Factors controlling the addition of carbon-centered radicals to alkenes

The addition rate constants of radicals to alkenes are strongly substituent dependent because of enthalpic, polar and steric effects. Recent absolute experimental and high level ab initio data for many prototype additions of small radicals are analyzed with the aid of the state correlation diagram. This leads to a unifying rationalization of the various effects and allows the prediction of rate constants to one order of magnitude or better. Propagation rate coefficients of homo- and copolymerizations and penultimate effects are also discussed.     

Absolute Rate Constants for the Addition of the 2‐(Methoxycarbonyl)propan‐2‐yl and the 3,3,3‐Trifluoracetonyl Radicals to Alkenes in Solution

Absolute rate constants and some of their Arrhenius parameters were obtained by time‐resolved electron spin resonance (ESR) spectroscopy for the addition of the 2‐(alkoxycarbonyl)propan‐2‐yl and 3,3,3‐trifluoroacetonyl (=3,3,3‐trifluoro‐2‐oxopropyl) radicals to a variety of mono‐ and 1,1‐disubstituted alkenes. Their analysis shows that the addition of 2‐(alkoxycarbonyl)propan‐2‐yl is mainly governed by the exothermicity of the reaction with slight modifications by nucleophilic and electrophilic effects giving rise to an overall ambiphilic behavior. In contrast, large electrophilic polar effects dominate the addition of the 3,3,3‐trifluoroacetonyl (=3,3,3‐trifluoro‐2‐oxopropan‐2‐yl) radical, as it is expected from its large electron affinity. For both radicals, the activation energies are well‐predicted by analytic equations for the enthalpic and polar terms. A comparison of the rate data of 2‐(alkoxycarbonyl)propan‐2‐yl with the homo‐ and copolymerization rate constants of the propagating radical of methyl methacrylate shows that the additions of these structurally related low‐ and high‐molecular‐weight radicals to alkenes are governed by very similar effects.     

Formation of CC Bonds by Addition of Free Radicals to Alkenes

There are many reactions in which CC bonds are formed by addition of free radicals to alkenes. Information about the mechanism is important for the synthesis of specific target molecules. The rate of addition of alkyl radicals to alkenes is controlled by steric and polar effects. The stabilities of the educts and products are of only limited importance, since the transition states for these exothermic reactions occur very early on the reaction coordinate. Variations in reactivity and selectivity can be described using frontier orbital theory: for nucleophilic radicals the dominant interactions are those between SOMO's and LUMO's, and for electrophilic radicals those between SOMO's and HOMO's. The large differences in the steric effects of α - and β- substituents of alkenes can be explained by postulating an unsymmetrical transition state— the radical approaches one of the C atoms preferentially. Regioand stereoselectivities can be predicted and are determined, in general, by steric effects.     

Absolute Rate Constants for the Addition of Benzyl (PhĊH2) and Cumyl (PhĊMe2) Radicals to Alkenes in Solution

Absolute rate constants and their temperature dependence were determined by time-resolved electron spin resonance for the addition of the radicals Ph?H₂ and Ph?Me₂ to a variety of alkenes in toluene solution. To vinyl monomers CH₂=CXY, Ph?H₂ adds at the unsubstituted C-atom with rate constants ranging from 14 M ^?1S ^?1 (ethoxyethene) to 6.7 · 10³ M ^?1S ^?1 (4-vinylpyridine) at 296 K, and the frequency factors are in the narrow range of log (A/M ^?1S ^?1) = 8.6 ± 0.3, whereas the activation energy varies with the substituents from ca. 51 kJ/mol to ca. 26 kJ/mol. The rate constants and the activation energies increase both with increasing exothermicity of the reaction and with increasing electron affinity of the alkenes and are mainly controlled by the reaction enthalpy, but are markedly influenced also by nucleophilic polar effects for electron-deficient substrates. For 1,2-disubstituted and trisubstituted alkenes, the rate constants are affected by additional steric substituent effects. To acrylate and styrenes, Ph?Me₂ adds with rate constants similar to those of Ph?H₂, and the reactivity is controlled by the same factors. A comparison with relative-rate data shows that reaction enthalpy and polar effects also dominate the copolymerization behavior of the styrene propagation radical.     

Directive effects and selectivity in radical addition reactions: A theoretical study

The factors determining the relative reactivities and orientation ratios in free radical additions to unsymmetrically substituted alkenes have been analysed in terms of intermolecular population analysis. The reactivity of trifluoromethyl radical additions was found to be primarily determined by charge transfer contributions characterising the extent of bond formation in the transition state, whereas the addition of the methyl radical is influenced predominantly by steric effects.     

