Kinetic solvent effects on hydrogen abstraction reactions

Kinetic solvent effects on hydrogen abstractions, namely, acceleration in nonpolar solvents, have been presumed to be restricted to O-H hydrogen donors. We demonstrate that also abstractions from C-H and even Sn-H bonds by cumyloxyl radicals and n,pi*-excited 2,3-diazabicyclo[2.2.2]oct-2-ene are fastest in the gas phase and nonpolar solvents but slowest in acetonitrile. Accordingly, solvent effects on hydrogen abstractions are more general, presumably due to stabilization of the reactive oxygen or nitrogen species in polar solvents.     

Kinetic effects in radical addition reactions to radicophiles

Beyond expectation from polar effects rate acceleration is observed when captodative (cd) substituted 1,1-diphenylethylenes 6 and styrenes 7 undergo addition of isobutyronitrile radicals. The effect can be rationalised in terms of frontier orbital interactions.     

Kinetic solvent effects on hydrogen abstraction reactions from carbon by the cumyloxyl radical. The importance of solvent hydrogen-bond interactions with the substrate and the abstracting radical

A kinetic study of the hydrogen atom abstraction reactions from propanal (PA) and 2,2-dimethylpropanal (DMPA) by the cumyloxyl radical (CumO?) has been carried out in different solvents (benzene, PhCl, MeCN, t-BuOH, MeOH, and TFE). The corresponding reactions of the benzyloxyl radical (BnO?) have been studied in MeCN. The reaction of CumO? with 1,4-cyclohexadiene (CHD) also has been investigated in TFE solution. With CHD a 3-fold increase in rate constant (k(H)) has been observed on going from benzene, PhCl, and MeCN to TFE. This represents the first observation of a sizable kinetic solvent effect for hydrogen atom abstraction reactions from hydrocarbons by alkoxyl radicals and indicates that strong HBD solvents influence the hydrogen abstraction reactivity of CumO?. With PA and DMPA a significant decrease in k(H) has been observed on going from benzene and PhCl to MeOH and TFE, indicative of hydrogen-bond interactions between the carbonyl lone pair and the solvent in the transition state. The similar k(H) values observed for the reactions of the aldehydes in MeOH and TFE point toward differential hydrogen bond interactions of the latter solvent with the substrate and the radical in the transition state. The small reactivity ratios observed for the reactions of CumO? and BnO? with PA and DMPA (k(H)(BnO?)/k(H)(CumO?) = 1.2 and 1.6, respectively) indicate that with these substrates alkoxyl radical sterics play a minor role.     

Kinetics and mechanism of peroxyl radical reactions with nitroxides

Cyclic nitroxides (>NO*) are stable radicals of diverse size, charge, lipophilicility, and cell permeability, which provide protection against oxidative stress via various mechanisms including SOD-mimic activity, oxidation of reduced transition metals and detoxification of oxygen- and nitrogen-centered radicals. However, there is no agreement regarding the reaction of nitroxides with peroxyl radicals, and many controversies in the literature exist. The question of whether nitroxides can protect by scavenging peroxyl radicals is important because peroxyl radicals are formed in biological systems. To further elucidate the mechanism(s) underlying the antioxidative effects of nitroxides, we studied by pulse radiolysis the reaction kinetics of piperidine, pyrrolidine, and oxazolidine nitroxides with several alkyl peroxyl radicals. It is demonstrated that nitroxides mainly reduce alkyl peroxyl radicals forming the respective oxoammonium cations (>N+=O). The most efficient scavenger of peroxyl radicals is 2,2,6,6-tetramethylpiperidine-N-oxyl (TPO), which has the lowest oxidation potential among the nitroxides tested in the present study. The rate constants of peroxyl reduction are in the order CH2(OH)OO*>CH3OO*>t-BuOO*, which correlate with the oxidation potential of these peroxyl radicals. The rate constants for TPO vary between 2.8x10(7) and 1.0x10(8) M-1 s-1 and for 3-carbamoylproxyl (3-CP) between 8.1x10(5) and 9.0x10(6) M-1 s-1. The efficacy of protection of nitroxides against inactivation of glucose oxidase caused by peroxyl radicals was studied. The results demonstrate a clear correlation between the kinetic features of the nitroxides and their ability to inhibit biological damage inflicted by peroxyl radicals.     

