Effect of structure in benzaldehyde oximes on the formation of aldehydes and nitriles under photoinduced electron-transfer conditions

The mechanistic aspects of the photosensitized reactions of a series of benzaldehyde oximes (1a-o) were studied by steady-state (product studies) and laser flash photolysis methods. Nanosecond laser flash photolysis studies have shown that the reaction of the oxime with triplet chloranil (3CA) proceeds via an electron-transfer mechanism provided the free energy for electron transfer (DeltaG(ET)) is favorable; typically, the oxidation potential of the oxime should be below 2.0 V. Substituted benzaldehyde oximes with oxidation potentials greater than 2.0 V quench 3CA at rates that are independent of the substituent and the oxidation potential. The most likely mechanism under these conditions is a hydrogen atom transfer mechanism as this reaction should be dependent on the O-H bond strength only, which is virtually the same for all oximes. Product studies have shown that aldoximes react to give both the corresponding aldehyde and the nitrile. The important intermediate in the aldehyde pathway is the iminoxyl radical, which is formed via an electron transfer-proton transfer (ET-PT) sequence (for oximes with low oxidation potentials) or via a hydrogen atom transfer (HAT) pathway (for oximes with larger oxidation potentials). The nitriles are proposed to result from intermediate iminoyl radicals, which can be formed via direct hydrogen atom abstraction or via an electron-transfer-proton-transfer sequence. The experimental data seems to support the direct hydrogen atom abstraction as evidenced by the break in linearity in the plot of the quenching rates against the oxidation potential, which suggests a change in mechanism. The nitrile product is favored when electron-accepting substituents are present on the benzene ring of the benzaldehyde oximes or when the hydroxyl hydrogen atom is unavailable for abstraction. The latter is the case in pyridine-2-carboxaldoxime (2), where a strong intramolecular hydrogen bond is formed. Other molecules that form weaker intramolecular hydrogen bonds such as 2-furaldehyde oxime (3) and thiophene-2-carboxaldoxime (4) tend to yield increasing amounts of aldehyde.     

Mechanism of stable radical generation in aromatic polyamides on exposure to nitrogen dioxide

By using the example of poly-m-phenylene isophthalamide, the mechanism of generation of stable nitrogen-containing radicals in aromatic polyamides in the presence of nitrogen dioxide is considered. The proposed mechanism is based on the reactions of dimers of nitrogen dioxide in the form of nitrosyl nitrate. As a result of a primary reaction of electron transfer from donor functional groups of macromolecules to nitrosyl nitrate, macromolecular radical cations and nitric oxide are formed. Amide groups and phenyl rings can act as electron donors. In the subsequent reactions with participation of radical cations, nitric oxide and nitrogen dioxide oximes, nitroso compounds and nitrites are formed. Generation of stable iminoxyl radicals occurs by reactions of oximes with nitrogen dioxide. Thermolysis of the polymer nitration products gives iminoxyl and acylarylaminoxyl radicals. The structure of iminoxyl radicals and features of dynamics of their formation have been confirmed by ab initio quantum-chemical calculations.     

Photosensitized reactions of oxime ethers: a steady-state and laser flash photolysis study

The mechanistic aspects of the photosensitized reactions of a series of oxime ethers were studied by steady-state (product studies) and laser flash photolysis methods. Nanosecond laser flash photolysis studies have shown that chloranil-sensitized reactions of the oxime ethers result in the formation of the corresponding radical cations. The radical cation species react with nucleophiles such as MeOH by clean second-order kinetics with rate constants of (0.7-1.4) x 10(6) M(-1) s(-1). Only a small steric effect is observed in these reactions, which is taken as an indication that the reaction center is not the O-alkyl moiety, but rather somewhere else in the molecule. Product studies in a polar nonnucleophilic solvent (MeCN) revealed that in order for the oxime ether radical cation to react more readily, alpha-protons must be available on the alkyl group. The O-methyl (1), O-ethyl (2), and O-benzyl (3) acetophenone oximes all reacted readily to give acetophenone oxime as the major product (as well as an aldehyde derived from the O-alkyl group), whereas O-tert-butyl acetophenone oxime (4) did not. The product formation can be explained by a mechanism that involves electron transfer followed by proton transfer (alpha to the oxygen) and subsequent beta-cleavage. When using 3 in MeOH, a change in the product formation is observed, the most important difference being the presence of benzyl alcohol rather than benzaldehyde as the major product. On the basis of the data from LFP and steady-state experiments, it is suggested that the competing mechanism under these conditions involves electron transfer, followed by a nucleophilic attack on the nitrogen, a MeOH-assisted [1,3]-proton transfer, and subsequent loss of benzyl alcohol. This mechanism is supported by DFT (B3LYP/6-31G) and AM1 calculations.     

