Preparation of beta-and gamma-lactams via ring closures of unsaturated carbamoyl radicals derived from 1-carbamoyl-1-methylcyclohexa-2,5-dienes

1-Carbamoyl-1-methylcyclohexa-2,5-dienes produced the corresponding delocalised 1-carbamoyl-1-methylcyclohexa-2,5-dienyl radicals on treatment with radical initiators. At temperatures above ca. 300 K dissociation to produce toluene and aminoacyl (carbamoyl) radicals took place. The alternative dissociation of the 1-carbamoyl-1-methylcyclohexa-2,5-dienyl radicals to release methyl radicals and an aromatic amide did not compete. Aminoacyl radicals with allyl, butenyl or similar side chains underwent cyclisations. Moderate yields of N-benzyl-azetidin-2-ones and N-benzyl-pyrrolidin-2-ones were isolated for a range of substituents. The main by-products were N-benzyl-N-alkenylformamides. Ring closure did not take place to a significant extent for precursors with alk-2-ynyl or 2-cyanoalkyl side chains. An improved yield of 1,3-dibenzylazetidin-2-one was obtained by use of lauroyl peroxide as initiator and by inclusion of methyl thioglycolate as polarity reversal catalyst.     

Radical alkylphosphanylation of olefins with stannylated or silylated phosphanes and alkyl iodides

Intermolecular conjugate radical addition reactions of secondary and tertiary alkyl radicals derived from the corresponding alkyl iodides to activated olefins such as α,β-unsaturated esters, amides, imides, nitriles, and sulfones are described. The adduct radicals are trapped by either diphenyl(trimethylstannyl)phosphane or the commercially available diphenyl(trimethylsilyl)phosphane as chain transfer reagents to give the corresponding phosphanylated products in moderate to good yields. The overall process comprises a C-C followed by a C-P bond formation.     

Organophosphorus antioxidants—VIII. Kinetics and mechanism of the reaction of organic phosphites with peroxyl radicals

Trialkyl phosphites react with cyanoisopropylperoxyl radicals, generated by thermolysis of azobis(isobutyronitrile) in the presence of oxygen, to give the corresponding phosphates with rate constants of the order of 10³ M⁻¹ sec⁻¹ at 65°C. Phenyl phosphites are oxidized also. A small amount of cyanoisopropyl phosphite is formed by substitution of the phosphite by alkyloxyl radicals leading to phenoxyl radicals. Sterically hindered aryl phosphites react with cyanoisopropylperoxyl radicals to yield the corresponding phosphates and alkoxyl radicals which in a second step react with phosphite by substitution releasing a sterically hindered phenoxyl radical. Therefore, sterically hindered phosphites are capable of acting as chain-terminating primary antioxidants. Because the rate constants of reaction of these phosphites with peroxyl radicals are only in the range of 10² M⁻¹ sec⁻¹ and 100 times smaller than those of phenols, phosphites should be less active as primary antioxidants than phenols.     

Mn(III)-based oxidative free-radical cyclizations of substituted allyl alpha-methyl-beta-ketoesters: syntheses,DFT calculations,and mechanistic studies

The cyclizations of the substituted allyl alpha-methyl-beta-ketoester radicals 11, 14, and 18 were studied by the DFT method at the UB3LYP/6-31G level; the results show that the cis cyclization is easier than the corresponding trans cyclization, but the generated cis radicals are not necessarily more stable than the corresponding generated trans radicals after the cyclizations. The free-radical cyclizations of 11, 14, and 18 in the presence of Mn(OAc)(3) in acetic acid or acetonitrile are all reversible and operate under thermodynamic control, and stereoselectivity of the cyclizations depends on relative stability of the cyclization-generated radicals. Therefore, the oxidative free-radical cyclization of allyl alpha-methyl-beta-ketoester 5a with Mn(OAc)(3) gives a cis product as a major product, while the same oxidative free-radical cyclizations of substituted allyl alpha-methyl-beta-ketoesters 5b and 5c with Mn(OAc)(3) produce trans products as major products.     

Synthesis of β-hydroxyphosphonates by iron-catalyzed oxidative addition of phosphonyl radicals to alkenes

Phosphorohydrazidates have been shown to work as radical precursors by iron-catalyzed aerobic oxidation to generate corresponding phosphonyl radicals. Generated radicals cause intermolecular addition to various alkenes in the presence of molecular oxygen to give β-hydroxyphosphonate compounds in good yield.     

