Diazotization kinetics

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. 

We begin the discussion on deaminations of open-chain amines with the only case in which the rate-limiting step is the formation of the alkanediazonium ion. This brings us to the evaluation of compounds in which the amino group is attached to C(l) of an -alkane. Two relatively recent investigations of Fishbein s and Kirmse s groups (Hovinen and Fishbein, 1992 Brosch and Kirmse, 1991), using diazotization kinetics of methylamine and the deamination products of two stereochemically pure 1-amino [1- H] alkanes, respectively, elucidated clearly fundamental problems of... 

The work of Hantzsch and Schumann apparently showed that diazotization is a second-order reaction. As it was carried out in relatively acidic media, it was assumed only too readily that the ammonium form of the amine reacts with free, undissociated nitrous acid. This would correspond to the kinetic equation of Scheme 3-2. ... 

Schmid (1936 a) was the first to observe a third-order reaction in the diazotization of aromatic amines in the presence of sulfuric acid, and he proposed the kinetic equation of Scheme 3-3. In subsequent work (1936b, 1937 Schmid and Muhr, 1937), he investigated the course of the reaction in dilute hydrochloric or hydrobromic acid, which could be described by incorporating an extra term for the halide ion with only a first-order dependence on (HNO2), as in Scheme 3-4. 

Although Hammett convincingly explained the nitrosation of aliphatic amines and the diazotization of aniline under the conditions employed by Schmid and others, one unsatisfactory point remained namely the second-order kinetic equation obtained by Hantzsch and the workers who followed him for diazotization in a more weakly acidic medium. Comparison of experimental details shows that at concentrations of free mineral acid below 0.05 m the reaction is apparently second-order, but it becomes third-order at higher concentrations of acid. 

The deuterium isotope effect is thought to arise from the effect on the equilibrium position of this A-nitrosation. This is also the case for the diazotization of aniline, but the isotope effect is larger, because two deprotonations are involved in the kinetics. 

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... 

The classical discoveries of the reacting nitrosation reagents mentioned above were mainly the result of kinetic investigations. There were some surprising results, e.g. the dependence of the diazotization rate on the square of the nitrous acid concentration in sulfuric or perchloric acid up to 0.3 M. Nitrous acid is a fairly weak acid (pK = 3.1569). Therefore, the low concentration of nitrite ions in the last step of the nitrous acid equilibria system of Scheme 5 does not appear to favor the formation of dinitrogen trioxide. N2O3 is, however, strongly indicated by the second order of rate on the (analytical) nitrous acid concentration. 

For a representative and relatively recent example of a comparative kinetic investigation of diazotization of aniline and 1-naphthylamine with various catalysts X-, reference is made to the work of Castro and coworkers98. These authors found that the (overall) rates decrease under comparable conditions in the order X = Cl- > Br- > N()2 >... 

Diazotization is a complex reaction (Scheme 1). When performed in acidic media with sodium nitrite, NOx or nitrosyl halides, its kinetics are dependent upon the acidity of the medium in media with a Hammett acidity constant (-H0) from — 1 to 3 the reaction rate increases with acidity and the formation of the nitroso cation is the rate-limiting step, in more acidic media (-H0 > 4) the reaction rate decreases when acidity increases and the deprotonation of intermediate 6 is the rate-limiting step.6-9... 

The first evidence for the involvement of these nitrosyl halides in nitrosation came from kinetic studies of diazotization. The rate equation for diazotization in aqueous hydrochloric and hydrobromic acids includes the kinetic term given in (15) where S stands for the free amine (Schmid, 1937 Schmid and Muhr, 1937). It was later recognized that this can be interpreted as the attack of the nitrosyl halides on the free amine (Hammett, 1940) and the kinetic term was rewritten as (16).7 The corresponding rate coefficients and activation energies calculated from the equilibrium concentration of the nitrosyl halides are given in Tables 3 and 4 together with later results (Williams, 1977). 

A number of the conjugate acids of aromatic amines also undergo diazotization with the kinetic form of equation (19) but these species are much less reactive than the free amines and are therefore excluded from the present discussion. In these reactions, the interaction of NO+ with the protonated amine appears to facilitate the proton loss. 

A kinetic study of the coupling of imidazole with diazotized sulfanilic acid in buffered aqueous solution has been performed.161... 

Binks and Ridd164 have made a complete kinetic study of the reaction of indole with several diazotized amines (p-nitroaniline, p-chloroaniline, sulfanilic acid, and aniline). Only the reaction with p-nitrodiazonium salt exhibits a simple kinetic form (pseudo first-order reaction) in the other cases the kinetics appear to be due to the superposition of two reactions, a normal azo-coupling reaction and an autocatalytic side reaction that removes diazonium ions, but does not form azo compounds. 

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