Acid-catalysed aryl hydroxylation of phenylazopyridines: reaction intermediates, kinetics and mechanism 1

Abstract

A kinetic and product analysis study of the reactions of the three isomeric phenylazopyridines (PAPys) in aqueous sulfuric acid media (30-97 wt% H 2 SO 4 ) 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 azo-compound and two reduced amines, is similar to that found in the disproportionation of di-psubstituted hydrazinobenzenes observed in benzidine rearrangement studies. Consequently it has been proposed that the corresponding [NЈ-(4-hydroxyphenylhydrazino)]pyridines were formed as reaction intermediates in the present system; this is confirmed by showing that [NЈ-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 ~72 wt% H 2 SO 4 for 4-PAPy and ~86 wt% H 2 SO 4 for 2-PAPy. To facilitate the kinetic analysis, values of pK BH 2 2؉ for the protonation of the substrates and the possible hydroxy products at the azo-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 HSO 4 ؊ ion or one H 2 O molecule in the activated complex. The proposed mechanism thus involves nucleophilic attack of HSO 4 ؊ or H 2 O at an aryl carbon of the diprotonated substrate in the slow step, resulting in an intermediate hydrazo species which gives the observed products in a subsequent fast step (cf. benzidine rearrangement).

Acid-catalysed disproportionation and benzidine rearrangement of phenylhydrazinopyridines: reaction pathways, kinetics and mechanism 1

“…9 Thus the product distribution found for the reaction of 1 indicates that only disproportionation is occurring. In the accompanying study 6 we have found that 1 is involved as the central intermediate in the reaction of 4-(phenylazo)pyridine (4) in aqueous sulfuric acid (Scheme 3). It was proposed that hydroxylation (k h ) is the slow step since 1 was not observed spectrally in the repetitively scanned UV-VIS spectra in the reaction of 4; if hydroxylation (k h ) was fast and disproportionation (k d ) was the rate-determining step, then the hydrazo intermediate would accumulate and be spectrally observable.…”

“…This large rate difference accounts for the fact that 1 is not observed spectrally in the reaction of 4. 6 Reaction of 4-(NЈ-phenylhydrazino)pyridine, 2. Since we have found that 1 gives rise to the corresponding azo product 3 via disproportionation, it follows by analogy that 2 is the precursor in the formation of 4.…”

“…[7][8][9] Evidence was presented that the hydroxylation of a phenylazopyridine involves formation of a phenylhydrazinopyridine as a transient reaction intermediate, which subsequently undergoes fast disproportionation to the observed oxidized and reduced products. 6 In the present work we have synthesized the surmised intermediate, 4-[NЈ-(4-hydroxyphenylhydrazino)]pyridine 1, as well as 4-(NЈ-phenylhydrazino)pyridine 2, and subjected them to the acid media used in the former study 6 in order to determine the products and evaluate the kinetics. Our study has revealed a sequence of reactions.…”

“…All the compounds synthesized were characterized by a combination of 1 H and 13 C NMR, UV and mass spectroscopic methods as before. 6 Compounds and products were purified by several techniques, recrystallization, column and thin layer chromatography (TLC) using silica gel 60 F 254 plates (BDH) in various eluting solvent systems. The products of the reactions of 1 and 2 in 65 wt% aq.…”

“…H 2 SO 4 were identified by direct isolation as previously described. 6 The structural identification of the semidine 5, formed during the reaction of 2, was achieved using The kinetic techniques used were similar to those previously described. 6…”