Nitroso compounds with amines

A very flexible method of preparing unsymmetrical azo compounds makes use of the condensation of C-nitroso compounds with amines. Thionylamines have also been condensed with substituted hydroxylamines to produce azo compounds not usually accessible by other means. Treatment of dialkylsulfuric diamides with sodium hypochlorite is one means of preparing aliphatic azo compounds. Aromatic amines and aromatic nitro compounds at high temperature produce azo compounds. 

The following paragraphs describe the methods of forming azo compounds in which an N-N bond is created (for preparation by coupling see the Section on Preparation of the C-N bond by replacement .) These methods can be classified as (a) oxidative junction of amines (b) oxidation of hydrazo compounds (c) disproportionation of hydrazo compounds (d) action of hypochlorite on iV,jV -diarylsulfamides (e) condensation of nitroso compounds with amines (f) reaction of nitro compounds with amines (g) reduction of nitro and nitroso compounds and (h) reaction of JV-arylhydroxylamines with sulfinylimines. 

The nucleophilic attack on the nitrogen atom of a nitroso group is the limiting stage of condensation reactions of nitroso compounds with amines, methylene-active, and organomagnesium compounds, of Ehrlich-Sachs, Fischer-Hepp, Burton, and other reaction [161,162]. 

Secondary and tertiary amines are not generally prepared in the laboratory. On the technical scale methylaniline is prepared by heating a mixture of aniline hydrochloride (55 parts) and methyl alcohol (16 parts) at 120° in an autoclave. For dimethylaniline, aniline and methyl alcohol are mixed in the proportion of 80 78, 8 parts of concentrated sulphuric acid are added and the mixture heated in an autoclave at 230-235° and a pressure of 25-30 atmospheres. Ethyl- and diethyl-anihne are prepared similarly. One method of isolating pure methyl- or ethyl-aniline from the commercial product consists in converting it into the Y-nitroso derivative with nitrous acid, followed by reduction of the nitroso compound with tin and hydrochloric acid ... 

A convenient synthetic procedure for the preparation of azo compounds, particularly unsymmetrically substituted ones, involves the reaction of aromatic nitroso compounds with aromatic amines [31a, b]. The reaction is of particular interest because the replacement of the amine by the corresponding hydroxylamine leads to the formation of the related azoxy compounds (see Chapter 15, Azoxy Compounds ). 

Instead of the peracetic acid oxidation just described, performic acid (prepared from 98 % formic acid and 90% hydrogen peroxide) may also be used as an oxidizing agent for the preparation of nitroso compounds. With this reagent, pentafluoronitrosobenzene and 4-nitrosotetrafluorobromobenzene have been prepared from the respective amines [85]. 

In the base-catalyzed condensation of nitroso compounds with hydroxyl-amines at low temperatures, if the starting materials are present in equimolar quantities modest yields of cis isomers may be isolated [49]. The present authors are not in a position to judge whether this procedure affords the cis isomers directly, or whether the normal trans isomer is formed initially and is subsequently converted into the cis form in the presence of the base. The latter sequence seems quite likely in view of other observations in which trans azoxy compounds were isomerized to the cis azoxy form in the presence of sodium methoxide [6, 7]. 

A considerable number of acylarylamines, among them o-chloroacet-anilide, 2,6-dichloro-4-nitroacetanilide, and l-acetamido-2-methylan-thraquinone, form abnormal nitroso compounds with nitrous fumes others, such as 4-dimethylamino-4 -acetamidoazobenzene, benzene-p-toluidide, and diacetyl-1,3-phenylene diamine, do not yield nitroso compounds with nitrous fumes a third group, which includes p-nitroacet-anilide and a- and /3-acetamidoanthraquinone, is recovered unchanged after the same treatment.63 In general, the acetamido group submits to nitrosation, whereas the benzoyl and benzenesulfonyl and toluenesul-fonyl derivatives of amines are resistant to the notion of nitrous fumes. 

