Nitro amines, preparation

Although this reduction is more expensive than the Bnchamp reduction, it is used to manufacture aromatic amines which are too sensitive to be made by other methods. Such processes are used extensively where selectivity is required such as in the preparation of nitro amines from dinitro compounds, the reduction of nitrophenol and nitroanthraquinones, and the preparation of aminoazo compounds from the corresponding nitro derivatives. Amines are also formed under the conditions of the Zinin reduction from aromatic nitroso and azo compounds. 

The above scheme satisfies much of the metabolic data however, some of it is speculative, and it is certainly incomplete. The evidence for the formation of the a-hydroxylated intermediate is circumstantial. The acetate ester of a-hydroxylated dimethylnitrosamine has been prepared (12.13) and has been found to be a potent, directly acting carcinogen (14). Other esters of a variety of a-hydroxylated nitros-amines have also been prepared (15). While it has been shown that DMN acetate is hydrolyzed to hydroxymethylmethyl-nitrosamine by an esterase enzyme, it has been pointed out that these derivatives of the a-hydroxylated nitrosamines also dissociate to N-nitrosoimmonium ions (15 16). 

The dinitrocubane 362 was prepared from the corresponding diisocyanate in this way404. In contrast, treatment of isocyanates with nitronium tetrafluoroborate and nitric acid yields A,A-dinitroalkylamines, e.g. BuN(NC>2)2 from butyl isocyanate405. N-Nitrosodialkylamines are oxidized to the corresponding nitro amines by hydrogen peroxide in aqueous acetic acid, e.g. equation 123406. 

Certain aliphatic diamines have been prepared by reduction of nitro amines with hydrogen or aluminum amalgam. The starting materials are readily obtained by the reaction of nitroparaffins with formaldehyde and amines (method 444). 

Many cyclic amines are prepared by reduction of cyclic imines (see Section 1.20.3), or amides (see Section 1.20.4). Nitro-, amine- and carboxyl-substituted cyclic amines are formed by Mannich condensations (see Section 1.20.6). 

Only a few of the many aromatic diamino ethers used to prepare macrocycles will be mentioned here. A reduction process has been used to prepare aromatic diamines from nitro- and azide-containing ethers. The preparation of an aromatic diamine using known methods was reported by Glinka (1982), who treated an aromatic nitro halide with hexamethylenetetraamine followed by hydrolysis to give an aromatic nitro amine. The nitro amine was... 

C. A typical aromatic amine. Best prepared by the prolonged action of concentrated ammonia solution at a high temperature upon anthraquinone-l-sulphonic acid in the presence of BaClj and by reduction of the corresponding nitro compound or by amination of the chloroanthraquinone. 

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. 

It is convenient to include under Aromatic Amines the preparation of m-nitroaniline as an example of the selective reduction of one group in a polynitro compound. When wt-dinitrobenzene is allowed to react with sodium polysulphide (or ammonium sulphide) solution, only one of the nitro groups is reduced and m-nitroanUine results. Some sulphur separates, but the main reaction is represented by ... 

This method cannot be applied to polynitro amines, since these are so weakly basic that they can be diazotised only under special conditions in strongly acidic solutions. In such cases use may, however, be made of the mobility oonfared upon halogen atoms by the presence of nitro groups in the orlko and para positions. Thus the valuable reagent 2 4-dinitrophenylhydrazine is readily prepared by the condensation of 2 4-dinitrochlorobenzene with hydrazine ... 

Hydroxyquinoline ( oxine ). The technique adopted in this preparation is based upon the fact that, in general, the reactants glycerol, amine, nitro compound and sulphuric acid can be mixed with temperature control, and then maintained at any convenient temperature below 120° without any appreciable chemical reaction taking place. A pre-mix of the amine, glycerol and sulphuric acid, maintained at a temperature which keeps it fluid (60-90°), is added in portions to a reaction vessel containiug the nitro compound and warmed with stirring to 140-170° at which temperature the Skraup reaction takes place. 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

Nitro groups are readily reduced to primary amines by a variety of methods Cat alytic hydrogenation over platinum palladium or nickel is often used as is reduction by iron or tin m hydrochloric acid The ease with which nitro groups are reduced is especially useful m the preparation of arylamines where the sequence ArH ArN02 ArNH2 IS the standard route to these compounds... 

The preparation of amines by the methods described m this section involves the prior synthesis and isolation of some reducible material that has a carbon-nitrogen bond an azide a nitrile a nitro substituted arene or an amide The following section describes a method that combines the two steps of carbon-nitrogen bond formation and reduction into a single operation Like the reduction of amides it offers the possibility of prepar mg primary secondary or tertiary amines by proper choice of starting materials... 

Mn2(H2P202)2) is the stable product in the potentiometric deterrnination of manganese. Manganese(III) does not coordinate with amines or nitro complexes, but it does make manganicyanides of the types M2(Mn(CN)g) and M2(Mn(CN) (OH)), which are similar to the ferricyanides. The K", Na", LC and manganicyanides have been prepared and slowly hydroly2e in water to MnO(OH). 

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 ... 

In the Bnchamp process, nitro compounds are reduced to amines in the presence of iron and an acid. This is the oldest commercial process for preparing amines, but in more recent years it has been largely replaced by catalytic hydrogenation. Nevertheless, the Bnchamp reduction is still used in the dyestuff industry for the production of small volume amines and for the manufacture of iron oxide pigments aniline is produced as a by-product. The Bnchamp reduction is generally mn as a batch process however, it can also be mn as a continuous (48) or semicontinuous process (49). 

Electrolytic reductions generally caimot compete economically with chemical reductions of nitro compounds to amines, but they have been appHed in some specific reactions, such as the preparation of aminophenols (qv) from aromatic nitro compounds. For example, in the presence of sulfuric acid, cathodic reduction of aromatic nitro compounds with a free para-position leads to -aminophenol [123-30-8] hy rearrangement of the intermediate N-phenyl-hydroxylamine [100-65-2] (61). 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

Z-Furan. 3-(5-Nitro-2-furanyl)-2-propenamide, is prepared by condensation of 5-nitro-2-furancarboxaldehyde diacetate with malonic ester followed by PCl chlorination and amination (29). The product was marketed in Japan as a food preservative. 

A -Heterocyclic-A -acetylsulfanilamides. These derivatives may be prepared by condensation of the heterocycUc amine with /)-nitroben2enesu1fony1 chloride foUowed by acetylation of the nitro compound. The product may be reduced under mild conditions to give the 4-amiQO-A/ -heterocychc-A/ -acetyl derivative. Other approaches, however, have been developed (46,47). 

The N,]S -dialkyl-/)-PDAs are manufactured by reductively alkylating -PDA with ketones. Alternatively, these compounds can be prepared from the ketone and -lutroaruline with catalytic hydrogenation. The /V-alkyl-/V-aryl- -PDAs are made by reductively alkylating -nitro-, -nitroso-, or /)-aminodipheny1 amine with ketones. The AijAT-dialkyl- PDAs are made by condensing various anilines with hydroquinone in the presence of an acid catalyst (see Amines-aromatic,phenylenediamines). 

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