Abstract
Multistep hydrogen isotope exchange reactions, such as the Γonization of a carbon acid via a carbanion intermediate in a protic solvent, when conducted using an isotopic tracer to monitor the exchange, have the unusual feature that their rateβdetermining steps always refer to the transfer of the tracer isotope and never to the isotope present in macroscopic amounts. This property of these reactions is discussed and rationalized using a free energy versus reaction coordinate diagram. It is further shown that this property does not invalidate a commonly used method of measuring kinetic isotope effects on carbon acid ionization in which rates of incorporation of tritium tracers into RH and RD substrates are compared, despite the fact that tritium transfer is rate determining in both exchanges, but it is valid only if initial rate measurements are used. When the comparison is made in a protio solvent, e.g., H~2~O, the portion of the initial reaction which may be used depends strongly on the magnitude of the isotope effect. It ranges from less than 1% tritium incorporation for large isotope effects to 10% or more for isotope effects near unity. On the other hand, when a deuterated solvent, e.g., D~2~O, is used, the range of validity of the method for large isotope effects is extended dramatically.