Hydrogen Atom Abstraction Reactions Research Articles

Correlation of hydrogen-atom abstraction reaction efficiencies for aryl radicals with their vertical electron affinities and the vertical ionization energies of the hydrogen-atom donors.

The factors that control the reactivities of aryl radicals toward hydrogen-atom donors were studied by using a dual-cell Fourier-transform ion cyclotron resonance mass spectrometer. Hydrogen-atom abstraction reaction efficiencies for two substrates, cyclohexane and isopropyl alcohol, were measured for 23 structurally different, positively charged aryl radicals, which included dehydrobenzenes, dehydronaphthalenes, dehydropyridines, and dehydro(iso)quinolines. A logarithmic correlation was found between the hydrogen-atom abstraction reaction efficiencies and the (calculated) vertical electron affinities (EA) of the aryl radicals. Transition state energies calculated for the reaction of three of the aryl radicals with isopropyl alcohol were found to correlate linearly with their (calculated) EAs. No correlation was found between the hydrogen-atom abstraction reaction efficiencies and the (calculated) enthalpy changes for the reactions. Measurement of the reaction efficiencies for the reactions of 15 different hydrogen-atom donors with two selected aryl radicals revealed a logarithmic correlation between the hydrogen-atom abstraction reaction efficiencies and the vertical ionization energies (IE) of the hydrogen-atom donors, but not the lowest homolytic X-H (X = heavy atom) bond dissociation energies of the hydrogen-atom donors. Examination of the hydrogen-atom abstraction reactions of 29 different aryl radicals and 18 different hydrogen-atom donors showed that the reaction efficiency increases (logarithmically) as the difference between the IE of the hydrogen-atom donor and the EA of the aryl radical decreases. This dependence is likely to result from the increasing polarization, and concomitant stabilization, of the transition state. Thus, the hydrogen-atom abstraction reaction efficiency for an aryl radical can be "tuned" by structural changes that influence either the vertical EA of the aryl radical or the vertical IE of the hydrogen atom donor.

The Selectivity of Charged Phenyl Radicals in Hydrogen Atom Abstraction Reactions with Isopropanol

The vertical electron affinity is demonstrated to be a key factor in controlling the selectivity of charged phenyl radicals in hydrogen atom abstraction from isopropanol in the gas phase. The measurement of the total reaction efficiencies (hydrogen and/or deuterium atom abstraction) for unlabeled and partially deuterium-labeled isopropanol, and the branching ratios of hydrogen and deuterium atom abstraction, by using a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, allowed the determination of the selectivity for each site in the unlabeled isopropanol. Examination of hydrogen atom abstraction from isopropanol by eight structurally different radicals revealed that the preferred site is the CH group. The selectivity of the charged phenyl radicals correlates with the radical's vertical electron affinity and the reaction efficiency. The smaller the vertical electron affinity of a radical, the lower its reactivity, and the greater the preference for the thermodynamically favored CH group over the CH3 group or the OH group. As the vertical electron affinity increases from 4.87 to 6.28 eV, the primary kinetic isotope effects decrease from 2.9 to 1.3 for the CD group, and the mixture of primary and alpha-secondary kinetic isotopes decreases from 6.0 to 2.4 for the CD3 group.

Hydrogen Atom Abstraction and Hydride Transfer Reactions by Iron(IV)–Oxo Porphyrins

Wahre Identität enthüllt: Die C-H-Aktivierung von Alkylarenen durch synthetische Eisen(IV)-Oxoporphyrin-Spezies und der Hydridtransfer von NADH-Analoga auf diese Spezies verläuft über H-Atom-Abstraktion bzw. protonengekoppelten Elektronentransfer. Mechanistische Studien ergaben, dass Eisen(IV)-Oxoporphyrine, nicht Eisen(IV)-Oxoporphyrin-π-Radikalkationen die eigentlichen Oxidationsmittel sind.

Hydrogen Atom Abstraction and Hydride Transfer Reactions by Iron(IV)–Oxo Porphyrins

True identity revealed: The CH bond activation of alkyl aromatics by synthetic iron(IV)–oxo porphyrin species and the hydride transfer of NADH analogues to them occur through H-atom abstraction and proton-coupled electron-transfer mechanisms, respectively. Mechanistic studies revealed that iron(IV)–oxo porphyrins, not iron(IV)–oxo porphyrin π-radical cations, are the true oxidant.

