Phthalimide N-oxyl Research Articles

Kinetic Study of the Hydrogen Abstraction Reaction of the Benzotriazole-N-oxyl Radical (BTNO) with H-Donor Substrates

[Reaction: see text]. The aminoxyl radical (>N-O*) BTNO (benzotriazole-N-oxyl) has been generated by the oxidation of 1-hydroxybenzotriazole (HBT; >N-OH) with a Ce(IV) salt in MeCN. BTNO presents a broad absorption band with lambda(max) 474 nm and epsilon 1840 M(-1) cm(-1), and spontaneously decays with a first-order rate constant of 6.3 x 10(-3) s(-1) in MeCN at 25 degrees C. Characterization of BTNO radical by EPR, laser flash photolysis, and cyclic voltammetry is provided. The spontaneous decay of BTNO is strongly accelerated in the presence of H-donor substrates such as alkylarenes, benzyl and allyl alcohols, and alkanols, and rate constants of H-abstraction by BTNO from a number of substrates have been spectroscopically investigated at 25 degrees C. The kinetic isotope effect confirms the H-abstraction step as rate-determining. Activation parameters have been measured in the 15-40 degrees C range with selected substrates. A correlation between E(a) and BDE(C-H) (C-H bond dissociation energy) for a small series of H-donors has been obtained according to the Evans-Polanyi equation, giving alpha = 0.44. From this plot, the experimentally unavailable BDE(C-H) of benzyl alcohol can be extrapolated, as ca. 79 kcal/mol. With respect to the H-abstraction step, peculiar differences in the DeltaS++ parameter emerge between an alkylarene, ArC(H)R2, and a benzyl alcohol, ArC(H)(OH)R. The data acquired on the H-abstraction reactivity of BTNO are compared with those recently reported for the aminoxyl radical PINO (phthalimide-N-oxyl), generated from N-hydroxyphthalimide (HPI). The higher reactivity of radical PINO is explained on the basis of the higher energy of the NO-H bond of HPI, as compared with that of HBT (88 vs ca. 85 kcal/mol, respectively), which is formed on H-abstraction from the RH substrate.

Electron-Transfer Mechanism in the N-Demethylation of N,N-Dimethylanilines by the Phthalimide-N-oxyl Radical

The reactivity of the phthalimide N-oxyl radical (PINO) toward the N-methyl C-H bond of a number of 4-X-substituted N,N-dimethylanilines (X = OMe, OPh, CF(3), CO(2)Et, CN) has been investigated by product and kinetic analysis. PINO was generated in CH(3)CN by reaction of N-hydroxyphthalimide (NHPI) with Pb(OAc)(4) or, for the kinetic study of the most reactive substrates (X = OMe, OPh), with tert-butoxyl radical produced by 266 nm laser flash photolysis of di-tert-butyl peroxide. The reaction was found to lead to the N-demethylation of the N,N-dimethylaniline with a rate very sensitive to the electron donating power of the substituent (rho(+) = -2.5) as well as to the oxidation potential of the substrates. With appropriately deuterated N,N-dimethylanilines the intermolecular and intramolecular deuterium kinetic isotope effects (DKIEs) were measured for some substrates (X = OMe, CO(2)Et, CN) with the following results. First, intramolecular DKIE [(k(H)/k(D))(intra)] was found to be always different and higher than intermolecular DKIE [(k(H)/k(D))(inter)]; second, no intermolecular DKIE [(k(H)/k(D))(inter) = 1] was observed for X = OMe, whereas substantial values of (k(H)/k(D))(inter) were exhibited by X = CO(2)Et (4.8) and X = CN (5.8). These results, while are incompatible with a single step hydrogen atom transfer from the N-C-H bond to the N-oxyl radical, as proposed for the reaction of PINO with benzylic C-H bonds, can be nicely interpreted on the basis of a two-step mechanism involving a reversible electron transfer from the aniline to PINO leading to an anilinium radical cation, followed by a proton-transfer step that produces an alpha-amino carbon radical. In line with this conclusion the reactivity data exhibited a good fit with the Marcus equation and a lambda value of 37.6 kcal mol(-1) was calculated for the reorganization energy required in this electron-transfer process. From this value, a quite high reorganization energy (>60 kcal mol(-1)) is estimated for the PINO/NHPI(-H)(-) self-exchange reaction. It is suggested that the N-demethylated product derives from the reaction of the alpha-amino carbon radical with PINO to form either a cross-coupling product or an alpha-amino carbocation. Both species may react with the small amounts of H(2)O present in the medium to form a carbinolamine that, again by hydrolysis, can be eventually converted into the N-demethylated product.

