Kinetic studies of the interaction of borane–amines with alkoxyl radicals and ketone triplets: relevance to polarity reversal catalysis

The study of triplet excited state behavior of nucleic acids and component mononucleotides is hampered by the very small yields produced by direct photolysis. We have used high energy triplet sensitizers to generate these species in high yield, thus facilitating the study of their photophysical and photochemical behavior. Acetone-sensitized triplet formation of all triplet state nucleotides allowed nucleotide triplet−triplet absorption spectra to be measured. Triplet−triplet absorption coefficients were determined using comparative actinometry. Self-quenching of the nucleotide triplet states was found to occur efficiently with rate constants, ksq > 107 M-1 s-1. The interaction of a variety of ketone triplet sensitizers with mononucleotides has been studied as a function of the relative energies of the sensitizer−nucleotide pair. In all cases, the triplet states of the sensitizers were efficiently quenched by the nucleotides, although different reaction mechanisms were observed depending on the reaction pair under study. Acetone, the sensitizer with the highest triplet energy, sensitized all triplet state nucleotides. Sensitizers with triplet energies, ET > 74 kcal mol-1, sensitized TMP and those with ET < 74 kcal mol-1 did not exhibit any triplet sensitization, although an efficient quenching reaction (kq > 108 M-1 s-1) was observed. Where energy transfer did not take place, sensitizers were quenched by electron transfer from the purines. The quantum yield for this process was determined as 0.31 for GMP and 0.09 for AMP. In DNA, triplet energy transfer from the same sensitizers was probed by determining the relative efficiency of pyrimidine dimer formation in pBR322, an exclusively triplet-mediated reaction under sensitized conditions. Our results allow some conclusions to be drawn on triplet properties and intramolecular energy transfer in DNA. Base triplet energy levels appear to be lower in DNA than in the isolated mononucleotides. In any system where ketone triplet states are generated, electron transfer from a purine should be considered as a significant reaction pathway.

ESR spectroscopy has been used to characterise the reactions of the amine–boryl radicals produced by hydrogen-atom abstraction from a variety of amine–borane complexes by photochemically generated t-butoxyl radicals. The complexes Me3N→BH2R (R = Me2CHCMe2, Bun, Bui, Bus), 1,1-dimethyl-1,2-azaborolidine, 1-methyl-cis-1-azonia-5-boratabicyclo[3.3.0]octane, Me2NCH2CH2NMe2·2lpcBH2(Ipc = isopinocampheyl), Me3SiCH2NMe2→BH3, and Me3N→BH3 were investigated. All the amine–boryl radicals rapidly abstract halogen from alkyl bromides and chlorides at 170 K. Specific alkyl radicals can be generated for ESR studies at low temperature by UV irradiation of a solution containing ButOOBut, Me3N→BH2Bun, and the corresponding alkyl chloride. The amine–borane complexes act as donor polarity reversal catalysts for the overall abstraction of acidic hydrogen from HCC(O) groups in esters, lactones, ketones, imides, and related compounds. Relative rates of catalysed hydrogen-atom abstraction from MeCO2Et, MeCH2CO2Et, and Me2CHCO2Et have been determined and competitive abstraction from the two different types of α-CH groups in MeC(O)CHMe2 has been similarly quantified. The relative reactivities of the amine–boryl radicals can be understood in terms of a balance between enthalpic, polar, and steric factors and the merits of the different amine–boranes as polarity reversal catalysts for the overall abstraction of hydrogen from acidic C–H groups by alkoxyl radicals are assessed. The origin of the polar effects observed in hydrogen-atom abstraction reactions is discussed in terms of the electronegativity difference between the attacking and departing radicals and a simple approach for the quantitative description of polar effects is outlined.

Sensitization of O 2( 1Δ g) by N-methylacridone. Solvent and O 2-concentration dependence and 16O/ 18O isotope exchange experiments

Rate constants for quenching of triplet excited acetone by primary and tertiary amines in solution have been measured directly by flash and pulsed laser techniques. The rate constants were found to be independent of solvent dielectric constant over the range ε 1.9 to ε 80, but were influenced by amine ionization potential. The results are interpreted as supporting a charge-transfer model for the quenching of triplet ketones by tertiary amines. The intervention of free ions in the quenching process is discussed. Free energy calculations indicate that electron transfer from N,N-dimethylaniline to triplet ketones is exothermic but is slightly more favorable for triplet aromatic ketones than for triplet acetone. Evidence for direct hydrogen atom transfer was obtained for quenching of triplet acetone by n-hexylamine.

