HEAVY-ATOM ISOTOPE EFFECTS ON THE ALKALINE-HYDROLYSIS AND HYDRAZINOLYSIS OF METHYL BENZOATE

A double-labeling procedure has been devised for use in measurement of heavy-atom isotope effects. This method is of particular value for measurement of isotope effects at sites which are not easily amenable to study by standard isotope-ratio techniques. Substrate is synthesized which is highly labeled at two positions-one the position of interest in the isotope effect experiment and the other a position whose isotope effect is easily measured by standard isotope-ratio methods. This labeled substrate is mixed with unlabeled substrate, and the “isotope effect” is measured for the measurable site. This apparent isotope effect is actually the product of the isotope effect at the measurable site and that at the site of interest. Separate measurement of the former isotope effect then permits calculation of the isotope effect at the site of interest. Heavy-atom isotope effects on the hydrolysis and hydrazinolysis of methyl benzoate at 25 °C in aqueous solution have been measured by this procedure, using the methyl carbon atom as the measurable site. In the alkaline hydrolysis the carbonyl oxygen isotope effect is k16/k18 = 1.0046 ± 0.0020;, the carbonyl carbon isotope effect is k12k13 = 1.0426 ± 0.0026; the ether oxygen isotope effect is k16/k18 = 1.0062 ± 0.0006; the methyl carbon isotope effect is k12/k13 = 1.0004 ± 0.0005. For the hydrazinolysis at pH 7.9 the values are carbonyl oxygen, 1.0184 ± 0.0014; carbonyl carbon, 1.0410 ± 0.0022; ether oxygen, 1.0413 ± 0.0028; methyl carbon, 1.0022 ± 0.0004. These isotope effects indicate that the rate-determining step in the alkaline hydrolysis is the formation of the tetrahedral intermediate. The small magnitudes of the oxygen isotope effects require that the transition state in this step be relatively reactant-like. The isotope effects on the hydrazinolysis indicate that the decomposition of the tetrahedral intermediate is rate determining and that the transition state for this step is relatively product-like. © 1979, American Chemical Society. All rights reserved.