Mechanisms of Reaction of Aminoxyl (Nitroxide), Iminoxyl, and Imidoxyl Radicals with Alkenes and Evidence that in the Presence of Lead Tetraacetate, N-Hydroxyphthalimide Reacts with Alkenes by Both Radical and Nonradical Mechanisms

1,2-dideuterio-cyclohexene, 1,2-dideuterio-cyclooctene, and trans-3,4-dideuterio-hex-3-ene were reacted with three >NO* radicals: 4-hydroxyTempo, di-tert-butyliminoxyl, both used as the actual radicals, and phthalimide-N-oxyl (PINO) generated from N-hydroxyphthalimide (NHPI) by its reaction with tert-alkoxyl radicals (t-RO*) and with lead tetraacetate. In all cases, except the NHPI/Pb(OAc)4 system, only mono >NO-substituted alkenes were produced. The 2H NMR spectra imply that 88-92% of monoadducts were formed by the initial abstraction of an allylic H-atom, followed by capture of the allylic radical by a second >NO*, while the remaining 12-8% appear to be formed by an initial addition of >NO* to the double bond followed by H-atom abstraction by a second >NO*. A substantial and sometimes the major product formed with the NHPI/Pb(OAc)4 system has two PINO moieties added across the double bond. Since such diadducts are not formed with the NHPI/t-RO* system, a heterolytic mechanism is proposed, analogous to that known for the Pb(OAc)4-induced acetoxylation of alkenes. A detailed analysis of the NHPI/Pb(OAc)4/alkene products indicates that monosubstitution occurs by both homolytic and heterolytic processes.

Kinetics of Self-Decomposition and Hydrogen Atom Transfer Reactions of Substituted Phthalimide N-Oxyl Radicals in Acetic Acid

Kinetic data have been obtained for three distinct types of reactions of phthalimide N-oxyl radicals (PINO(.)) and N-hydroxyphthalimide (NHPI) derivatives. The first is the self-decomposition of PINO(.) which was found to follow second-order kinetics. In the self-decomposition of 4-methyl-N-hydroxyphthalimide (4-Me-NHPI), H-atom abstraction competes with self-decomposition in the presence of excess 4-Me-NHPI. The second set of reactions studied is hydrogen atom transfer from NHPI to PINO(.), e.g., PINO(.) + 4-Me-NHPI <=> NHPI + 4-Me-PINO(.). The substantial KIE, k(H)/k(D) = 11 for both forward and reverse reactions, supports the assignment of H-atom transfer rather than stepwise electron-proton transfer. These data were correlated with the Marcus cross relation for hydrogen-atom transfer, and good agreement between the experimental and the calculated rate constants was obtained. The third reaction studied is hydrogen abstraction by PINO(.) from p-xylene and toluene. The reaction becomes regularly slower as the ring substituent on PINO(.) is more electron donating. Analysis by the Hammett equation gave rho = 1.1 and 1.8 for the reactions of PINO(.) with p-xylene and toluene, respectively.

Reactivity of Phthalimide N-Oxyl Radical (PINO) toward the Phenolic O−H Bond. A Kinetic Study

The reactivity of the phthalimide N-oxyl radical (PINO) toward the OH bond of a series of substituted phenols was kinetically investigated in CH(3)CN. The reaction selectivity and the deuterium kinetic isotope effect were determined. Information on the kinetic solvent effect was also obtained with phenol as the substrate.

Transition Metal Salts Catalysis in the Aerobic Oxidation of Organic Compounds: Thermochemical and Kinetic Aspects and New Synthetic Developments in the Presence of N‐Hydroxy Derivative Catalysts

AbstractFor Abstract see ChemInform Abstract in Full Text.

