Showing papers on "Hydrogen atom abstraction published in 2006"
TL;DR: Solid evidence is shown to show that water really can act as a complete hydrogen-atom source rather than as a simple proton donor for radical reductions mediated by Ti and, presumably, other metals that react by single-electron transfer.
Abstract: The reactivity of water with both carbanion and carbocation intermediates is well known, but until now it has generally been believed that water is inert towards free radicals. This hypothetical passivity has been attributed to the strong H OH bond, which, with a bond-dissociation energy of 117.59 0.07 kcalmol , would impede any potential hydrogen-atom transfer from water. Some years ago, however, we chanced to observe that tertiary radicals were reduced effectively in the presence of bis(cyclopentadienyl)titanium(III) chloride ([Cp2TiCl]) and water. [4] This observation further facilitated the control of the final step in titanocene-catalyzed radical cyclizations, which are useful for the straightforward synthesis of complex polycyclic terpenoids. However, as, at the time, the idea of water acting as a hydrogen-atom source seemed to be counterintuitive, this phenomenon was rationalized by invoking either the formation and subsequent hydrolysis of alkyl–Ti complexes or a virtually intramolecular hydrogen transfer via a quite sophisticated cyclic transition state. 5] We now have solid evidence to show that water really can act as a complete hydrogen-atom source rather than as a simple proton donor for radical reductions mediated by Ti and, presumably, other metals that react by single-electron transfer. Many highly selective free-radical reactions have been developed and have proved to be very useful in the total synthesis of complex organic compounds owing to the mild conditions required and their compatibility with many functional groups. Within this context, RajanBabu and Nugent introduced a novel concept: homolytic oxirane opening induced by [Cp2TiCl]. [7] This reaction generates the most substituted (i.e., most stable) b-titanoxy radical, which, among other transformations, could be either trapped by a second [Cp2TiCl] species to provide an alkene (epoxide deoxygenation) by “TiO” elimination or, in the presence of a hydrogen-atom donor such as cyclohexa-1,4-diene (1,4CHD), reduced to an alcohol with the opposite regiochemistry to that expected from the reduction with metal hydrides (Scheme 1).
158 citations
TL;DR: Ab initio calculations of portions of the C2H5O potential energy surface critical to the title reaction are presented and it is found that a significant fraction of the total rate coefficient is due to the formation of vinyl alcohol above this temperature.
Abstract: Ab initio calculations of portions of the C2H5O potential energy surface critical to the title reaction are presented. These calculations are based on QCISD geometries and frequencies and RQCISD(T) energies extrapolated to the complete-basis-set limit. Rate coefficients for the reaction of C2H4 with OH are calculated using this surface and the two transition-state model of Greenwald and co-workers [J. Phys. Chem. A 2005, 109, 6031] for the association of OH with C2H4. The present calculations reproduce most of the experimental data, including the temperature and pressure dependence of the rate coefficients, with only a small (0.4 kcal/mol) adjustment to the energy barrier for direct hydrogen abstraction. We confirm the importance of this channel above 800 K and find that a significant fraction of the total rate coefficient (∼10%) is due to the formation of vinyl alcohol above this temperature. Calculations of the vinyl alcohol channel are consistent with the recent observation of this molecule in low-pres...
151 citations
148 citations
TL;DR: HmaS and HPPD have similar substrate-bound complexes and that the role of the protein pocket in determining the different reactivities exhibited by these enzymes is to properly orient the substrate, allowing for ligand field geometric changes along the reaction coordinate.
Abstract: (4-Hydroxy)mandelate synthase (HmaS) and (4-hydroxyphenyl)pyruvate dioxygenase (HPPD) are two α-keto acid dependent mononuclear non-heme iron enzymes that use the same substrate, (4-hydroxyphenyl)pyruvate, but exhibit two different general reactivities. HmaS performs hydrogen-atom abstraction to yield benzylic hydroxylated product (S)-(4-hydroxy)mandelate, whereas HPPD utilizes an electrophilic attack mechanism that results in aromatic hydroxylated product homogentisate. These enzymes provide a unique opportunity to directly evaluate the similarities and differences in the reaction pathways used for these two reactivities. An FeII methodology using CD, magnetic CD, and variable-temperature, variable-field magnetic CD spectroscopies was applied to HmaS and compared with that for HPPD to evaluate the factors that affect substrate interactions at the active site and to correlate these to the different reactivities exhibited by HmaS and HPPD to the same substrate. Combined with density functional theory calculations, we found that HmaS and HPPD have similar substrate-bound complexes and that the role of the protein pocket in determining the different reactivities exhibited by these enzymes (hydrogen-atom abstraction vs. aromatic electrophilic attack) is to properly orient the substrate, allowing for ligand field geometric changes along the reaction coordinate. Elongation of the FeIVO bond in the transition state leads to dominant FeIIIO•− character, which significantly contributes to the reactivity with either the aromatic π-system or the CH σ-bond.