The Addition of tert-Butyl (Me3Ċ) and (tert-Butoxy)carbonylmethyl (Me3CO2CĊH2) radicals to alkynes in solution studied by ESR spectroscopy

Absolute rate constants and their temperature dependence are determined by time-resolved electron spin resonance for the addition of Me₃? to 20 and of Me₃CO₂C?H₂ to six mono- and disubstituted alkynes in solution. For Me₃? the rate constants show polar alkyne-substituent effects which are, however, weaker than for the corresponding alkenes. For Me₃CO₂?H₂, the rate constants do not vary strongly with alkyne substitution and probably increase with increasing reaction exothermicity. Both radicals react generally slower with alkynes than with alkenes which is discussed in terms of the state correlations. Several vinyl-type radical adducts of Me₃? to alkenes are characterized by electron spin resonance, and their spectral data indicate linear or bent configurations of the radical carbon depending on the substitution.     

Respective contributions of polar vs enthalpy effects in the addition/fragmentation of mercaptobenzoxazole-derived thiyl radicals and analogues to double bonds

The formation and the reactivity of three selected sulfur-centered radicals formed from mercaptobenzoxazole, mercaptobenzimidazole, and mercaptobenzothiazole toward four double bonds (methyl acrylate, acrylonitrile, vinyl ether, and vinyl acetate) are investigated. The reversibility of the addition/fragmentation reaction in these widely used photoinitiating systems of radical polymerization was studied, for the first time, through the measurement of the corresponding rate constants by time-resolved laser spectroscopy. The combination of these results with quantum mechanical calculations clearly evidences that, contrary to previous studies on other aryl thiyl radicals, the addition rate constants (ka) are governed here by the polar effects associated with the very high electrophilic character of these radicals. However, interestingly, the back-fragmentation reaction (k-a) is mainly influenced by the enthalpy effects as supported by the relationship between the rate constants and the addition reaction enthalpy DeltaHR. The addition and fragmentation rate constants calculated from the transition state theory (TST) are in satisfactory agreement with the experimental ones. Therefore, molecular orbital (MO) calculations offered new opportunities for a better understanding of the sulfur-centered radical reactivity.     

Structure-activity relationship for the addition of OH to (poly)alkenes: site-specific and total rate constants

A novel site-specific structure-activity relationship was developed for the site-specific addition of OH radicals to (poly)alkenes at 298 K. From a detailed structure-activity analysis of some 65 known OH + alkene and diene reactions, it appears that the total rate constant for this reaction class can be closely approximated by a sum of independent partial rate constants, ki, for addition to the specific (double-bonded) C atoms that depend only on the stability type of the ensuing radical (primary, secondary, etc.), that is, on the number of substituents on the neighboring C atom in the double bond. The (nine) independent partial rate constants, ki, were derived, and the predicted rate constants (kOH,pred = Sigmak(i)) were compared with experimental k(OH,exp) values. For noncyclic (poly)alkenes, including conjugated structures, the agreement is excellent (Delta < 10%). The SAR-predicted rate constants for cyclic (poly)alkenes are in general also within <15% of the experimental value. On the basis of this SAR, it is possible to predict the site-specific rate constants for (poly)alkene + OH reactions accurately, including larger biogenic compounds such as isoprene and terpenes. An important section is devoted to the rigorous experimental validation of the SAR predictions against direct measurements of the site-specific addition contributions within the alkene, for monoalkenes as well as conjugated alkenes. The measured site specificities are within 10-15% of the SAR predictions.     

Influence of the nitroxide structure on the homolysis rate constant of alkoxyamines: a Taft-Ingold analysis

Alkoxyamines and persistent nitroxyl radicals are important regulators of living radical polymerizations. Because polymerization times decrease with the increasing rate of the homolytic C-O bond cleavage between the polymer chain and the nitroxide moiety, the factors influencing the homolysis rate are of considerable interest. Here, we present an analysis of the cleavage rate constants for 28 alkoxyamines carrying the styryl (PhEt) group as leaving alkyl radical in terms of polar inductive/field (sigmaL) and steric (Es) effects of the nitroxide substituents, using the Taft-Ingold equation, i.e., log(k/k0) = rhoLsigmaL + deltaEs. The rate constants are shown to increase with the increasing electron-donating capacities, the steric demand, and the intramolecular (hydrogen) bonding capabilities of the substituents. A good correlation, (R2 = 0.95, 23 data) log kd = -3.07sigmaL - 0.88Es - 5.88, is obtained, which should facilitate the design of new nitroxyl radicals and alkoxyamine regulators.     