Theoretical study on the reaction path and rate constants of the hydrogen atom abstraction reaction of CH2O with CH3/OH

Abstract The direct dynamics of the hydrogen abstraction reactions of CH 2 O with CH 3 /OH are studied using ab initio molecular orbital theory. Both the geometry optimizations of all the stationary points and the vibrational frequency calculations are carried out at the UQCISD/6-311G(d, p) level. The single-point energy is obtained by the multicoefficient Gaussian 3-version 3s (MCG3/3) method. The analysis to the changes of the interatomic distances on the minimum energy paths show that, the breaking of C–H bonds of CH 2 O and (i) the forming of C–H bond of CH 4 in the reaction of CH 2 O with CH 3 , (ii) the forming of O–H bond of H 2 O in the reaction of CH 2 O with OH, are both concerted. For each reaction, there exists a reactive vibrational normal-mode, and its frequencies change is relevant to the forming and breaking of the above covalent bond. Furthermore, the theoretical forward reaction rate constants in the temperature range 300–3000 K are computed by canonical variational transition state theory with small-curvature tunneling correction (CVT/SCT) method. The computed values of the rate constants are in good agreement with the available experimental data in the measured temperature range. Moreover, the tunneling effects are found to contribute significantly to the rate constants at low temperatures.

Absolute rate constants for some hydrogen atom abstraction reactions by a primary fluoroalkyl radical in water.

A combination of laser flash photolysis and competitive kinetic methods have been used to measure the absolute bimolecular rate constants for hydrogen atom abstraction in water from a variety of organic substrates including alcohols, ethers, and carboxylic acids by the perfluoroalkyl radical, *CF(2)CF(2)OCF(2)CF(2)SO(3)(-) Na(+). Comparison, where possible, of these rate constants with those previously measured for analogous reactions in the non-polar organic solvent, 1,3-bis(trifluoromethyl)benzene (J. Am. Chem. Soc, 1999, 121, 7335) show that the alcohols react 2-5 times more rapidly in the water solvent and that the ethers react at the same rate in both solvents. A transition state for hydrogen abstraction that is more reminiscent of an "intimate ion pair" than a "solvent separated ion pair" is invoked to explain these modest solvent effects.

Gas-phase hydrogen atom abstraction reactions of S− with H2, CH4, and C2H6

Reaction cross sections, product axial velocity distributions, and potential energy surfaces are presented for the hydrogen atom abstraction reactions S−+RH→R+HS− (R=H, CH3, C2H5) as a function of collision energy. The observed threshold energy, E0, for S−+H2→H+HS− agrees with the reaction endothermicity, ΔrH0. At low collision energies, the H+HS− products exhibit symmetric, low-recoil-velocity scattering, consistent with statistical reaction behavior. The S−+CH4→CH3+HS− and S−+C2H6→C2H5+HS reactions, in contrast, show large excess threshold energies when compared to ΔrH0. The excess energies are partly explained by a potential energy barrier separating products from reactants. However, additional dynamical constraints must account for more than half of the excess threshold energy. The observed behavior seems to be general for collisional activation of anion-molecule reactions that proceed through a tight, late transition state. For RH=CH4 and C2H6, the HS− velocity distributions show anisotropic backward scattering at low collision energies indicating small impact parameters and a direct rebound reaction mechanism. At higher collision energies, there is a transition to HS− forward scattering and high velocities consistent with grazing collisions and a stripping mechanism.

Hydrogen atom abstraction reactions of charged polyaromatic sigma-radicals related to the active intermediates of the enediyne antitumor drugs.

