Generation and reactivity of ketyl radicals with lignin related structures. On the importance of the ketyl pathway in the photoyellowing of lignin containing pulps and papers

[reaction: see text] Ketyl radicals with lignin related structures have been generated by means of radiation chemical and photochemical techniques. In the former studies ketyl radicals are produced by reaction of alpha-carbonyl-beta-aryl ether lignin models with the solvated electron produced by pulse radiolysis of an aqueous solution at pH 6.0. The UV-vis spectra of ketyl radicals are characterized by three main absorption bands. The shape and position of these bands slightly change when the spectra are recorded in alkaline solution (pH 11.0) being now assigned to the ketyl radical anions and a pKa = 9.5 is determined for the 1-(3,4,5-trimethoxyphenyl)-2-phenoxyethanol-1-yl radical. Decay rates of ketyl radicals are found to be dose dependent and, at low doses, lie in the range (1.7-2.7) x 10(3) s(-1). In the presence of oxygen a fast decay of the ketyl radicals is observed (k2 = 1.8-2.7 x 10(9) M(-1) s(-1)) that is accompanied by the formation of stable products, i.e., the starting ketones. In the photochemical studies ketyl radicals have been produced by charge-transfer (CT) photoactivation of the electron donor-acceptor salts of methyl viologen (MV2+) with alpha-hydroxy-alpha-phenoxymethyl-aryl acetates. This process leads to the instantaneous formation of the reduced acceptor (methyl viologen radical cation, MV+*), as is clearly shown in a laser flash photolysis experiment by the two absorption bands centered at 390 and 605 nm, and an acyloxyl radical [ArC(CO2*))(OH)CH2(OC6H5)], which undergoes a very fast decarboxylation with formation of the ketyl radicals. Steady-state photoirradiation of the CT ion pairs indicates that 1-aryl-2-phenoxyethanones are formed as primary photoproducts by oxidation of ketyl radicals by MV2+ (under argon) or by molecular oxygen. Small amounts of acetophenones are formed by further photolysis of 1-aryl-2-phenoxyethanones and not by beta-fragmentation of the ketyl radicals. The high reactivity of ketyl radicals with oxygen coupled with the low rates of beta-fragmentation of the same species have an important bearing in the context of the photoyellowing of lignin containing pulps and papers.     

Photoreaction between 2-benzoylthiophene and phenol or indole

Laser flash photolysis, density functional theory (DFT) calculations, and product studies have been performed to understand the mechanism of photoreduction of 2-benzoylthiophene (BT) in the presence of phenol or indole. Time-resolved experiments showed that BT ketyl (BTH) and phenoxy (PhO) or indolyl (In) radicals are generated with high rate constants and quantum yields close to 1. However, low conversions (specially in the case of indole) of the starting reagents are obtained upon prolonged lamp irradiation, indicating that recombination within the radical pairs must occur to a large extent, regenerating the starting materials. The solvent-dependence of the quenching rate constants, together with DFT theoretical studies, indicate fundamental differences between the mechanisms of the reaction of BT triplet with phenol and indole. Thus, data for phenol agree with the involvement of a hydrogen-bonded exciplex BT(.)HOPh, where concerted electron and proton transfer leads to the BTH(.)OPh radical pair. However, in the case of indole, electron transfer at the BT(.)HIn stage precedes proton transfer. Finally, C-C cross-coupling products have been isolated and characterized in the preparative irradiation of BT in the presence of phenol and indole. The structures of the products have been confirmed by alternative synthesis.     

NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation of 1,3-enynes for tetrasubstituted allenyl ketones

The modulation of selectivity of highly reactive carbon radical cross-coupling for the construction of C–C bonds represents a challenging task in organic chemistry. N-Heterocyclic carbene (NHC) catalyzed radical transformations have opened a new avenue for acyl radical cross-coupling chemistry. With this method, highly selective cross-coupling of an acyl radical with an alkyl radical for efficient construction of C–C bonds was successfully realized. However, the cross-coupling reaction of acyl radicals with vinyl radicals has been much less investigated. We herein describe NHC and visible light-mediated photoredox co-catalyzed radical 1,4-sulfonylacylation of 1,3-enynes, providing structurally diversified valuable tetrasubstituted allenyl ketones. Mechanistic studies indicated that ketyl radicals are formed from aroyl fluorides via the oxidative quenching of the photocatalyst excited state, allenyl radicals are generated from chemo-specific sulfonyl radical addition to the 1,3-enynes, and finally, the key allenyl and ketyl radical cross-coupling provides tetrasubstituted allenyl ketones.