N-Hydroxyphthalimides and Metal Cocatalysts for the Autoxidation of p-Xylene to Terephthalic Acid

N-Hydroxyphthalimide (NHPI) and its derivatives, such as 3-F-NHPI, 4-Me-NHPI, N-acetoxyphthalimide, and N,N-dihydroxypyromelitimide, were used as promoters with Co(OAc)2 catalyst for the autoxidation of p-xylene (pX) and other methyl arenes. All the promoters gave acceptable rates and yields of terephthalic acid. The initial reaction rates, measured by the rate of oxygen uptake, were analyzed by a rate equation in terms of [pX], [Co(II)], and [NHPI]. The metal cocatalysts Mn(II) and Ce(III) accelerated the reaction significantly at millimolar concentrations. The reaction occurs by a chain mechanism that involves formation of the phthalimide N-oxyl radical, PINO• (that is, R2NO•), which abstracts a hydrogen atom from the methyl group of p-xylene to form the carbon-centered radical ArCH2•. In a stepwise fashion, the sequence progresses through alcohol, aldehyde, and carboxylic acid; at each stage, C−H abstraction by PINO• is involved. A significant kinetic isotope effect on the overall oxidation of p-xylene...

Kinetic study of the phthalimide N-oxyl radical in acetic acid. Hydrogen abstraction from substituted toluenes, benzaldehydes, and benzyl alcohols.

The phthalimide N-oxyl (PINO) radical was generated by the oxidation of N-hydroxyphthalimide (NHPI) with Pb(OAc)4 in acetic acid. The molar absorptivity of PINO* is 1.36 x 10(3) L mol(-1) cm(-1) at lambda(max) 382 nm. The PINO radical decomposes slowly with a second-order rate constant of 0.6 +/- 0.1 L mol(-1) s(-1) at 25 degrees C. The reactions of PINO(*) with substituted toluenes, benzaldehydes, and benzyl alcohols were investigated under an argon atmosphere. The second-order rate constants were correlated by means of a Hammett analysis. The reactions with toluenes and benzyl alcohols have better correlations with sigma+ (rho = -1.3 and -0.41), and the reaction with benzaldehydes correlates better with sigma (rho = -0.91). The kinetic isotope effect was also studied and significantly large values of k(H)/k(D) were obtained: 25.0 (p-xylene), 27.1 (toluene), 27.5 (benzaldehyde), and 16.9 (benzyl alcohol) at 25 degrees C. From the Arrhenius plot for the reactions with p-xylene and p-xylene-d(10), the difference of the activation energies, E(a)(D) - E(a)(H), was 12.6 +/- 0.8 kJ mol(-1) and the ratio of preexponential factors, A(H)/A(D), was 0.17 +/- 0.05. These findings indicate that quantum mechanical tunneling plays an important role in these reactions.

Transition metal salts catalysis in the aerobic oxidation of organic compounds Thermochemical and kinetic aspects and new synthetic developments in the presence of N-hydroxy-derivative catalysts

Abstract The catalytic system formed by Mn(II) and Co(II) or Cu(II) nitrates has shown to be particularly effective for the oxidation of ketones and aldehydes by molecular oxygen under mild conditions. The process has a general character, but it is particularly selective for the oxidation of alkyl–aryl ketones to aromatic carboxylic acids, alkyl-cyclopropyl ketones to cyclopropane carboxylic acids and cycloalkanones to dicarboxylic acids. Mn salt plays a key role in this catalysis, which catalyses the enolisation of the carbonyl compound and initiates a free-radical redox chain with oxygen by an electron-transfer process. Co and Cu salts alone are inert, but they exalt the catalytic activity of the Mn salt, being more effective in the decomposition of the hydroperoxides. The same metal salt complexes, associated with TEMPO revealed particularly effective for the aerobic oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones under mild conditions (with air or oxygen at room temperature and atmospheric pressure); the mechanism of the catalysis is discussed. Thermochemical and kinetic investigations by EPR spectroscopy, concerning N-hydroxy compounds, have allowed to evaluate the Bond Dissociation Enthalpies (BDE) of several OH bonds and the absolute rate constants for the formation of the phthalimide-N-oxyl (PINO) radical from N-hydroxyphthalimide (NHPI) and for the hydrogen abstraction from several CH bonds by the PINO radical. The thermochemical and kinetic results have allowed us to explain the opposite catalytic behaviour of the two nitroxyl radicals, TEMPO and PINO, the former being an inhibitor of free radical processes, the latter a promoter of free-radical chain, and to develop new selective processes concerning the aerobic oxidation of alcohols, amines, amides, silanes and the substitution of heteroaromatic bases.

