CONCERTED OR STEPWISE MECHANISMS FOR ACYL TRANSFER-REACTIONS OF P-NITROPHENYL ACETATE - TRANSITION-STATE STRUCTURES FROM ISOTOPE EFFECTS

Isotope effects have been measured for the acyl transfer reactions of p-nitrophenyl acetate (PNPA) with the oxyanion nucleophiles hydroxide, phenolate, and the anion of hexafluoroisopropyl alcohol; with the sul fur anions of mercaptoethanol and methyl 3-mercaptopropionate; and wit h the nitrogen nucleophile methoxyethylamine. The kinetic isotope effe cts measured were the oxygen-18 isotope effects in the carbonyl oxygen , (18)k(carbonyl), and in the phenolic oxygen atom of the leaving grou p, (18)k(lg); the beta-deuterium isotope effect in the acetyl group, ( D)k; and the nitrogen-15 isotope effect in the leaving group, (15)k. T he equilibrium phenolic oxygen-18 (K-18(eq) = 1.0277 +/- 0.0007) and n itrogen-15 (K-15(eq) = 1.0016 +/- 0.0006) isotope effects for the equi librium between p-nitrophenolate anion and PNPA were also determined. The (15)k and (18)k(lg) kinetic isotope effects for the hydroxide reac tion with PNPA are smaller than for the other oxyanion nucleophiles, s uggesting an earlier transition state. For the other oxyanion nucleoph iles (15)k was about 1.0010, versus near unity for the sulfur nucleoph iles; (18)k(carbonyl) for oxyanions ranged from 1.0039 to 1.0058; vers us from 1.0117 to 1.0119 for thiolates. Values for (18)k(lg) were betw een 1.0182 and 1.0210 for oxyanions, and 1.0172 and 1.0219 for thiolat es. The (D)k effects were between 0.9481 and 0.9617 for oxyanions, and 0.9765 and 0.9780 for thiolates. The transition state structures impl ied by these data are consistent with studies by others using phenolat e nucleophiles which concluded that the acyl transfer process is conce rted, with no intermediate. The isotope effect data indicate that the transition state for the reaction with phenolate is not substantively different from that with an aliphatic oxyanion nucleophile of similar pK(a). The reactions with thiolate nucleophiles have a considerably di fferent transition state structure, characterized by greater loss of t he carbonyl pi-bond and the maintenance of more positive charge on the carbonyl carbon atom. The degree of transition state bond cleavage to the leaving group is similar for oxyanion and thiolate nucleophiles. Acyl transfer to the nitrogen nucleophile methoxyethylamine gave (15)k = 1.0011, (18)k(lg) = 1.0330, (18)k(carbonyl) = 1.0064, and (D)k = 0. 9682. These data require that bond fission to the leaving group is wel l advanced in the rate-limiting step.