Kinetic isotope effects hydroxylation

Typical non-enolising aldehydes are formaldehyde and benzaldehyde, which are oxidised by Co(III) Ce(IV) perchlorate and sulphate , and Mn(III) . The main kinetic features and the primary kinetic isotope effects are the same as for the analogous cyclohexanol oxidations (section 4.3.5) and it is highly probable that the same general mechanism operates. kif olko20 for Co(III) oxidation of formaldehyde is 1.81 (ref. 141), a value in agreement with the observed acid-retardation, i.e. not in accordance with abstraction of a hydroxylic hydrogen atom from H2C(OH)2-The V(V) perchlorate oxidations of formaldehyde and chloral hydrate display an unusual rate expression, viz. 

One-step hydroxylation of aromatic nucleus with nitrous oxide (N2O) is among recently discovered organic reactions. A high eflSciency of FeZSM-5 zeolites in this reaction relates to a pronounced biomimetic-type activity of iron complexes stabilized in ZSM-5 matrix. N2O decomposition on these complexes produces particular atomic oj gen form (a-oxygen), whose chemistry is similar to that performed by the active oxygen of enzyme monooxygenases. Room temperature oxidation reactions of a-oxygen as well as the data on the kinetic isotope effect and Moessbauer spectroscopy show FeZSM-5 zeolite to be a successfiil biomimetic model. 

An interesting catalytic ruthenium system, Ru(7/5-C5Ar4OH)(CO)2H based on substituted cyclopentadienyl ligands was discovered by Shvo and coworkers [95— 98]. This operates in a similar fashion to the Noyori system of Scheme 3.12, but transfers hydride from the ruthenium and proton from the hydroxyl group on the ring in an outer-sphere hydrogenation mechanism. The source of hydrogen can be H2 or formic acid. Casey and coworkers have recently shown, on the basis of kinetic isotope effects, that the transfer of H+ and TT equivalents to the ketone for the Shvo system and the Noyori system (Scheme 3.12) is a concerted process [99, 100]. 

Blackburn AC, Doe WF, Buffinton GD (1998) Salicylate hydroxylation as an indicator of OH radical generation in dextran sulfate-induced colitis. Free Rad Biol Med 25 305-313 Bonifacic M, Stefanic I, Hug GL, Armstrong DA, Asmus K-D (1998) Glycine decarboxylation The free radical mechanism. J Am Chem Soc 120 9930-9940 Bonifacic M, Armstrong DA, Stefanic I, Asmus K-D (2003) Kinetic isotope effect for hydrogen abstraction by OH radicals from normal and carbon-deuterated ethyl alcohol in aqueous solution. J Phys Chem B 107 7268-7276... 

Kinetic isotope effects for C-H hydroxylation of /V,/V-dimethylaniline by cytochrome P450 enzymes indicate that a low-spin mechanism applies.292... 

Reactions may exhibit kinetic isotope effects as a result of the lighter isotope reacting faster. To illustrate this type of isotope effect, consider the oxidation of methane in the atmosphere (22). The oxidation is initiated by a reaction with the hydroxyl free radical (OH) in which OH irreversibly abstracts a hydrogen atom from the carbon. Methane molecules containing the lighter carbon isotope react faster, and as a consequence, the 613C value of the product is lower. 

The oxidation of DMS is initiated by the hydroxyl free radical which either abstracts a hydrogen from DMS or undergoes an addition reaction (46-48). Kinetic isotope effects would be associated with these types of reactions. However, the remaining oxidation steps may involve larger equilibrium isotope effects resulting in heavier end products. These effects have not been measured. The S S values for sulfate and methane sulfonate should be related if they are derived from the same DMS pool (4 ). At this time there are no fi34S measurements for methane sulfonate or sulfate which are unambiguously from the oxidation of DMS. 

In atmospheric chemistry, kinetic isotope effects have been measured for the reaction of hydroxyl radicals with acetone using the relative-rate method over a range of temperatures.334 Water vapour had relatively little effect on rates. Product studies have allowed partitioning of the reaction flux into routes that produce acetic acid directly, and secondary processes. 

Complex (2) is an effective catalyst for the asymmetric hydroxylation of aromatic hydrocarbons with 2,6-dichloropyridine IV-oxide as terminal oxidant. Up to 76% ee was achieved for the catalytic hydroxylation of 4-ethyltoluene, 1,1-diethylindane, and benzylcyclopropane. Both electron-donating and -withdrawing substituents were found to accelerate the catalytic oxidation reaction. A large primary kinetic isotope effect (kH/kD = 11 at 298 K) was observed for the catalytic ethylbenzene-dio oxidation. A... 