Kinetic Study of the Phthalimide N-Oxyl (PINO) Radical in Acetic Acid. Hydrogen Abstraction from C−H Bonds and Evaluation of O−H Bond Dissociation Energy of N-Hydroxyphthalimide

The reactions of the phthalimide N-oxyl (PINO) radical with several hydrocarbons having different C−H bond dissociation energies (BDEs) were investigated in HOAc at 25 °C. The slope of the Evans−Polanyi plot is 0.38, which indicates that the reactions are mildly exothermic or almost thermoneutral. This finding is supported by the O−H BDE of N-hydroxyphthalimide (NHPI), 375 ± 10 kJ mol-1, obtained by means of a thermodynamic cycle. The observed kinetic isotope effects (KIEs) are related to the reaction free-energy changes, which can be explained by a Marcus-type equation. The comparison of the PINO radical reactions with analogous hydrogen atom abstraction reactions of the dibromide radical implies that HBr2• reactions are more exothermic than the PINO radical reactions. This factor is put forth to explain the different KIEs.

Hydroxylamines as oxidation catalysts: thermochemical and kinetic studies.

Bond dissociation enthalpies (BDE) of hydroxylamines containing alkyl, aryl, vinyl, and carbonyl substituents at the nitrogen atom have been determined by using the EPR radical equilibration technique in order to study the effect of the substituents on the O-H bond strength of these compounds. It has been found that substitution of an alkyl group directly bonded to the nitrogen atom with vinyl or aryl groups has a small effect, while substitution with acyl groups induces a large increase of the O-H BDE value. Thus, dialkyl hydroxylamines have O-H bond strengths of only ca. 70 kcal/mol, while acylhydroxylamines and N-hydroxyphthalimide (NHPI), containing two acyl substituents at nitrogen, are characterized by BDE values of ca. 80 and 88 kcal/mol, respectively. Since the phthalimide N-oxyl radical (PINO) has been recently proposed as an efficient oxidation catalyst of hydrocarbons or other substrates, the large BDE value found for the parent hydroxylamine (NHPI) justifies this proposal. Kinetic studies, carried out in order to better understand the mechanism of the NHPI-catalyzed aerobic oxidation of cumene, are consistent with a simple kinetic model where the rate-determining step is the hydrogen atom abstraction from the hydroxylamine by cumylperoxyl radicals.

Aerobic oxidation of N-alkylamides catalyzed by N-hydroxyphthalimide under mild conditions. Polar and enthalpic effects.

The oxidation of N-alkylamides by O(2), catalyzed by N-hydroxyphthalimide (NHPI) and Co(II) salt, leads under mild conditions to carbonyl derivatives (aldehydes, ketones, carboxylic acids, imides) whose distribution depends on the nature of the alkyl group and on the reaction conditions. Primary N-benzylamides lead to imides and aromatic aldehydes at room temperature without any appreciable amount of carboxylic acids, while under the same conditions nonbenzylic derivatives give carboxylic acids and imides with no trace of aldehydes, even at very low conversion. These results are explained through hydrogen abstraction by the phthalimide-N-oxyl (PINO) radical, whose reactivity with benzyl derivatives is governed by polar effects, so that benzylamides are much more reactive than the corresponding aldehydes. The enthalpic effect is, however, dominant with nonbenzylic amides, making the corresponding aldehydes much more reactive than the starting amides. The importance of the bond dissociation energy (BDE) of the O-H bond in NHPI is emphasized.

Catalytic oxyalkylation of alkenes with alkanes and molecular oxygen via a radical process using N-hydroxyphthalimide.

A novel catalytic method for the radical addition of alkanes and molecular oxygen to electron-deficient alkenes was achieved by the use of N-hydroxyphthalimide (NHPI) combined with a Co species as the catalyst. This reaction is referred to as oxyalkylation of alkenes with alkanes and O(2). For instance, the reaction of 1,3-dimethyladamantane with methyl acrylate under molecular oxygen in the presence of catalytic amounts of NHPI and Co(acac)(3) at 70 degrees C for 16 h gave oxyalkylated products in 91% yield. Other alkenes such as fumarate and acrylonitrile also serve as good acceptors of alkyl radicals and O(2) to afford the corresponding adducts in high yields. The generality of the present reaction was examined between various alkanes and alkenes under dioxygen. The behavior of Co ions during the reaction course was discussed. The present reaction involves (i) an alkyl radical generation via hydrogen abstraction of alkane by phthalimide N-oxyl generated in situ from NHPI and O(2) assisted by Co(II), (ii) the addition of the resulting alkyl radical to an electron-deficient alkene to form an adduct radical, (iii) trapping of the adduct radical by O(2) yielding a hydroperoxide, and (iv) the decomposition of the hydroperoxide by Co ions to form an adduct in which a hydroxy or a carbonyl function is incorporated.

