The chemistry of nitroso-compounds. Part 17. Formation of N-nitrosamines in solution from dissolved nitric oxide in the presence of hydriodic acid or metal iodides

Abstract

The rapid formation of N-nitrosamines from the reaction of N-methylpiperazine, morpholine, and piperidine with nitric oxide (NO) in the presence of Hl (Kl plus HCl), neutral metal iodides, and acid halides plus Kl is reported for ethanolic and aqueous ethanolic solutions at 25 °C. Spectroscopic studies show that a feature common to all these reactions is the oxidation of iodide ion to molecular iodine by NO under acidic conditions with concurrent formation of nitrous oxide (N₂O). Since interaction of NO with iodine produces nitrosyl iodide (NOl), this reagent is considered to form the N-nitrosamine by reaction with unprotonated amine. Kinetic studies with N-methylpiperazine in the presence of Kl and HCl suggest that the formation of nitrosyl iodide and its interaction with the N-methylpiperazinium ion are rate-limiting under neutral and mildly acidic conditions, respectively. This gives a complicated kinetic–acidity dependence with a maximum rate at pH *ca. 2.1. When NO is not bubbled into the reaction solution continuously, there is strong evidence that diffusion of NO from the gaseous phase becomes ratelimiting for the fastest reactions. Because of their higher basicity, significant reaction by morpholine and piperidine is only observed with equimolar Kl and HCl where passage of NO effectively neutralises the solution by converting Hl into I₂, H₂O, and N₂O. In the presence of Znl₂, N-methylpiperazine, morpholine, and piperidine in EtOH all react readily with NO at 25 °C to give limiting yields of N-nitrosamine in ca. 25 min. Reaction also proceeds in aqueous EtOH but not significantly in MeCN, which suggests that initial solvolysis of Znl₂ to Hl is important. This conclusion is supported by observation that N-nitrosamine formation is rapid in the presence of soluble (e.g. Fel₂, Snl₄, Bil₃) compared to insoluble metal iodides (e.g. Pdl₂, Mnl₂, Cdl₂, Cu₂l₂). The formation of N-nitrosopiperidine is promoted less readily by ZnBr₂ than Znl₂, and to an even lesser extent by ZnCl₂, Zn(OAc)₂, and ZnSO₄. Independent measurements confirm that Hl is oxidised to I₂ by NO in solution. This effectively neutralises the solution by converting Hl into H₂O.