Aromatic rings, oxidation isotope effects

Aromatic hydrocarbons are mainly hydroxylated to phenolic products. Complex (12) hydroxylated benzene in MeCN at 20 °C into phenol in ca. 55% yield, and no isotope effect was found for this reaction. Hydroxylation of toluene mainly occurs at the ring positions, with minor amounts of benzylic oxidation products. Hydroxylation of 4-deuterotoluene by (12) occurred with 70% retention and migration of deuterium in the formation of p-cresol. This high NIH shift value is in the same range as that found for liver microsome cytochrome P-450 hydroxylase, and suggests the transient formation of arene oxide intermediates. 

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. 

In some instances, particularly in hydroxyla-tions meta to a halide substituent, the hydrogen on the hydroxylated carbon is quantitatively lost (i.e., there is no NIH shift), and a small deuterium kinetic isotope effect is observed These hydroxylations could result from direct oxygen insertion into the C-H bond, as in a true hydrox-ylation mechanism, but they are more likely to result from oxidation of the aromatic ring without the formation of a discrete epoxide intermediate. Isotope effect studies with deuterated benzenes bearing a variety of substituents have shed some light on this process A small, normal isotope effect is observed for weta-hydroxylation when deuterium is located meta- to the halogen in chlorobenzene = 1.1-1.3), but a small,... 

Sen and coworkers have examined systems based on Pd(OAc)2 in triflic acid (TfOH) at 80 °C (equation 5). Na2Cr207/Pd(0Ac)2/Tf0H aromatizes cyclohexanes for example, decalin gives naphthalene (9%) and a-tetralone (4%). Normally the functionalization product of an alkane is more reactive than the alkane itself and so only the low conversion prevents the initial product from being oxidized further. Shilov and Sen s use of triflic acid in this context means that the initial functionalization product at the alcohol oxidation level is protected as the triflate ester, which is relatively insensitive to oxidation. 1,4-Dimethylbenzene is oxidized to triflates with a 50 1 preference for oxidation at the ring rather than of the side chain, unlike the selectivity expected in a radical process. A kinetic isotope effect of 5 was measured. In certain cases the reaction can be... 

However, evidence contradictory to the arene oxide intermediate has been reported [128]. The kinetic isotope effects on the PAH-catalyzed oxygenation have been studied using three deuterium-labeled phenylalanines, [4- H]-, [3,5- H]-, and [2,3,4,5,6- H]phenylalanine. It is expected that the yield of tyrosine with [4- H]phenylalanine decreases relative to that with non-labeled substrate because of kinetic isotope effect, and that the decrease in the yield of tyrosine is balanced by a commensurate increase in the amounts of 3-hydroxyphenylalanine if the reaction occurs via an arene oxide intermediate. The kinetic isotope effects obtained from the experiments, however, are actually 1.22 for the formation of tyrosine and 1.01 for that of 3-hydroxyphenylalanine, indicating that the amount of 3-hydroxyphenylalanine is not affected by the deuteriumlabeling at 4-position of the aromatic ring and is independent of the consumption of tyrosine. The experiments with the other labeled substrates also supported the independent formation of tyrosine and 3-hydroxyphenylalanine. Thus, these results... 

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