135 citations
TL;DR: The molecular basis of the hydroxylation reaction of the Calpha of a C-terminal glycine catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) was investigated and the most reactive oxygenated species was identified and new insights into the hydrogen abstraction (H-abstraction) mechanism operative in PHM were presented.
Abstract: The molecular basis of the hydroxylation reaction of the Cα of a C-terminal glycine catalyzed by peptidylglycine α-hydroxylating monooxygenase (PHM) was investigated using hybrid quantum-classical (QM-MM) computational techniques. We have identified the most reactive oxygenated species and presented new insights into the hydrogen abstraction (H-abstraction) mechanism operative in PHM. Our results suggest that O2 binds to CuB to generate CuBII−O2•- followed by electron transfer (ET) from CuA to form CuBI−O2•-. The computed potential energy profiles for the H-abstraction reaction for CuBII−O2•-, CuBI−O2•-, and [CuBII−OOH]+ species indicate that none of these species can be responsible for abstraction. However, the latter species can spontaneously form [CuBO]+2 (which consists of a two-unpaired-electrons [CuBO]+ moiety ferromagneticaly coupled with a radical cation located over the three CuB ligands, in the quartet spin ground state) by abstracting a proton from the surrounding solvent. Both this monooxygena...
133 citations
131 citations
TL;DR: Findings support a hypothesis regarding how certain heme enzymes can perform difficult H-atom abstractions while avoiding the generation of high-valent metal-oxo intermediates with oxidation potentials that would lead to the destruction of the surrounding protein environment.
Abstract: High-valent metal-oxo complexes are postulated as key intermediates for a wide range of enzymatic and synthetic processes. To gain an understanding of these processes, the reactivity of an isolated, well-characterized Mn(V)-oxo complex, (TBP8Cz)MnVO (1), (TBP8Cz = octakis(para-tert-butylphenyl)corrolazinato(3-)) has been examined. This complex has been shown to oxidize a series of substituted phenols (4-X-2,6-t-Bu2C6H2OH, X = C(CH3)3 (3), H, Me, OMe, CN), resulting in the production of phenoxyl radicals and the MnIII complex [(TBP8Cz)MnIII] (2). Kinetic studies have led to the determination of second-order rate constants for the phenol substrates, which give a Hammett correlation ((log k''x/k''H) vs sigmap+) with rho = -1.26. A plot of log k versus BDE(O-H) also reveals a linear correlation. These data, combined with a KIE of 5.9 for 3-OD, provide strong evidence for a concerted hydrogen-atom-abstraction mechanism. Substrates with C-H bonds (1,4-cyclohexadiene and 9,10-dihydroanthracene) are also oxidized via H-atom abstraction by 1, although at a much slower rate. Given the stability of 1, and in particular its low redox potential, (-0.05 V vs SCE), the observed H atom abstraction ability is surprising. These findings support a hypothesis regarding how certain heme enzymes can perform difficult H-atom abstractions while avoiding the generation of high-valent metal-oxo intermediates with oxidation potentials that would lead to the destruction of the surrounding protein environment.
128 citations
TL;DR: The abundance of H· and −CO losses from the precursor ion changed upon deuterium labeling indicating the presence of a kinetic isotope effect, which suggests that the values reported here represent an underestimation of radical migration and H/D scrambling in the observed fragments.
121 citations
TL;DR: The activation energy for hydrogen abstraction by compound I in cytochrome P450 for a diverse set of 24 small organic substrates is estimated using state-of-the-art density functional theory (B3LYP) and can be reproduced by computationally less demanding methods.