Understanding kinetic solvent effects on hydrogen abstraction reactions from carbon by the cumyloxyl radical

A kinetic study of the hydrogen abstraction reactions from tetrahydrofuran (THF) and cyclohexane (CHX) by the cumyloxyl radical was carried out in different solvents. With THF, a 4.5-fold decrease in rate constant (k(H)) was observed on going from isooctane to 2,2,2-trifluoroethanol. An opposite behavior was observed with CHX, where k(H) increased by a factor 4 on going from isooctane to 2,2,2-trifluoroethanol. The important role of substrate structure and of the solvent hydrogen bond donor ability is discussed.     

Kinetic measurements on methylidyne radical reactions with several hydrocarbons at low temperatures

The temperature dependences of the methylidyne radical reactions with methane, allene, methylacetylene and propene were studied. This work was carried out in a supersonic flow reactor coupled with pulsed laser photolysis (PLP) and laser-induced fluorescence (LIF) techniques. Three Laval nozzles were designed to provide uniform supersonic expansions of nitrogen at Mach 2 and of argon at Mach 2 and 3 to reach low temperatures, e.g. 170, 128 and 77 K, respectively. CH radicals were produced by PLP of CHBr3 at 266 nm and probed by LIF. The exponential decays of the CH fluorescence were acquired, hydrocarbons being introduced in excess. The rate constants for the CH+CH4 reaction are in good agreement with the temperature dependence proposed by Canosa et al. (A. Canosa, I. R. Sims, D. Travers, I. W. M. Smith and B. R. Rowe, Astron. Astrophys., 1997, 323, 644-651, ) i.e. 3.96x10(-8)(T/K)(-1.04) exp(-36.1 K/T) in the range 23-298 K. The rate constants of the CH+C3H4(allene), CH+C3H4(methylacetylene) and CH+C3H6(propene) reactions exhibit a small temperature dependence between 77 and 170 K, with a maximum rate around 100 K close to (4.3-4.6)x10(-10) cm3 molecule-1 s-1.     

Peroxyesters as precursors to peroxyl radical clocks

The reactions of peroxyl radicals are at the center of the oxidative degradation of essentially all petroleum-derived hydrocarbons and biological lipids and consequently, the inhibition of these processes by radical-trapping antioxidants. Recently described peroxyl radical clocks offer a simple, convenient, and inexpensive method of determining rate constants for H-atom transfer reactions to peroxyl radicals, greatly enabling the kinetic and mechanistic characterization of compounds with antioxidant properties. We follow up our preliminary communication on the development of a methodology utilizing tert-butyl styrylperacetate as a precursor to a versatile peroxyl radical clock with the present paper, wherein we describe a novel naphthyl analogue, which provides for much improved product resolution for analysis, and provide the complete details associated with its development and application. Using this new precursor, and with consideration of the expanded set of reaction products, inhibition rate constants were measured for a variety of representative phenolic and diarylamine radical-trapping antioxidants. We also provide details for the use of this methodology for the determination of mechanistic information, such as kinetic solvent effects, Arrhenius parameters, and kinetic isotope effects.     

Elucidation of the mechanisms of peroxyl radical reactions in aqueous solutions using the pulse radiolysis technique

In the investigation of peroxyl radicals the pulse radiolysis technique can be used with some advantage to determine the rate of their unimolecular or bimolecular decay. If the identities of the products of the peroxyl radical reactions are known, pulse radiolysis often provides evidence for mechanistic details. The absorptions of the peroxyl radicals are neither very specific nor strong and optical detection is usually of little help. However, there are many peroxyl radical reactions which result in the formation of HO ₂ ^. /H+O ₂ ^. (pK_a(HO ₂ ^. )=4.7) or other acids. Thus in neutral and alkaline solutions such species can be monitored even quantitatively by the pulse conductometric method. Furthermore, O ₂ ^. can be detected by its rapid reaction with tetranitromethane which yields the strongly absorbing nitroform anion. Since O ₂ ^. is only a short-lived intermediate in neutral solutions, it can be distinguished from permanent acids which are often formed in peroxyl radical reactions. In alkaline solutions, where O ₂ ^. is more stable, superoxide dismutase might be used with advantage to reduce its lifetime and to determine the yield of permanent acids. Some details of the fate of the peroxyl radicals derived from acetate, the -hydroxyethyl-peroxyl radicals, and the cyclopentylperoxyl radicals will be reviewed.     

