Benzidine rearrangement reaction

As pointed out, the dihydrazozene would undergo a rapid benzidine rearrangement reaction to benzidine. When the nucleophile is water, which is also a good nucleophile, the product would be p-aminophenol (PAP), which is produced from the hydrolysis reaction of the nitrene cation according to the reaction. 

Kim s benzidine rearrangement reactions of polyether tethered cyclic X,X -diaryl hydrazides... 

Hydrazobenzene 1 (1,2-diphenyl hydrazine) is converted to benzidine 2 (4,4 -diaminobiphenyl) under acidic conditions.This unusual reaction is called the benzidine rearrangement, and can be observed with substituted diphenyl hydrazines as well. 

Heating of an aryl hydrazone 1 in the presence of a catalyst leads to elimination of ammonia and formation of an indole 2. This reaction is known as the Fischer indole synthesisy and is somewhat related to the Benzidine rearrangement. 

It is important for acid-catalysed reactions to determine whether the reaction is specifically catalysed by hydrogen ions or whether general acid catalysis takes place. Specific acid catalysis has been conclusively demonstrated for the benzidine rearrangement by three different sorts of kinetic experiments. In the first, it has been shown41 by the standard test for general acid catalysis (by measuring the rate of reaction in a buffered solution at constant pH over a range of concentration... 

Secondly, it has been found that the benzidine rearrangement is subject to a solvent isotope effect d2o/ h2o > 1- If a proton is transferred from the solvent to the substrate in a rate-determining step the substitution of protium by deuterium will lead to a retardation in the rate of reaction (primary isotope effect) whereas if a proton is transferred in a fast equilibrium step preceeding the rate-determining step as in... 

There is one further piece of kinetic evidence which throws light on an aspect of the benzidine rearrangement mechanism, and this is comparison of the rates of reaction of ring-deuterated substrates with the normal H compounds. If the final proton-loss from the benzene rings is in any way rate-determining then substitution of D for H would result in a primary isotope effect with kD < kH. This aspect has been examined in detail42 for two substrates, hydrazobenzene itself where second-order acid dependence is found and l,l -hydrazonaphthalene where the acid dependence is first-order. The results are given in Tables 2 and 3. 

Other evidence, for instance the observation of a semidine as one of the reaction products,256 led to the realization that the reaction is a benzidine disproportionation, such as those observed when benzidines with two p-substituents are subjected to benzidine rearrangement conditions 260,261 this also very conveniently explains the products formed. The mechanism is given in Scheme 13.258... 

Scheme 13 may look unfavorable on the face of it, but in fact the second two reactions are thermally allowed 10- and 14-electron electrocyclic reactions, respectively. The aromatic character of the transition states for these reactions is the major reason why the benzidine rearrangement is so fast in the first place.261 The second bimolecular reaction is faster than the first rearrangement (bi-molecular kinetics were not observed) it is downhill energetically because the reaction products are all aromatic, and formation of three molecules from two overcomes the entropy factor involved in orienting the two species for reaction. 

Micellar rate enhancements of bimolecular, non-solvolytic reactions are due largely to increased reactant concentrations at the micellar surface, and micelles should favor third- over second-order reactions. The benzidine rearrangement typically proceeds through a two-proton transition state (Shine, 1967 Banthorpe, 1979). The first step is a reversible pre-equilibrium and in the second step proton transfer may be concerted with N—N bond breaking (17) (Bunton and Rubin, 1976 Shine et al., 1982). Electron-donating substituents permit incursion of a one-proton mechanism, probably involving a pre-equilibrium step. 

As a result of these heavy-atom KIE experiments the principal features of the benzidine rearrangements have now been firmly established. The two main products arise from two parallel reactions one of which is concerted and the other is not. Other concerted processes have been identified and all of the concerted processes can be readily classified in the terminology of sigmatropic rearrangements within the general class of percyclic reactions. 

The benzidine rearrangements can also be brought about thermally, but very few mechanistic studies have been carried out. One set of heavy-atom KIE measurements has been made in the reaction of 2,2 -hydrazonaphthalene (18)21. Substantial nitrogen (1.0611 for the [15N, 15N ]) and carbon (1.0182 for the [1,1 -13C2]) KIE values were obtained showing that, just as for the acid catalysed reaction, this is a [3,3]-sigmatropic rearrangement, this time presumably of the non-protonated reactant. 

In some way formally similar to the benzidine rearrangement is the Wallach rearrangement of azoxybenzene 23 to give 4-hydroxyazobenzene 24 in concentrated (typically 95%) H2SO4. The 2-hydroxy isomer is sometimes formed in low yield with some substituted azoxybenzenes, and it is the main product in the photochemically induced reaction. Much of what is known about the reaction has been covered in earlier review articles28-30. This contribution will report work published since 1981. 

Disproportionation (equation 13) is one of the side reactions that can occur in benzidine rearrangements. Shine and coworkers measured the nitrogen and carbon kinetic isotope effects for the disproportionation reaction of 4,4 -diiodohydrazobenzene, which only yielded disproportionation products, at 25 °C in 70% aqueous dioxane that was 0.376 M in perchloric acid29. The reaction was first order in hydrazobenzene and it has been assumed that an intermediate was involved in the disproportionation reaction. This intermediate must be one of a radical ion30 (equations 14 and 15), a jr-complex31 (equation 16) or a quinonoid structure32 (equation 17). 

Shine and coworkers36 also investigated the mechanism of the one-proton benzidine rearrangement of 2,2/-dimethoxyhydrazobenzene. The doubly labelled 2,2 -dimethoxy-[15N,15N]hydrazobenzene, the 2,2 -dimethoxy-[4,4 2H2]hydrazobenzene and the 2,2 -dimethoxy-[4,4 13C2]hydrazobenzene required for this study were synthesized using the reactions in Schemes 15, 16 and 17, respectively. 

The most recent addition to Shine s extensive study of the benzidine-type rearrangements41 involved remeasuring the nitrogen and the carbon-13 and carbon-14 kinetic isotope effects at the 4- and at the 4- and 4 -carbons as well as determining the carbon-13 and carbon-14 isotope effects at the 1- and at the 1- and l -carbons in the benzidine rearrangement of hydrazobenzene (equation 30). The reaction, which was carried out in 75% aqueous ethanol that was 0.1 M in hydrochloric acid and 0.3 M in lithium chloride at 0°C, gave an 86% yield of benzidine (11) and a 14% yield of diphenyline (12). The kinetic isotope effects found for the formation of benzidine and diphenyline under these reaction conditions are presented in Table 5. 

All ECi adsorption coupled mechanisms have been verified by experiments with azobenzene/hydrazobenzene redox couple at a hanging mercury drop electrode [86,128,130]. As mentioned in Sect. 2.5.3, azobenzene undergoes a two-electron and two-proton chemically reversible reduction to hydrazobenzene (reaction 2.202). In an acidic medium, hydrazobenzene rearranges to electrochemically inactive benzidine, through a chemically irreversible follow-up chemical reaction (reaction 2.203). The rate of benzidine rearrangement is controlled by the proton concentration in the electrolyte solution. Both azobenzene and hydrazobenzene, and probably benzidine, adsorb strongly on the mercury electrode surface. 

Benzidine yellow is an example of a large class of organic pigments that contain an azo linkage, -N=N-. Its synthesis relies very heavily on diazonium salt coupling reactions and the benzidine rearrangement. Although benzidine is banned in the U.S. because of suspected... 

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