Abstract: We have estimated the activation energy for hydrogen abstraction by compound I in cytochrome P450 for a diverse set of 24 small organic substrates using state-of-the-art density functional theory (B3LYP). We then show that these results can be reproduced by computationally less demanding methods, for example, by using small organic mimics of compound I with both B3LYP and the semiempirical AM1 method (mean absolute error of 3-4 kJ/mol) or by calculating the bond dissociation energy, without relaxation of the radical (B3LYP) or estimated from three-point fit to a Morse potential (AM1; errors of 4 and 5 kJ/mol, respectively). We can assign activation energies of 74, 61, 53, 47, and 30 kJ/mol to primary carbons, secondary/tertiary carbons, carbons with adjacent sp(2) or aromatic groups, ethers/thioethers, and amines, respectively, which gives a very simple and predictive model. Finally, some of the less demanding methods are applied to study the CYP3A4 metabolism of progesterone and dextromethorphan.
113 citations
TL;DR: In this paper, the authors proposed a method for controlling a class of low temperature chemical reactions, such as formaldehyde H2CO and the hydroxyl radical OH, through either the molecular state or an external electric field.
Abstract: We propose a method for controlling a class of low temperature chemical reactions. Specifically, we show the hydrogen abstraction channel in the reaction of formaldehyde H2CO and the hydroxyl radical OH can be controlled through either the molecular state or an external electric field. We also outline experiments for investigating and demonstrating control over this important reaction. To this end, we report the first Stark deceleration of H2CO. We have decelerated a molecular beam of H2CO essentially to rest, producing molecules at 100 mK with a density of 10 6 cm �3 .
111 citations
TL;DR: Experimental and theoretical evidence is provided and an attractive mechanism for the role of ABLM in double-strand cleavage is proposed, which would generate a reactive Fe(IV)=O species, capable of a second DNA strand cleavage, as observed in vivo.
Abstract: Bleomycin (BLM), a glycopeptide antibiotic chemotherapy agent, is capable of single- and double-strand DNA damage. Activated bleomycin (ABLM), a low-spin FeIII−OOH complex, is the last intermediate detected prior to DNA cleavage following hydrogen-atom abstraction from the C-4‘ of a deoxyribose sugar moiety. The mechanism of this C−H bond cleavage reaction and the nature of the active oxidizing species are still open issues. We have used kinetic measurements in combination with density functional calculations to study the reactivity of ABLM and the mechanism of the initial attack on DNA. Circular dichroism spectroscopy was used to directly monitor the kinetics of the ABLM reaction. These experiments yield a deuterium isotope effect, kH/kD ≈ 3 for ABLM decay, indicating the involvement of a hydrogen atom in the rate-determining step. H-atom donors with relatively weak X−H bonds accelerate the reaction rate, establishing that ABLM is capable of hydrogen-atom abstraction. Density functional calculations were...
TL;DR: The discrepancies between the published QM/MM studies on H-abstraction of camphor in P450cam have largely been resolved and spin density at the A-propionate side chain of heme can occur in the case of incomplete screening but has no major effect on the computed barrier.
Abstract: The discrepancies between the published QM/MM studies (Schoneboom, J. C.; Cohen, S.; Lin, H.; Shaik, S.; Thiel, W. J. Am. Chem. Soc. 2004, 126, 4017; Guallar, V.; Friesner, R. A. J. Am. Chem. Soc. 2004, 126, 8501) on H-abstraction of camphor in P450cam have largely been resolved. The crystallographic water molecule 903 situated near the oxo atom of Compound I acts as a catalyst for H-abstraction, lowering the barrier by about 4 kcal/mol. Spin density at the A-propionate side chain of heme can occur in the case of incomplete screening but has no major effect on the computed barrier.
TL;DR: The Fe(III)-OH complex is isolated and identified by a combination of solution and solid-state methods, including EPR and IR spectroscopy, supporting the generally accepted idea that Mn(III) is the thermodynamically superior oxidant at parity of coordination sphere.
Abstract: The lipoxygenase mimic [FeIII(PY5)(OH)](CF3SO3)2 is synthesized from the reaction of [FeII(PY5)(MeCN)](CF3SO3)2 with iodosobenzene, with low-temperature studies suggesting the possible intermediacy of an Fe(IV) oxo species. The Fe(III)−OH complex is isolated and identified by a combination of solution and solid-state methods, including EPR and IR spectroscopy. [FeIII(PY5)(OH)]2+ reacts with weak X−H bonds in a manner consistent with hydrogen-atom abstraction. The composition of this complex allows meaningful comparisons to be made with previously reported Mn(III)−OH and Fe(III)−OMe lipoxygenase mimics. The bond dissociation energy (BDE) of the O−H bond formed upon reduction to [FeII(PY5)(H2O)]2+ is estimated to be 80 kcal mol-1, 2 kcal mol-1 lower than that in the structurally analogous [MnII(PY5)(H2O)]2+ complex, supporting the generally accepted idea that Mn(III) is the thermodynamically superior oxidant at parity of coordination sphere. The identity of the metal has a large influence on the entropy of ...
