when the first step is slow, but once the anion is formed the product quickly follows (k2 ≫ k−1[conjugate acid]). This leads to an irreversible first step but unlike E1cBanion, deprotonation is rate determining. Kinetic isotope effect Deuterium Deuterium exchange and a deuterium kinetic isotope effect can help distinguish among E1cBrev, E1cBanion, and E1cBirr. If the solvent is protic and contains deuterium in place of hydrogen (e.g., CH3OD), then the exchange of protons into the starting material can be monitored. If the recovered starting material contains deuterium, then the reaction is most likely undergoing an E1cBrev type mechanism. Recall, in this mechanism protonation of the carbanion (either by the conjugate acid or by solvent) is faster than loss of the leaving group. This means after the carbanion is formed, it will quickly remove a proton from the solvent to form the starting material. If the reactant contains deuterium at the β position, a primary kinetic isotope effect indicates that deprotonation is rate determining. Of the three E1cB mechanisms, this result is only consistent with the E1cBirr mechanism, since the isotope is already removed in E1cBanion and leaving group departure is rate determining in E1cBrev. Fluorine-19 and carbon-11 Another way that the kinetic isotope effect can help distinguish E1cB mechanisms involves the use of 19F. Fluorine is a relatively poor leaving group, and it is often employed in E1cB mechanisms. Fluorine kinetic isotope effects are also applied in the labeling of Radiopharmaceuticals and other compounds in medical research. This experiment is very useful in determining whether or not the loss of the leaving group is the rate-determining step in the mechanism and can help distinguish between E1cBirr and E2 mechanisms. 11C can also be used to probe the nature of the transition state structure. The use of 11C can be used to study the formation of the carbanion as well as study its lifetime which can not only show that the reaction is a two-step E1cB mechanism (as opposed to the concerted E2 mechanism), but it can also address the lifetime and stability of the transition state structure which can further distinguish between the three different types of E1cB mechanisms. Aldol reactions The most well known reaction that undergoes E1cB elimination is the aldol condensation reaction under basic conditions. This involves the deprotonation of a compound containing a carbonyl group that results in the formation of an enolate. The enolate is