Polar effects are demonstrated to play an important role in controlling the reactivity of polyaromatic sigma-radicals that are structurally related to the active intermediates of the enediyne anticancer type antibiotics. This was accomplished by measuring the rate constants of hydrogen atom abstraction for novel, charged dehydroquinolines, dehydroisoquinolines, dehydrobenzenes, and dehydronaphthalenes in the gas phase by using Fourier-transform ion cyclotron resonance mass spectrometry. The reactivity trends observed for these radicals upon hydrogen atom abstraction from tetrahydrofuran and 2-methyltetrahydrofuran, simple models of deoxyribose, do not reflect differences in reaction exothermicities, radical sizes, exact location of the radical site in the ring system, or heteroatom-radical site distances. However, the reactivity trends match the trend in the calculated electron affinities of the radicals. The radicals' different electrophilicities result in variations in the reaction barrier due to different extents of polarization of the transition state. Generally, the reaction efficiencies are the greatest when the formally charged heteroatom is contained within the same ring system as the radical site. In this case, polar effects have the greatest influence on radical reactivity. Hence, insertion of a basic heteroatom (which gets protonated in biological systems) into specific locations in the polyaromatic ring system of the sigma-biradicals, which ultimately cause cleavage of DNA exposed to the enediyne antitumor drugs, should allow tuning of the reactivity of these radicals.

Examination of barriered and barrierless hydrogen atom abstraction reactions by organic radical cations: the cytosine radical cation

The radical cations of the nucleobases cytosine and adenine are easily generated in a dual cell Fourier transform ion cyclotron resonance mass spectrometer by using the technique of laser-induced acoustic desorption coupled with electron ionization. The cytosine radical cation is found to undergo facile hydrogen atom abstraction reactions with a variety of neutral reagents even when barrierless, exothermic electron transfer reactions are expected to dominate. In contrast, the adenine radical cation undergoes hydrogen atom abstraction only slowly in most of the cases studied. The ionic curve-crossing model is used to rationalize these results. Some of the thermodynamic and molecular properties of a radical cation that are favorable for efficient hydrogen atom abstraction are described in this article. Based on this analysis, dimethyl sulfoxide radical cation was predicted to abstract hydrogen atoms efficiently. Indeed, it was found to abstract hydrogen atoms at rates similar to cytosine radical cation. The transition from barriered to barrierless hydrogen atom abstraction that occurs as the ionization energy of the neutral hydrogen atom donor is lowered was used to “bracket” the recombination energy of cytosine radical cation at 8.9 ± 0.2 eV.

Hydrogen atom abstraction and addition reactions of charged phenyl radicals with aromatic substrates in the gas phase

In order to investigate competition between radical substitution and addition reactions, the gas-phase reactivity of phenyl radicals bearing a chemically inert, positively charged group and a neutral substituent (CH3, Cl, or Br), both at a meta position with respect to the radical site, was examined toward several aromatic substrates in a dual-cell Fourier transform ion cyclotron resonance mass spectrometer. The radicals undergo hydrogen atom abstraction from the substituent and/or addition to the phenyl ring of benzeneselenol, thiophenol, benzaldehyde, toluene, aniline, and phenol. The presence of an electron-withdrawing substituent Cl or Br on the phenyl ring of the radical slightly increases the rates for both hydrogen atom abstraction and addition due to favorable polarization of the reactions’ transition states. The observation of a stable ion-molecule addition product in most reactions was unexpected since in a low-pressure gas-phase environment, adducts are typically unable to release their excess energy before dissociation to products or back to reactants. However, the addition products discussed here are low in energy [addition is exothermic by 24–30 kcal/mol; B3LYP/6-31Gd+ZPVE] and hence are long lived enough to become stabilized by infrared emission. The extent to which the charged radicals are able to abstract a hydrogen atom from the aromatic substrate and form stable products via addition to the aromatic ring was found to vary greatly. The outcome of this competition can be rationalized by reaction exothermicities only in extreme cases, i.e. for benzeneselenol and thiophenol, that predominantly react by hydrogen atom abstraction due to their especially weak heteroatom-hydrogen bonds and aniline that undergoes almost exclusive addition due to particularly stable resonance-stabilized addition products. For the other substrates, competition between the two reaction pathways is controlled by a complex interplay of polar effects that affects the energies of both transition states but to different extents.

