Alcohol deuterium isotope effect

To explore the mechanism of allylic hydroxylation, three probe substrates, 3,3,6,6-tetradeuterocyclohexene, methylene cyclohexane, and /l-pinenc, were studied (113). Each substrate yielded a mixture of two allylic alcohols formed as a consequence of either retention or rearrangement of the double bond. The observation of a significant deuterium isotope effect (4-5) in the oxidation of 3,3,6,6-tetradeuterocyclohexene together with the formation of a mixture of un-rearranged and rearranged allylic alcohols from all three substrates is most consistent with a hydrogen abstraction-oxygen rebound mechanism (Fig. 4.48). 

Prakash et al. (1985) used the deuterium isotope effect on the l3C NMR spectrum of [47] to provide further evidence for the symmetrical, homoaromatic nature of this ion. They prepared the specifically deuterated trishomocyclopropenyl cation [57] by superacid treatment of the corresponding alcohol [58]. The 13C NMR spectrum of [57] displayed a triplet for the deuterated methine only 0.2 ppm to higher field than the undeuterated methine, indicating only an isotopic perturbation of resonance and not a rapidly equilibrating classical ion system (see Siehl, 1987). 

Ru" (0)(N40)]"+ oxidizes a variety of organic substrates such as alcohols, alkenes, THE, and saturated hydrocarbons. " In all cases [Ru (0)(N40)] " is reduced to [Ru (N40)(0H2)] ". The C— H deuterium isotope effects for the oxidation of cyclohexane, tetrahydrofuran, 2-propanol, and benzyl alcohol are 5.3, 6.0, 5.3, and 5.9 respectively, indicating the importance of C— H cleavage in the transitions state. For the oxidation of alcohols, a linear correlation is observed between log(rate constant) and the ionization potential of the alcohols. [Ru (0)(N40)] is also able to function as an electrocatalyst for the oxidation of alcohols. Using rotating disk voltammetry, the rate constant for the oxidation of benzyl alcohol by [Ru (0)(N40)] is found to be The Ru electrocatalyst remains active when immobilized inside Nafion films. 

It was shown that the patterns of the relative rates of reaction of DPC and DPC with alcohols are essentially identical and followed the relative acidity of the alcohols (MeOH > /-PrOH > f-BuOH) and showed a kinetic deuterium isotope effect on reaction with the OH bond (Table 9.13). These results indicate that DPC attacks the O—H bond rather than the C—H bond of the alcohol. If the C—H bonds of the alcohol were attacked by DPC, as in the ground triplet state reaction, then one would expect 2-propanol would react faster than methanol. Lack of any dis-cernable quenching of DPC by diethyl ether and THF indicates that DPC ... 

In contrast, the acid-catalyzed hydrolysis of alkyl selenates is A-2158. The actual species which undergoes decomposition to alcohol and sulfur trioxide is probably the zwitterion as in the case of phosphate monoester monoanions. Evidence for sulfur trioxide as the reactive initial product of the A-1 solvolysis is obtained from the product compositions arising with mixed alcohol-water solvents. The product distribution is identical to that found for sulfur trioxide solvolysis, with the latter exhibiting a three-fold selectivity for methanol. Although the above entropies of activation and solvent deuterium isotope effects do not distinguish between the conventional A-l mechanism and one involving rate-limiting proton transfer, a simple calculation, based on the pKa of the sulfate moiety and the fact that its deprotonation is diffusion controlled. 

Of the numerous nicotinamide model studies done since about 1970, the one that had perhaps the greatest impact on mechanistic thinking revealed a discrepancy between the kinetic deuterium isotope effect and the H/D ratio in the alcohol product formed upon reduction of trifluoroacetophenone by 4-protio- and 4-deuterio-A-alkyl-l,4-dihy-dronicotinamides (Scheme 2) (71JA6694). For example, while the reduction of... 

Two types of inhibitors, pyrazoles and imidazoles (with E-NAD+) and iso-butyramide (with E-NADH), form tight ternary complexes with E-coenzyme, allowing single turnover to be observed (through photometry at 290 nm or fluorescence caused by NADH) and thus titration of the active sites (see Section 9.2.3.). Pyrazole and isobutyramide are kinetically competitive with ethanol and acetaldehyde, respectively. If the reaction E + NADH + aldehyde is run in the presence of a high concentration of pyrazole, the complex E-NAD+ formed by dissociation of alcohol immediately binds pyrazole for a single turnover only. Under favorable conditions, a single NADH oxidation can be observed by stopped-flow techniques to find a kcat of about 150 s 1 and a deuterium isotope effect kD 4 as expected (see Section 9.2.5). 

Flynn, K. G. and Neortas, D. R. Kinetics and mechanism of reaction between phenyl isocyanate and alcohols - strong base catalysis and deuterium isotope effects, J. Org. Chem., 1963, 28, 3527-3530. 

In a study of the effect of azide ion on the solvolysis of 2-octyl brosylate in aqueous acetone, Raaen et al. (1974) showed that the a-deuterium isotope effects for both the alcohol and azide produced were almost identical (1-097 0-007 and 1-106 0-007 respectively). These results imply that the rate determining step(s) for formation of alcohol and azide are either identical or very similar. A likely explanation is that the two products are formed in parallel... 

The role of steric factors has been examined in the opening of polyfluorinated oxiranes. Accounts have been given of the alcoholysis of steroid oxiranes and their transformation with phenol.The kinetics of the reactions of oxiranes with alcohols and phenols have been reported in a number of publications. The catalytic influence of transition metals has been examined. A secondary deuterium isotope effect has been studied in the course of methanolysis, and the solvent effect has been considered in reactions with phenols. ... 

Deuterium isotope effects on chemical shifts of phenols of which the OH proton has been exchanged by deuterium can be measured in two different ways. If the OH(D) proton is exchanging slowly (see Section II.B) two different resonances are observed, one due to the protio and one due to the deuterio species (see Figure 1). The relative intensities will depend on the H D ratio, perhaps not in a quantitative way due to fractionation (see Section II.O). If exchange is fast on the NMR time scale only one resonance for the X-nuclei (e.g. C) is observed, the position of which depends on the H D ratio. In order to determine the isotope effects properly, a series of experiments must be conducted varying the H D ratios of the exchanging species, typically 1 5, 1 2, 1 1, 2 1 and pure solvent . The exchanging species is typically H2O D2O but could equally well be deuteriated alcohols, ROD. 

General base catalysis of Sn 2-type reactions of ordinary aliphatic alcohols by oxy-anions is observed in the cydization of 4-chlorobutanol [26], and of the sulfonium cation 2.6 [27] (Scheme 2.12) at 50 °C and 40 °C, respectively. (Amine buffers prefer to demethylate 2.6.) In all cases (including the reaction of 2.5 discussed above) catalysis by oxyanions shows a low solvent deuterium isotope effect and a Bronsted coefficient p of 0.26 + 0.1. This reaction may be something of a curiosity, but there is little doubt that it has been properly identified. 

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