Carboamination of Unactivated Alkenes through Three‐Component Radical Conjugate Addition

Two‐component Giese type radical additions are highly practical and established reactions. Herein, three‐component radical conjugate additions of unactivated alkenes to Michael acceptors are reported. Amidyl radicals, oxidatively generated from α‐amido oxy acids using redox catalysis, act as the third reaction component which add to the unactivated alkenes. The adduct radicals engage in Giese type additions to Michael acceptors to provide, after reduction, the three‐component products in an overall alkene carboamination reaction. Transformations which can be conducted under practical mild conditions feature high functional group tolerance and broad substrate scope.     

Atmospheric reactions of alkoxy and β-hydroxyalkoxy radicals

Alkoxy and β-hydroxyalkoxy radicals are key intermediates formed in the atmospheric degradations of alkanes and alkenes, respectively. In the troposphere, these alkoxy radicals can decompose, isomerize, and react with O₂. The literature data concerning the rates of these reactions are evaluated, and predictive schemes allowing the calculation of rate constants for these alkoxy radical reactions for atmospheric purposes are proposed. Good agreement between calculated reaction rates and experimental data concerning the absolute and relative importance of these reaction pathways is obtained, and alkoxy and β-hydroxyalkoxy radical reaction rates for radicals for which experimental data are not presently available can now be calculated for use in atmospheric modeling. © 1997 John Wiley & Sons, Inc.     

Enthalpic and polar effects in the reactions of perfluoroalkyl radicals: New selective synthetic developments with alkenes and heteroaromatic bases

Perfluoroalkyl radicals, generated by iodine abstraction from perfluoroalkyl iodides by phenyl radical, react with low selectivity with protonated heteroaromatic bases, due to their electrophilic character and the prevalent enthalpic effect on the reaction. In the presence of alkenes, perfluoroalkyl radicals add very rapidly to the double bond and the polar character of the radical adduct is reversed, allowing the selective substitution of protonated heteroaromatic bases. The mechanism of the reaction and the key role of enthalpic and polar effects are discussed.     

Overall rate constant measurements of the reaction of chloroalkylperoxy radicals with nitric oxide

The overall rate constants of the NO reaction with chloroalkylperoxy radicals derived from the Cl-initiated oxidation of several atmospherically abundant alkenes-ethene, propene, 1-butene, 2-butene, 2-methylpropene, 1,3-butadiene, and isoprene (2-methyl-1,3-butadiene)-were determined for the first time via the turbulent flow technique and pseudo-first-order kinetics conditions with high-pressure chemical ionization mass spectrometry for the direct detection of chloroalkylperoxy radical reactants. The individual 100 Torr, 298 K rate constants for each monoalkene system were found to be identical within the 95% confidence interval associated with each separate measurement, whereas the corresponding rate constants for 1,3-butadiene and isoprene were both approximately 20% higher than the monoalkene mean value. Our previous study of the reaction of hydroxylalkylperoxy radicals (derived from the OH-initiated oxidation of alkenes) with NO yielded identical rate constants for all of the alkenes under study, with a rate constant value within the statistical uncertainty of the value determined here for the NO reaction of chloroalkylperoxy radicals derived from monoalkenes. Thus, the reaction of NO with chloroalkylperoxy radicals derived from dialkenes is found to be significantly faster than the NO reaction with either chloroalkylperoxy radicals derived from monoalkenes or hydroxyalkylperoxy radicals derived from either mono- or dialkenes.     

Separation of polar and steric effects on absolute rate constants and arrhenius parameters for the reaction of tert-butyl radicals with alkenes

Absolute rate constants and their temperature dependencies were measured for the reaction of tert-butyl radicals with 24 substituted ethenes and several other compounds in 2-propanol solution by time-resolved electron spin resonance. At 300 K the rate constants cover the range from 60 M^?1 s^?1 (1,2-dimethylene) over 16,500 M^?1 s^?1 (vinyl-chloride) to 460,000 M^?1 s^?1 (2-vinylpyridine). For the mono- and 1,1-disubstituted ethenes log k₃₀₀ increases and the activation energy decreases with increasing electron affinity of the olefins. The frequency factors are in the range log A/M^?1 s^?1 = 7.5 ± 1.0 as typical for addition reactions, with minor exceptions. Electron affinity (polar) and steric effects on reactivity are separated for the addition of tert-butyl to chloro- and methyl-substituted ethylenes. A comparison with rate data for methyl, ethyl, 2-propyl, and other radicals indicates both polar and steric effects on radical substitution.     

