Solvent‐Free One‐Step Photochemical Hydroxylation of Benzene Derivatives by the Singlet Excited State of 2,3‐Dichloro‐5,6‐dicyano‐p‐benzoquinone Acting as a Super Oxidant

Photoinduced hydroxylation of neat deaerated benzene to phenol occurred under visible‐light irradiation of 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ), which acts as a super photooxidant in the presence of water. Photocatalytic solvent‐free hydroxylation of benzene derivatives with electron‐withdrawing substituents such as benzonitrile, nitrobenzene, and trifluoromethylbenzene used as neat solvents has been achieved for the first time by using DDQ as a super photooxidant to yield the corresponding phenol derivatives and 2,3‐dichloro‐5,6‐dicyanohydroquinone (DDQH₂) in the presence of water under deaerated conditions. In the presence of dioxygen and tert‐butyl nitrite, the photocatalytic hydroxylation of neat benzene occurred with DDQ as a photocatalyst to produce phenol. The photocatalytic reactions are initiated by oxidation of benzene derivatives with the singlet and triplet excited states of DDQ to form the corresponding radical cations, which associate with benzene derivatives to produce the dimer radical cations, which were detected by the femto‐ and nanosecond laser flash photolysis measurements to clarify the photocatalytic reaction mechanisms. Radical cations of benzene derivatives react with water to yield the OH‐adduct radicals. On the other hand, DDQ ^{. ?} produced by the photoinduced electron transfer from benzene derivatives reacts with the OH‐adduct radicals to yield the corresponding phenol derivatives and DDQH₂. DDQ is recovered by the reaction of DDQH₂ with tert‐butyl nitrite when DDQ acts as a photocatalyst for the hydroxylation of benzene derivatives by dioxygen.     

Scavenging activity of C4‐hydroxyphenyl‐ and polyhydroxyphenyl‐1,4‐dihydropyridines toward free radicals

The radical‐scavenging ability of synthesized C4‐phenolic‐substituted 1,4‐dihydropyridines (1,4‐DHPs) toward 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH^?) and alkyl/alkylperoxyl ABAP‐derived radicals at pH 7.4 was assessed by UV–visible spectroscopy. Reactivity of 1,4‐DHPs toward DPPH^? was measured by following the decay of the absorption corresponding to the radical λ_max at 525 nm, permitting the calculation of EC₅₀, t_EC50, and antiradical efficiency values. Pseudo–first‐order kinetic rate constants for the reactivity between the C4‐phenolic‐substituted 1,4‐DHP compounds and alkyl/alkylperoxyl ABAP‐derived radicals were followed by the decrease in λ_max at 356 nm corresponding to 1,4‐DHP moiety. C4‐phenolic‐substituted 1,4‐DHPs were more reactive toward alkyl free radicals than the other tested radicals. The 3,4,5‐trihydroxyphenyl‐1,4‐DHP was the most reactive derivative toward this radical with a kinetic rate constant value of 513.2 s^?1. Also, this derivative was the most effective toward the DPPH^? radical with the lowest EC₅₀ value (5.08 µM). Comparative studies revealed that synthesized 1,4‐DHPs were more reactive than commercial 1,4‐DHPs. The scavenging mechanism involves the contribution of both pharmacophores, that is, hydroxyphenyl and 1,4‐DHP rings, which was supported by the identification of the reaction products. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 810–820, 2012     

Ion-molecule reactions of primary radical cations in the liquid-phase radiolysis of <Emphasis Type="Italic">n</Emphasis>-alkanes: An EPR study

Radiation-chemical yields the liquid-phase radiolysis of C₅–C₁₂ n-alkanes were measured using the spin trap technique. The yields of n-alkyl radicals depended only slightly on the chain length in C₅–C₉ alkanes and amounted up to 30% of the total yield of trapped radicals; they were inhibited by the addition of charge scavengers. An analysis of the experimental results together with data on radicals in irradiated crystalline alkanes and radical cations in freon matrices showed that n-alkyl radicals results from the ion-molecule reactions of primary radical cations, whereas the protonated ions RH₂⁺ as products of these reactions are a source of sec-alkyl radicals. At least 60% of primary radical cations are consumed via these reaction pathways. A part of sec-alkyl radicals is due to gauche-conformers. The relative amount of primary alkyl radicals formed in the degradation of excited states and the subsequent charge neutralization processes should be insignificant.Translated from Khimiya Vysokikh Energii, Vol. 39, No. 1, 2005, pp. 5–14.Original Russian Text Copyright © 2005 by Belevskii, Belopushkin.     