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.     

A DFT Study of the Nitric Oxide and Tyrosyl Radical Interaction: A Proposed Radical Mechanism

The present study employs a complete theoretical investigation, at the B3LYP/cc‐pVTZ level of theory, of the interactions between the tyrosyl radical and nitric oxide, exploring in detail the nitrotyrosine formation radical mechanism. Tyrosyl radicals play an essential role in catalytic reactions of numerous enzymes and biological systems have regulated appropriate mechanisms for their formation. Nitric oxide reacts with the tyrosyl radical and affords a weak intermediate complex which, through a sequence of non‐ionic water catalyzed and biologically feasible intermediate reactions, yields the iminoxyl radical. The iminoxyl radical further combines with hydroxyl radical, a species present in pathophysiological conditions, to yield nitrotyrosine.     

Features of stable radical generation in lignin on exposure to nitrogen dioxide

The mechanism of stable radical generation in lignin under the action of nitrogen dioxide and NO₂ - air mixture is considered. The formation of phenoxyl, iminoxyl and acylaminoxyl radicals has been detected by EPR. The proposed mechanism involves a primary oxidative reaction of phenol groups with dimers of NO₂ (nitrosyl nitrate) resulting in the formation of phenoxyl radicals and nitric oxide. In the subsequent recombination of phenoxyl radicals and nitric oxide, nitroso compounds and oximes are formed. By reaction of oximes with radicals NO₂, stable iminoxyl radicals are formed. This mechanism is confirmed by kinetic dependencies obtained over a wide range of NO₂ concentrations. From IR spectroscopy measurements it follows that hydroxyl groups of non-phenolic structures of lignin are oxidised to aldehydes producing acylaminoxyl radicals by reaction with NO₂. The kinetic data show that the adsorption of NO₂ on the lignin surface is the rate-determining factor in stable radical formation.     

An ESR on formation of iminoxy free radicals—solvent effect on hyperfine splitting constants

The solvent effect on hyperfine interaction in three different types of iminoxy radicals obtained by oxidation of di-2-pyridiketoxime (1), diethyl hydroxyimino(2-fluorophenyl)methanephosphonate (2) and isonitrosoacetophenone (3) have been analyzed. Linear correlations of hyperfine constants of ¹⁴N (both iminoxyl and pyridyl nitrogens of the iminoxyl derived from 1), ³¹P (isomer Z of the iminoxyl derived from 2) and ¹⁹F (both Z and E isomer of iminoxyls derived from 2 on E_T (30) solvent parameters have been found. Opposite directions of the dependencies for different nuclei of the same radical have been established. Anisotropic spectra of the radical derived from 1 and iminoxy radicals derived from -furildioxime have been obtained by γ-irradiation of solid oximes.     

Copper-catalyzed synthesis of oxime ethers from iminoxy radical (CN–O) and maleimides via radical addition

An efficient Cu(II)-catalyzed radical addition of maleimides has been achieved. The identified copper catalyst enables the formation of oxime radicals (N–O) by cleaving the O–H bond in ketoximes, followed by the radical addition to N-substituted maleimides. The oxime radicals (N–O) were detected and confirmed by EPR spectroscopy and variable-temperature ¹H NMR. The simple one-pot reaction realizes the facile preparation of a variety of oxime ether adduct products in moderate to good yields.     

Evidence of an electron-transfer mechanism in the peroxynitrite-mediated oxidation of 4-alkylphenols and tyrosine

The mechanism of interaction of the peroxynitrite with some 4-alkylphenols and tyrosine was mainly studied by means of ESR spectroscopy and product analysis. The radical intermediates, detected as spin adducts to the 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO), were identified as carbon-centered radicals to the benzene ring. The reaction seems to proceed via an electron transfer process (ET), most likely mediated by a NOx derivative, leading to the intermediacy of a phenoxyl-type radical as proved by the detection of the corresponding Pummerer-type ketone. No evidence of the formation of hydroxyl radicals, due to the homolytic cleavage of the peroxynitrite at physiological pH was obtained, even though DEPMPO hydroxyl spin adducts were detected: the latter most likely arises from the direct attack of the spin trap by the oxidant species. The possible involvement of HCO(3)(-)/CO(2), i.e., the formation of the nitrosoperoxycarbonate, ONOOCO(2)(*)(-), was also investigated.     

