N-hydroxy-compounds as acyl transfer agents. Part 1. Kinetics and mechanism of nucleophilic displacements on 1-hydroxybenzotriazole esters and crystal and molecular structure of 1-benzoyloxybenzotriazole

Abstract

1-Hydroxybenzotriazole esters (3) show surprisingly rapid acyl transfer to HO^–, H₂O, and to primary amines; the reactions are ca. 10³-fold faster than with p-nitrophenyl esters where the leaving group has a similar pK_a. The acylating ability of (3) is therefore akin to that of anhydrides or N-acylimidazoles. No evidence however was found to indicate that the esters exist in the N-acyl form (9) or (10) and an X-ray crystallographic study on (3; X = H, R = Ph) shows the O-acyl structure : in solution this ester retains the spectral characteristics of the solid. The ρ value for HO^– attack on (3; X = H), is + 1.83 while electron-withdrawing substituents in the hydroxybenzotriazole leaving group also enhance the reactivity of the ester (ruling out a nitrenium ion mechanism). For aminolysis β_Nuc= 0.80 (primary amines) and 0.92 (α-effect amities). For water attack on (3; R = Ar), the Hammett ρ=+ 1.39, while k_H2O/k_D2O= 2.2 and general base catalysis by acetate ion and by tertiary amines (where β= 0.46) is observed. Carbonate esters (3; R = PhO) show similar enhanced reactivity as do N-protected amino-acid esters (3; R = CH₂NHCO₂CH₂Ph or CH₂NHCOPh); the i.r. spectrum of the N-benzoyloxycarbonylglycine ester is unusual however in that no carbonyl absorptions >1 800 cm^–1 were observed in the solid or solutions.