An Olefinic 1,2‐Boryl‐Migration Enabled by Radical Addition: Construction of gem‐Bis(boryl)alkanes

A series of in situ formed alkenyl diboronate complexes from alkenyl Grignard reagents (commercially available or prepared from alkenyl bromides and Mg) with B₂Pin₂ (bis(pinacolato)diboron) react with diverse alkyl halides by a Ru photocatalyst to give various gem‐bis(boryl)alkanes. Alkyl radicals add efficiently to the alkenyl diboronate complexes, and the adduct radical anions undergo radical‐polar crossover, specifically, a 1,2‐boryl‐anion shift from boron to the α‐carbon sp² center. This transformation shows good functional‐group compatibility and can serve as a powerful synthetic tool for late‐stage functionalization in complex compounds. Measurements of the quantum yield reveal that a radical‐chain mechanism is operative in which the alkenyl diboronates acts as reductive quencher for the excited state of the photocatalyst.     

Radical‐Based C−C Bond‐Forming Processes Enabled by the Photoexcitation of 4‐Alkyl‐1,4‐dihydropyridines

We report herein that 4‐alkyl‐1,4‐dihydropyridines (alkyl‐DHPs) can directly reach an electronically excited state upon light absorption and trigger the generation of C(sp³)‐centered radicals without the need for an external photocatalyst. Selective excitation with a violet‐light‐emitting diode turns alkyl‐DHPs into strong reducing agents that can activate reagents through single‐electron transfer manifolds while undergoing homolytic cleavage to generate radicals. We used this photochemical dual‐reactivity profile to trigger radical‐based carbon–carbon bond‐forming processes, including nickel‐catalyzed cross‐coupling reactions.     

Type I Photosensitization of 2′‐deoxyadenosine 5′‐monophosphate (5′‐dAMP) by Biopterin and its Photoproduct Formylpterin

Biopterin (Bip) and its photoproducts 6‐formylpterin (Fop) and 6‐carboxypterin (Cap) accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder where the protection against UV radiation fails because of the lack of melanin. These compounds absorb in the UV‐A inducing a potential photosensitizing action that can cause damage to DNA and other biomolecules. In this work, we have investigated the capability of these pterin derivatives (Pt) to act as photosensitizers under UV‐A irradiation for the degradation of 2′‐deoxyadenosine 5′‐monophosphate (5′‐dAMP) in aqueous solutions, as model DNA target. Steady‐state and time‐resolved experiments were performed and the effect of pH was evaluated. The results showed that photosensitized degradation of 5′‐dAMP was only observed under acidic conditions, and a mechanistic analysis revealed the participation of the triplet excited state of the pterin derivatives (³Pt*) by electron transfer yielding the corresponding pair of radical ions (Pt^?? and 5′‐dAMP^?+), with successive photosensitizer recovery by electron transfer from Pt^?? to O₂. Finally, 5′‐dAMP^?+ participates in subsequent reactions to yield degradation products.     

Type I Photosensitized Oxidation of Methionine†

Methionine (Met) is an essential sulfur‐containing amino acid, sensitive to oxidation. The oxidation of Met can occur by numerous pathways, including enzymatic modifications and oxidative stress, being able to cause relevant alterations in protein functionality. Under UV radiation, Met may be oxidized by direct absorption (below 250 nm) or by photosensitized reactions. Herein, kinetics of the reaction and identification of products during photosensitized oxidation were analyzed to elucidate the mechanism for the degradation of Met under UV‐A irradiation using pterins, pterin (Ptr) and 6‐methylpterin (Mep), as sensitizers. The process begins with an electron transfer from Met to the triplet‐excited state of the photosensitizer (Ptr or Mep), to yield the corresponding pair of radicals, Met radical cation (Met^?+) and the radical anion of the sensitizer (Sens^??). In air‐equilibrated solutions, Met^?+ incorporates one or two atoms of oxygen to yield methionine sulfoxide (MetO) and methionine sulfone (MetO₂), whereas Sens^?? reacts with O₂ to recover the photosensitizer and generate superoxide anion (O₂^??). In anaerobic conditions, further free‐radical reactions lead to the formation of the corresponding dihydropterin derivatives (H₂Ptr or H₂Mep).     

