals can be generated through visible-light-induced electron transfer with sodium iodide and triphenylphosphine as the catalyst. The alkoxy radicals subsequently undergo β-scission to generate carbon-centered radicals, which are trapped by cinnamic acids, aryl alkenes, vinylboronic acid and silyl enol ether to deliver the corresponding C—C bond forming products. This catalytic method for ring-opening alkenylation reaction of cyclic hemiacetal derivatives under visible-light irradiation conditions demonstrates the compatibility of the visible light-promoted alkoxy radical generation method with various carbon radical trapping processes. This work opens up new possibilities for the application of alkoxy radicals in organic synthesis.      

Photocatalytic Degradation of Ethyl tert‐Butyl Ether in Aqueous Solution Mediated by TiO2 Suspensions: Parameter and Reaction Pathway Investigations

Degradation of ethyl tert‐butyl ether (ETBE) with UV/TiO₂ was studied by solid‐phase microextraction and gas chromatography‐mass spectrometry. The complete removal of 0.1 g L^?1 of ETBE was achieved after 20 h of treatment. Factors such as pH of the system, catalyst and substrate concentration, and the presence of anions influenced the degradation rate. Establishment of the degradation pathway was made possible by a thorough analysis of the reaction mixture, which identified the main intermediate products generated. The possible degradation pathways were proposed and discussed in this research. The attack on the C–H bond in ETBE by ·OH forms an alkyl radical, which consequently produces a peroxyl radical upon reaction with oxygen. Peroxyl radicals react with one another and produce an alkoxy radical. The β‐bond fragmentation of the alkoxy radical produces different intermediates.     

Free radical induced oxidation of alkoxyphenols: Some insights into the processes of photoyellowing of papers

The photoyellowing of lignin-rich papers has been demonstrated to depend on the formation of phenoxyl radical intermediates and their ultimate conversion into various products, including quinones. Molecular oxygen has also been observed as a necessary adjunct to this process, although the mechanism is not understood. This work demonstrates the requirement for the reaction of O² with active radical intermediates (in processes analogous to autoxidation reactions) in order for the photoyellowing of the phenolic moieties to occur. Photo-oxidations of a variety of alkoxyphenols and their reactions with model alkyl, alkoxy and alkylperoxy radicals are studied by CIDEP.     

Mechanistic insight into the aromatic hydroxylation by high-valent iron(IV)-oxo porphyrin pi-cation radical complexes

Mechanistic studies of the aromatic hydroxylation by high-valent iron(IV)-oxo porphyrin pi-cation radicals revealed that the aromatic oxidation involves an initial electrophilic attack on the pi-system of the aromatic ring to produce a tetrahedral radical or cationic sigma-complex. The mechanism was proposed on the basis of experimental results such as a large negative Hammett rho value and an inverse kinetic isotope effect. By carrying out isotope labeling studies, the oxygen in oxygenated products was found to derive from the iron-oxo porphyrin intermediates.     

Radiolysis of aqueous DCH18C6 solutions at 77 K

Low-temperature (77 K) γ- and X-ray radiolysis of aqueous DCH18C6 solutions was studied by ESR-spectroscopy. OH radicals, trapped electrons and macrocyclic radicals -CH₂-CH-O- resulting from H-atom abstraction from methylene groups of polyether ring were identified as predominant radiolysis products. Increasing the crown ether concentration in aqueous solution leads to the growth of relative yields of the trapped electron and macrocyclic radicals as well as the decrease of that of hydroxyl radical. Neither radical products of macrocycle rupture nor H-atom abstraction from cyclohexane rings were observed.     

Reactivity of (eta(6)-arene)tricarbonylchromium complexes toward additions of anions, cations, and radicals.