TL;DR: In this article, the authors performed density functional slab model studies on water adsorption and decomposition at Pd(1.1/1) surface and found that water was weakly bound to the Pd surface.
TL;DR: Comparison with the results of experiments on the reaction of phenoxyl radical with alpha-naphthol indicates that the barrier height for the preferred PCET mechanism is calculated more accurately by MPW1K than by B3LYP.
Abstract: DFT calculations have been performed with the B3LYP and MPW1K functional on the hydrogen atom abstraction reactions of ethenoxyl with ethenol and of phenoxyl with both phenol and alpha-naphthol. Comparison with the results of G3 calculations shows that B3LYP seriously underestimates the barrier heights for the reaction of ethenoxyl with ethenol by both proton-coupled electron transfer (PCET) and hydrogen atom transfer (HAT) mechanisms. The MPW1K functional also underestimates the barrier heights, but by much less than B3LYP. Similarly, comparison with the results of experiments on the reaction of phenoxyl radical with alpha-naphthol indicates that the barrier height for the preferred PCET mechanism is calculated more accurately by MPW1K than by B3LYP. These findings indicate that the MPW1K functional is much better suited than B3LYP for calculations on hydrogen abstraction reactions by both HAT and PCET mechanisms.
TL;DR: In this article, free radical polymerization of methyl methacrylate (MMA) is initiated upon irradiation at A > 350 nm in CH 2 Cl 2 that contains benzoxazine (P-a) and one of the following photosensitizers: benzophenone (BP), thioxanthone (TX), 2-chlorothioxanthones, 2-isopropyl ITX, and camphorquinone (CQ).
Abstract: Free radical polymerization of methyl methacrylate (MMA) is initiated upon irradiation at A > 350 nm in CH 2 Cl 2 that contains benzoxazine (P-a) and one of the following photosensitizers: benzophenone (BP), thioxanthone (TX), 2-chlorothioxanthone (CTX), 2-isopropyl thioxanthone (ITX), and camphorquinone (CQ). The postulated mechanism is based on the intermolecular reaction of the excited photosensitizer with the tertiary amino moiety of the ground state P-a and a subsequent hydrogen abstraction reaction. The resulting aminoalkyl radicals initiate the polymerization. The incorporation of P-a groups into polymers is demonstrated by spectroscopic methods. The possibility of deep curing using the described photoinitiating system followed by the thermal ring opening of the incorporated P-a groups is also demonstrated.
TL;DR: There is no clear correlation between the computed A‐propionate spin density and the hydrogen abstraction barrier, and hence, no support for a previously proposed side‐chain mediated transition state stabilization mechanism.
Abstract: The hydrogen abstraction reaction of camphor in cytochrome P450cam has been investigated in the native enzyme environment by combined quantum mechanical/molecular mechanical (QM/MM) calculations and in the gas phase by density functional calculations. This work has been motivated by contradictory published QM/MM results. In an attempt to pinpoint the origin of these discrepancies, we have systematically studied the factors that may affect the computed barriers, including the QM/MM setup, the optimization procedures, and the choice of QM region, basis set, and protonation states. It is found that the ChemShell and QSite programs used in the published QM/MM calculations yield similar results at given geometries, and that the discrepancies mainly arise from two technical issues (optimization protocols and initial system preparation) that need to be well controlled in QM/MM work. In the course of these systematic investigations, new mechanistic insights have been gained. The crystallographic water 903 placed near the oxo atom of Compound I lowers the hydrogen abstraction barrier by ca. 4 kcal/mol, and thus acts as a catalyst for this reaction. Spin density may appear at the A-propionate side chain of the heme if the carboxylate group is not properly screened, which might be expected to happen during protein dynamics, but not in static equilibrium situations. There is no clear correlation between the computed A-propionate spin density and the hydrogen abstraction barrier, and hence, no support for a previously proposed side-chain mediated transition state stabilization mechanism. Standard QM/MM optimizations yield an A-propionate environment close to the X-ray structure only for protonated Asp297, and not for deprotonated Asp297, but the computed barriers are similar in both cases. An X-ray like A-propionate environment can also be obtained when deprotonated Asp297 is included in the QM region and His355 is singly protonated, but this Compound II-type species with a closed-shell porphyrin ring has a higher hydrogen abstraction barrier and should thus not be mechanistically relevant. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1324–1337, 2006
TL;DR: Tetrabutylammonium decatungstate (TBADT, 2 x 10(-3) m) is an effective photocatalyst for the alkylation of electrophilic alkenes by alkanes, alcohols, and ethers through an experimentally very simple procedure.