Aromatic and aliphatic primary amines can be oxidized to the corresponding nitro compounds by peroxy acids and by a number of other reagents. The peroxy acid oxidations probably go by way of intermediate hydroxylamines and nitroso compounds (Scheme 2). Various side reactions can therefore take place, the nature of which depends upon the structure of the starting amine and the reaction conditions. For example, aromatic amines can give azoxy compounds by reaction of nitroso compounds with hy-droxylamine intermediates aliphatic amines can give nitroso dimers or oximes formed by acid-catalyz rearrangement of the intermediate nitrosoalkanes (Scheme 3). 

SAFETY PROFILE Confirmed carcinogen with experimental carcinogenic and tumorigenic data. Poison by intravenous route. An eye irritant. Solutions with thorium salts are unstable explosives above 15°C. Solutions with titanium or zirconium salts are unstable explosives above 40°C. When heated to decomposition it emits very toxic NH3 and NOx. See also N-NITROSO COMPOUNDS and AMINES. 

The conversion of an amino group into a nitro group can be useful when specific substitution patterns are required. The synthesis of 1,4-dinitrobenzene from 4-nitroaniline is illustrative (Scheme 7.5). Oxidation can be accomplished directly using peroxytrifluoroacetic acid or in two steps using H2SO5 (monoperoxysulfuric acid) and oxidation of the resulting nitroso compound with hydrogen peroxide. Alternatively, the amine can be diazotized in fluoroboric acid and then reacted with sodium nitrite in the presence of copper powder. 

Condensation of aromatic nitroso compounds with primary amines is a satisfactory procedure for obtaining azo compounds. An example is the combination of nitrosobenzene and aniline in acetic acid, which results in a quantitative yield of azobenzene. Similarly, a series of methyl-substituted azobenzenes have been prepared, although the yields are poor in the case of the oriAo-substituted compounds. As an illustration of the versatility of the reaction, nitrosobenzene can be condensed with o-methoxyaniline (o-anisidine)," p-aminobenzoic acid, o-phenylene-diamine monobenzoate, and m-nitroaniline to form the corresponding substituted azobenzenes. 

Reactivity With Nitroso Compounds. Functionalization of diene based rubbers with aromatic nitroso compounds bearing aminic or phenolic moieties 174, like with iV,A-diethyl-4-nitrosoaniline, 4-nitrosodiphenylamine, 4-nitrosodiphenylhy-droxylamine or 4-nitrosophenol represents an effective way for the synthesis of polymer-bound antioxidants [233], The respective nitroso compound can be mixed with rubbers during compounding or with concentrated rubber latexes. The chemical attachement of stabilizing active moieties takes place during subsequent... 

Oxidation of Primary Aromatic Amines to Nitroso Compounds with Peroxyacetic Acid [753] ... 

The 1-methylamino derivative 71 behaves like a typical secondary amine, forming a benzoyl derivative with benzoyl chloride and a N-nitroso compound with nitrous acid. Alkaline hydrolysis results in ring opening to give caffeidine (75). The parent heterocycle and its 3-methyl derivative form 7-oxides on treatment with m-chloroperbenzoic acid. The 3-thioxo compound 65 is readily desulfurized by Raney nickel in ammonium hydroxide solution. ... 

Oxidation of aromatic amines to nitro-compounds is not normally required. However, in the case of deactivated molecules or in order to obtain specific substitution patterns, this transformation may be useful. The reaction can be carried out by peracids [179], and is readily achieved by the sodium perborate/acetic acid system, in the absence of metal catalysts [180]. Less forcing conditions with peracids can be used to make nitroso-compounds [181]. However, the use of a low excess of oxidant, or of conditions where reaction is slow, encourages coupling of the nitroso-compound with unreacted amine to give a diazo-compound. This can be made deliberately as the major product [182], and will itself undergo further oxidation to the azoxy-compound, which is then hard to oxidise further [183]. 

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