Nitration of alkanes with nitric acid catalyzed by N-hydroxyphthalimide

Catalytic nitration of alkanes with nitric acid was first successfully achieved by the use of N-hydroxyphthalimide (NHPI) under mild conditions; the key to the present nitration was found to be the in situ generation of NO2 and phthalimide N-oxyl radical by the reaction of NHPI with nitric acid.

Ternary reactive blends of nylon-6 matrix with dispersed rigid brittle polymer and elastomer : Kelnar, L, Stephan, M., Jakisch, L., Fortelny, I., Academy of Sciences of the Czech Republic, Prague, Czech Republic in journal of applied polymer science, vol 74, issue 6, 1999

Acetophenone is an important industrial intermediate and generally produced by the Friedel-Crafts acylation reaction, suffering from a low reactivity and serious equipment corrosion. Direct oxidation of ethylbenzene to acetophenone by molecular oxygen will be benign and cost-effective. The catalytic performance of NHPI/Co(II) herein was investigated by selective oxidation of ethylbenzene to acetophenone in different solvents at room temperature. The solvent hexafluoropropan-2-ol (HFIP) was found to markedly enhance the transformation efficiency from ethylbenzene to acetophenone in comparison with acetic acid, pyridine and ethanol, and the ethylbenzene conversion and the selectivity to acetophenone was high up to 87.9 % and 61.2 %, respectively. A higher concentration of phthalimide-N-oxyl (PINO) radicals was observed by an in situ electron paramagnetic resonance spectrometer (EPR) in HFIP with respect to other solvents, suggesting that HFIP may facilitate the generation of the N-oxyl radical and thus promote the selective oxidation of ethylbenzene to acetophenone. Furthermore, the benzylic carbon radical (PhCHCH3) from ethylbenzene was trapped by tetramethylpiperidine N-oxyl radical (TEMPO) and observed by a high resolution mass spectrometer. The findings of both PINO and PhCHCH3 under reaction conditions indicated that the selective oxidation of ethylbenzene to acetophenone catalyzed by NHPI/Co(II) should proceed via a radical mode. The selective oxidation of ethylbenzene to acetophenone using molecular oxygen by NHPI/Co(II) in HFIP exhibited an important industrial application prospect.

Direct Conversion of Cyclohexane into Adipic Acid with Molecular Oxygen Catalyzed by N-Hydroxyphthalimide Combined with Mn(acac)2 and Co(OAc)2

Direct conversion of cyclohexane into adipic acid was achieved by the use of the radical catalyst, N-hydroxyphthalimide (NHPI), in the presence of a small amount of a transition metal. For instance, cyclohexane could be converted into adipic acid in 73% selectivity at 73% conversion under atmospheric oxygen (1 atm) in the presence of NHPI (10 mol %) and Mn(acac)2 (1 mol %) at 100 °C for 20 h. ESR measurements show that the formation of phthalimide N-oxyl generated from NHPI with O2 was assisted by Co(II) species. Thus, the oxidation of cyclohexane to adipic acid was found to be enhanced by the addition of a small amount of Co(OAc)2 to the NHPI/Mn(acac)2 system. The NHPI-catalyzed oxidation of cyclohexane provides an attractive direct method which has long been desired in the chemical industry for the manufacturing of adipic acid. The present oxidation seems to be the first practical environmentally friendly process, in which nitric acid is not used as the oxidant, for the production of adipic acid from cyclohexane.

Catalytic Oxidation of Alkylbenzenes with Molecular Oxygen under Normal Pressure and Temperature by N-Hydroxyphthalimide Combined with Co(OAc)2

A practical catalytic method to convert alkylbenzenes into the corresponding carboxylic acids under atmospheric dioxygen at ambient temperature using a combined catalytic system consisting of N-hydroxyphthalimide (NHPI) and Co(OAc)2 was developed. For instance, the oxidation of toluene was completed by NHPI combined with Co(OAc)2 under an oxygen atmosphere at room temperature to give benzoic acid in 81% yield. Under these conditions, o- and p-xylenes were selectively converted into the corresponding monocarboxylic acids without the formation of the dicarboxylic acids. ESR measurements showed that Co(II) species assists in the formation of phthalimide-N-oxyl (PINO), which is a key species in this oxidation, from NHPI.

