Benzidines hydrazo

Benzidine chemistry involves reduction. The nitro precursor is reduced either by zinc and alkali or electrolyticaUy to the hydrazo intermediate, which is then transformed to the benzidine by treatment with acid. 

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. 

Reduction of the nitroaromatic with NaBH4 in DMSO or Zn in NaOH/EtOH leads to the hydrazo derivative and treatment with aqueous HC1 gives benzidine rearrangement.115... 

Alkaline reduction of o-nitro-anisole leads (as in the case of nitrobenzene) to the hydrazo-compound, which undergoes a benzidine trans-... 

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. 

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. 

Further complications of the reduction of aromatic nitro compounds are the possibility of complete reduction to aromatic amines (which may condense with nitroso compounds to give the desired azo compounds), reduction of azo compounds to the corresponding hydrazo compounds, followed by a benzidine (or semidine) rearrangement. It is clear, therefore, that the level of reducing agent used and other reaction conditions are quite critical. 

The bimolecular reduction of aromatic nitro compounds, depending on reaction conditions, may produce azoxy compounds, azo compounds, hydrazo compounds (1,2-diarylhydrazines), benzidines, or amines. Whereas the reduction with zinc and sodium hydroxide leads to azo compounds, zinc and acetic acid/acetic anhydride produces azoxy compounds. Other reducing agents suggested are stannous chloride, magnesium with anhydrous methanol, a sodium-lead alloy in ethanol, thallium in ethanol, and sodium arsenite. 

Hydrazobenzene, 628, 629, 632 conversion into benzidine, 633 Hydrazo compounds, 1074 table of, 1085 ... 

Reaction LI. (a) Action of Acids on the non-para substituted Hydrazo Compounds. (A., 270, 330 287, 97 B 26, 681, 688, 99.)—When hydrazobenzene is treated with mineral acids, an intermolecular rearrangement to benzidine (pj-pg-diaminodiphenyl) takes place. 

This reaction can be extended to almost all non -para substituted hydrazo compounds if one or both para-positions are substituted, either ortAo-benzidine or diphenylamine derivatives known as ortho- or para-semidines are formed. 

Good agitation is essential, and a solvent may be used in some cases. This, however, is not always necessary if the agitation is efficient. The compounds are isolated by dissolving out the zinc with ice-cold hydrochloric acid. The hydrazo compounds, when heated with mineral acids, undergo a rearrangement (benzidine conversion). 

Better yields of azo and hydrazo compounds are sometimes obtained by reducing the azoxy compound in preference to the nitro compound. Certain hydrazo compounds, e.g., hydrazo-naphthalenes, undergo the benzidine conversion (see p. 160) in alkaline as well as in neutral solution, so that the product finally isolated in the reduction is a diamino base. (J. C. S., 125, 1108.)... 

Haussermann 2 reduced nitrobenzene and nitrotoluenes both in alkaline and acid solution, the former with iron, the latter with platinum, electrodes. By reduction in alkaline solution, he obtained as principal product hydrazobenzene and hydrazo-toluene respectively in sulphuric-acid solution he got from nitrobenzene, as chief products, benzidine sulphate and azoxy-benzene, besides an easily changeable body which was not further determined. o-Nitrotoluene3 under like conditions gave o-tolui-dine sulphate besides small quantities of o-toluidine p-nitro-toluene yielded principally p-toluidine. 

The ferrocene nucleus proved to be absolutely unable to undergo the rearrangements characteristic of the benzene ring, so the Claisen rearrangement of allyl ferrocenyl ether 291), the benzidine rearrangement of hydrazo-ferrocene 294-296), and the Sommelet rearrangement in the ferrocene series were all unsuccessful. 

Reductions of aromatic nitro compounds often proceed to generate mixtures of nitroso and hydroxyl-amine products which then condense to form azoxy and, eventually, azo compounds. This bimolecular reduction is practical only for the generation of symmetrically substituted azo compounds. The situation can be further complicated if the reduction continues such that aromatic amines are formed the amines may then condense with the intermediate nitroso compounds to generate hydrazo compounds which can then undergo a benzidine rearrangement. 

As noted, the bimolecular reduction of aromatic nitro compounds may produce azoxy compounds, azo compounds, hydrazo compounds (1,2-diaryIhydrazines), benzidines or amines (Scheme 1) depending on the reaction conditions. Zinc reduction under basic conditions generates azo compounds, whereas the use of acetic anhydride/acetic acid as the solvent system affords symmetrical azoxy compounds. Although unsymmetrical azoxy compounds are accessible in the aliphatic series, aromatic reagents yield only sym-... 

Benzidine Dyes.— The importance of hydrazo compounds in connection with dyes is not on their own account for, as has been stated, they are colorless compounds but because they are easily oxidized to azo compounds which are dye compounds and because of the above rearrangement into compounds like benzidine which yield dyes known as benzidine dyes (p. 787). 

This 4- 4-di-amino di-phenyl is benzidine which yields a very important group of dyes and which is formed by a molecular rearrangement from hydrazo benzene (p. 578). ... 

If, in hydrazo-compounds, the para position to the imido (NH) group is occupied as, e.g., in p-hydrazotoluene, then the benzidine transformation cannot occur. ... 

Some examples of a benzidine-type of rearrangement are known for N-arylamines which, to some extent, may be considered as analogues of hydrazo compounds. Thus, 1-anilinoimidazole (279), on heating in concentrated hydroxhloric acid, is transformed to 4(5)-p-aminophenyl derivative (280) (70ZC289). 

In a series of papers Lewis and co-workers have reported a comprehensive study of the photochemical reactions of azobenzenes in sulfuric acid. In the case of azobenzene itself, the products obtained were benzo[c]cinnoline (48%) together with benzidine (35%), and other azobenzenes gave products derived from the corresponding hydrazo compounds. The mechanism proposed is outlined in Scheme 2. There is an initial rapid establishment of a cis-trans equilibrium of monoprotonated azobenzene, with cyclization involving an excited form (14) of the cis-isomer, the lowest transition now being n-n. In the final step, dehydrogenation of the photocyclization product, 5,6-dihydrobenzo[c]cinnoline, is brought about by a second molecule of azobenzene, which is itself reduced to hydrazobenzene and... 

However, the benzidine and semidine rearrangements may occur in acid solution if the hydrazo stage is not further reduced sufficiently fast, and in such cases it is preferable to carry out the reduction in an alkaline medium. 

Metal and alkali. This method is used mainly for the production of azoxy, azo, and hydrazo compounds. The latter are important in the manufacture of the benzidine series. 

A number of patents have been issued on the catalytic reduction of nitro compounds in the presence of alkali to give hydrazo compounds. These are useful intermediates for the benzidine series by acid rearrangement. 

When nitrobenzene or its homologues are treated in alkaline solution in the presence of finely divided zinc or iron, they can be reduced step by step to the hydrazo stage. Such hydrazo compounds— hydrazobenzene, hy-drazotoluene, hydrazoanisole—may be converted readily to benzidine, tolidine, and dianisidine by intramolecular rearrangement in cold concentrated hydrochloric or sulfuric acid. 

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