Synthesis and characterization of a new family of spin bearing TTF ligands

The syntheses and characterization of two new tetrathiafulvalene (TTF) derivatives bearing pyridine-based substituents and 1,5'-dimethyl-6-oxoverdazyl radicals are described. The TTF-pyridine and bipyridine aldehydes were prepared via a palladium-catalyzed cross-coupling reaction between mono(tributylstannyl)tetrathiafulvalene (3) and the appropriate formylpyridyl halides (4). The radical precursors, the corresponding 1,2,4,5-tetrazanes, were prepared by condensation of the bis(1-methylhydrazide) of carbonic acid with the TTF bearing pyridyl aldehyde. Oxidation of tetrazanes 8 and 9 with 1,4-benzoquinone afforded the donor radicals 1 and 2 as 1:1 complexes with hydroquinone. Both complexes are stable in the solid state and their electronic properties have been characterized by EPR, cyclic voltammetry, and UV/vis spectroscopy. The TTF core of both compounds was oxidized both chemically and electrochemically to afford the corresponding cation diradical species. The electronic properties of both donor radicals have been probed by cyclic voltammetry, UV-vis spectroscopy, and preliminary EPR measurements.     

Electrochemical and ESR studies of aromatic nitroso spin traps

The oxidation and reduction potentials of 23 nitroso compounds among which were included the most important spin traps have been determined by means of cyclic voltammetry and voltammetry at the rotating electrode. The electron transfer generally involved one electron, leading to the corresponding ion radicals. When persistent species resulted from the electron transfer, their ESR spectra were recorded and analyzed with the help of EHT calculations. The observed anion radicals are typical delocalized Π radicals, while the cation radicals are Σ radicals with a SOMO orthogonal to the Π system. Secondary species formed from these primary ion radicals were also observed and identified by e.s.r.     

Visible-Light-Promoted Ring-Opening Alkynylation,Alkenylation, and Allylation of Cyclic Hemiacetals through β-Scission of Alkoxy Radicals

The alkoxy radicals that are derived from cyclic hemiacetals have been generated through the visible-light-promoted reaction of the corresponding N-alkoxyphthalimides with Hantzsch ester as the reductant. The alkoxy radicals subsequently undergo β-scission of the C−C bond to generate carbon-centered radicals, which are trapped by alkynyl-, alkenyl-, or allylsulfones.     

Mechanism of action of sensors for reactive oxygen species based on fluorescein-phenol coupling: the case of 2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid

We demonstrate the ability of a sensor containing a tethered fluorescein-phenol structure to react with peroxyl radicals and with an oxidizing agent such as potassium ferricyanide. This latter reaction yields the corresponding peroxyl radical as observed by EPR analysis. We propose that the reaction of the sensor with peroxyl and alkoxyl radicals is also initiated by the formation of the phenoxyl radicals, which is followed by radical-radical reactions and product hydrolysis responsible for the release of fluorescein. The proposed mechanism is based on results obtained by laser flash photolysis, HPLC and EPR studies of the reaction of peroxyl and alkoxyl radicals with 4-phenoxylphenol, a molecule used to mimic the behavior of the sensor.     

Confirmed assignments of isomeric dimethylbenzyl radicals generated by corona discharge

The controversial vibronic assignments of isomeric dimethylbenzyl radicals were clearly resolved by using different precursors. By employing corresponding dimethylbenzyl chlorides as precursors, we identified the origins of the vibronic bands of the dimethylbenzyl radicals generated by corona discharge of 1,2,4-trimethylbenzene. From the analysis of the spectra observed from the dimethylbenzyl chlorides in a corona excited supersonic expansion, we revised previous assignments of the 3,4-, 2,4-, and 2,5-dimethylbenzyl radicals. Spectroscopic data of electronic transition and vibrational mode frequencies in the ground electronic state of each isomer were accurately determined by comparing them with those obtained by an ab initio calculation and with the known vibrational data of 1,2,4-trimethylbenzene.     

Radical ions from and spin adducts to 1,2-dimethyl-3,4-bis[(2,4,6-tri-<Emphasis Type="Italic">tert</Emphasis>-butylphenyl) phosphinidene]-1-cyclobutene

The radical cation and anion of the title compound were obtained either by treatment with mercury trifluorocatetate in trifluoroacetic acid or by reduction with potassium in tetrahydrofurane. For both species the ESR spectra indicated magnetic non-equivalence of the two phosphorus atoms, as well as of the two methyl groups. Spectra attributed to the corresponding spin adducts were also observed when reacting the title compound with in situ-generated alkoxyl and thiyl radicals. MO calculations carried out for both the ionic radicals and the neutral spin adducts led to questioning the actual nature of some of the latter species.     