Unprecedented NHC and photocatalysis co-catalyzed radical 1,4-sulfonylacylation of 1,3-enynes has been realized, providing structurally diversified tetrasubstituted allenyl ketones via allenyl and ketyl radical cross-coupling.     

Reactivity of cyclopropanic δ-oxo-α,β-unsaturated esters towards SmI2: 3-exo-trig cyclisation versus cyclopropane ring opening

trans-(2′,2′-Diphenyl-bicyclopropyl-2-yl)-4,4-dimethyl-5-oxo-pent-2-enoic acid methyl ester 9, undergoes 3-exo-trig cyclisation in the presence of SmI₂ without competitive ring opening of Newcomb's bicyclopropylic probe next to the carbonyl group. From this result, it may be concluded that the absence of ring opening observed earlier in the case of 5-cyclopropyl-4,4-dimethyl-5-oxo-pent-2-enoate 7 is not due to the potentially reversible character of this process. Meanwhile, as deduced from kinetic considerations based on data of the literature, the absence of ring opening does not necessarily mean that formation of ketyl radicals is not involved in the 3-exo-trig cyclisations of δ-oxo-α,β-unsaturated esters.Compounds 7 and 9 cyclise with total syn selectivity, leading ultimately to lactones. This syn selectivity contrasts with that of other alkylic δ-oxo-α,β-unsaturated esters.     

An efficient synthesis of a potent PPARpan agonist

An efficient synthesis of 2-{4-[({4-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)thio]phenoxy}-2-methylpropanoic acid (1), a potent PPARpan agonist, is described. The seven-step synthesis, which afforded 1 in 30% overall yield, includes a highly regioselective carbon-sulfur bond formation via coupling of a bishydroxymethylthiazole (3) with 4-hydroxythiophenol, displacement of the remaining alcohol through a three-step telescoped sequence involving an efficient cleavage of an aryl mesylate, and an efficient and practical method of introducing an isobutyric acid fragment.     

Reactions of aliphatic ketones R2CO (R=Me, Et, iPr and tBu) with the MCI4/Li(Hg) system (M=U or Ti): mechanistic analogies between the McMurry, Wittig, and Clemmensen reactions

Analysis of the products of the reactions of ketones R2CO (R = Me, Et, iPr, tBu) with the MCl4/Li(Hg) system (M = U, Ti) at 20 degrees C revealed significant differences. For R = Me, the reaction proceeded exclusively (M = U) or preferentially (M = Ti) via a metallopinacol intermediate resulting from dimerization of ketyl radicals. Pinacol was liberated by hydrolysis, and tetramethylethylene was obtained after further reduction at 65 degrees C. For R=iPr, formation of iPr2C=CiPr2 as the only coupling product, the nonproduction of this alkene by reduction of the uranium pinacolate [U]-OCR2CR2O-[U] (R= iPr) at 20 degrees C, and the instability of the corresponding titanium pinacolate towards rupture of the pinacolic C-C bond indicated that reductive coupling of iPr2CO did not proceed by dimerization of ketyl radicals. Formation of 2,4-dimethyl-2-pentene was in favor of a carbenoid intermediate resulting from deoxygenative reduction of the ketyl. These results revealed that for sterically hindered ketones, McMurry reactions can be viewed as Wittig-like olefination reactions. For R=tBu, no coupling product was obtained and the alkane tBu2CH2 was the major product. The involvement of the carbenoid species [M]=CtBu2 was confirmed by its trapping with H2O, leading to tBu2CH2, and with the aldehydes RCHO, giving the cross-coupling products tBu2C=C(R)H (R = Me, tBu). Therefore, in the case of severely congested ketones, McMurry reactions present strong similarities to the Clemmensen reduction of ketones, owing to the involvement in both reactions of carbenoid species which exhibit similar reactivity.     

Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides

Complete (1)H and (13)C NMR signal assignments of two lactucin-type sesquiterpene lactone glycosides, derivatives of 11β,13-dihydrolactucin, isolated from roots of Picris conyzoides, were achieved by one- and two-dimensional NMR experiments, allowing the correction of previously published data for cichorioside B and the structure elucidation of its new ester with 3-hydroxy-2-methylpropanoic acid. In addition, seven known sesquiterpene lactones and three phenolic compounds were isolated from the plant material.     

Chain mechanism in the photocleavage of phenacyl and pyridacyl esters in the presence of hydrogen donors

[reaction: see text] Excited phenacyl and 3-pyridacyl esters of benzoic acid react with an excess of aliphatic alcohols in a chain reaction process involving hydrogen transfer from the ketyl radical intermediates, leading to benzoic acid in addition to acetophenone and 3-acetylpyridine, respectively, as the byproducts. While the maximum quantum yields reached 4 in both cases, the 2- or 4-pyridacyl ester photoreduction proceeded with the efficiency below 100% under the same conditions. The investigation indicates that a radical coupling between ketyl radicals, both formed from the excited ester by hydrogen abstraction from an alcohol, is accompanied by the elimination of benzoic acid from the ester ketyl radical itself. A partitioning between two reactions was found to be remarkably sensitive to the chromophore nature, such as a position of the nitrogen atom in the pyridacyl moiety. The magnitude of a radical chain process is dependent on the efficiency of consecutive steps that produce free radicals capable of a subsequent ester reduction. The driving force of a possible electron transfer from the ketyl radicals to the ester has been excluded on the basis of cyclic voltametry measurements. The observed quantum yields of photoreduction were found to be diminished by formation of relatively long-lived light absorbing transients, coproducts obtained apparently by secondary photochemical reactions. Additionally, it is shown that basic additives such as pyridine can further increase the efficiency of the photoreduction by a factor of 4. A radical nature of the reduction mechanism was supported by finding a large kinetic chain length of an analogous reaction initiated by free radicals generated thermally yet again when phenacyl or 3-pyridacyl benzoate was used. Both phenacyl and pyridacyl chromophores are pronounced to be valuable as the photoremovable protecting groups when high quantum and chemical yields of carboxylic acid elimination are important, but higher concentrations of the hydrogen atom donors are not destructive for a reaction system or are experimentally impractical.     

Nickel catalyzed cross-coupling of aryl C-O based electrophiles with aryl neopentylglycolboronates

The efficiency of mesylates, sulfamates, esters, carbonates, carbamates, and methyl ethers as C-O-based electrophiles attached to the 1- or 2-position of naphthalene and to activated and nonactivated phenyl substrates was compared for the first time in Ni-catalyzed cross-coupling with phenyl neopentylglycolboronates containing electron-rich and electron-deficient substituents in their para-position. These experiments were performed in the presence of four different Ni(II)- and Ni(0)-based catalysts. Ni(II)-based catalysts mediate the cross-coupling of most 2-naphthyl C-O electrophiles with both arylboronic acids and with neopentylglycolboronates when K(3)PO(4) is used as base. The same catalysts are not efficient when CsF is used as base. However, Ni(0)-based catalysts exhibit selective efficiency, and when reactive, their efficiency is higher than that of Ni(II)-based catalysts in the presence of both K(3)PO(4) and CsF. These results provide both reaction conditions for the cross-coupling, and for the elaboration of orthogonal cross-coupling methodologies of various C-O based electrophiles with aryl neopentylglycolboronates. With the exception of mesylates and sulfamates the efficiency of all other 2-naphthyl C-O electrophiles was lower in cross-coupling with aryl neopentylglycolboronates than with arylboronic acids.     

Topically applied vitamin C and cysteine derivatives protect against UVA-induced photodegradation of suprofen in ex vivo pigskin