Regioselectivity and reactivity in the addition of trichloromethyl radicals to amides of unsaturated carboxylic acids

The AM1 method was used to analyze the factors that correlate with regioselectivity in the addition of radicals to 1,2-disubstituted unsaturated compounds. The rate constants of the addition of^.CCl₃ radicals to RCH=CHC(O)X (R = Ph, Me; X = N-pyrrolidyl) were determined by ESR. The analysis of the spin density distribution in mono- and 1,2-disubstituted alkenes and the experimental values for the rate constants of the addition of^.CCl₃ radicals to these alkenes allowed the authors to conclude that the efficiency of the addition of^.CC1₃ to unsaturated compounds depends only on steric effects.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 452–455, March, 1995.     

Unimolecular Reaction Properties for the Long‐Chain Alkenyl Radicals

Although alkenyl radicals are important intermediates involved in both alkanes and alkenes combustion, previous kinetic studies on them are very limited, especially for the long‐chain alkenyl radicals. To deeply investigate unimolecular reaction activities of long‐chain alkenyl radicals, a series of octenyl (C₈H₁₅) radicals were chosen to study the reaction kinetics of three typical types of reactions (i.e., intramolecular radical addition, internal H‐migration, and bond dissociation) in this work. The CBS‐QB3 method was used to build potential energy surfaces for these reactions, and the transition state theory was applied to obtain the high‐pressure limit rate constants. Some general rules are observed from our systematic calculations in respect of structure–activity relationships.     

Direct determination of rate constants for coupling between aromatic radical anions and alkyl and benzyl radicals by laser-flash photolysis

Coupling rates between the radicals methyl, n-, sec-, tert-butyl and benzyl (R.) and the aromatic radical anions of 1,4-dicyanonaphthalene, 9,10-dicyanoanthracene and fluorenone (A-.) have been obtained using a new laser-flash photolysis method. The radicals R. and the radical anions A-. were generated by a photoinduced electron transfer reaction between the aromatic compound A and the alkyl or benzyl triphenylborate anion RB(Ph)3-. For the first time the rate constants of the coupling reaction between methyl and benzyl radicals with aromatic radical anions have been obtained. For all the measured coupling rate constants an average value of k1 = 1.9 x 10(9) M-1 s-1 was found with a relatively small variation in the coupling rates (0.8-2.9 x 10(9) M-1 s-1). The results demonstrate that the coupling rate k1 is insensitive to changes in the steric and electronic properties of the radicals and the structure and standard potentials of the aromatic radical anions.     

Absolute rate constants of alkene addition reactions of a fluorinated radical in water

Absolute rate constants of *R(f)SO(3)(-) radical addition to a series of water-soluble alkenes containing ionic, carboxylate substituents were measured by laser flash photolysis experiments in water. The observed rate constants were all considerably larger than those of structurally similar analogues in a nonpolar organic solvent, with rate factors of 3-9-fold being observed. It is concluded that such rate enhancements derive at least in part from stabilization of the polar transition state for addition of the electrophilic fluorinated radical to alkenes by the polar solvent water.     

Absolute Rate Constants for the Addition of Cyanomethyl (·CH2CN) and (tert-Butoxy)carbonylmethyl (·CH2CO2C(CH3)3) radicals to alkenes in solution

Absolute rate constants and their temperature dependence were determined by time-resolved electron spin resonance for the addition of the radicals ·CH₂CN and ·CH₂CO₂C(CH₃)₃ to a variety of mono- and 1,1-disubstituted and to selected 1,2- and trisubstituted alkenes in acetonitrile solution. To alkenes CH₂?CXY, ·CH₂CN adds at the unsubstituted C-atom with rate constants ranging from 3.3·10³ M ^?1S ^?1 (ethene) to 2.4·10⁶ M ^?1S ^?1 (1,1-diphenylethene) at 278 K, and the frequency factors are in the narrow range of log (A/M ^?1S ^?1) = 8.7 ± 0.3. ·CH₂CO₂C(CH₃)₃ shows a very similar reactivity with rate constants at 296 K ranging from 1.1·10⁴ M ^?1S ^?1 (ethene) to 10⁷ M ^?1S ^?1 (1,1-diphenylethene) and frequency factors log (A/M ^?1S ^?1) = 8.4 ± 0.1. For both radicals, the rate constants and the activation energies for addition to CH₂?CXY correlate well with the overall reaction enthalpy. In contrast to the expectation of an electro- or ambiphilic behavior, polar alkene-substituent effects are not clearly expressed, but some deviations from the enthalpy correlations point to a weak electrophilicity of the radicals. The rate constants for the addition to 1,2- and to trisubstituted alkenes reveal additional steric substituent effects. Self-termination rate data for the title radicals and spectral properties of their adducts to the alkenes are also given.     

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.