ADDITION OF HYDROXYLAMINE TO CYCLOHEXANONE AND BICYCLIC KETONES - STERIC, ELECTRONIC AND HYDROGEN-BONDING EFFECTS ON THE GENERAL MECHANISM OF ADDITION OF AMINES TO CARBONYL-COMPOUNDS

Three different types of pH-rate profiles were observed for the addition of amines to carbonyl compounds, depending on the relative predominance, at weakly acidic pH, of either a concerted or a stepwise mechanism. The predominant mechanism depends on the basicity of the amine and the mutual equilibrium affinity for adduct formation between the carbonyl compound and the amine. The reaction of hydroxylamine with cyclohexanone and bicyclic ketones was studied in order to examine the roles of steric and electronic effects in this mechanism. Cyclohexanone and 3-chlorobicyclo [2.2.1]heptan-2-one exhibit the profile expected for a single change in the rate-determining step with increasing pH from uncatalysed attack of the amine on the carbonyl group to hydronium ion-catalysed dehydration of the carbinolamine. In contrast, both bicyclo [2.2.1]heptan-2-one and bicyclo [2.2.2]octan-2-one show an unexpected profile with two negative breaks and five kinetically significant regions. This profile is explained by stabilization of the zwitterionic intermediate T+/- by intramolecular hydrogen bonding, leading to the formation of the carbinolamine by a stepwise mechanism at weakly acidic pH.