Exposure of the nonsteroidal anti-inflammatory drug suprofen (SUP) to UV-radiation results in the formation of radicals, reactive oxygen species (ROS), photodecarboxylated products and photoadducts with biomacromolecules. Using an ex vivo pigskin explant model, we investigated whether topical coapplication of the water-soluble antioxidants vitamin C (Lascorbic acid, ASC), N-acetyl-L-cysteine (NAC) or L-cysteine ethylester (CYSET) with SUP reduced ultraviolet A (UVA)-induced decomposition of SUP. UVA-induced changes in antioxidant bioavailability in the stratum corneum and epidermis were also studied. Epidermal bioavailability of SUP in sham-irradiated pigskin increased 2.2- to 4.1-fold after the lowest antioxidant doses (P < 0.05). As compared with no applied antioxidant, increasing doses of all tested antioxidants resulted in increased levels of SUP and decreased levels of photoproducts (P < 0.05). A maximal protection against SUP photodegradation of 70% was found after an ASC dose of 1 micromol/cm2; these values were 60% for a NAC dose of 10 micromol/cm2 and 50% for a CYSET dose of 5 micromol/cm2. Skin antioxidant levels increased with increasing applied dose (P < 0.05); the bioavailability of CYSET was approximately three-fold lower than that of ASC and NAC. UVA exposure resulted in 30-50% consumption of the topically applied ASC or NAC in the stratum corneum, whereas CYSET was not consumed. In conclusion, the topically applied water-soluble antioxidants ASC, NAC and CYSET protect against UVA-induced decomposition of SUP by scavenging radicals and ROS. Coapplication of these antioxidants may therefore be an effective way to reduce or prevent the phototoxic effects of SUP in vivo.     

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.     

Properties of excited ketyl radicals of benzophenone analogues affected by the size and electronic character of the aromatic ring systems

The properties of benzophenone ketyl radical analogues with large aromatic ring systems, such as naphthylphenylketone (2), 4-benzoylbiphenyl (3), and bis(biphenyl-4-yl)methanone (4), were investigated in the excited state by using nanosecond-picosecond two-color two-laser flash photolysis. Fluorescence and transient absorption spectra of ketyl radicals of 2-4 in the excited state were observed for the first time. The fluorescence and properties of the excited ketyl radicals were significantly affected by the size and electronic properties of the aromatic ring systems. The reactivity of the ketyl radicals in the excited state with several quenchers was examined and they were found to show reactivity toward N,N-diethylaniline. In addition, for the benzophenone ketyl radical, a unique quenching process of the radical in the excited state by the ground-state parent molecule was found. The factors regulating the fluorescence lifetime of the ketyl radicals in the excited state are discussed quantitatively.     

Synthesis and reactivity of a 5-azido analogue of neuraminic acid

A peracetylated phenyl 2-thioglycoside (1) of a 5-azido analogue neuraminic acid methyl ester was prepared from a known 5-amino precursor by a diazo transfer reaction. Glycosidation of 1 by alcohols proceeded smoothly in CH3CN to give alpha-sialylated products in good yield.     

Carbazole-substituted dehydroalanine main chain polymers. Synthesis and characterization of poly[methyl 2-(9-carbazolyl) acetylaminopropenoate] and poly[2-(9-carbazolyl) acetylaminopropenoic acid]

The preparation and radical-initiated polymerization of a carbazole-substituted N-acylated dehydroalanine, namely, 2-(9-carbazolyl)acetylaminopropenoic acid ( 7 ) and its methyl ester ( 6 ) is reported. The monomers 6 and 7 were prepared by dehydrochlorination of N-acylated β-chloroalanine derivatives. The monomer model compounds for the two polymers, namely, 2-(9-carbazolyl)acetylamino-2-methylpropanoic acid ( 11 ) and its methyl ester ( 10 ), were also prepared. The polymers and their monomer model compounds were characterized by elemental analysis, IR and ¹H-NMR spectra. The polymers 12 and 13 of different molecular weights could be obtained by changing the monomer-to-initiator ratios used in polymerization experiments.     

Enantiospecific synthesis of (+)-N(a)-methylpericyclivine and (-)-N(a)-methylakuammidine as well as the ring-A oxygenated natural products, (+)-10-methoxy N(a)-methylpericyclivine and 10-hydroxy N(a)-methylpericyclivine

[reaction: see text] The first enantiospecific, regiospecific total synthesis of the enantiomers of N(a)-methylpericyclivine and N(a)-methylakuammidine as well as the ring-A oxygenated natural products (+)-10-methoxy N(a)-methylpericyclivine and 10-hydroxy N(a)-methylpericyclivine was achieved. The lactones (see 19, 22, and 25) are key to the formation of the beta-axial methyl ester moiety.     