Kinetic studies of NHx radical reactions

Combined experimental and theoretical studies of the reactions

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and

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were carried out in the present work. The rate constant of reaction (1) was investigated in the temperature range 293 K T612 K using the laser photolysis continuous-wave laser-induced fluorescence technique for the production and detection of NH₂. The results are well described by k₁(T)=5.43×T^−4.02 exp(−1034K/T) cm³ molecule⁻¹ s⁻¹. Stationary points on the potential energy surface were characterized using the gaussian-2 (G2) ab initio method. The surface is complex, with hydrogen-atom transfers and cis—trans isomerization connecting five stable adduct species.The product distribution of reaction (2) was studied at room temperature using the discharge flow technique with mass spectrometric detection of the reaction products. Measured branching fractions for the production of N₂O+H(D) were k_2a/k₂ = 0.84±0.4 for NH+NO and k_2a/k₂ = 0.87±0.17 for ND+NO. Stationary points on the ground ²A′ surface were calculated using the G2 method. The transition state energy for the dissociation of the cis isomer into H+N₂O was found to be lower than the transition state energy for dissociation into OH+N₂. Additionally, trans-HNNO was found to isomerize to cis-HNNO before dissociation.For reaction (3), the molecular properties of all relevant intermediates and transition states on the ground state potential energy surface were determined using the G2 method. The results predict the formation of three intermediates, H₂NO, trans-HNOH and cis-HNOH, all exothermic relative to the reactants. The transition states separating these intermediates from one another and their products (H₂+NO, H+HNO(¹A′) or NH+OH) were also characterized, several for the first time.     

Evident solvent effect on propagation reactions during radical copolymerization of maleimide and alkene

The radical copolymerization of N-(2,6-dimethylphenyl)maleimide (DMPhMI) and 2,4,4-trimethylpentene (TP) was investigated in several solvents at 60°C. The copolymerization rate and the molecular weight of the resulting copolymers were dependent on the kind of solvent used. It was also revealed that the monomer reactivity ratios depended on the solvent; r₁ = 0.086 and r₂ = 0 in chloroform and r₁ = 0.25 and r₂ = 0 in benzene, where DMPhMI and TP are M₁ and M₂, respectively. The propagation rate constants were determined for the homopolymerization and copolymerization in chloroform and benzene using electron spin resonance spectroscopy. The homo- and crosspropagation rate constants (k₁₁ and k₁₂, respectively) were revealed to depend on the solvent: k₁₁ is 20 and 37 L/mol·s and k₁₂ is 230 and 150 L/mol·s in chloroform and in benzene, respectively. The interaction between the maleimide moiety and the solvent molecules was discussed based on the acceptivity of the solvents. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1515–1525, 1997     

13C NMR studies on radical anions. Special solvent effects

The determination of radical ions is crucial in mechanistic studies of reactions in which single electron transfer is suspected. A ¹³C NMR method based on the interaction of radical anions with tetrahydrofuran (THF) molecules is presented; measurements of the broadening of the THF α-carbon signal allow determination of the substrate concentration in the range 0.2–1.2 M . The spectacular effect observed on addition of small amounts of benzene greatly improved the method. In addition, studies of the spin-lattice, T₁, and of the transverse nuclear, T₂, relaxation times and of the effects of added co-solvents allow the proposal of the bonding situation and of the degree of coordination in the radical anion-cation-THF molecules' complex.     

Acceleration of organic reactions through aqueous solvent effects

The parallels between organic reactions conducted with water as the solvent and reactions conducted under high pressure can be understood in light of theories of aqueous solvation and hydrophobic effects. Such parallels provide powerful tools for promoting reactions of nonpolar compounds.     

Kinetic parameters of radical reactions of 2-mercaptobenzothiazole with quinone imines

The chain reaction of N,N′-diphenyl-1,4-benzoquinone diimine with 2-mercaptobenzothiazole was studied by two methods developed earlier for the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole. In the methods used, the kinetic scheme of the reaction is simplified by creating conditions under which the rates of all stages except radical generation and decay can be neglected. One of the methods was updated. For the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole, both methods gave close results; for the chain reaction of N,N′-diphenyl-1,4-phenylenediamine with 2-mercaptobenzothiazole, the results differed by approximately one order of magnitude.     

Triethylborane-induced bromine atom-transfer radical addition in aqueous media: study of the solvent effect on radical addition reactions.

