Hydrazines from diazonium compounds

The ligand NNR has been referred to as alkyl- or arylazo, diazo, or diazenato, but diazenido is preferred. The aryl compounds are commonest they can be obtained from diazonium compounds (ArN2) and from hydrazines such as PhNNH2 or ArC(0)NNH. They are also formed by electrophilic or nucleophilic attacks on dinitrogen compounds, for example,... 

Complete protonation of dinitrogen results in hydrazine, which can bind throngh either one (11) or both (bridging) N atoms, but high oxidation state metals are readily rednced. The nomenclature for substituted hydrazines is very confusing (63-67). Three types of hgands are available with a formal double bond between the two N atoms (1) diazenido (6), obtained from diazonium compounds (ArN2+),... 

Toluene from Toluidine.—It is often desirable to obtain tbe hydiocarbon from the base. The process of diazotisntion offers the only convenient method. The diazonium salt may be reduced by alcohol (Reaction 1, p. 162) or, as in the piesent instance, by sodium stannite. Less direct methods are the con-veision of the diazonium compound into (i) the hydrazine (see p. 174), (2) the acid and distillation with lime (p. 200), (3) the halogen derivative and reduction with sodium amalgam, 01, finally (4) the phenol and distillation with zinc dust. 

P-coupling occurs in the formation of azophosphonic esters [ArN2PO(OCH3)2] from diazonium salts and dimethyl phosphite [HPO(OCH3)2] (Suckfull and Hau-brich, 1958). P-coupled intermediates are formed in the reaction between diazonium salts and tertiary phosphines, studied by Horner and Stohr (1953), and by Horner and Hoffmann (1956). The P-azo compound is hydrolyzed to triphenylphosphine oxide, but if a second equivalent of the tertiary phosphine is available, phenyl-hydrazine is finally obtained along with the phosphine oxide (Scheme 6-26 Horner and Hoffmann, 1958). It is likely that an aryldiazene (ArN = NH) is an intermediate in the hydrolysis step of the P-azo compounds. 

This reaction can be employed to remove a primary amino group from an aromatic compound, especially. when the ordinary method of direct reduction of the diazonium compound by sodium stannite or alcohol is not applicable. Although in the application of this method the hydrazine can be prepared as the hydrochloride, and reduced in the same solution, yet it is better to isolate the free base and oxidise it separately, since in the oxidation of the hydrochloride there is a tendency for the hydrazine radical to be replaced by chlorine. 

The present, straightforward, two-step synthesis of 5.6-dimethoxyindazole from 3,5-dimethoxyacetophenone illustrates the usefulness of this amination reaction. With standard chemistry the introduction of a hydrazine group into the acetophenone molecule would have required four steps 1) nitration, 2) reduction of the nitro group to the aniline, 3) diazotization and 4) reduction of the diazonium compound to the hydrazine. 

Several reactions of the triazepine (7) have been examined. Heating (7) at 80°C in benzene results in isomerization to form quantitatively benzo[c]dnnoline iV-imide (8), which is also obtained directly from the diaminobiphenyl (5) by aprotic diazotization without isolation of the triazepine intermediate (7). The triazepine (7) reacts as a masked diazonium compound with hydrazine, hydriodic acid, hydrobromic acid and copper, or diethyl malonate to give the corresponding products (9)-(12), respectively (Scheme 2). 

This reaction was initially reported by Dutt, Whitehead, and Wormall in 1921. It is the preparation of aromatic azide via the basic hydrolysis of aromatic diazoaminosulfinate that can be easily synthesized from aromatic diazonium salt and arylsulfonamide or alkyl-sulfonamide. Therefore, this reaction is known as the Dutt-Wormall reaction. Similarly, azides can be prepared via the cleavage of compounds from diazonium salt with ammonia, hydrazine," hydroxylamine, etc. 

Since A,A -disubstituted hydrazines are readily available from a variety of sources (see Volume I, Chapter 14), their dehydrogenation constitutes a widely applicable route to both aliphatic and aromatic azo compounds. Such oxidative procedures are of particular value in the aliphatic series because so many of the procedures applicable to aromatic compounds, such as the coupling with diazonium salts, have no counterpart. The oxidation reactions permit the formation not only of azoalkanes, but also of a host of azo compounds containing other functional groups, e.g., a-carbonyl azo compounds [83], a-nitrile azo compounds [84], azo derivatives of phosphoric acid [85], phenyl-phosphoric acid derivatives [86],... 

Isocyanates and isothiocyanates are reduced to methylamines on treatment with LiAlH4. LiAIH4 does not usually reduce azo compounds622 (indeed these are the products from LiAIH4 reduction of nitro compounds, 9-67), but these can be reduced to hydrazo compounds by catalytic hydrogenation or with diimide623 (see 5-9). Diazonium salts are reduced to hydrazines by sodium sulfite. This reaction probably has a nucleophilic mechanism.624... 

The esters also react readily with aryl hydrazines to give aryl hydrazone derivatives. Examples of the latter were first synthesized (prior to the availability of tetraalkyl carbonylphosphonates) from tetraalkyl methylenebisphosphonates and aryl diazonium salts, analogously to the phosphonoglyoxylate hydrazone synthesis described in a previous section. First made as possible precursors in a ketone synthesis, several of these compounds, converted to free acid salts by treatment with BTMS followed by dicyclohexylamine in methanol, proved to have unexpected inhibitory activity vs the pyrophosphate-dependent phospho-fructokinase of the parasite T. gondii, which causes a potentially lethal opportunistic infection in immunocompromised persons such as AIDS patients [94]. In fact, the 2,4-dinitrophenylhydrazone of carbonylbisphosphonic acid (as the tetrasodium salt) dramatically abated toxoplasmosis lesions in infected human foreskin fibroblasts [94]. Animal toxicity in this compound, probably arising from in vivo hydrolysis to the highly toxic hydrazine, precluded its future development, but the result remains an interesting lead. 

PCBs are produced synthetically by chlorinating the biphenyl (Figure 9.1) with anhydrous chlorine in the presence of iron filings or ferric hydroxide as a catalyst. The crude product is distilled with alkali to remove color, traces of HCl, and the catalyst, resulting in a mixture of chlorobiphenyls with a varying number of chlorine atoms per molecule. Chlorobiphenyls could also be synthesized from (i) arylation of aroyl peroxides, diazonium salts, phenyl hydrazines, and other aryl compounds, (ii) aryl condensation reactions, (iii) addition of chlorine to biphenyl systems, (iv) decarboxylation, and (v) dechlorination reactions. 

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