Theoretical study on the kinetics and mechanism of the hydrogen atom abstraction reactions of CF 3O+H 2O and CF 3OH+OH

Quantum mechanical ab initio calculations have been performed at various levels of theory to study kinetics of the reactions leading to formation/decay of CF 3OH in the gas phase. It is shown that two considered reactions i.e., CF 3O+H 2O (reaction (1)) and CF 3OH+OH (−1) proceed via formation of intermediate complexes. Mechanism of the reactions appears to be more complex, and may consist of three consecutive processes. Calculated rate constants are in excellent agreement with available experimental data. Derived expressions: k 1=2.5×10 −13×(T/300) 1.4× exp(−3130/T) cm 3 molec −1 s −1 and k −1=1.9×10 −12×(T/300) 1.0× exp(−3650/T) cm 3 molec −1 s −1 allow a description of the kinetics of the reactions under investigation in the temperature range 300–1000 K.

Ab initio study on reaction path and rate constant of the hydrogen atom abstraction reaction HNCO+N→NCO+NH

The reaction HNCO+N→NCO+NH has been studied using ab initio molecular orbital theory. The geometries of the reactant, complex, transition state, and products have been optimized at the UMP2/6-311G** level of theory. The forward and reverse reaction potential barriers were calculated accurately at the UMP4/6-311G** and UQCISD(T)/6-311G** levels of theory at the UMP2/6-311G** optimized geometries. The minimum energy path was calculated by the intrinsic reaction coordinate (IRC) theory at the UMP2/6-311G** level with a gradient step size of 0.05 (amu) 1/2 bohr. The changes of the geometries and normal mode vibrational frequencies along IRC were discussed. The MEP profile was refined by the UQCISD(T)/6-311G** level. The forward and the reverse reaction rate constants for the temperature range 1000–3000 K were obtained by the conventional and variational transition state theory. The theoretical rate constants of the forward reaction at the UQCISD(T) level are in good agreement with the rough estimate rate constants.

The interplay of electronic, steric and stereoelectronic effects in hydrogen-atom abstraction reactions of SO4−˙, revealed by EPR spectroscopy

Attack by SO4–˙ (generated by photolysis and one-electron transfer) on a number of carbohydrates and some model compounds has been followed directly by EPR spectroscopy.SO4–˙ is a reactive, electrophilic species but is more selective (less reactive) than HO˙. We present evidence for the importance of polar effects and radical stabilisation, especially in determining trends in selectivity. Examples include the preference for C–H abstraction α to a ring oxygen atom in a five-membered ring (e.g. THF, sucrose, β-D-fructofuranose) and abstraction of the axial C1 hydrogen atom from β-D-glucose.The reaction of SO4–˙ with α-D-glucose is selective towards the C2, C5 and C6 positions. This reflects the activating effect of a β-oxygen substituent where the radical orbital can eclipse the β-C–O bond providing a SOMO–σ* interaction which stabilises the developing radical centre. For myo-inositol, abstraction is also observed from axial C–H bonds for which the resulting radicals are stabilised by an axial β-OH substituent but, due to the absence of a ring oxygen atom, more rapid abstraction occurs from the equatorial C–H bond.

Polarity-reversal catalysis of hydrogen-atom abstraction reactions: concepts and applications in organic chemistry

The rates and selectivities of the hydrogen-atom abstraction reactions of electrically-neutral free radicals are known to depend on polar effects which operate in the transition state. Thus, an electrophilic species such as an alkoxyl radical abstracts hydrogen much more readily from an electron-rich C–H bond than from an electron-deficient one of similar strength. The basis of polarity-reversal catalysis (PRC) is to replace a single-step abstraction, that is slow because of unfavourable polar effects, with a two-step process in which the radicals and substrates are polarity-matched. This review explores the concept of PRC and describes its application in a variety of situations relevant to mechanistic and synthetic organic chemistry.

Protonation and Hydrogen Atom Abstraction Reactions in the Synthesis of the [HP7M(CO)3]2- Ions (M = Cr, W)

