Acyl Substituent Effects on Rates of Acyl Transfer to Thiolate, Hydroxide, and Oxy Dianions

Article abstract of DOI:10.1021/ja00410a032

The rates of transfer of a series of polar aliphatic acyl groups (-0.3 (*) (*) (*) 1.05) from p-nitrophenol to hydroxide, to the thiol anion of N-acetyl-L-cysteine, and to a series of phosphonate dianions have been determined in aqueous solution.The rate constants for the alkaline hydrolysis of ten p-nitrophenyl esters can be correlated reasonably well (r = 0.981) to the single-parameter Hammett-Taft equation based on the polar substituent constant.The reaction constant for the alkaline hydrolysis is (*) = 2.9 with an interval estimator (90percent confidence) of +/-0.3.The (*) value for the thiolysis reaction is only slightly larger (16 +/- 13percent) than the corresponding value for the alkaline hydrolysis reaction.These kinetic (*) values are essentially identical with the equlibrium (*) for hydroxide or thiolate addition to aldehydes (Kanchuger and Byers).To the extent that gem diolate and thiohemiacetalate formation are appropriate model reactions for the formation of the anionic tetrahedral intermediates in the corresponding acyl transfer reactions, the magnitude of the kinetic (*) values suggests that the transition states for the alkaline hydrolysis and for the thiolysis reactions are similar, in geometry and charge distribution, to the intermediates.Acyl transfer from p-nitrophenol to phosphonate dianions involves an uncatalyzed nucleophilic displacement by the oxy dianion.The (*) value for the reaction of (chloromethyl)phosphonate with the p-nitrophenyl esters is 2.4 (+/-0.3).The second-order rate constants for the reactions between the phosphonates and p-nitrophenyl acetate, p-nitrophenyl chloroacetate, and p-nitrothiophenyl acetate show a small sensitivity to the basicity (pK_a2) of the nucleophile (β_nuc ca. 0.3).An explanation of the magnitudes of the (*) and β_nuc values, and of the anomalously low reaction rates (relative to oxy monoanions and amines of comparable basicities) for acyl transfer to the phosphonates, is that electrostatic interactions and desolvation of the oxy dianion make substantial contributions to the activation energy barrier for nucleophilic attack.