Kinetic Analysis of the Ring Opening of an N-Alkyloxazolidine. Hydrolysis of 2-(4-Methylphenyl)-2,3-dimethyl-1,3-oxazolidine

Article abstract of DOI:10.1021/jo00335a004

Hydrolysis of the title oxazolidine, III, occurs in two separate reaction stages, reversible ring opening to a cationic Schiff base, IV, followed by a considerably slower formation of hydrolysis products.The ring opening occurs in an H⁺-catalyzed reaction and in a pH-independent reaction, with the crossover between the two occurring at about pH 5.A general acid catalyzed pathway (α = 0.70) is also observed.The equilibrium constant (pK_I(+)) for IV * III + H⁺ is 7.45, this number being obtained spectroscopically and in a kinetic analysis.The kinetic analysis also furnishes a dissociation constant (pK_SH(+)) for the protonated oxazolidine of 6.19, the difference between pK_SH(+) and pK_I(+) showing that after attainment of equilibrium the conjugate acid of III is a 19:1 mixture of cationic Schiff base and protonated oxazolidine.The formation of hydrolysis products involves rate-limiting addition of water or hydroxide ion to IV, although a small percentage of a reaction via an oxocarbonium ion derived from C-N cleavage of the protonated oxazolidine cannot be ruled out.Rate constants for the water and hydroxide addition are slower than their intramolecular counterparts, this being particulary true in comparing hydroxide ion reactions.This occurs despite the fact that the ring closure is a supposedly disfavored 5-endo-trigonal process.