Kinetic modelling of synthesis of N-aminopiperidine from hydroxylamine-O-sulfonique acid and piperidine

A new route to synthesize N-aminopiperidine (NAPP) from hydroxylamine-O-sulfonique acid (HOSA) and piperidine was described. Kinetics of the reaction was investigated to optimize the conditions of the synthesis. Since the reaction is fast, this study was carried out in a diluted medium (10⁻³ to 10⁻² mol/l). To determine the concentration of the reaction product, NAPP was allowed to react with formaldehyde and the product was analysed by UV and HPLC techniques. The formation of NAPP is consistent with the first-order reaction to two reagents, governed by the nucleophilic substitution via SN2 mechanism. Oxidation of NAPP by HOSA was identified as the main secondary reaction which consistently reduced the yield of NAPP. A number of differential equations were elaborated and solution of these equations serves to predict the behavior of the system as a function of the reagent concentrations, pH and temperature. From the corresponding mathematical treatment a unique implicit expression was derived that characterizes the reaction medium. It was found that the [PP]₀/[HOSA]₀ molar ratio (p), the initial concentrations of [PP]₀ and [HOSA]₀, the ratio of rate constants k ₂/k ₁ and temperature are the only parameters that affect the yield of NAPP from HOSA. The results calculated from this model are in good agreement with the experimental data and they can be used to determine the optimal conditions of the reaction.