A novel catalysis of N-hydroxyphthalimide (NHPI) combined with Co(acac) n ( n = 2 or 3) in the oxidation of organic substrates with molecular oxygen

A novel class of catalysts for aerobic oxidation for a wide variety of organic substrates was developed. Benzylic compounds such as fluorene were oxidized with molecular oxygen in the presence of N-hydroxyphthalimide (NHPI) to give the corresponding oxygenated products such as fluorenone. For the oxidation of cycloalkanes, polycyclic alkanes and alkylbenzenes, which are difficult to be oxidized by NHPI alone, a combined catalytic system of NHPI with Co(acac) n ( n = 2 or 3) was found to be efficient for the oxidation of these substrates. Thus cycloalkanes were successfully oxidized with dioxygen in the presence of a catalytic amount of NHPI (10 mol%) and Co(acac) 2 (0.5 mol%) in acetic acid at 100°C to give cycloalkanones and dicarboxylic acids as principal products. Alkylbenzenes were also oxidized by this catalytic system to form the corresponding carboxylic acids and/or carbonyl compounds in good yields. Exposure of NHPI to atmospheric oxygen in benzonitrile at 80°C generated phthalimide N-oxyl (PINO), a key intermediate, in this oxidation. The formation of PINO from the NHPI and dioxygen was significantly accelerated by adding Co(acac) 2 to the reaction system.

5505920 Process for treatment of waste gas from a cyclohexane oxidation reactor

A novel class of catalysts for aerobic oxidation for a wide variety of organic substrates was developed. Benzylic compounds such as fluorene were oxidized with molecular oxygen in the presence of N-hydroxyphthalimide (NHPI) to give the corresponding oxygenated products such as fluorenone. For the oxidation of cycloalkanes, polycyclic alkanes and alkylbenzenes, which are difficult to be oxidized by NHPI alone, a combined catalytic system of NHPI with Co(acac)n (n = 2 or 3) was found to be efficient for the oxidation of these substrates. Thus cycloalkanes were successfully oxidized with dioxygen in the presence of a catalytic amount of NHPI (10 mol%) and Co(acac)2 (0.5 mol%) in acetic acid at 100°C to give cycloalkanones and dicarboxylic acids as principal products. Alkylbenzenes were also oxidized by this catalytic system to form the corresponding carboxylic acids and/or carbonyl compounds in good yields. Exposure of NHPI to atmospheric oxygen in benzonitrile at 80°C generated phthalimide N-oxyl (PINO), a key intermediate, in this oxidation. The formation of PINO from the NHPI and dioxygen was significantly accelerated by adding Co(acac)2 to the reaction system.

Alkane Oxidation with Molecular Oxygen Using a New Efficient Catalytic System: N-Hydroxyphthalimide (NHPI) Combined with Co(acac)(n)() (n = 2 or 3).

A novel class of catalysts for alkane oxidation with molecular oxygen was examined. N-Hydroxyphthalimide (NHPI) combined with Co(acac)(n)() (n = 2 or 3) was found to be an efficient catalytic system for the aerobic oxidation of cycloalkanes and alkylbenzenes under mild conditions. Cycloalkanes were successfully oxidized with molecular oxygen in the presence of a catalytic amount of NHPI and Co(acac)(2) in acetic acid at 100 degrees C to give the corresponding cycloalkanones and dicarboxylic acids. Alkylbenzenes were also oxidized with dioxygen using this catalytic system. For example, toluene was converted into benzoic acid in excellent yield under these conditions. Ethyl- and butylbenzenes were selectively oxidized at their alpha-positions to form the corresponding ketones, acetophenone, and 1-phenyl-1-butanone, respectively, in good yields. A key intermediate in this oxidation is believed to be the phthalimide N-oxyl radical generated from NHPI and molecular oxygen using a Co(II) species. The isotope effect (k(H)/k(D)) in the oxidation of ethylbenzene and ethylbenzene-d(10) with dioxygen using NHPI/Co(acac)(2) was 3.8.