Mechanistic aspects of the formation of aldehydes and nitriles in photosensitized reactions of aldoxime ethers

The photooxidation of a series of aldoxime ethers was studied by laser flash photolysis and steady-state (product studies) methods. Nanosecond laser flash photolysis studies have shown that chloranil (CA)-sensitized reactions of the O-methyl (1), O-ethyl (2), O-benzyl (3), and O-tert-butyl (4) benzaldehyde oximes result in the formation of the corresponding radical cations. In polar non-nucleophilic solvents such as acetonitrile, there are several follow-up pathways available depending on the structure of the aldoxime ether and the energetics of the reaction pathway. When the free energy of electron transfer (DeltaGET) becomes endothermic, syn-anti isomerization is the dominant pathway. This isomerization pathway is a result of triplet energy transfer from CA to the aldoxime ether. For substrates with alpha-protons (aldoxime ethers 1-3), the follow-up reactions involve deprotonation at the alpha-position followed by beta-scission to form the benziminyl radical (and an aldehyde). The benziminyl radical reacts to give benzaldehyde, the major product under these conditions. A small amount of benzonitrile is also observed. In the absence of alpha-hydrogens (aldoxime ether 4), the major product is benzonitrile, which is thought to occur via reaction of the excited (triplet) sensitizer with the aldoxime ether. Abstraction of the iminyl hydrogen yields an imidoyl radical, which undergoes a beta-scission to yield benzonitrile. An alternative pathway involving electron transfer followed by removal of the iminyl proton was not deemed viable based on charge densities obtained from DFT (B3LYP/6-31G*) calculations. Similarly, a rearrangement pathway involving an intramolecular hydrogen atom transfer process was ruled out through experiments with a deuterium-labeled benzaldehyde oxime ether. Studies involving nucleophilic solvents have shown that all aldoxime ethers reacted with MeOH by clean second-order kinetics with rate constants of 0.7 to 1.2 x 10(7) M(-1) s(-1), which suggests that there is only a small steric effect in these reactions. The steady-state experiments demonstrated that under these conditions no nitrile is formed. This is explained by a mechanistic scheme involving nucleophilic attack on the nitrogen of the aldoxime ether radical cation, followed by solvent-assisted [1,3]-proton transfer and elimination of an alcohol, similar to the results obtained for a series of acetophenone oxime ethers.     

Interaction of polypyromellitimide with nitrogen dioxide

The mechanism of interaction of nitrogen dioxide with aromatic polyimides is considered by the example of polypyromellitimide. The formation of stable radicals of acylarylaminoxyl, iminoxyl and phenoxyl types has been detected by electron paramagnetic resonance spectroscopy. Acylarylaminoxyl radicals were detected in polypyromellitimide after its exposure to nitrogen dioxide at room temperature followed by pumping nitrogen dioxide from the samples. Iminoxyl and phenoxyl radicals were formed during thermolysis of the nitration products of the polymer at 373 K. The proposed mechanism is based on the reaction of dimers of nitrogen dioxide in the form of nitrosyl nitrate. It was observed that intermediate radical cations and nitric oxide were formed in the primary reaction of electron transfer from the polyimide to nitrosyl nitrate. The subsequent cage reactions with participation of radical cations and nitric oxide give nitroso compounds and nitrates which are precursors of stable nitrogen-containing and phenoxyl radicals.     

Stabilization of sulfide radical cations through complexation with the peptide bond: mechanisms relevant to oxidation of proteins containing multiple methionine residues

