Rate and equilibrium constants for oxazolidine and thiazolidine ring-opening reactions

Rate and equilibrium constants have been measured for opening and closing 2-[(4 dimethylamino)phenyl]- 1,3-oxazolidinc and-thiazolidine rings to form iminium ions in aqueous solution at 2 5 O. Comparing rates of closure of the oxazolidine ring with attack of external hydroxide ion on the iminium ion yields a ratio of rate constants of 25 for intra- and inter-molecular attack of oxyanion nucleophiles in this endo-cyclic ring-closure reaction. This ratio is significantly lcss than the factor of 103-104 commonly observed for similar exo-cyclic ring closures and is consistent with the presence of ring strain in the endo-cyclic transition state as envisaged in Baldwin’s rules. Changes in N-alkyl substituent (Me, Et, Bu, Pri, But and phenyl) lead to mild (and parallel) changes in reaction rates and equilibrium constants for oxazolidine ring closure. For the corresponding thiazolidine rings, comparison of the N-H thiazolidine derivative of benzaldehyde with N-butyl and N-phenyl derivatives of cinnamaldehyde shows a much larger variation in rate constants for ring closure with N-substituent (lO*-fold), but still small changes in equilibrium constants and rate constants for attack of hydroxide ion upon the iminium ion (<loo-fold). This surprising contrast in kinetic and equilibrium behaviour is discussed in terms of non-bonded interactions in the transition state for ring-closure reactions