The β-Hydrogen Secondary Isotope Effect in Acyl Transfer reactions. Origins, Temperature Dependence, and Utility as a Probe of Transition-State Structure

Article abstract of DOI:10.1021/ja00526a039

The anomalous temperature dependence of the β-deuterium (β-D) secondary isotope effect reported by Halevi and Margolin for the hydroxide-promoted hydrolysis of ethyl acetate has been observed also with methyl acetate 3H/k_3D = 1.01 +/- 0.02 (0 deg C), 0.90 +/- 0.02 (25 deg C), 1.03 +/- 0.10 (50 deg C)>.In contrast, the β-D effects for the rates of acidic hydrolysis of methyl acetate (0.93 +/- 0.02, 0-42 deg C), basic hydrolysis of phenyl acetate (0.98 +/- 0.02, 5-45 deg C), basic methanolysis of phenyl acetate (0.98 +/- 0.02, 5-40 deg C), basic methanolysis of p-methoxyphenyl acetate (0.96 +/- 0.02, 5-45 deg C), and the equilibrium hydration of 1,3-dichloroacetone (ClCH2COCH2Cl vs.ClCD2COCD2Cl: K_4H/K_4D = 0.83 +/- 0.02, 15-46 deg C) over the indicated temperature ranges were statistically indistinguishable from the mean values cited.This constitutes "regular", expected behavior.Both kinds of cases are consistent with a cascade model for acyl-transfer reactions in which solvent-reorganization and heavy-atom-reorganization transition states along parallel reaction paths alternate in dominating rate limitation in the 0-70 deg C temperature range.Such a model also explains anomalous temperature dependences of solvent isotope effects for anhydride hydrolyses, reported by Rossall and Robertson.Observed transition-state properties would refer to a virtual, weighted-average, transition-state structure, according to the cascade model.