The recent study on the *OH-induced oxidation of calmodulin, a regulatory "calcium sensor" protein containing nine methionine (Met) residues, has supported the first experimental evidence in a protein for the formation of S therefore N three-electron bonded radical complexes involving the sulfur atom of a methionine residue and the amide groups in adjacent peptide bonds. To characterize reactions of oxidized methionine residues in proteins containing multiple methionine residues in more detail, in the current study, a small model cyclic dipeptide, c-(L-Met-L-Met), was oxidized by *OH radicals generated via pulse radiolysis and the ensuing reactive intermediates were monitored by time-resolved UV-vis spectroscopic and conductometric techniques. The picture that emerges from this investigation shows there is an efficient formation of the Met (S therefore N) radicals, in spite of the close proximity of two sulfur atoms, located in the side chains of methionine residues, and in spite of the close proximity of sulfur atoms and oxygen atoms, located in the peptide bonds. Moreover, it is shown, for the first time, that the formation of Met(S therefore N) radicals can proceed directly, via H+-transfer, with the involvement of hydrogen from the peptide bond to an intermediary hydroxysulfuranyl radical. Ultimately, the Met(S therefore N) radicals decayed via two different pH-dependent reaction pathways, (i) conversion into sulfur-sulfur, intramolecular, three-electron-bonded radical cations and (ii) a proposed hydrolytic cleavage of the protonated form of the intramolecular, three-electron-bonded radicals [Met(S therefore N)/Met(S therefore NH)+] followed by electron transfer and decarboxylation. Surprisingly, also alpha-(alkylthio)alkyl radicals enter the latter mechanism in a pH-dependent manner. Density functional theory computations were performed on the model c-(L-Met-Gly) and its radicals in order to obtain optimizations and energies to aid in the interpretation of the experiments on c-(L-Met-L-Met).     

Sulfonyl Nitrene and Amidyl Radical: Structure and Reactivity

Photocatalytic generation of nitrenes and radicals can be used to tune or even control their reactivity. Photocatalytic activation of sulfonyl azides leads to the elimination of N₂ and the resulting reactive species initiate C−H activations and amide formation reactions. Here, we present reactive radicals that are generated from sulfonyl azides: sulfonyl nitrene radical anion, sulfonyl nitrene and sulfonyl amidyl radical, and test their gas phase reactivity in C−H activation reactions. The sulfonyl nitrene radical anion is the least reactive and its reactivity is governed by the proton coupled electron transfer mechanism. In contrast, sulfonyl nitrene and sulfonyl amidyl radicals react via hydrogen atom transfer pathways. These reactivities and detailed characterization of the radicals with vibrational spectroscopy and with DFT calculations provide information necessary for taking control over the reactivity of these intermediates.     

Photochemical generation of a primary vinyl cation from (E)-bromostyrene: mechanisms of formation and reaction

The photochemistry of (E)-bromostyrene was investigated to determine the nature of the product-forming intermediates and to clarify the mechanism of formation of vinylic cations and vinylic radicals. Both a cation- and a radical-derived product are formed, and the ionic origin of the former product is demonstrated by significant scrambling of the label, starting from specifically deuterated (E)-bromostyrene. MO calculations show that the isolated incipient primary vinyl cation is not a metastable species, but that specific interaction with a counterion in combination with a polar environment makes it metastable. The effects of variation of the wavelength of irradiation, solvent polarity, temperature, and isotopic substitution all agree with a mechanism of direct heterolytic C-Br bond cleavage producing an ion pair followed by formation of a radical pair via electron transfer. The vinylic cation is proposed to stem directly from the indirectly populated lowest excited singlet state of bromostyrene with an energy of activation of 6.7 kcal/mol. Branching between proton loss and electron transfer in the resulting ion pair determines the ratio of cation- to radical-derived product. The E/Z-isomerization occurs in a separate process and does not involve C-Br bond cleavage.     

Photochemical reactivity of 1-substituted-1-aza-1,4-dienes promoted by electron-acceptor sensitizers. Di-pi-methane rearrangements and alternative reactions via radical-cation intermediates

Irradiation of a series of beta,gamma-unsaturated imines, oxime acetates, and oxime methyl ethers, using 9,10-dicyanoanthrathene (DCA) or dicyanodurene (DCD) as electron acceptor sensitizers, affords the corresponding cyclopropanes resulting from 1-aza-di-pi-methane rearrangements via radical cations. In some cases, alternative reactions of these intermediates occur to yield nitriles, dihydroquinolines, dihydronaphthalene derivatives, and cycloaddition products. Some of these products result from reactions via alkene radical-cation intermediates while others arise by pathways involving imine radical-cation intermediates. The yields of products formed in these processes were significantly higher when DCD was used as electron-acceptor sensitizer instead of DCA.     

