Structure-Reactivity Studies on the Equilibrium Reaction between Phenolate Ions and 2-Aryloxazolin-5-ones: Data Consistent with a Concerted Acyl-Group-Transfer Mechanism
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.
Curran, Terence C,Farrar, Charles R.,Niazy, Omima,Williams, Andrew
p. 6828 - 6837
(2007/10/02)
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