Benzimidazole-arylhydrazone hybrids showed promising potential as multifunctional drugs for the treatment of neurodegenerative disorders. The neuroprotection studies conducted using an in vitro model of H2O2-induced oxidative stress on the SH-SY5Y cell line revealed a remarkable activity of the compound possessing a vanilloid structural fragment. The cell viability was preserved up to 84% and this effect was significantly higher than the one exerted by the reference compounds melatonin and rasagiline. Another compound with a catecholic moiety demonstrated the second-best neuroprotective activity. Computational studies were further conducted to characterize in depth the antioxidant properties of both compounds. The possible radical scavenging mechanisms were estimated as well as the most reactive sites through which the compounds may deactivate a variety of free radicals. Both of the compounds are able to deactivate not only the highly reactive hydroxyl radicals but also alkoxyl and hydroperoxyl radicals, following hydrogen atom transfer or radical adduct formation mechanism. In nonpolar medium, 3e is predicted to react slightly faster than 3a with alkoxyl radicals and around two orders of magnitude faster than 3a with hydroperoxyl radicals. The most reactive sites for formal hydrogen atom transfer in 3a are the meta-hydroxy group in the phenyl ring in water and the amide N-H group in benzene; in 3e, the amide N-H group is more reactive in both solvents. The radical adduct formation can occur at several positions in 3a and 3e, the most active being C4, C6, and C14. The stability of the formed radicals was estimated by NBO calculations. The NBO calculations indicated that the spin density in the radicals formed by the abstraction of a hydrogen atom from the amide groups of both compounds is delocalized over the phenyl ring and the hydrazone chain. The obtained theoretical data for the better radical scavenging ability of the vanilloid hybrid corroborate its experimentally established better neuroprotective activity.

Due to the high reactivity of alkoxyl (RO·) radicals and their propensity to easily undergo β-scission or Hydrogen Atom Transfer (HAT) reactions, intermolecular alkoxylations involving RO· radicals are barely described. We report herein for the first time the efficient intermolecular trapping of alkoxyl radicals by silyl enol ethers. This photoredox-mediated protocol enables the introduction of both structurally simple and more complex alkoxy groups into a wide range of ketones and amides.

Review: 50 refs.

Hydrogen atom transfer (HAT) is a fundamental reaction that takes part in a wide variety of chemical and biological processes, with relevant examples that include the action of antioxidants, damage to biomolecules and polymers, and enzymatic and biomimetic reactions. Moreover, great attention is currently devoted to the selective functionalization of unactivated aliphatic C-H bonds, where HAT based procedures have been shown to play an important role. In this Account, we describe the results of our recent studies on the role of structural and medium effects on HAT from aliphatic C-H bonds to the cumyloxyl radical (CumO(•)). Quantitative information on the reactivity and selectivity patterns observed in these reactions has been obtained by time-resolved kinetic studies, providing a deeper understanding of the factors that govern HAT from carbon and leading to the definition of useful guidelines for the activation or deactivation of aliphatic C-H bonds toward HAT. In keeping with the electrophilic character of alkoxyl radicals, polar effects can play an important role in the reactions of CumO(•). Electron-rich C-H bonds are activated whereas those that are α to electron withdrawing groups are deactivated toward HAT, with these effects being able to override the thermodynamic preference for HAT from the weakest C-H bond. Stereoelectronic effects can also influence the reactivity of the C-H bonds of ethers, amines, and amides. HAT is most rapid when these bonds can be eclipsed with a lone pair on an adjacent heteroatom or with the π-system of an amide functionality, thus allowing for optimal orbital overlap. In HAT from cyclohexane derivatives, tertiary axial C-H bond deactivation and tertiary equatorial C-H bond activation have been observed. These effects have been explained on the basis of an increase in torsional strain or a release in 1,3-diaxial strain in the HAT transition states, with kH(eq)/kH(ax) ratios that have been shown to exceed one order of magnitude. Medium effects on HAT from aliphatic C-H bonds to CumO(•) have been also investigated. With basic substrates, from large to very large decreases in kH have been measured with increasing solvent hydrogen bond donor (HBD) ability or after addition of protic acids or alkali and alkaline earth metal ions, with kinetic effects that exceed 2 orders of magnitude in the reactions of tertiary alkylamines and alkanamides. Solvent hydrogen bonding, protonation, and metal ion binding increase the electron deficiency and the strength of the C-H bonds of these substrates deactivating these bonds toward HAT, with the extent of this deactivation being modulated by varying the nature of the substrate, solvent, protic acid, and metal ion. These results indicate that through these interactions careful control over the HAT reactivity of basic substrates toward CumO(•) and other electrophilic radicals can be achieved, suggesting moreover that these effects can be exploited in an orthogonal fashion for selective C-H bond functionalization of substrates bearing different basic functionalities.

If a mixture of an aliphatic ketone and a trialkylborane is irradiated with u.v. light, the ketone triplet brings about a bimolecular homolytic substitution at the boron centre, and the superimposed e.s.r. spectra of the two radicals which are formed can be observed; the ultimate products of the reaction result from the coupling of these radicals. R1R2CO*+ BR33→ R1R2ĊOBR32+ R3·→ productsBy monitoring the intensities of the spectra when two different boranes, or a borane and an olefinic quencher, compete for reaction with acetone triplets, or when substitution and fragmentation reactions of di-isopropyl ketone triplet compete, the above mechanism was established, and kinetic parameters for the substitution reaction were derived. Typically, the reaction between triplet acetone and tri-n-butylborane has a rate constant of 7 × 106M–1 s–1 at 20°.

