Hydrazo compounds amines

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

Azo-compounds can be obtained by reduction of nitro-compounds, or by oxidation of hydrazo-compounds. They are usually prepared, however, by reacting a phenol or amine with a diazonium salt. The coupling usually takes place in the position para to the hydroxyl or amino group, but if this position is occupied it goes to the ortho position, e.g. 

In catalytic hydrogenation, a compound is reduced with molecular hydrogen in the presence of a catalyst. This reaction has found appHcations in many areas of chemistry including the preparation of amines. Nitro, nitroso, hydroxylamino, azoxy, azo, and hydrazo compounds can all be reduced to amines by catalytic hydrogenation under the right conditions. Nitriles, amides, thioamides, and oximes can also be hydrogenated to give amines (1). Some examples of these reactions foUow ... 

A great variety of solvents has been used with success. Reactive solvents, such as acetic anhydride, will react with the amine as formed. Basic solvents cause the formation of azo, azoxy. and hydrazo compounds, paralleling chemical reductions (39,73). 

It has already been known that the reaction of primary amines with alkaline hypobromite gives nitriles, and the reaction of hydrazo compounds with bromine affords azo compounds. Recently, we also found that the reaction of primary amines and hydrazo compounds with BTMA Br3 in aq. sodium hydroxide or in water gave corresponding nitriles and azo compounds in satisfactory yields, respectively (Fig. 27) (ref. 35). 

Fig. 27. Oxidation of primary amines and hydrazo compounds with BTMA Br3...

Azo, azoxy, and hydrazo compounds can all be reduced to amines. Metals (notably zinc) and acids, and Na2S204, are frequently used as reducing agents. Borane reduces azo compounds to amines, though it does not reduce nitro compounds. " Lithium aluminum hydride does not reduee hydrazo compounds or azo compounds, though with the latter, hydrazo compounds are sometimes isolated. With azoxy compounds, LiAHLj gives only azo compounds (19-48). 

With concentrated mineral acids azobenzene gives red salts, as may be shown by pouring hydrochloric acid on it. Addition of hydrogen leads to the re-formation of the hydrazo-compound. Oxygen is added on and the azoxy-compound formed by the action of hydrogen peroxide or nitric acid. The synthesis of asymmetrical aromatic azo-compounds from nitroso-compounds and primary amines was discussed above. 

Reductions with zinc are carried out in aqueous [160 as well as anhydrous solvents [163 and at different pHs of the medium. The choice of the reaction conditions is very important since entirely different results may be obtained under different conditions. While reduction of aromatic nitro groups in alkali hydroxides or aqueous ammonia gives hydrazo compounds, reduction in aqueous ammonium chloride gives hydroxylamines, and reduction in acidic medium amines (p. 73). Of organic solvents the most efficient seem to be dimethyl formamide [164 and acetic anhydride [755]. However, alcohols have... 

Hydrazo compounds were hydrogenolyzed to primary amines by catalytic hydrogenation over palladium [740]. Since hydrazo compounds are intermediates in the reductive cleavage of azo compounds to amines it is very likely that all the reducing agents converting azo compounds to amines cleave also the hydrazo compounds (p. 96). 

Azo compounds can be reduced either to hydrazo compounds or else cleaved to two molecules of amines. 

Pyridine reacts with sodium hydrazide in the presence of hydrazine to yield 2-hydrazinopyridine in the absence of free hydrazine a hydrazo compound is formed (Scheme 88) (64AG(E)342). A difference between hydrazination and amination is the formation of 1,4-adducts which cannot be rearomatized even on heating. This is reflected in the behaviour of quinoline, which gives only a 0.5% yield of a -hydrazino product, whereas 4-methylquino-line is hydrazinated in 76% yield (64AG(E)342). Acridine behaves differently with sodium hydrazide/hydrazine, 9,10-dihydroacridine is formed almost quantitatively, but reaction in the absence of hydrazine yields 9-aminoacridine (65%). An even higher yield of 9-amino-acridine is obtained when sodium Af.AC-dimethylhydrazide is used (Scheme 89). Good evidence for intermediacy of (151) comes from the isolation of (152) on hydrolysis of (151). 

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 reaction of 1 equivalent of the azocarboxylate with the amine or hydrazo compound, in the dark, at room temperature, in anhydrous benzene, for up to 3 days. By this method, hydrazobenzene is converted into azobenzene in a 98 % yield within hr. 

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. 

The oxidation of nonfluorinated aromatic amines with free peracids (not acyl peroxides) proceeded best with the basic amines. The reaction did not pass through the azo stage of oxidation since azo compounds could not be converted under the reaction conditions and hydrazo compounds were oxidized to azo compounds. Under the reaction conditions, p-toluidine was converted only into p-nitrotoluene [31]. 

Oxidative cleavage of amines 9-39 Reduction of amides 9-47 Reduction of nitro compounds 9-50 Reduction of nitroso compounds or hydroxylamincs 9-51 Reduction of oximes 9-52 Reduction of azides 9-53 Reduction of isocyanates, isothiocyanates, or N-nitroso compounds 9-55 Reduction of amine oxides 9-59 Reduction of azo, azoxy, or hydrazo compounds... 

The other reaction mixtures were analyzed by GLC (OV 101 FID). In these cases it was possible to identify the following compounds substrate, dehalogenated nitro compound, desired aniline dehalogenated aniline. Two reaction intermediates (hydroxy I amine and azo- or hydrazo-compound) were determined as a sum. The selectivities given were determined at the end of the hydrogenation and are defined as... 

Nickel or mercury cathodes increase the amount of azoxy- or azo-body formed, but lead, zinc, copper, and tin favour the formation of azo- and hydrazo-compounds.2 Addition of copper powder to the electrolyte increases amine formation. 

It seems probable that with azo compounds the reaction is a reduction to the hydrazo compound, condensation of the latter with the aldehyde, followed by reduction and further alkylation to the secondary or tertiary amine. 

Methods of oxidation of hydrazo to azo compounds and hydroxylamino to nitroso compounds have been reviewed. Reagents which oxidize aromatic primary amines to azo compounds are also suitable for the oxidation of aromatic hydrazo compounds, since the hydrazo compounds are intermediates in the oxidation of the amines. Thus, manganese dioxide, mercury(II) oxide and lead tetraacetate are all suitable oxidants. Silver carbonate on Celite rapidly oxidizes both diarylhydrazines and acylhydrazines to the corresponding azo compounds in good yield. Another supported oxidant which can convert hy-drazobenzene into azobenzene in high yield is sodium periodate on silica gel. ... 

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-... 

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