Alkaloids of the flora of Siberia and Altai: XX. Synthesis of 5-aryl(hetaryl)-substituted anthranilic acid esters

Cross-coupling of methyl 2-acetylamino-5-bromobenzoate and 5′-bromolappaconitine with aryl-, furyl-, pyridyl-, and 5-acetylthiophen-2-ylboronic acids or 1-(2-fluoroquinolin-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane gave the corresponding 5-aryl(hetaryl)-substituted anthranilic acid derivatives. The use of the two-phase toluene-water system as reaction medium and addition of tetrabutylammonium bromide allows the cross-coupling to be accomplished under mild conditions. The catalytic system Pd(dba)₂-AsPh₃ was found to be efficient in the cross-coupling of methyl 2-acetylamino-5-bromobenzoate with furyl- and pyridylboronic acids, whereas the system Pd(OAc)₂-(o-Tol)₃P ensured good results in the reactions of 5′-bromolappaconitine with hetarylboronic acids. Facile esterification at the C⁸-OH and C⁹-OH groups of the aconitane skeleton was observed in the reactions of 5′-bromolappaconitine and 5′-phenyllappaconitine with phenylboronic acid. 5′-Bromo-8,9-O-(phenylboranediyl)lappaconitine under the Suzuki reaction conditions underwent hydrolysis of the boronic ester moiety with formation of the cross-coupling product of 5′-bromolappaconitine with phenylboronic acid.     

Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product

13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.     

ELECTRON AND ENERGY TRANSFER IN ILLUMINATED POROUS VYCOR GLASS

Abstract— Porous Vycor glass samples containing adsorbed molecules were illuminated at 77 K by a mercury lamp jacketed by a filter cutting off wavelengths below 250 nm. Oxygen or carbon dioxide on Vycor produces an asymmetric electron paramagnetic resonance (EPR) signal best described as holes trapped in the glass. Methyl bromide produces an identical EPR signal plus four other lines due to methyl radicals. Evidence is presented that the products result from excitonic energy transfer from the Vycor to the adsorbed materials. Triphenylamine (TPA) adsorbed on Vycor can also be photoionized by similar illumination, and the cation radical TPA⁺ can be stabilized at 77 K if an electron acceptor is also adsorbed. Attachment of the photoejected electron by carbon dioxide forms CO₂^-, and that by methyl bromide leads to methyl radicals. The CH₃ radical yield is dependent on the surface separation between the electron donor (TPA) and the acceptor (CH₃Br). By monitoring the relative quantum yield of the methyl radicals as a function of distance separating the TPA and CH₃Br, it is shown that the photoelectron is capable of migrating on the Vycor glass surface.     

Stereochemical studies of 5-methyl-3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-2-thiooxazolidin-4-ones

The synthesis and stereochemical aspects of the aldol products, 5-methyl-3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-2-thiooxazolidin-4-ones, are discussed.     

In situ direct sampling mass spectrometric study on formation of polycyclic aromatic hydrocarbons in toluene pyrolysis

The gas-phase reaction products of toluene pyrolysis with and without acetylene addition produced in a flow tube reactor at pressures of 8.15-15.11 Torr and temperatures of 1136-1507 K with constant residence time (0.56 s) have been detected in an in situ direct sampling mass spectrometric study by using a vacuum ultraviolet single-photon ionization time-of-flight mass spectrometry technique. Those products range from methyl radical to large polycyclic aromatic hydrocarbons (PAHs) of mass 522 amu (C(42)H(18)) including smaller species, radicals, polyynes, and PAHs, together with ethynyl, methyl, and phenyl PAHs. On the basis of observed mass spectra, the chemical kinetic mechanisms of the formation of products are discussed. Especially, acetylene is mixed with toluene to understand the effect of the hydrogen abstraction and acetylene addition (HACA) mechanism on the formation pathways of products in toluene pyrolysis. The most prominent outputs of this work are the direct detection of large PAHs and new reaction pathways for the formation of PAHs with the major role of cyclopenta-fused radicals. The basis of this new reaction route is the appearance of different sequences of mass spectra that well explain the major role of aromatic radicals mainly cyclopenta fused radicals of PAHs resulting from their corresponding methyl PAHs, with active participation of c-C(5)H(5), C(6)H(5), C(6)H(5)CH(2) ,and C(9)H(7) in the formation of large PAHs. The role of the HACA only seemed important for the formation of stable condensed PAHs from unstable primary PAHs with zigzag structure (having triple fusing sites) in one step by ring growth with two carbon atoms.