Kinetic study of the formation and rupture of stable tetrahedral intermediates. CO, CN and CS bond formation

Measured pseudo‐first‐order rate constants for intramolecular formation of tetrahedral intermediates from N ‐2‐hydroxyethylphthalimide, N ‐2‐aminoethylphthalimide and N ‐2‐thioethylphthalimide at pH > 6 are reported. The reaction is specific and general base catalysed, with β(Brønsted) values 0·44, 0·52 and 0·52 respectively. From a plot of log k b (general base rate constants) vs γ′ [the affinities of EtXH (X = O, NH, S) toward the carbonylic carbon], β′ nuc values of 0·01 (with OH − as specific base), 0·25 (with imdidazole as general base) and 0·27 (with HPO   4 2−as general base were obtained). The observed relationships p xy = ϑβ′/ − ϑp K a = −ϑ(Brønsted)/ϑγ′ = 0·03 is supported by the predictions of an energy contour diagram, which, on extrapolation to a non‐stable tetrahedral intermediate, predicts a late and slightly protonated transition state for the cleavage process. At pH < 3, these intermediates cleave to yield only the corresponding diacylimides. These reactions are general base and acid catalysed with β > 0·3 and α < 0·1. A fast equilibrium between the intermediate and its N ‐protonated (amide) form is reached. The general base rupture of the latter is faster than that of the corresponding non‐protonated intermediate by a factor of ca 10 9 − 10 10 ‐fold.