Rapid acid-catalysed and uncatalysed hydration of ketenimines

Abstract

The rates of hydration of a series of ketenimines (9) have been examined in water (µ 1.0; 25°) over the pH range 2–13. Three mechanisms of hydration to the amides (8) were noted: (a) general acid catalysis by proton transfer from H₃O⁺ in the pH range 2–7 (giving k_H3O⁺/k_D3O⁺ 2.65); (b) general acid catalysis by H₂O at pH > 7 (where k_H2O⁺/k_D2O⁺= 4.8); (c) rate-determining HO^– attack. The last mechanism was only shown by N-arylketenimines, e.g.(9e); other N-alkylketenimines continue to react by rate-determining proton transfer from water even at pH 13. This result is confirmed by the incorporation of just one deuterium when (9a) reacted in acidic or basic D₂O, while the deuteriated ketenimine (9f) does not loose the label on reaction in water. Substituent effects are parallel for reactions involving H⁺ transfer from H₃O⁺ or H₂O; the major effects are obtained on changing substituents at carbon (the protonation site). For example, replacement of C–H by C–Me reduces the reactivity by 10–20-fold, while replacement of C–Me by C–Ph reduces the rate of hydration by > 100-fold. Ammonium ions also generally react with ketenimines by rate-determining H⁺ transfer to the ketenimine followed by trapping of the nitrilium ion formed by the free amine. Only with the strongest amine base studied (piperidine) does direct nucleophilic attack on the ketenimine compete.