Abstract: Tetrabutylammonium decatungstate (TBADT, 2 x 10(-3) m) is an effective photocatalyst for the alkylation of electrophilic alkenes (0.1 m, alpha,beta-unsaturated nitriles, esters, ketones) by alkanes, alcohols, and ethers. The products are in most cases obtained in >70 % isolated yields, through an experimentally very simple procedure. The kinetics of the radical processes following initial hydrogen abstraction by excited TBADT in deoxygenated MeCN have been studied. In the absence of a trap, back hydrogen transfer from reduced tungstate is the main pathway for alkyl radicals, while alpha-hydroxyalkyl radicals are oxidized to ketones by ground-state TBADT. With both radical types the reaction ceases at a few percent conversion. However, trapping by electrophilic alkenes is followed by reduction of the radical adduct and regeneration of the catalyst, which allows the alkylation to proceed up to complete alkene conversion with the mentioned good yields of products. With a nucleophilic (alpha-hydroxyalkyl) radical, alkylation is efficient (Phi = 0.58) and can also be carried out when degassing is omitted, the only difference being a short induction period. With a less reactive (cyclohexyl) radical, the quantum yield is lower (Phi = 0.06) and the reaction is considerably slowed in aerated solutions, but the chemical yield remains good.
TL;DR: The mechanism and energy balance, chemical kinetics involving the different metals and the reaction rate constant of e(aq)(-) and e(TiO)(2)(-) with AuCl(4)(-) is reported.
Abstract: Reduction of H+ by TiO2 electrons (eTiO2-) in aqueous colloidal solution takes place in the presence of surface metal catalysts. The catalytic reduction gives rise to adsorbed hydrogen atoms. In the presence of Pd0 or Pt0, material balance shows that most of the adsorbed H atoms combine to molecular hydrogen. When the TiO2 nanoparticles are partially coated with Au0 instead of Pd0 or Pt0, a higher than expected molecular hydrogen level is observed, attributed to a short chain reaction involving hydrogen abstraction from 2-propanol. This unusual hydrogen abstraction reaction has not been reported before. The mechanism and energy balance are discussed. The surface modification of TiO2 nanoparticles was carried out by reduction of K2PdCl4, H2PtCl6, or HAuCl4 with eTiO2-. The latter had been generated through electron injection from hydrated electrons, hydrogen atoms, or 2-propanol radicals, produced by γ or pulse radiolysis prior to the addition of the metal compounds. Upon addition of the metal compounds, i...
TL;DR: It was found that the group contribution method yields accurate activation energies for hydrogen-transfer reactions between hydrogen molecules, alkylic hydrocarbons, and vinylic hydro carbons, with the largest deviations being less than 6 kJ mol(-1).
Abstract: The group contribution method for activation energies is applied to hydrogen abstraction reactions. To this end an ab initio database was constructed, which consisted of activation energies calculated with the ab initio CBS-QB3 method for a limited set of well-chosen homologous reactions. CBS-QB3 is shown to predict reaction rate coefficients within a factor of 2-4 and Arrhenius activation energies within 3-5 kJ mol(-1) of experimental data. Activation energies in the set of homologous reactions vary over 156 kJ mol(-1) with the structure of the abstracting radical and over 94 kJ mol(-1) with the structure of the abstracted hydrocarbon. The parameters required for the group contribution method, the so-called standard activation group additivity values, were determined from this database. To test the accuracy of the group contribution method, a large set of 88 additional activation energies were calculated from first principles and compared with the predictions from the group contribution method. It was found that the group contribution method yields accurate activation energies for hydrogen-transfer reactions between hydrogen molecules, alkylic hydrocarbons, and vinylic hydrocarbons, with the largest deviations being less than 6 kJ mol(-1). For reactions between allylic and propargylic hydrocarbons, the transition state is believed to be stabilized by resonance effects, thus requiring the introduction of an appropriate correction term to obtain a reliable prediction of the activation energy for this subclass of hydrogen abstraction reactions.