A computational and experimental study of additions of electrophiles, nucleophiles, and radicals to tricarbonylchromium-complexed arenes is reported. Competition between addition to a complexed arene and addition to a noncomplexed arene was tested using 1,1-dideuterio-1-iodo-2-((phenyl)tricarbonylchromium)-2-phenylethane. Reactions under anionic and cationic conditions give exclusive formation of 1,1-dideuterio-1-((phenyl)tricarbonylchromium)-2-phenylethane arising from addition to the complexed arene. Radical conditions (SmI(2)) afford two isomeric products, reflecting a 2:1 preference for radical addition to the noncomplexed arene. In contrast, intermolecular radical addition competition experiments employing ketyl radical addition to benzene and (benzene)tricarbonylchromium show that addition to the complexed aromatic ring is faster than attack on the noncomplexed species by a factor of at least 100,000. Density functional theory calculations using the B3LYP method, employing a LANL2DZ basis set for geometry optimizations and a DZVP2+ basis set for energy calculations, for all three reactive intermediates showed that tricarbonylchromium stabilizes all three types of intermediates. The computational results for anionic addition agree well with established chemistry and provide structural and energetic details as reference points for comparison with the other reactive intermediates. Intermolecular radical addition leads to exclusive reaction on the complexed arene ring as predicted by the computations. The intramolecular radical reaction involves initial addition to the complexed arene ring followed by an equilibrium leading to the observed product distribution due to a high-energy barrier for homolytic cleavage of an exo bond in the intermediate cyclohexadienyl radical complex. Mechanisms are explored for electrophilic addition to complexed arenes. The calculations strongly favor a pathway in which the cation initially adds to the metal center rather than to the arene ring.     

Vibrationally resolved LIF spectrum of tertiary methylcyclohexoxy radical

Cyclohexoxy radical and its substitutes are intermediates of the combustion reaction in automobile engines, and hence play an important role in the atmospheric chemistry. Spectroscopic and conformational studies can provide convenient methods to monitor these species. In this work, we report the observation of the laser induced fluorescence (LIF) excitation spectrum of 1-methylcyclohexoxy, a tertiary ring alkoxy radical, in supersonic jet condition. The spectrum was assigned preliminarily to the chair-axial and chair-equatorial conformers of 1-methylcyclohexoxy. No C-O stretch progression was observed in 1-methylcyclohexoxy spectrum, which was different from t-butoxy. The short lifetime of excited state 1-methylcyclohexoxy and increased C-O bond length suggested a less stable excited state induced by the increased steric repulsion via methyl substitution on the alkoxy carbon. Dissociation rather than H transfer was suggested as the major nonradiative relaxation process, which competed with the fluorescence path.     

Photocatalytic alkoxy radical-mediated transformations

Alkoxy radicals have been intensively studied as versatile synthetic intermediates with well-established reactivity and selectivity. Due to the difficulties associated with the generation of these transient and high-energy radicals, the utilization of the unique reactivity of alkoxy radicals in catalytic platforms has become a rather challenging task. Recent studies on the alkoxy radical-mediated transformations have benefited tremendously from advances in modern photoredox catalysis. In this digest, we aim to highlight reported transformations that utilize alkoxy radicals in a photocatalytic fashion, in particular, underline novel catalytic platforms which we anticipate will find broad application in the near future.     

Identification of primary free radicals in trehalose dihydrate single crystals X-irradiated at 10 K

Primary free radical formation in trehalose dihydrate single crystals X-irradiated at 10 K was investigated at the same temperature using X-band Electron Paramagnetic Resonance (EPR), Electron Nuclear Double Resonance (ENDOR) and ENDOR-induced EPR (EIE) techniques. The ENDOR results allowed the unambiguous determination of six proton hyperfine coupling (HFC) tensors. Using the EIE technique, these HF interactions were assigned to three different radicals, labeled R1, R2 and R3. The anisotropy of the EPR and EIE spectra indicated that R1 and R2 are alkyl radicals (i.e. carbon-centered) and R3 is an alkoxy radical (i.e. oxygen-centered). The EPR data also revealed the presence of an additional alkoxy radical species, labeled R4. Molecular modeling using periodic Density Functional Theory (DFT) calculations for simulating experimental data suggests that R1 and R2 are the hydrogen-abstracted alkyl species centered at C5' and C5, respectively, while the alkoxy radicals R3 and R4 have the unpaired electron localized mainly at O2 and O4'. Interestingly, the DFT study on R4 demonstrates that the trapping of a transferred proton can significantly influence the conformation of a deprotonated cation. Comparison of these results with those obtained from sucrose single crystals X-irradiated at 10 K indicates that the carbon situated next to the ring oxygen and connected to the CH(2)OH hydroxymethyl group is a better radical trapping site than other positions.     

