Kinetic Solvent Isotope Effect and Proton Inventory Study of the Carbon Protonation of Amine Adducts of Benzylidene Meldrum's Acid and Other Meldrum's Acid Derivatives. Evidence for Concerted Intramolucular Proton Transfer

Article abstract of DOI:10.1021/ja00245a036

Rate constants for carbon protonation of the glycinamide and morpholine adducts of benzylidene Meldrum's acid (T_A^-(gly) and T_A^-(mor)) and of the anions of 5-benzyl and 5-(1-phenylethyl) Meldrum's acid (13 and 14) were determined in H2O and D2O.For protonation by L3O⁺ the kinetic solvent isotope effects for T_A^-(gly) and T_A^-(mor) are very low (0.82 and 0.72 respectively) and about threefold lower than those of 13 (2.48) and 14 (2.52); for protonation by L3⁺NCH2CONH2 the isotope effects are all normal, i.e., 6.01 for T_A^-(gly), 6.57 for 13, and 7.68 for 14.It is shown that the unusually low isotope effects for protonation of T_A^-(gly) and T_A^-(mor) by L3O⁺ are the result of a two-step mechanism which involves equilibrium protonation on the amine nitrogen, followed by rate limiting intramolecular proton switch from nitrogen to carbon.On the basis of this mechanism one may calculate a kinetic isotope effect for the intramolecular proton switch step of 3.66 (T_A^-(gly)) and 3.29 (T_A^-(mor)), respectively.Plausible alternative mechanisms such as carbon protonation by L3O⁺ with transition-state stabilization by hydrogen bonding between the amine nitrogen and L3O⁺, or preequilibrium protonation on the amine nitrogen followed by rate-limiting carbon protonation by water, with transition-state stabilization by hydrogen bonding between the protonated amine nitrogen and the incipient hydroxide ion, are not consistent with the data.A proton inventory on the intramolecular proton switch step shows that the transition state includes a water molecule that acts as a bridge for the proton transfer.On the other hand, the proton inventory on the intermolecular protonation of T_A^-(gly) by L3⁺NCH2CONH2 indicates that the proton transfer is direct, in agreement with prevailing views.