The rate constants for quenching of triplet acetone by a series of halobenzenes have been determined by flash emission technique. Quenching was found to be approximately a hundred times faster than that for triplet benzophenone. For both triplet ketones, quenching did not decrease with the increase in triplet energy difference between ketone and quencher (as expected for normal endothermic triplet energy transfer) and did not correlate with the i.p. of all of the quenchers studied. All of the qualitative features of the quenching results can be simply interpreted in terms of enhanced coupling of the locally excited triplet ketone and quencher states as a result of interaction with the charge transfer state.

Nanosecond transient absorption spectroscopy was used to generate ethoxyl radicals and demonstrate that they react with 2,6-lutidine and 4-phenylpyridine to give the corresponding N-hydropyridinyl radicals-products of a novel hydrogen atom transfer from the alkoxyl radical to the nitrogen atom of the substituted pyridines. Nanosecond kinetics show that both reactions are rapid (k ∼ 107 M-1 s-1) in acetonitrile at room temperature. Rate constants measured for reaction of the ethoxyl vs. d5-ethoxyl radical with 2,6-lutidine and 4-phenylpyridine show that both reactions exhibit primary H/D kinetic isotope effects for the hydrogen (deuterium) atom transfer reactions.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new quenching mechanism of the (.pi..pi.*) ketone triplet stateArthur G. Schultz, Charles D. DeBoer, William G. Herkstroeter, and Richard H. SchlessingerCite this: J. Am. Chem. Soc. 1970, 92, 20, 6086–6088Publication Date (Print):October 1, 1970Publication History Published online1 May 2002Published inissue 1 October 1970https://doi.org/10.1021/ja00723a060RIGHTS & PERMISSIONSArticle Views50Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (403 KB) Get e-Alerts Get e-Alerts

The molecular structures of optically active quinuclidine–isopinocampheylborane and of the polycyclic amine–borane formed by cyclisation of N-nopylpyrrolidine–borane have been determined by X-ray crystallography. These and related amine–borane complexes have been used previously as polarity-reversal catalysts to bring about kinetic resolution of racemic esters and ketones. The key step in these resolutions is enantioselective H-atom abstraction from an α-C–H group in the carbonyl compound by the chiral amine–boryl radical derived from the catalyst. Ab initio and semi-empirical molecular orbital calculations have been carried out for representative transition states involved in H-atom transfer to amine–boryl radicals and the roles of dipole–dipole interactions, stereoelectronic effects and hydrogen-bonding have been investigated. The steric demands of a variety of amine–boryl radicals in H-atom transfer reactions have been assessed by determining the relative rates of abstraction from the α-C–H bonds in diethyl malonate and diethyl methylmalonate.

Part I: Photoreduction of 1-naphthaldehyde and 2-acetonaphthone has been accomplished by the use of tributylstannane as a hydrogen donor. Rate constants for hydrogen abstraction and thermal deactivation of the excited species have been estimated. The π-π* triplet states of the two carbonyl compounds are responsible for the hydrogen abstraction reaction. The naphthoyl compounds do not undergo photoreduction by secondary alcohols. Their low reactivity is attributed to the fact that the π-π* rather than the n-π* triplet is involved. Carbonyl compounds that are easily photoreduced have the n-π* configuration in their lowest triplets. Part II: The phenomenon of energy transfer between triplet states of molecules in solution has been investigated. Two methods have been employed in this investigation. The first involves the photosensitized cis-trans isomerization of piperylene. Aromatic carbonyl compounds were used as sensitizers. The trans/cis ratio in the photostationary state was related to the energy of the lowest triplet state of the sensitizer. The second method involved the study of the effects of quenchers on the quantum yield in the photoreduction of benzophenone by benzhydrol. Many of the quenchers were found to have about the same efficiency. It was concluded that the energy transfer (quenching) reaction is probably diffusion controlled.

Liquid-phase e.s.r. studies show that photochemically generated t-butoxyl radicals abstract hydrogen from secondary amine–boranes R2NH→BH3 to give the corresponding amine–boryl radical R2NH→ḂH2 as the kinetically controlled product. Depending on the nature of the N-alkyl groups, the amine–boryl may undergo β-scission or may rapidly abstract hydrogen from the parent amine–borane to give the isomeric aminyl–borane radical R2Ṅ→BH3 which is thermodynamically more stable. Deuterium labelling experiments exclude 1,2-hydrogen atom migration as the mechanism of the isomerisation. The less electrophilic cyclopropyl radical reacts with R2NH→BH3 to yield the aminyl–borane directly by abstraction of hydrogen from nitrogen. In the reactions with t-butoxyl radicals, intermediate amine–boryl radicals may be intercepted by halogen atom transfer from alkyl bromides or by addition to 2-methyl-2-nitrosopropane; with one amine–borane, But(Pri)NH→BH3, the amine–boryl radical was detected directly by e.s.r. spectroscopy. The e.s.r. spectra of the aminyl–borane radicals indicate appreciable hyperconjugative delocalisation of the unpaired electron onto the BH3 group. Ab initio and/or semi-empirical molecular orbital calculations for H3N→ḂH2, H2Ṅ→BH3, and their N-methylated derivatives support the conclusions reached by experiment.