TL;DR: The OH abstraction of a hydrogen atom from both the side chain and the ring of toluene has been studied in the range 275-1000 K using quantum chemistry methods and the best method of calculation is to perform geometry optimization and frequency calculations at the BHLYP/6-311++G(d,p) level, followed by CCSD(T) calculations of the optimized structures with the same basis set.
Abstract: The OH abstraction of a hydrogen atom from both the side chain and the ring of toluene has been studied in the range 275-1000 K using quantum chemistry methods. It is found that the best method of calculation is to perform geometry optimization and frequency calculations at the BHandHLYP/6-311++G(d,p) level, followed by CCSD(T) calculations of the optimized structures with the same basis set. Four different reaction paths are considered, corresponding to the side chain and three possible ring hydrogen abstractions, and the branching ratio is determined as a function of temperature. Although negligible at low temperatures, at 1000 K ring-H abstraction is found to contribute 11% to the total abstraction reaction. The calculated rate coefficients agree very well with experimental results. Side chain abstraction is shown to occur through a complex mechanism that includes the reversible formation of a collisionally stabilized reactant complex.
TL;DR: The VB analysis shows that the unusually high barrier for the fluorine exchange reaction emerges as an experimental manifestation of charge-shift bonding.
Abstract: This paper shows that the differences between the barriers of the halogen exchange reactions, in the H + XH systems, and the hydrogen abstraction reactions, in the X + HX systems (X = F, Cl, Br), measure the covalent-ionic resonance energies of the corresponding X-H bonds These processes are investigated using CCSD(T) calculations as well as the breathing-orbital valence bond (BOVB) method Thus, the VB analysis shows that (i) at the level of covalent structures the barriers are the same for the two series and (ii) the higher barriers for halogen exchange processes originate solely from the less efficient mixing of the ionic structures into the respective covalent structures The barrier differences, in the HXH vs XHX series, which decrease as X is varied from F to I, can be estimated as one-quarter of the covalent-ionic resonance energy of the H-X bond The largest difference (22 kcal/mol) is calculated for X = F in accord with the finding that the H-F bond possesses the largest covalent-ionic resonance energy, 87 kcal/mol, which constitutes the major part of the bonding energy The H-F bond belongs to the class of "charge-shift" bonds (Shaik, S; Danovich, D; Silvi, B; Lauvergnat, D L; Hiberty, P C Chem Eur J 2005, 21, 6358), which are all typified by dominant covalent-ionic resonance energies Since the barrier difference between the two series is an experimental measure of the resonance energy quantity, in the particular case of X = F, the unusually high barrier for the fluorine exchange reaction emerges as an experimental manifestation of charge-shift bonding
TL;DR: Overall, the high-level G3-RAD composite procedure, URCCSD(T), and the cost-effective DFT methods BMK, BB1K, and MPW1K give the best results among the methods assessed for calculating the thermochemistry and kinetics of hydrogen abstraction by the methyl radical from benzene.
Abstract: The reaction enthalpy (298 K), barrier (0 K), and activation energy and preexponential factor (600-800 K) have been examined computationally for the abstraction of hydrogen from benzene by the methyl radical, to assess their sensitivity to the applied level of theory. The computational methods considered include high-level composite procedures, including W1, G3-RAD, G3(MP2)-RAD, and CBS-QB3, as well as conventional ab initio and density functional theory (DFT) methods, with the latter two classes employing the 6-31G(d), 6-31+G(d,p) and/or 6-311+G(3df,2p) basis sets, and including ZPVE/thermal corrections obtained from 6-31G(d) or 6-31+G(d,p) calculations. Virtually all the theoretical procedures except UMP2 are found to give geometries that are suitable for subsequent calculation of the reaction enthalpy and barrier. For the reaction enthalpy, W1, G3-RAD, and URCCSD(T) give best agreement with experiment, while the large-basis-set DFT procedures slightly underestimate the endothermicity. The reaction barrier is slightly more sensitive to the choice of basis set and/or correlation level, with URCCSD(T) and the low-cost BMK method providing values in close agreement with the benchmark G3-RAD value. Inspection of the theoretically calculated rate parameters reveals a minor dependence on the level of theory for the preexponential factor. There is more sensitivity for the activation energy, with a reasonable agreement with experiment being obtained for the G3 methods and the hybrid functionals BMK, BB1K, and MPW1K, especially in combination with the 6-311+G(3df,2p) basis set. Overall, the high-level G3-RAD composite procedure, URCCSD(T), and the cost-effective DFT methods BMK, BB1K, and MPW1K give the best results among the methods assessed for calculating the thermochemistry and kinetics of hydrogen abstraction by the methyl radical from benzene.