Antioxidant properties of natural and synthetic chromanol derivatives: study by fast kinetics and electron spin resonance spectroscopy

[structure: see text] Chromanol-type compounds act as antioxidants in biological systems by reduction of oxygen-centered radicals. Their efficiency is determined by the reaction rate constants for the primary antioxidative reaction as well as for disproportionation and recycling reactions of the antioxidant-derived radicals. We studied the reaction kinetics of three novel chromanols: cis- and trans-oxachromanol and the dimeric twin-chromanol, as well as ubichromanol and ubichromenol, in comparison to alpha-tocopherol and pentamethylchromanol. The antioxidant-derived radicals were identified by optical and electron spin resonance spectroscopy (ESR). The kinetics of the primary antioxidative reaction and the disproportionation of the chromanoxyl radicals were assessed by stopped-flow photometry in different organic solvents to simulate the different polarities associated with biomembranes. Furthermore, the reduction of the chromanoxyl radicals by ubiquinol and ascorbate was measured after laser-induced one-electron chromanol oxidation in ethanol and in a micellar system, respectively. The rate constants showed that twin-chromanol had better radical scavenging properties than alpha-tocopherol and a significantly slower disproportionation rate of its corresponding chromanoxyl radical. In addition, the radical derived from twin-chromanol is reduced by ubiquinol and ascorbate at a faster rate than the tocopheroxyl radical. Finally, twin-chromanol can deliver twice as many reducing equivalents, which makes this compound a promising new candidate as artificial antioxidant in biological systems.     

On the question of heavy-atom blocking of intramolecular vibrational energy transfer

The possibility that a heavy atom can block internal energy transfer in excited species has been further investigated by chemical activation study of 4-(trimethyl lead)-2-butyl and 5-(trimethyl tin)-2-pentyl radicals. These radicals were prepared and excited by the reaction of H atoms with the corresponding 1-olefins. Energy randomization was found to occur on a subpicosecond time scale in all the radicals studied.     

Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin

Free radicals/reactive oxygen species (ROS) generated in skin by UV irradiation were measured by electron spin resonance (ESR). To increase the sensitivity of measurement the short life free radicals/ROS were scavenged and accumulated by using the nitroxyl probe 3-carboxy-2,2,5,5-tetrametylpyrrolidine-1-oxyl (PCA). The spatial distribution of free radicals/ROS measured in pig skin biopsies with ESR imaging after UV irradiation corresponds to the intensity decay of irradiance in the depth of the skin. The main part of free radicals/ROS were generated by UVA (320-400 nm) so that the spatial distribution of free radicals reaches up to the lower side of the dermis. In vivo measurements on human skin were performed with a L-band ESR spectrometer and a surface coil integrating the signal intensities from all skin layers to get a sufficient signal amplitude. Using this experimental arrangement the protection of UVB and UVA/B filter against the generation of free radicals/ROS in skin were measured. The protection against ROS and the repair of damages caused by them can be realized with active antioxidants characterized by a high antioxidative power (AP). The effect of UV filter and antioxidants corresponding to their protection against free radicals/ROS in skin generated by UVAB irradiation can be quantified by the new radical sun protection factor (RSF). The RSF indicates the increase of time for staying in the sun to generate the same number of free radicals/ROS in the skin like for the unprotected skin. Regarding the amount of generated free radicals/ROS in skin as an biophysical endpoint the RSF characterizes both the protection against UVB and UVA radiation.     

Pulse EPR and ENDOR study of 1,2,3-benzodithiazolyl, 2,1,3-benzothiaselenazolyl and 1,2,3-benzodiselenazolyl radicals

1,2,3-Benzodithiazolyl, 2,1,3-benzothiaselenazolyl and 1,2,3-benzodiselenazolyl radicals were generated by the reduction of the corresponding cations and investigated by pulse EPR and ENDOR in frozen CHCl(3) solutions at 30 and 80 K. These methods, in combination with density functional theory calculations, were used to study the magnetic parameters of the radicals, namely the principal values of the nitrogen and proton hyperfine interactions and g-tensors. The spin density distribution was shown to be nearly the same for all investigated radicals and, therefore, replacement of sulfur by selenium leads to a limited perturbation of the radicals' electronic structure. A high anisotropy of the g-tensors was found for the selenium-containing radicals.     