Oxidation of Cyclohexane by Molecular Oxygen Photoassisted by meso-Tetraarylporphyrin Iron(III)-Hydroxo Complexes

The photochemical and photocatalytic properties of iron meso-tetraarylporphyrins bearing an OH(-) axial ligand and different substituents in the beta-positions of the porphyrin ring are reported. Irradiation (lambda = 365 nm) in the absence of dioxygen leads to the reduction of Fe(III) to Fe(II) with the formation of OH(*) radicals. Substituents at the pyrrole beta-positions are found to markedly affect the photoreduction quantum yields. Under aerobic conditions, this photoreaction can induce the subsequent oxidation of cyclohexane to cyclohexanone and cyclohexanol by O(2) itself. The process occurs under mild conditions (22 degrees C; 760 Torr of O(2)) and without the consumption of a reducing agent. The polarity of the solvent and the nature of the porphyrin ring have a remarkable effect on the selectivity of the photooxidation process, likely controlling the cleavage of O-O bonds of possible iron peroxoalkyl intermediates. In particular, in pure cyclohexane, oxidation occurs with the selective formation of cyclohexanone; in contrast, in dichloromethane/cyclohexane mixed solvent, the main oxidation product is cyclohexanol. Phenyl-tert-butylnitrone (pbn) has been found to quench the radical chain autooxidation of the substrate thus increasing the yield of cyclohexanol. This becomes the only oxidation product when iron 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin hydroxide (Fe(III)(TDCPP)(OH)) is used as photocatalyst.     

Some new aspects of benzyne and radical mediated cyclisations

KNH₂/NH₃ cyclisations of some alkoxy substituted arylhalides proceed in poor yields. This shortcoming may be overcome by the use of LDA/THF to effect the ring closure which may occur through benzyne or radical intermediates. Besides ortho halogenated dihydroanils and amides, the cyclisation of the benzylamine Schiff bases also provides a convenient route to isoquinoline alkaloids.     

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.     

Radical carbonylation of ω-alkynylamines leading to α-methylene lactams. Synthetic scope and the mechanistic insights

Tin hydride mediated radical carbonylation and cyclization reaction was investigated using a variety of ω-alkynyl amines as substrates. In this reaction α-methylene and α-stannylmethylene lactams having five to eight membered rings were obtained as principal products. In cases where the nitrogen has a substituent capable of giving stable radicals, such as an α-phenethyl group, the lactam ring formation again took place with extrusion of an α-phenethyl radical. Coupled with the subsequent protodestannylation procedure (TMSCl plus MeOH), these reactions provide a useful entry to α-methylene lactams with incorporation of CO as a lactam carbonyl group. In cases where the amines do not have a substituent acting as a radical leaving group, a reaction course involving a 1,4-H shift is chosen so as to liberate tin radicals ultimately. Thus the proposed mechanism involves (i) nucleophilic attack of amine nitrogen onto a carbonyl group of α,β-unsaturated acyl radicals/α-ketenyl radicals via lone pair-π* interaction, which leads to zwitterionic radical species, (ii) the subsequent proton shift from N to O to give hydroxyallyl radicals, (iii) 1,4-hydrogen shift from O to C, and (iv) β-scission to give lactams with liberation of tin radicals. DFT calculations reveal that the 1,4-hydrogen shifts, the key step of the reaction mechanism, can proceed under usual reaction conditions. On the other hand, an S(H)i type reaction to give lactams may be the result of the β-scission of the similar zwitterionic radical intermediates. DFT calculations also predict that an S(H)i type reaction would result when the intermediate has a good (radical) leaving group such as a phenethyl group.     

Hydrogen atom abstraction reactions of charged polyaromatic sigma-radicals related to the active intermediates of the enediyne antitumor drugs

Polar effects are demonstrated to play an important role in controlling the reactivity of polyaromatic sigma-radicals that are structurally related to the active intermediates of the enediyne anticancer type antibiotics. This was accomplished by measuring the rate constants of hydrogen atom abstraction for novel, charged dehydroquinolines, dehydroisoquinolines, dehydrobenzenes, and dehydronaphthalenes in the gas phase by using Fourier-transform ion cyclotron resonance mass spectrometry. The reactivity trends observed for these radicals upon hydrogen atom abstraction from tetrahydrofuran and 2-methyltetrahydrofuran, simple models of deoxyribose, do not reflect differences in reaction exothermicities, radical sizes, exact location of the radical site in the ring system, or heteroatom-radical site distances. However, the reactivity trends match the trend in the calculated electron affinities of the radicals. The radicals' different electrophilicities result in variations in the reaction barrier due to different extents of polarization of the transition state. Generally, the reaction efficiencies are the greatest when the formally charged heteroatom is contained within the same ring system as the radical site. In this case, polar effects have the greatest influence on radical reactivity. Hence, insertion of a basic heteroatom (which gets protonated in biological systems) into specific locations in the polyaromatic ring system of the sigma-biradicals, which ultimately cause cleavage of DNA exposed to the enediyne antitumor drugs, should allow tuning of the reactivity of these radicals.