Charge-remote fragmentation and the two-step elimination of alkanols from fast atom bombardment-desorbed (M + H)+, (M + Cat)+, and (M - H)− ions of aromatic β-hydroxyoximes

Aromatic β-hydroxyoximes undergo unusual fragmentation reactions as protonated or cationized species, as radical cations, or as (M - H)^? ions, As protonated species, they expel OH ’ from the oxime functionality in violation of the even electron rule. Parallel eliminations of alkyl radicals follow OH’ loss when the aromatic ring is substituted with an alkyl chain. Alkyl radical losses appear to be characteristic of radical cations that can isomerize to ions in which the alkyl chain bears a radical site and the charged site is the conjugate acid of a basic functionality (e.g., oxime or imine). Evidence for the mechanisms was found in the ion chemistry of oxime and imine radical cations. The imine reference compounds were conveniently generated by fast atom bombardment-induced reduction of oximes, removing the requirement for using conventional chemical synthesis. Protonated imines and the (M - H)^? ions of oximes fragment extensively via charge-remote processes to eliminate the elements of alkanes. This chemistry is not shared by the protonated oximes.     

Computational studies on the reactions of 3‐butenyl and 3‐butenylperoxy radicals

The reactions of 3‐butenyl (^?CH₂CH₂CH?CH₂) radicals—unimolecular decomposition, isomerization, as well as reaction with O₂—and the subsequent unimolecular rearrangement reactions of the 3‐butenylperoxy radicals have been investigated and are compared to the analogous reactions of butyl (^?CH₂CH₂CH₂CH₃) and butylperoxy radicals using transition‐state theory based on the quantum chemical calculations at the CBS‐QB3 level. For alkyl‐analogue processes, the reactions of 3‐butenyl and 3‐butenylperoxy radicals can be well characterized by the decreased and increased bond dissociation energies at the allylic and vinylic sites, respectively. The intramolecular addition reactions of the radical center atoms to the double bonds were found to be important non‐alkyl‐analogue reactions of 3‐butenyl and 3‐butenylperoxy radicals. As a consequence, the thermal decomposition of 3‐butenyl radicals was found to be slower than that of butyl radicals by one order of magnitude at temperature near 1000 K. Intramolecular addition reactions are suggested to be the predominant unimolecular rearrangement processes of 3‐butenylperoxy radicals over the entire temperature range investigated (500–1200 K). The intramolecular addition reactions of the alkenyl peroxy radicals, which have not been included in combustion kinetic models, and their implications for the autoignition of alkenes are discussed. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 273–288, 2010     

Mechanism for the Nonadiabatic Photooxidation of Benzene to Phenol: Orientation‐Dependent Proton‐Coupled Electron Transfer

An efficient catalytic one‐step conversion of benzene to phenol was achieved recently by selective photooxidation under mild conditions with 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ) as the photocatalyst. Herein, high‐level electronic structure calculations in the gas phase and in acetonitrile solution are reported to explore the underlying mechanism. The initially populated ¹ππ* state of DDQ can relax efficiently through a nearby dark ¹nπ* doorway state to the ³ππ* state of DDQ, which is found to be the precursor state involved in the initial intermolecular electron transfer from benzene to DDQ. The subsequent triplet‐state reaction between DDQ radical anions, benzene radical cations, and water is computed to be facile. The formed DDQH and benzene‐OH radicals can undergo T₁→S₀ intersystem crossing and concomitant proton‐coupled electron transfer (PCET) to generate the products DDQH₂ and phenol. Two of the four considered nonadiabatic pathways involve an orientation‐dependent triplet PCET process, followed by intersystem crossing to the ground state (S₀). The other two first undergo a nonadiabatic T₁→S₀ transition to produce a zwitterionic S₀ complex, followed by a barrierless proton transfer. The present theoretical study identifies novel types of nonadiabatic PCET processes and provides detailed mechanistic insight into DDQ‐catalyzed photooxidation.     

Effect of Molecular Interactions on Electron‐Transfer and Antioxidant Activity of Bis(alkanol)selenides: A Radiation Chemical Study

Understanding electron‐transfer processes is crucial for developing organoselenium compounds as antioxidants and anti‐inflammatory agents. To find new redox‐active selenium antioxidants, we have investigated one‐electron‐transfer reactions between hydroxyl (^.OH) radical and three bis(alkanol)selenides (SeROH) of varying alkyl chain length, using nanosecond pulse radiolysis. ^.OH radical reacts with SeROH to form radical adduct, which is converted primarily into a dimer radical cation (>Se∴Se<)⁺ and α‐{bis(hydroxyl alkyl)}‐selenomethine radical along with a minor quantity of an intramolecularly stabilized radical cation. Some of these radicals have been subsequently converted to their corresponding selenoxide, and formaldehyde. Estimated yield of these products showed alkyl chain length dependency and correlated well with their antioxidant ability. Quantum chemical calculations suggested that compounds that formed more stable (>Se∴Se<)⁺, produced higher selenoxide and lower formaldehyde. Comparing these results with those for sulfur analogues confirmed for the first time the distinctive role of selenium in making such compounds better antioxidants.     