Radical/Cation Transformation Polymerization and Its Application to the Preparation of Block Copolymers

Abstract

ESR study on the primary radicals obtained by decomposition of azo-compounds showed that primary radicals with electron donating substituents were transformed to the corresponding cations in the presence of electron acceptors such as ph₂I⁺PF^? ₆. Accordingly, propagating radicals are transformed to the corresponding cations in the polymerization of p-methoxy-styrene (MOS), n-butyl vinyl ether (BVE), and N-vinylcarbazole (VCZ) with azoinitiators such as AIBN in the presence of electron acceptors such as Ph₂I⁺PF^? ₆. In the case of BVE, the polymer formation was caused by cationic species produced by the transformation of the initiating radical. The polymerizations of MOS and VCZ were ascribed to the transformation of the growing radical to the corresponding cation during the propagation step which was classified as the radical/cation transformation polymerization. Block copolymers of MOS/cyclohexene oxide (CHO) and VCZ/CHO were effectively prepared by the radical/cation transformation polymerization of the appropriate monomers in the presence of AIBN, electron acceptor and CHO. The formation of block copolymers was characterized by turbidimetry, thin-layer chromatography, and solubility tests.     

Generation and spectroscopic profiles of stable multiarylaminium radical cations bridged by fluorenes

A series of arylaminofluorene derivatives (DTFA-1, TTFA-2, TAFB-3, and TAFA-4) were synthesized, and the generation of their corresponding arylaminium cation radicals was readily achieved by Cu(ClO(4))(2) in CH(3)CN. Moreover, the cation radicals were stable at ambient temperature with substantially long life times and exhibited distinct colors. The oxidation mechanism and spectroscopic features of the resulting cation radicals were probed by UV-vis-NIR spectroscopy and electron spin resonance experiments.     

Sila- and Germacarboxylic Acids: Precursors for the Corresponding Silyl and Germyl Radicals

Silicon-containing compounds are widely used as synthetic building blocks, functional materials, and bioactive reagents. In particular, silyl radicals are important intermediates for the synthesis and transformation of organosilicon compounds. Herein, we describe the first protocol for the generation of silyl radicals by photoinduced decarboxylation of silacarboxylic acids, which can be easily prepared in high yield on a gram scale and are very stable to air and moisture. Irradiation of silacarboxylic acids with blue LEDs (455 nm) in the presence of a commercially available photocatalyst releases silyl radicals, which can further react with various alkenes to give the corresponding silylated products in good-to-high yields with broad functional-group compatibility. This reaction proceeds in the presence of water, enabling efficient deuterosilylation of alkenes with D₂O as the deuterium source. Germyl radicals were similarly obtained.     

Theoretical and experimental investigation on the oxidation of gallic acid by sulfate radical anions

By monitoring the decay of SO4*- after flash photolysis of aqueous solutions of S2O82- at different pH values, the kinetics of the reaction of SO4*- radicals with gallic acid and the gallate ion was investigated. The bimolecular rate constants for the reactions of the sulfate radicals with gallic acid and the gallate ion were found to be (6.3 +/- 0.7) x 10(8) and (2.9 +/- 0.2) x 10(9) M(-1) s(-1), respectively. On the basis of the oxygen-independent second-order decay kinetics and on their absorption spectra, the organic radicals formed as intermediates of these reactions were assigned to the corresponding phenoxyl radicals. DFT calculations in the gas phase and aqueous solution support formation of the phenoxyl radicals by H abstraction from the phenols to the sulfate radical anion. The observed recombination of the phenoxyl radicals of gallic acid to yield substituted biphenyls and quinones is also supported by the calculations. HPLC/MS product analysis showed formation of one of the predicted quinones.     

Single-component organic semiconductors based on novel radicals that exhibit electrochemical amphotericity: preparation, crystal structures, and solid-state properties of N,N'-dicyanopyrazinonaphthoquinodiiminides substituted with an N-alkylpyridinium unit.

N,N'-Dicyanonaphthoquinodiimines fused with a pyrazine ring 1 were prepared from the corresponding quinones 4. The new acceptors 1 have a planar pi-system and undergo reversible two-stage 1e-reduction. Quaternization of the pyridyl substituent in 1d-f gave pyridinium derivatives 2d+, 2e+, and R-3+, respectively, which are stronger acceptors that undergo three-stage 1e-reduction. Upon electrochemical reduction of these cations, novel radicals 2d., 2e., and R-3. were generated and isolated as stable solids. The molecular geometries determined by X-ray analysis indicated that these radicals adopt a zwitterionic structure, in which the unpaired electron is located on the quinodiimine unit but not on the pyridyl group. These novel radicals undergo facile and reversible 1e-oxidation as well as two-stage 1e-reduction. The observed amphotericity endows the radicals with electrical conductivities (10(-5) to 10(-9) S cm-1), and these thus represent a new motif for single-component organic semiconductors.