Ethylenediamine (en) solutions of [P7M(CO)3]3– (M = Cr, W) react with weak acids to give [HP7M(CO)3]2– ions where M = Cr (4 a) and W (4 b) in high yields. Competition studies with known acids revealed a pKa range for 4 b in DMSO of 17.9 to 22.6. The [P7M(CO)3]3– complexes also react with one-half equivalent of I2 to give 4 through an oxidation/hydrogen atom abstraction process. Labeling studies show that the abstracted hydrogen originates from the [K(2,2,2-crypt)]+ ions or from the solvent (DMSO-d6) in the absence of [K(2,2,2-crypt)]+ or other good hydrogen atom donors. In the solid state, the ions have no crystallographic symmetry but in solution they show virtual Cs symmetry (31P NMR spectroscopy) due to an intramolecular wagging process. Crystallographic data for [K(2,2,2-crypt)]2[HP7W(CO)3]: triclinic, P 1, a = 10.9709(8) Å, b = 13.9116(10) Å, c = 19.6400(14) Å, α = 92.435(6)°, β = 93.856(6)°, γ = 108.413(6)°, V = 2831.2(4) Å3, Z = 2, R(F) = 7.65%, R(wF2) = 14.17% for all 7400 reflections. For [K(2,2,2-crypt)]2[HP7Cr(CO)3]: triclinic, P 1, a = 12.000(3) Å, b = 14.795(3) Å, c = 17.421(4) Å, α = 93.01(2)°, β = 93.79(2)°, γ = 110.72(2)°, V = 2877(2) Å3, Z = 2. Protonierung und Wasserstoffatom-Abstraktions-Reaktionen bei der Synthese von [HP7M(CO)3]2–-Ionen (M = Cr, W) Ethylendiamin(en)-Lösungen von [P7M(CO)3]3– (M = Cr, W) reagieren mit schwachen Säuren unter Bildung von [HP7M(CO)3]2–-Ionen (M = Cr (4 a) und W (4 b)) in hohen Ausbeuten. Vergleichende Untersuchungen mit bekannten Säuren zeigen einen pKa-Bereich für 4 b in DMSO von 17,9 bis 22,6. Die [P7M(CO)3]3–-Komplexe reagieren auch mit einem halben Äquivalent I2 zu 4 durch einen Oxidations/Wasserstoffabstraktions-Prozeß. Markierungsexperimente zeigen, daß das abstrahierte Wasserstoffatom von [K(2,2,2-crypt)]+-Ionen stammt bzw. vom Lösungsmittel (DMSO-d6) bei Abwesenheit von [K(2,2,2-crypt)]+ oder von anderen guten Wasserstoffatom-Donatoren. Im festen Zustand haben die Ionen keine kristallographische Symmetrie, hingegen zeigen sie in Lösung etwa Cs-Symmetrie (31P-NMR-spektroskopisch) aufgrund eines intramolekularen „Wagging”︁-Prozesses. Die kristallographischen Daten für [K(2,2,2-crypt)]2[HP7W(CO)3] sind: triklin, P 1, a = 10,9709(8) Å, b = 13,9116(10) Å, c = 19,6400(14) Å, α = 92,435(6)°, β = 93,856(6)°, γ = 108,413(6)°, V = 2831,2(4) Å3, Z = 2, R(F) = 7,65%, R(wF2) = 14,17% for all 7400 reflections. For [K(2,2,2-crypt)]2[HP7Cr(CO)3]: triklin, P 1, a = 12,000(3) Å, b = 14,795(3) Å, c = 17,421(4) Å, α = 93,01°, β = 93,79(2)°, γ = 110,72(2)°, V = 2877(2) Å3, Z = 2.

The hydrogen atom abstraction reaction CO++H2→HCO++H: Translational and internal energy dependence of the integral cross section

The widely accepted model descriptions of ion–molecule reactions suggest identical rate constants for the title reaction and the analogous, isoelectronic system N2++H2, which has been the topic of a previous publication from this laboratory. A comparison of both data sets, however, reveals substantial disagreement which we attribute to the absence of energetic resonances between the reagents which characterized the N2+/H2 system. Resonantly enhanced photoionization was exploited to accomplish the state-specific preparation of CO+ (X 2Σ+, v+=0,1). A monoenergetic beam of vibrationally selected ions, tuned within the range 0.01 eV⩽Ecm⩽10 eV, transits a scattering chamber which confines the neutral, H2. The title reaction was the only channel observed—no evidence of charge transfer or dissociative ionization could be detected. The hydrogen atom transfer turns out to proceed directly. The reactive cross section fails to show the E−1/2 dependence indicative of collision determined processes. The experimental data are perfectly mimicked by an expanded Langevin model which includes additional attractive potential terms. In contrast to the N2+/H2 case, vibrational excitation does not affect the rate of the reaction.