Electrochemical oxidation of aldoximes

Conclusions The electrochemical oxidation of aldoximes was found to proceed with the loss of one electron and formation of the corresponding iminoxyl radical, which undergoes subsequent chemical reactions more rapidly than undergoing oxidation on the electrode.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1687–1691, July, 1989.     

Electrochemical oxidation of vicinal dioximes

First-wave oxidation of vicinal dioximes corresponds to the transfer of two electrons and two protons to give furoxans, which are further oxidized at the potentials of the second wave. It is shown that the key step in the electrochemical cyclization of vicinal dioximes is oxidation of the intermediate iminoxyl radicals to oxoimmonium cations, which react with the adjacent oxime group.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 630–634, March, 1990.     

Annulation of the cyclohexane ring by tandem free radical alkylation of a nonactivated delta-carbon atom-intramolecular carbanion cycloalkylation

Annulation of the cyclohexane ring by a combination of free radical and ionic reactions sequences was achieved. Free radical alkylation of the remote nonactivated delta-carbon atom involves addition of delta-carbon radicals, generated by 1,5-hydrogen transfer in alkoxy radical intermediates, to radicophilic olefins, while the polar sequence involves enolate anions as intermediates which undergo a cycloalkylation reaction. Thus, the cyclohexane ring was constructed using diverse acyclic and cyclic structures as precursors of alkoxy radicals.     

Detection and Reaction of Oxaphosphetanes Derived from Benzaldehyde and 1-Adamantylmethylidene Ylide

The Wittig reaction of (1-adamantylmethylidene)triphenylphosphorane (Ph(3)P=CH(1-Ad)) with benzaldehyde was investigated, and the results were compared with those of other ylides. The substituent effect in the reaction of the ylide with benzaldehydes was determined by competition experiments, which gave a Hammett rho value of 3.2. The rho value is much larger than those reported for analogous reactions of Ph(3)P=CH(CH(2))(2)CH(3) (rho = 0.20) and Ph(3)P=CH(CH(3))(2) (rho = 0.59), indicating that the reaction mechanism differs for Ph(3)P=CH(1-Ad) and the other ylides. The cis/trans ratio of the product alkene is 74/26 for the reaction with the parent benzaldehyde and highly depends on the position of the substituent; ortho substituted benzaldehydes gave the trans alkenes up to 90%. Monitoring the reaction by means of (31)P NMR revealed that both cis and trans oxaphosphetane intermediates were formed and that the formation and decomposition of the cis oxaphosphetane are 7-12 times faster than those of the trans oxaphosphetane. From the comparison of the reaction of Ph(3)P=CH(1-Ad) + benzaldehyde with those of Ph(3)P=CH(CH(2))(2)CH(3) + benzaldehyde and benzophenone, and Ph(3)P=CH(CH(3))(2) + benzophenone, it was concluded that all the reactions with these nonstabilized ylides proceed via an electron-transfer mechanism and that the rate-determining step changes from the electron transfer step to that of radical combination when the substrate or ylide becomes more sterically demanding.     

O-H bond dissociation enthalpies of oximes: a theoretical assessment and experimental implications

By using a multilayer composite ab initio method ONION-G3B3, we calculated O-H bond dissociation enthalpies (BDEs) of 58 oximes that were measured experimentally. Experimental BDEs derived from thermal decomposition kinetics and calorimetric measurements were found to be consistent with the theory. However, the electrochemical method was found to give questionably high BDEs possibly due to errors in the measurement of pKa's or redox potentials. Subsequently, the performances of a variety of DFT functionals including B3LYP, B3P86, B3PW91, BHandH, BHandHLYP, BMK, PBE1PBE, MPW1KCIS, mPWPW91, MPW1B95, and MPW1K were tested to calculate oxime O-H BDEs, where ROBHandHLYP was found to be the most accurate. By using this method, we calculated O-H BDEs of over 140 oximes in a systematic fashion. All of the calculated O-H BDEs fell in the range from 76.8 to 89.8 kcal/mol. An amino group on the azomethine carbon was found to strengthen the O-H bond, whereas bulky alkyl substituents on oximes decreased O-H BDEs due to their large steric-strain-relieving effects in the process of O-H bond cleavage. Para substituents had little effect on the BDEs of benzaldoximes and phenyl methyl ketoximes. Finally, on the basis of a spin distribution calculation, aryl-, alkyl-, and carbonyl-substituted iminoxyl radicals were found to be sigma-radicals, whereas amino-substituted iminoxyl radicals were of pi-structure.