Robertson [28] proposed that an additional possibility was that the destruction of the substrates may be mediated by hydroxyl radicals generated via the superoxide radical anion produced at the conduction band. This is subsequently hydrated or deuterated by the solvent. This may be rate determining since the O2 has to be generated at the conduction band prior to interaction with the solvent and subsequent formation of OH or OD" species. Therefore the kinetic isotope effect could be due to the interaction of the solvent with the superoxide species rather than the attack on the toxin. If this is the case it was suggested that a similar kinetic isotope effect would be observed no matter what substrate was being destroyed. Further kinetic isotope studies will help elucidate the potential of this proposed mechanism. 

Significant characteristics of the porphyrin iron monoxide are seen in the chemical reactivity. Naphthalene is converted initially to the corresponding arene oxide on treatment with P 450 (19), consistent with a molecular mechanism of oxygen transfer from an iron monoxide to the aromatic nucleus. Retention of stereochemistry in the P-450 catalyzed hydroxylation of d ethylbenzene also supports the molecular mechanism. The unusually large kinetic isotope effect observed for the P-450 oxidation of dideutero 1,3-diphenylpropane, kJkD = 11, demonstrates that C—H cleavage is involved in the rate determining step (20), probably in a very unusual environment, not incompatible with a molecular mechanism. 

We know that this is the mechanism because we can make the green H a deuterium atom. We then find that deuterium is present in the tyrosine product ortho to the phenolic hydroxyl group. When the migration occurs, the deuterium atom must go as there is no alternative, but in the next step there is a choice and H loss will be preferred to D loss because of the kinetic isotope effect (Chapter 19). Most of the D remains in the product. 

Another series of publications from Ken s group compared kinetic isotope effects, computed for different possible transition structures for a variety of reactions, with the experimental values, either obtained from the literature or measured by Singleton s group at Texas A M. These comparisons established the most important features of the transition states for several classic organic reactions — Diels-Alder cycloadditions, Cope and Claisen rearrangements, peracid epoxidations, carbene and triazolinedione cycloadditions and, most recently, osmium tetroxide bis-hydroxylations. Due to Ken s research, the three-dimensional structures of many transition states have become nearly as well-understood as the structures of stable molecules. 

The use of a titanium dioxide photocatalyst for the removal of microcystin-LR in water has been demonstrated by Robertson et al. [163]. They reported a rapid photocatalytic degradation of this toxin using a Degussa P25 photocatalyst. In a subsequent study [68] a primary kinetic isotope effect of approximately 3 was observed when the destruction was performed in a heavy water solvent. Hydroxylated compounds were observed as products of the destruction process, while no destruction was observed when the process was investigated under a nitrogen atmosphere. 

A. T. Pudzianowski and G. H. Loew, /. Phys. Chem., 87, 1081 (1983). Hydrogen Abstractions from Methyl Groups by Atomic Oxygen. Kinetic Isotope Effects Calculated from MNDO/UHF Results and an Assessment of Their Applicability to Monooxygenase-Dependent Hydroxylations. 

Liu, K. E., Johnson, C. C., Newcomb, M., and Lippard, S. J., 1993, Radical clock substrate probes and kinetic isotope effect studies of the hydroxylation of hydrocarbons by methane monooxygenase, J. Am. Chem. Soc. 115 939n947. 

Perdenteration of the methylene hnker affords a relatively kinetically stable complex, which allows for the monitoring of exogenons snbstrate oxidations. When (7) is exposed to cold (-95 °C) acetone solntions of the lithium salts of para-substituted phenolates, clean conversion to the corresponding o-catechols is observed. Deuterium kinetic isotope effects (KIEs) for these hydroxylation reactions of 1.0 are observed, which is consistent with an electrophilic attack of the peroxo ligand on the arene ring. An electrophilic aromatic substitution is also consistent with the observation that lithium jo-methoxy-phenolate reacts substantially faster with (7) than lithium / -chloro-phenolate. Furthermore, a plot of observed reaction rates vs. / -chloro-phenolate concentration demonstrated that substrate coordination to the metal center is occurring prior to hydroxylation, and thus may be an important feature in these phenolate o-hydroxylation reactions. 

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