TL;DR: absolute rate constants for hydrogen abstraction from 4-methylphenol (para-cresol) by the lowest triplet states of 24 aromatic ketones have been determined in acetonitrile solution at 23°C, and the results combined with previously reported data for roughly a dozen other compounds under identical conditions are consistent with reaction via two mechanisms.
Abstract: Absolute rate constants for hydrogen abstraction from 4-methylphenol (para-cresol) by the lowest triplet states of 24 aromatic ketones have been determined in acetonitrile solution at 23 degrees C, and the results combined with previously reported data for roughly a dozen other compounds under identical conditions. The ketones studied include various ring-substituted benzophenones and acetophenones, alpha,alpha,alpha-trifluoroacetophenone and its 4-methoxy analog, 2-benzoylthiophene, 2-acetonaphthone, and various other polycyclic aromatic ketones such as fluorenone, xanthone and thioxanthone, and encompass n,pi*, pi,pi*(CT) and arenoid pi,pi* lowest triplets with (triplet) reduction potentials (E(red)*) varying from about -10 to -38 kcal mol(-1). The 4-methylphenoxyl radical is observed as the product of triplet quenching in almost every case, along with the corresponding hemipinacol radical in most instances. Hammett plots for the acetophenones and benzophenones are quite different, but plots of log k(Q) vs E(red)* reveal a common behavior for most of the compounds studied. The results are consistent with reaction via two mechanisms: a simple electron-transfer mechanism, which applies to the n,pi* triplet ketones and those pi,pi* triplets that possess particularly low reduction potentials, and a coupled electron-/proton-transfer mechanism involving the intermediacy of a hydrogen-bonded exciplex, which applies to the pi,pi* ketone triplets. Ketones with lowest charge-transfer pi,pi* states exhibit rate constants that vary only slightly with triplet reduction potential over the full range investigated; this is due to the compensating effect of substituents on triplet state basicity and reduction potential, which both play a role in quenching by the hydrogen-bonded exciplex mechanism. Ketones with arenoid pi,pi* states exhibit the fall-off in rate constant that is typical of photoinduced electron transfer reactions, but it occurs at a much higher potential than would be normally expected due to the effects of hydrogen-bonding on the rate of electron-transfer within the exciplex.
TL;DR: Asymmetric transformation using chiral crystals which are derived from chiral crystallization of achiral materials has been summarized in this article, which provides the reproducible absolute asymmetric synthesis via the cycloaddition reaction, hydrogen abstraction reaction, di-π-methane rearrangement, electrocyclization, and the bond-cleavage reaction.
Abstract: Asymmetric transformation using chiral crystals which are derived from chiral crystallization of achiral materials has been summarized. Solid-state photoreaction in the chiral crystal environment provides the reproducible absolute asymmetric synthesis via the cycloaddition reaction, hydrogen abstraction reaction, di-π-methane rearrangement, electrocyclization, and the bond-cleavage reaction. Furthermore, asymmetric syntheses using chiral crystals except solid-state photoreactions such as solid–gas reaction, catalytic asymmetric automultiplication, and the reaction in homogeneous conditions are also reviewed.
TL;DR: High-level quantum mechanical computations indicate that hydrogen abstraction using the ethynyl radical has an activation energy of less than 3 kcal mol(-1) for hydrogens bonded to an sp(2) or sp(3) carbon, which corroborate previous studies suggesting that Ethynyl-type radicals would make good tooltips for abstracting hydrogens from diamondoid surfaces during mechanosynthesis.
