Isopropyl alcohol, isotope effect

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. 

The kgjko isotope effect for the solvolysis of chloromethyl methyl ether in isopropyl alcohol at 0° is 1.24 + 0.08 per deuterium atom " . This is in the range of other unimolecular reactions. The values of and AS for the chloroether in isopropyl alcohol are 10.7 0.6 kcal.mole" and —28.8 + 1.6 eu, respectively. In contrast, the corresponding values for solvolysis of alkyl chlorides are in the range of about 20-25 kcal.mole and —4 to —12 eu. The lower values of A/f and AS for the solvolysis of chloromethyl methyl ether are tentatively attributed to the double bond character between oxygen and carbon at the transition state (see above) . 

The isopropyl group of ezlopitant, which bears a 2-methoxy-5-isopropylbenzylamino group, is oxidized by both CYP3A4 and CYP2D6 to the tertiary alcohol and the desaturated 1-methylvinyl moiety . The alcohol was specifically shown not to be a precursor of the unsaturated product, and a small primary isotope effect was observed when deuterium was placed at the benzylic but not methyl carbons of the isopropyl group. Although not studied in detail, concurrent hydroxylation and... 

While the evidence on bromination of acetone merely confirmed a mechanism that was already considered highly likely on other grounds, the deuterium isotope effect contributed very importantly to work on the mechanism of oxidation of isopropyl alcohol by chromic acid (Westheimer and Nicolaides, 1949). The isotope effect was 6.7 when the hydrogen on the carbinol carbon was replaced by deuterium. Other evidence had indicated that a chromate ester of isopropyl alcohol was an intermediate. The isotope effect showed that its decomposition to acetone and a lower valence state of chromium was the slow step [Eq. (28) ] ... 

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