Acid-catalysed aryl hydroxylation of phenylazopyridines: reaction intermediates, kinetics and mechanism

A kinetic and produce analysis study of the reactions of the three isomeric phenylazopyridines (PAPys) in aqueous sulfuric acid media (30-97 wt% H2SO4) is reported. The final products obtained from the reaction of 4-(phenylazo)pyridine (4-PAPy) are the hydroxylated product 4-(4-hydroxyphenylazo)pyridine, the reduction products 4-aminophenol and 4-aminopyridine, and a small amount of a dimerized product. 3-(Phenylazo)pyridine is unreactive, but 2-(phenylazo)pyridine gives the equivalent 2-(4-hydroxyphenylazo)pyridine, 4-aminophenol and 2-aminopyridine products. This product pattern, an oxidized ate-compound and two reduced amines, is similar to that found in the disproportionation of di-p-substituted hydrazinobenzenes observed in benzidine rearrangement studies. Consequently it has been proposed that the corresponding [N'-(4-hydroxyphenylhydrazino)]pyridines were formed as reaction intermediates in the present system; this is confirmed by showing that [N-4-(4-hydroxyphenylhydrazino)pyridine synthesized independently gave the same products as 4-PAPy under the same conditions. The kinetic study shows that the 4-isomer reacted faster than the 2-isomer at all the acid concentrations investigated (the 3-isomer being inert). Rate maxima are observed, at similar to 72 wt% H2SO4 for 4-PAPy and similar to 86 wt% H2SO4 for 2-PAPy. To facilitate the kinetic analysis, values of pK(BH22+) for the protonation of the substrates and the possible hydroxy products at the ate-group were determined, using the excess acidity method; the first protonation occurs on the pyridine nitrogen in the pH region. An excess acidity analysis of the observed pseudo-first-order rate constants as a function of acidity indicate an A2 mechanism, with the diprotonated substrate and either one HSO4- ion or one H2O molecule in the activated complex. The proposed mechanism thus involves nucleophilic attack of HSO4- or H2O at an aryl carbon of the diprotonated substrate in the slow step, resulting in an intermediate hydrate species which gives the observed products in a subsequent fast step (cf. benzidine rearrangement).