Secondary equilibrium isotope effects acidity

This chapter is a review of secondary equilibrium isotope effects (IEs) on acidity, primarily on the comparison of protium with deuterium (and also tritium), but also addressing the IEs of 13C, 14C, 15N, and lsO. Secondary IEs are those where the bond to the isotope remains intact, whereas primary IEs are those where the bond is broken. Primary isotope effects are generally... 

C.L. Perrin, Secondary equilibrium isotope effects on acidity, Adv. Phys. Organic Chem. 44 (2010), pp. 123-171. 

The a-secondary IE of two deuteriums on the rate of base-catalyzed CD exchange of toluene, 3A ( PhC112D)/k(PhCD is 1.31, and the [3-secondary D IE on the rate of base-catalyzed a-C-D exchange of ethylbenzene, k(PhCHDCH3)//t(PhCHDCD3), is 1.11 0.03.58 Similarly, from the rates of base-catalyzed a-C-D exchange of tolucne-a,4-r/2, -a,2,4,6-c/4, and -a,2,3,4,5,6-d6 and with an assumption of linearity of IEs, the contributions of ortho, meta, and para deuteration lead to rate retardations of 2.4, 0.4, and 1.8%, respectively.59 These are all kinetic IEs, but to the extent that the transition state resembles closely the carbanion, or to the extent that the reverse reprotonation is encounter-controlled and independent of isotopic substitution, these kinetic IEs represent equilibrium IEs on acidity. The IEs were interpreted in terms of an electron-donating inductive effect of D relative to H. 

With the phenomena already discussed we are in a position to understand observed isotope effects in many acid- and base-catalyzed reactions. These isotope effects can operate in three main ways. First, there can be a secondary isotope effect arising from more effective solvation by H2O than D2O. Second, the equilibrium... 

---