How does an alkoxy group at the benzylic carbon affect the transition state of the hydrogen-atom abstraction reaction? Correlation analysis of relative rates for 14 p-Y-substituted α,α-ethylenedioxytoluenes

Correlation analysis of the relative rates for the H-atom abstraction reaction of 14 2-(4-Y-phenyl)dioxolanes (p-Y-substituted α,α-ethylenedioxytoluenes, 1-Y) by N-bromosuccinimide (NBS) shows that the spin-delocalization effect is also operating at the transition state of the H-atom abstraction reaction and that the ethylenedioxy group at the benzylic carbon makes the spindelocalization more observable than do two methyl groups.

Understanding the rates of hydrogen-atom abstraction reactions: empirical, semi-empirical and ab initio approaches

The performance of the empirical algorithm proposed by Roberts and Steel (J. Chem. Soc., Perkin Trans. 2, 1994, 2155), which relates the activation energy for the H-atom transfer reaction (A) to properties of the A˙+ HB → AH + B˙(A) four molecules involved, is assessed. This approach has been strongly criticised by Zavitsas in two recent papers (J. Chem. Soc., Perkin Trans. 2, 1996, 391 and J. Am. Chem. Soc., 1995, 117, 10 645), mainly on the grounds that it performs badly in comparison with his semi-empirical method for estimating Ea. These criticisms are examined and, in the main, are found to be without foundation. The identity reaction H3Si˙+ H4Si is viewed as a test case and it is shown that our empirical approach predicts an activation energy in accord with that estimated here by ab initio methods and with published experimental data on related reactions. The value of Ea predicted by Zavitsas' published method (71.5 kJ mol–1) is very much higher than the value deduced from our empirical analysis (37.6 kJ mol–1) or that obtained by the ab initio procedure (46.2 kJ mol–1, which itself is probably too high). It is argued that polar effects are important in H-atom abstraction from thiols by alkyl radicals and that hydrogen-bonding interactions between A˙ and HB can be important, in particular when the leading atoms of A and B are oxygen or nitrogen. It is concluded that empirical models have a role to play in aiding the understanding of radical reactivity and that the approach of Roberts and Steel is relatively successful, given the limitations implicit in the model.

Kinetic effects of fluorine substituents in free-radical chemistry. Hydrogen-atom abstraction reactions of perfluoro-n-alkyl radicals

Using competitive methods, the rates of hydrogen-atom abstraction by a typical perfluoro-n-alkyl radical, n-C 7F 15·, have been determined for a series of silane and stannane reductants including nBu 3SnH (2.03×10 8 M −1 s −1), Et 3SiH (7.5×10 5), (TMS) 2SiMeH (1.63×10 7) and (TMS) 3SiH (5.1×10 7), all of which exhibited substantial rate enhancements relative to their analogous reductions of hydrocarbon radicals. The reduction by PhSH is, in contrast, ∼400-times slower than for hydrocarbon radicals. Transition state polar effects are invoked to rationalize the relative reactivity of perfluoro- versus hydrocarbon radicals in these hydrogen-transfer reactions. A Hammett study for H-atom transfer from arene thiols ( p + = −0.56) provided further substantiation for this conclusion. A discussion of the relative reactivity of t-butoxyl and perfluoro-n-alkyl radicals is presented.

Can the spin-delocalization effect express itself at the transition state of the hydrogen-atom abstraction reaction? Correlation analysis of relative rates measured by a rigorous methodology for eleven p-Y-substituted isopropylbenzenes

A rigorous procedure has been developed for measuring the relative rates, i.e., k r(Y) = k Y/ k H, of hydrogen-abstraction from eleven substituted iso-propylbenzenes ( 1-Y, with Y = NO 2, CN, F, Cl, Br, CO 2Me, Me, tBu, COMe, OMe and SMe) by bromine atoms. The reaction was run in cyclohexane in the presence of HBr, O 2 and dibutyl peroxyoxalate at 5O°C. It has been demonstrated that the H-atom on step shown by is the measured step, and all products are derived from the intermediate benzylic radical 4. Correlation analysis of these rate data seems to suggest that a spin effect is also operating at the transition state of H-atom abstraction reaction, even though the polar effect predominates. Among various combinations of σ x and σ . for the dual-parameter, the (σ p+σ . jj) combination yields the best correlation.