Heavy-atom isotope effects on the alkaline hydrolysis and hydrazinolysis of methyl benzoate

Abstract

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/sup 0/C in aqueous solution have been measured, using the methyl carbon atom. In the alkaline hydrolysis the carbonyl oxygen isotope effect is k/sup 16//k/sup 18/ = 1.0046 +- 0.0020; the carbonyl carbon isotope effect is k/sup 12/k/sup 13/ = 1.0426 +- 0.0026; the ether oxygen isotope effect is k/sup 16//k/sup 18/ = 1.0062more » +- 0.0006; the methyl carbon isotope effect is k/sup 12//k/sup 13/ = 1.0004 +- 0.0005. For the hydrozinolysis at pH 7.9 the valuesare 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.« less