Reaction Progress at the Transition State for Nucleophilic Attack on Esters

Article abstract of DOI:10.1021/ja00545a023

β-Deuterium isotope effects (k_CH3/k_CD3) at 25 deg C in aqueous solution for reaction of the following nucleophiles and substrate acetate esters are as follows: CH3CO2(-), 2,4-(NO2)2C6H3O2CCL3 (L = H,D), 0.950 +/-0.008; C6H5O(-), 4-NO2C6H4O2CCL3, 0.971 +/-0.020; C6H5O(-), 2,4-(NO2)2C6H4O2CCL3, 0.968 +/-0.009; HO(-), 4-NO2C6H4O2CCL3, 0.970 +/-0.009; HO(-), C6H5O2CCL3, 0.980 +/-0.009.These are consistent with fractions of reactant progress at the transition state of 0.37, 0.21, 0.22, 0.22, and 0.15, respectively.Agreement is reasonably good with fractions of reaction progress estimated from α-deuterium isotope effects in formate ester reactions, measured by Cordes et al.For the nucleophilic reaction of water with C6H5O2CCL3, protolytically catalyzed by CH3CO2(-), the β-D effect is 0.914 +/-0.023 (fraction of reaction progress 0.65).This corresponds well with fractions of reaction progress of 0.58-0.66 from α-D effects for carboxylate general catalysis of three formate ester hydrolyses, studied by Cordes et al.For very strong bases (pK > 12) reacting as nucleophiles, the value of β_nuc(ca. 0.2) is similar to, or smaller than, the fraction of reaction progress estimated from the isotope effects (ca. 0.2-0.4).The value of β_nuc for nucleophilic reactions of weaker bases (pK = ca. 8-11) is larger than the fractions of reaction progress calculated from isotope effects (0.2-0.4 while β_nuc = ca. 0.7).This evidence is consistent with negative deviations both for aryloxide ions and for strongly basic nucleophiles such as alkoxide and hydroxide ions from a hypothetical line of β_nuc greater than 0.2 but smaller than 0.7.The major reason for negative deviation of aryloxide ions is probably disproportionate loss of resonance energy and of alkoxide ions is disproportionate loss of solvation energy, upon nucleophilic binding at the transition state.These two factors may be linked and may not be entirely separable.