Abstract: Symmetric and nonsymmetric hydrogen abstraction reactions are studied using state-of-the-art ab initio electronic structure methods. Second-order Moller-Plesset perturbation theory (MP2) and the coupled-cluster singles, doubles, and perturbative triples [CCSD(T)] methods with large correlation consistent basis sets (cc-pVXZ, where X = D,T,Q) are used in determining the transition-state geometries, activation barriers, and thermodynamic properties of several representative hydrogen abstraction reactions. The importance of basis set, electron correlation, and choice of zeroth-order reference wave function in the accurate prediction of activation barriers and reaction enthalpies are also investigated. The ethynyl radical (*CCH), which has a very high affinity for hydrogen atoms, is studied as a prototype hydrogen abstraction agent. Our high-level quantum mechanical computations indicate that hydrogen abstraction using the ethynyl radical has an activation energy of less than 3 kcal mol(-1) for hydrogens bonded to an sp(2) or sp(3) carbon. These low activation barriers further corroborate previous studies suggesting that ethynyl-type radicals would make good tooltips for abstracting hydrogens from diamondoid surfaces during mechanosynthesis. Modeling the diamond C(111) surface with isobutane and treating the ethynyl radical as a tooltip, hydrogen abstraction in this reaction is predicted to be barrierless.
TL;DR: The potential of photomediated reactions for the generation of radicals from unusual precursors and the synthetic significance of this method are discussed in this paper, where the synthesis of β-cycloalkylketones is discussed.
TL;DR: It is suggested that a conventional hydrogen abstraction/hydroxyl recombination mechanism at C-H bonds in 1-4 leads to nonrearranged carbinolamine intermediates and thereby to "ordinary" N-dealkylation products including cyclopropanone hydrate.
Abstract: The suicide substrate activity of N-benzyl-N-cyclopropylamine (1) and N-benzyl-N-(1‘-methylcyclopropyl)amine (2) toward cytochrome P450 and other enzymes has been explained by a mechanism involving single electron transfer (SET) oxidation, followed by ring-opening of the aminium radical cation (protonated aminyl radical) and reaction with the P450 active site. Although the SET oxidation of N-cyclopropyl-N-methylaniline (3) by horseradish peroxidase leads exclusively to ring-opened (non-cyclopropyl) products, P450 oxidation of 3 leads to formation of cyclopropanone hydrate and no ring-opened products, and 3 does not inactivate P450. To help reconcile these discrepant behaviors we have determined the complete metabolic fate of 1 with P450 in vitro. 3-Hydroxypropionaldehyde (3HP), the presumptive “signature metabolite” for SET oxidation of a cyclopropylamine, was observed for the first time in 57% yield, along with cyclopropanone hydrate (34%), cyclopropylamine (9%), benzaldehyde (6%), benzyl alcohol (12%), ...
TL;DR: Hypotheses that oxidation of organic impurities in the snowpack can produce volatile hydroxy and carbonyl compounds, which may consequently be released to the atmosphere are supported.
Abstract: Oxidation of aromatic and saturated aliphatic hydrocarbons (c = 10-3−10-5 mol L-1) by the hydroxyl radicals, photochemically produced from hydrogen peroxide (c = 10-1−10-5 mol L-1), in frozen aqueous solutions was investigated in the temperature range of −20 to −196 °C. While aromatic molecules (benzene, phenol, naphthalene, naphthalen-2-ol, or anthracene) underwent primarily addition−elimination reactions to form the corresponding hydroxy compounds, saturated hydrocarbons (cyclohexane, butane, methane) were oxidized to alcohols or carbonyl compounds via hydrogen abstraction and termination reactions. The results suggest that these photoreactions, taking place in a highly concentrated liquid or solidified layers covering the ice crystals, are qualitatively similar to those known to occur in liquid aqueous solutions; however, that probability of any bimolecular reaction in the environment ultimately depends on organic contaminant concentrations and oxidants availability at specific locations of the ice mat...
TL;DR: Intramolecular hydrogen atom (H-atom) abstraction from the o-OCH3 group effectively intercepts the p-benzyne intermediate in the Bergman cycloaromatization of 2,3-diethynyl-1-methoxybenzene before this intermediate undergoes either retro-Bergman ring opening or external H-atom abstraction.
Abstract: Intramolecular hydrogen atom (H-atom) abstraction from the o-OCH3 group effectively intercepts the p-benzyne intermediate in the Bergman cycloaromatization of 2,3-diethynyl-1-methoxybenzene (1) before this intermediate undergoes either retro-Bergman ring opening or external H-atom abstraction. This process leads to the formation of a new diradical and renders the cyclization step essentially irreversible. Chemical and kinetic consequences of this phenomenon were investigated through the combination of computational and experimental studies.