Structure-Reactivity Studies on the Equilibrium Reaction between Phenolate Ions and 2-Aryloxazolin-5-ones: Data Consistent with a Concerted Acyl-Group-Transfer Mechanism

Article abstract of DOI:10.1021/ja00542a028

The rate and equilibrium constants for the reaction between phenolate anions and 2-aryloxazolin-5-ones have been measured as a function of the structures Ar and Ar'.The change in "effective" charge on both phenol-leaving oxygen and endocyclic oxygen from ground to transition state, as determined from the relevant Broensted parameters, is substantial and essentially additive consistent with a concerted displacement mechanism.The stepwise mechanism requires a small change in effective charge on the phenol oxygen because departure of phenolate ion from the tetrahedral intermediate cannot be rate limiting.Hydroxide ion attack on the C-5 atom of the oxazolinone to yield a benzoylglycine has a Hammett ?^- dependence which can only arise from a concerted displacement; the rate-limiting step for the stepwise mechanism is the addition of hydroxide and the transition state of the rate-limiting step will therefore not involve much endocyclic C-O bond fission.An inverse deuterium oxide solvent isotope effect indicates that the observed general-acid catalysis has a specific-acid/nucleophilic mechanism; both hydroxide and oxonium ion catalysis are demonstrated by using 18O-labeling experiments to involve nucleophilic attack at the carbonyl (C-5) center.The equilibrium constant for reaction of azide ion with 2-phenyloxazolin-5-ones has been measured; it is suggested that the absence of racemization during azide coupling in peptide synthesis is related to the very unfavorable equilibrium constant for oxazolinone formation compared with that of activated oxygen esters.