Isotope effects, permanganate oxidations

Kinetic isotope effect. The oxidation of benzaldehyde by permanganate ions is believed to occur by hydride abstraction. What value of k /kD do you predict for C6H5CHO/ C6H5CDO For C6H5CHO/C6D5CHO ... 

The oxidation by basic permanganate of phenyltrifluoromethyl carbinols which has the same rate law as benzydrol, is characterised by very large primary kinetic isotope effects (c/. Cr(VI) p. 307). 

A few results have been reported on the oxidation of cyclohexanol by acidic permanganate In the absence of added fluoride ions the reaction is first-order in both alcohol and oxidant , the apparent first-order rate coefficient (for excess alcohol) at 25 °C following an acidity dependence k = 3.5-1-16.0 [H30 ]sec fcg/A , depends on acidity (3.2 in dilute acid, 2.4 in 1 M acid) and D2o/ H20 is f-74. Addition of fluoride permitted observation of the reaction for longer periods (before precipitation) and under these conditions methanol is attacked at about the same rates as di-isopropyl ether, although dioxan is oxidised over twenty times more slowly. The lack of specificity and the isotope effect indicates that a hydride-ion abstraction mechanism operates under these conditions. (The reactivity of di-isopropyl ether towards two-equivalent oxidants is illustrated by its reaction with Hg(II).) Similar results were obtained with buffered permanganate. 

A small solvent isotope effect was found by Bell and Onwood kuiolkoiO = 1.08) in contradiction to that of only 0.38 reported by Taylor and Halpern . Over one-third of the oxygen present in the carbonate originated from the oxidant when 0-labelled permanganate was used . The reaction is subject to pronounced catalysis by ferric ions . 

Rosenblatt etal have examined the effect of structure and isotopic substitution upon the permanganate oxidation of some alky famines (Table 4). The isotope effect of 1.84 is considered to be sufficiently low to be compatible with aminium radical-cation formation, and it is felt that, while C-H cleavage is significant for oxidation of primary amines, the dominant mode of oxidation of tertiary amines is electron-transfer, e.g. 

Fig. I. Isotope effect for acid permanganate oxidation of mandelic acid. Temperature = 26.2 °C [MnO -] = 1.4x10- M [H SO ] = 1.69 M.

The authors have also synthesized134 fatty acids labelled with deuterium and carbon-11 in order to investigate if kinetic isotope effects related to fatty acid metabolism can be observed in vivo by pet133,135-137. In vitro, the large kinetic deuterium isotope effects are observed in the oxidation of deuteriated aliphatic carboxylic acids with alkaline permanganate and manganate135-139. 

Experimental studies of the oxidative cleavage of cinnamic acid by acidic permanganate [35] resulted in secondary kinetic isotope effects, kn/kp, of 0.77 (a) and 0.75 (P), while another paper from the same group on the same reaction with quaternary ammonium permanganates [36] reported very different isotope effects of 1.0 (a) and 0.91 - 0.94 (P) depending on the counterion. Different mechanisms were discussed in the literature [37, 38] to explain the variety of experimental results available, but the mechanistic issues were unresolved. The reported activation energy for the oxidation of... 

It can be concluded that the [3+2] pathway seems to be the only feasible reaction pathway for the dihydroxylation by permanganate. The study on the free activation energies for the oxidation of a. P unsaturated carboxylic acids by permanganate shows that the [3+2] mechanism is in better agreement with experimental data than the [2+2] pathway. Experimentally determined kinetic isotope effects for cinnamic acid are in good agreement with calculated isotope effects for the [3+2] pathway, therefore it can be concluded that a pathway via an oxetane intermediate is not feasible. 

The mechanisms of permanganate oxidations have been the subject of a fairly intensive study which has now lasted for almost a century. While many of these studies were carried out in aqueous solutions, much of what was learned is also germane to an understanding of the reactions which occur in phase transfer assisted reactions. Although most of these studies are interrelated they can conveniently be discussed under the following headings products, substituent effects, isotope effects, and solvent effects, with the latter being of particular importance to the phase transfer assisted reactions. 

Table IV. Isotope Effects on the Oxidation of Alkenes by Potassium Permanganate...

Houk, K. N., Strassner, T. Establishing the (3 + 2) mechanism forthe permanganate oxidation of alkenes by theory and kinetic isotope effects. J. Org. Chem. 1999, 64, 800-802. 

Non-peer-reviewed publications are still available on the isotopic effects related to the two main abiotic pathways for ethers, oxidation and hydrolysis under acidic conditions. However, preliminary results on isotopic fractionation associated with the reaction of potassium permanganate (KMn04) with MTBE showed a carbon enrichment factor between -4.2 and -4.9%o [18]. These eC values seem higher than the ones reported upon aerobic biodegradation of MTBE (from -0.28 to -2.4%o) suggesting potentially different reaction pathways and opening new lines of research and discussion for the future. 

Most of our general considerations about hydrogen isotope effects should be equally valid for the transfer of hydride ions or hydrogen atoms, and in fact these classes of reaction have provided much of the evidence for tunnel corrections. Some of it will be summarized briefly here, beginning with solution reactions. Many oxidation reactions are believed to involve hydride ion transfer, and large isotope effects have been reported in the oxidation of l-phenyI-2,2,2-trifluoroethanol by alkaline permanganate (fc //c° = 16,/c /fc = 57, both at 25 C). The activation energies for this reaction are not known accurately, but the reported values lead to — = 2.3 kcal mol A /A = 3.0. The chromic acid oxidation... 

A deuterium kinetic isotope effect of 6.1 was observed in the oxidation of acetaldehyde by permanganate in aqueous HC104, implying a hydride... 

Oxidation of methyl( )-cinnamate with quarternary ammonium permanganates in CH2Cl2 is fastest for the ions which minimize the interionic distance in the quarternary ammonium ion pair. An inverse secondary deuteriom isotope effect was observed. The reaction is initiated by an electrophilic attack, followed by a slower conversion of a 7r-complex to a cyclic manganate(V) diester (2). 

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