Kinetics and Mechanism of Diazotization

Secondary aliphatic amines form stable N-nitrosoamines, however, and therefore, their investigation will be discussed briefly in this section, although N-nitroso derivatives of secondary aliphatic amines do not fall within the scope of this book. We will see that kinetics and mechanisms of nitrosation of secondary amines display many similarities with the diazotization of primary aromatic amines. 

A potentially very important use for HF Py was developed by Yoneda and coworkers, who used this complex as an efficient diazotization agent on route to various fluoroaromatics (equation 17). This variation of the old Balz-Schiemann reaction can be carried in chlorobenzene where HF Py is not soluble but the resulting soluble ArF enables a flow reaction to be devised31. This was successfully tested on various pyridines as well32 and, because of the reaction importance, its mechanism and kinetics were carefully studied33. 

The kinetics of diazotization 2 and the reaction of nitrous acid with alkyl amines 1 is consistent with this interpretation of the mechanism of reaction. 

Aminopyridines, aminopyridine oxides, and 3-aminoquinoline are obviously diazotized by analogous mechanisms. Kalatzis (1967 b) studied the diazotization of 4-aminopyridine over a very large range of acid concentrations (0.0025-5.0 m HC104). This compound is comparable to 2-aminothiazole in its acid-base properties the heterocyclic nitrogen is easily protonated at pH 10, whereas the amino group is a very weak base (pKa = -6.5). Therefore, the kinetics indicate that the (mono-protonated) 4-aminopyridinium ion reacts with the nitrosyl ion. The... 

Neither the 2- nor 4-aminopyridine-l-oxides nor their substitution products can be protonated at the heterocyclic nitrogen. The findings regarding the diazotization kinetics of these compounds indicate that, under the reaction conditions studied by Kalatzis and Mastrokalos (1977), two simultaneous mechanisms take place. In the first of these, nitrosyl ions attack the free amine, whereas in the second they attack the protonated amine. 

The kinetics of the diazotization of 4-aminopyridine in 0.0025-5.0 M perchloric acid were studied, and the reaction was believed to proceed by only one mechanism whose kinetic form is first order with respect to the amine as well as to nitrous acid. The rate of the reaction showed an exponential catalytic dependence on the concentration of added perchloric acid and sodium perchlorate. In solutions of constant ionic strength the rate was directly related to the acidity function Hq). The 4-diazonium ion was characterized as 4-(2-hydroxy-l-naphthylazo)pytidine. When 4-aminopyridine is diazotized and treated with Ar,7 A-dimethylaniline, 4-(p-dimethylaminophenylazo)pyridine (DC-95) is obtained. 2-(p-Dimethylaminophenyl)pyridine is isolated when 2-aminopyridine is used instead of 4-aminopyridine. ... 

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