Oxime Ether Radical Cations Stabilized by N‐Heterocyclic Carbenes

N‐heterocyclic carbene (NHC) nitric oxide (NHCNO) radicals, which can be regarded as iminoxyl radicals stabilized by NHCs, were found to react with a series of silyl and alkyl triflates to generate the corresponding oxime ether radical cations. The structures of the resulting oxime ether radical cations were determined by X‐ray crystallography, along with EPR and computational analysis. In contrast, lutidinium triflate produced a 1:1 mixture of [NHCNO⁺][OTf^?] and [NHCNHOH⁺][OTf^?] upon the reaction with NHCNO. This study adds an important example of stable singlet carbenes for stabilizing main‐group radicals because of their π‐conjugating effect, the synthesis and structures of which have not been reported previously.     

Organophotoredox‐Catalyzed Cascade Radical Annulation of 2‐(Allyloxy)arylaldehydes with N‐(acyloxy)phthalimides: Towards Alkylated Chroman‐4‐one Derivatives

An organophotoredox catalyzed efficient and robust approach for the synthesis of highly important 3‐alkyl substituted chroman‐4‐one scaffold is developed using visible light induced radical cascade cyclization strategy. The reaction is initiated through the generation of alkyl radicals from N‐(acyloxy)phthalimides under photoredox conditions, which subsequently undergo intermolecular cascade radical cyclization on 2‐(allyloxy)arylaldehydes to afford chroman‐4‐one scaffolds. The presented strategy is attractive with regard to mild reaction conditions, operational simplicity, high functional group tolerance and broad substrate scope.     

Synthesis of α‐Chiral Ketones and Chiral Alkanes Using Radical Polar Crossover Reactions of Vinyl Boron Ate Complexes

Vinyl boron ate complexes of enantioenriched secondary alkyl pinacolboronic esters undergo stereospecific radical‐induced 1,2‐migration in radical polar crossover reactions. In this three‐component process various commercially available alkyl iodides act as radical precursors and light is used for chain initiation. Subsequent oxidation and protodeborylation leads to valuable α‐chiral ketones and chiral alkanes, respectively, with excellent enantiopurity.     

Aromatic Monochlorination Photosensitized by DDQ with Hydrogen Chloride under Visible‐Light Irradiation

Photochlorination of aromatic substrates by hydrogen chloride with 2,3‐dichloro‐5,6‐cyano‐p‐benzoquinone (DDQ) occurs efficiently to produce the corresponding monochlorinated products selectively under visible‐light irradiation. The yields for the chlorination of phenol were 70 % and 18 % for p‐ and o‐chlorophenol, respectively, without formation of further chlorinated products. The photoinduced chlorination is initiated by electron transfer from Cl^? to the triplet excited state of DDQ. The radical intermediates involved in the photochemical reaction have been detected by time‐resolved transient absorption measurements.     

Synthesis of Structurally Well‐Defined Telechelic Polymers by Organostibine‐Mediated Living Radical Polymerization: In Situ Generation of Functionalized Chain‐Transfer Agents and Selective ω‐End‐Group Transformations

Several organostibine chain‐transfer agents possessing polar functional groups have been prepared by the reactions of azo initiators and tetramethyldistibine ( 1 ). Carbon‐centered radicals thermally generated from the azo initiators were trapped by 1 to yield the corresponding organostibine chain‐transfer agents. The high yields observed in the synthesis of the chain‐transfer agents strongly suggest that distibines have excellent radicophilic reactivity. As the reactions proceeded under neutral conditions, functional groups that are incompatible with ionic conditions were incorporated into the chain‐transfer agents. The chain‐transfer agents were used in living radical polymerization to synthesize the corresponding α‐functionalized polymers. As the functional groups in the chain‐transfer agents did not interfere with the polymerization reaction, well‐controlled polymers possessing number‐average molecular weights (M_ns) predetermined by the monomer/transfer agent ratios were synthesized with low polydispersity indices (PDIs). The organostibanyl ω‐polymer ends were transformed into a number of different functional groups by radical‐coupling, radical‐addition, and oxidation reactions. Therefore, it was possible to synthesize well‐controlled telechelic polymers with the same and also with different functional groups at their α‐ and ω‐polymer ends. Distibine 1 was also found to increase PDI control in the living radical polymerization of styrene and methyl methacrylate (MMA) using a purified organostibine chain‐transfer agent. Well‐controlled poly(methyl methacrylate)s with M_n values ranging from 10 000 to 120 000 with low PDIs (1.05–1.15) were synthesized by the addition of a catalytic amount of 1 . The results have been attributed to the high reactivity of distibine 1 towards polymer‐end radicals, which are spontaneously deactivated to yield organostibine dormant species.     