A mixture of ethyl bromoacetate and 1-octene was treated with triethylborane in water at ambient temperature to provide ethyl 4-bromodecanoate in good yield. The bromine atom-transfer radical addition in benzene was not satisfactory. The addition proceeded smoothly in polar solvents such as DMF and DMSO, protic solvents such as 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol, and aqueous media. Ab initio calculations were conducted to reveal the origin of the solvent effect of water in the addition reaction. The polar effect of solvents, which is judged by the dielectric constant, on the transition states in the bromine atom-transfer and radical addition steps is moderately important. Calculations show that a polar solvent tends to lower the relative energies of the transition states. The coordination of a carbonyl group to a proton in a protic solvent, like a Lewis acid, would also increase the efficiency of the propagation.     

Calculations of substituent and solvent effects on the kinetic isotope effects of Menshutkin reactions

Nitrogen, deuterium, halogen, and carbon kinetic isotope effects have been modeled for the Menshutkin reaction between methyl halides and substituted N,N-dimethylaniline at the HF/6-31G(d) level of theory augmented by the C-PCM continuum solvent model for several solvents. Systematic changes in geometries of the transition states and Gibbs free energies of activation have been found with phenyl ring substituents, solvent, and the leaving group. Kinetic isotope effects also change systematically; however, these changes are predicted to be small, inside the usual precision of the experimental measurements. On the contrary, no correlation has been found between the kinetic isotope effects and the Hammett constants for para substituents. Thus opposite to previous assumptions, our results indicate that kinetic isotope effects on the Menshutkin reaction cannot be used to predict the position of the transition state on the reaction coordinate.     

Methyl substituent effects in radical cation Diels-Alder reactions

The effect of methyl substitution on the Diels-Alder radical cation reaction was studied using B3LYP with a 6-31G* basis set. Five separate pathways, one concerted and four stepwise, were examined for each possible position of a methyl substituent. None of the concerted transition structures could be located without symmetry constraints, and all but one of the structures obtained under these conditions were destabilized by a second-order Jahn-Teller distortion. A concerted pathway with simultaneous bond formation at C1 and C4 is therefore excluded. Stepwise pathways that had the methyl group either on a carbon involved in the initial bond formation or in a position where it could not stabilize the radical/cation were a few kcal/mol above alternate pathways. High transition state energies for the formation of vinylcyclobutane derivatives cause it to be a minor product in general. The pathway that proceeds through an anti-intermediate is the most favored, while the pathways forming the gauche-out intermediate that converts to the anti-intermediate is also strongly represented. Both of the major pathways lead directly to the formation of the methylcyclohexene product.     

Theoretical study on peroxyl radical additions to methyl‐substituted ethenes

The electrophilic additions of hydroperoxyl (HO$_{2}^{\mbox{\mathversion{bold}$\cdot$}}$) and alkylperoxyl (RO$_{2}^{\mbox{\mathversion{bold}$\cdot$}}$) radicals to substituted ethenes were studied using the AM1 semiempirical molecular orbital (MO) methods at the self‐consistent field/unrestricted Hartree–Fock (SCF/UHF) level. Reactantlike transition states were predicted for the title additions. The reactivity of an alkylperoxyl radical toward ethenes was found to be decreased as the degree of methyl (Me) substitution on the alkyl group of the radical increased. The relative reactivity and regioselectivity in HO$_{2}^{\mbox{\mathversion{bold}$\cdot$}}$ additions to substituted ethenes was suggested to be SOMO (singly occupied)‐HOMO controlled. A good correlation was established between the activation enthalpy $(\Delta H_{f}^{\ast})$ for the studied additions and the Taft polar substituent constants (σ*) of RO$_{2}^{\mbox{\mathversion{bold}$\cdot$}}$. The Evans–Polanyi correlation between $\Delta H^{\mbox{\mathversion{bold}$\cdot$}}_{f}$ and $\Delta H^{\circ}_{r}$ was justified and the validity of the Hammond postulate was indicated. The calculated results were compared with the available experimental data. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 77: 761–771, 2000     

The influence of paramagnetic impurities on magnetic effects in radical reactions

The influence of paramagnetic impurities on magnetic and spin effects in radical reactions in liquid solutions is treated. The recombination probability of a radical pair is obtained. It is shown, that at high impurity concentration or in high-viscosity solvents the effect of the magnetic field vanishes.     

Kinetic isotope effects on thio-substituted biological phosphoryl transfer reactions from density-functional theory

Primary and secondary kinetic and equilibrium isotope effects are calculated with density-functional methods for the dianionic methanolysis of the native (unsubstituted) and thio-substituted ethylene phosphates.