Benzidine rearrangement mechanisms

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. 

The conversion of a hydrazobenzene into a diaminodiphenyl upon treatment with acid is termed the benzidine rearrangement. The following mechanism for the formation of benzidine from hydrazobenzene appears reasonable ... 

Two other theories as to the mechanism of the benzidine rearrangement have been advocated at various times. The first is the rc-complex mechanism first put forward and subsequently argued by Dewar (see ref. 1 pp 333-343). The theory is based on the heterolysis of the mono-protonated hydrazo compound to form a n-complex, i.e. the formation of a delocalised covalent it bond between the two rings which are held parallel to each other. The rings are free to rotate and product formation is thought of as occurring by formation of a localised a-bond between appropriate centres. Originally the mechanism was proposed for the one-proton catalysis but was later modified as in (18) to include two-protons, viz. 

A. Cooper, Mechanism of the benzidine rearrangement, Ph. D. Thesis, London, 1966. 

Diaminobiphenyl is formed by a completely different mechanism, though the details are not known. There is rate-determining breaking of the N—N bond, but the C—C bond is not formed during this step. The formation of the o-semidine also takes place by a nonconcerted pathway. Under certain conditions, benzidine rearrangements have been found to go through radical cations. 

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... 

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. 

The mechanism of this elegant, surprising, and widely applicable synthesis of indole derivatives was only explained recently (R. Robinson). It must be assumed that the keto-phenylhydrazones, in tautomeric hydrazo-form, undergo a species of benzidine rearrangement which, like the latter, can often occur even in dilute acid solution, e.g. with the phenylhydrazone of pyruvic acid. 

Details of the mechanism of the ort/zo-benzidine rearrangement were examined using the two hydrazonaphthalene derivatives 17 and 1817,21. Both showed nitrogen and carbon... 

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. 

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. 

The bimolecular reduction of nitro compounds is believed to involve reduction of some of the starting material to a nitroso compound and another portion to either a substituted hydroxylamine or an amine. These intermediates, in turn, condense to form the azo compound. The exact mechanism of the reaction requires critical study. On the one hand, reducing conditions are always on the alkaline side to prevent the benzidine rearrangement of an intermediate hydrazo compound under acidic conditions, yet it is difficult to visualize the formation of hydrazo compounds by the indicated condensation. As a practical matter, this method is of value only if symmetrically substituted azo compounds are desired. 

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