Tetrahedral Intermediate in Acyl Transfer Reactions. A Revaluation of the Significance of Rate Data Used in Deriving Fundamental Linear Free Energy Relationships

Article abstract of DOI:10.1021/ja00389a051

A theoretical investigation of model mechanisms applicable to acyl transfer reactions in solution has shown that the interpretations of experimental rate constants in terms of mechanistic constants are all subject to an ambiguity that is well-known in principle but usually ignored or incorrectly evaluated in practice.For all models involving reversibly formed tetrahedral intermediates, the experimental constants are products of the form k_ff_p in which k_f is equal to k_i+>ⁿ or to k_i and f_p is a product distribution fraction.Each assesible pH range can give a maximum of one constant that depends on the pH; there is no way to dissect out the desired mechanistic constants or the equilibrium constants for several tetrahedral intermediates unless some independent means can be developed to measure the f_p.These conclusions are of major concern to all studies that attempt to relate reactivity to structure.Representative acyl transfer reactions have been reinterpreted.One example of the so-called trialkyl lock acceleration is now shown to amount to a factor of about 4000 for the mechanistic rates in contrast to the factor of 5*10¹⁰ originally proposed.Most of the decrease in estimate arises from recent reevaluations on observed rates, but there is a further decrease by a factor of 100 in the mechanistic rates due to considerations treated in present study.Evidence is also presented that certain acyl transfer reactions in solution may proceed by direct displacement rather than though a reversibly formed tetrahedral intermediate.