Copper‐Catalyzed Alkylarylation of Unactivated Alkenes: Synthesis of 3‐Alkyl Indolines from N‐Allyl Anilines and Alkanes

A rare example of C(sp³)?H functionalization of simple alkanes with unactivated alkenes is presented. In the presence of a copper salt and di‐tert‐butyl peroxide (DTBP), N‐allyl anilines underwent exo‐selective alkylation/cyclization cascade with unactivated alkenic bonds as radical acceptors and simple alkanes as radical precursors, providing a direct access to 3‐alkyl indolines. The present protocol features simple operation, broad substrate scope and great exo selectivity.     

Copper‐Catalyzed Remote C(sp3)−H Trifluoromethylation of Carboxamides and Sulfonamides

Reported herein is an unprecedented protocol for trifluoromethylation of unactivated aliphatic C(sp³)?H bonds. With Cu(OTf)₂ as the catalyst, the reaction of N‐fluoro‐substituted carboxamides (or sulfonamides) with Zn(CF₃)₂ complexes provides the corresponding δ‐trifluoromethylated carboxamides (or sulfonamides) in satisfactory yields under mild reaction conditions. A radical mechanism involving 1,5‐hydrogen atom transfer of N‐radicals followed by CF₃‐transfer from Cu^II?CF₃ complexes to the thus formed alkyl radicals is proposed.     

High‐molecular‐weight side‐chain liquid‐crystalline polyethers based on 4′‐cyanobiphenyl‐4‐oxy mesogenic groups

A set of poly[ω‐(4′‐cyano‐4‐biphenyloxy)alkyl‐1‐glycidylether]s were synthesized by the chemical modification of the corresponding poly(ω‐bromoalkyl‐1‐glycidylether)s with the sodium salt of 4‐cyano‐4′‐hydroxybiphenyl. New high‐molecular‐weight side‐chain liquid‐crystalline polymers were obtained with excellent yield and almost quantitative degree of modification. All side‐chain liquid‐crystalline polymers were rubbers soluble in tetrahydrofuran. The characterization by ¹H and ¹³C NMR revealed no changes in the regioregular isotactic microstructure of the starting polymer and the absence of undesirable side reactions such as deshydrobromination. The liquid crystalline behavior was analyzed by DSC and polarized optical microscopy, and mesophase assignments were confirmed by X‐ray diffraction. Polymers that had alkyl spacers with n = 2 and 4 were nematic, those that had spacers with n = 6 and 8 were nematic cybotactic, and those that had longer spacers (n = 10 and 12) were smectic C and showed some crystallization of the side alkyl chains. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3002–3012, 2004     

EPR Study on the Complex Formed by Charge‐Transfer Process between Ground‐state Acceptor 2, 3‐Dicyano‐5, 6‐dichloro‐1, 4‐benzoquinone and Some Donors and on Cation Radical of Perylene (or Pyrene)

EPR study showed that the semi‐quinone radical anion of 2,3‐dicyano‐5,6‐dichloro‐1,4‐benzoquinone (DDQ) was formed in a charge transfer process between ground‐state DDQ as acceptor and each one of following ground state donors, i.e., 4‐methyl‐4′‐tridecyl‐2, 2′‐bipyridyl; 4‐methyl‐4′‐nonyl‐2, 2′‐bipyridyl; bis (2,2′‐bipyridyl) (4‐methyl‐4′‐heptadecyl‐2, 2′‐bipyridyl)ruthenium(2+) perchlorate and perylene. EPR study also showed that there are perylene cation radical and pyrene cation radical in the following experimental conditions: (a) in 98% sulfuric add. (b) 10^?3 mol/L perylene (or pyrene) was dissolved in trifluoroacetic acid‐nitrobenzene (1: 1 V/V).