Amines condensation with nitroso compounds

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. 

While the condensation of amines with nitroso compounds appears to have wide applicability in the benzene series, it seems to lead to complex dye molecules in the naphthalene series. A method has been developed using a somewhat complex reaction between thionylamines and substituted hydroxylamines which does produce azo compounds derived from naphthalenes. This synthesis is of particular interest because it helped to settle the question whether true naphthylazo compounds with hydroxyl groups could exist [36]. 

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]. 

Aromatic nitroso compounds are able to condense with numerous compounds containing reactive methylene groups this, the Ehrlich-Sachs reaction,430 affords Schiff bases, whence the corresponding carbonyl compound and amine can be obtained by hydrolysis ... 

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. 

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. 

Aliphatic C-nitroso compounds have also been condensed with aliphatic amines and oximes. Among the products isolated have been fair yields of aliphatic azoxy compounds [17]. The detailed analysis to account for the stoichiometry of the reactions is still lacking. These reactions may require further development, and only one example is given here for reference. 

In the oxidation of pentafluoroaniline with performic acid, along with the expected pentafluoronitrosobenzene, a 17% yield of decafluoroazoxy-benzene was isolated. Separate experiments showed that the condensation of the nitrosobenzene with the residual amine did not lead to the clean-cut preparation of the azoxy compound, whereas the thermal degradation of the nitroso compound did afford the azoxy compound. The implications of these observations are that either the azoxy product was formed, at least in part, by direct oxidation of the amine or the thermal history of the reaction permitted its formation from the intermediate nitroso compound [29]. 

Ready addition of 2-nitrosopyridine to 1,3-dienes gives 3,6-dihydro-1,2-oxazines, e.g. (774) — (773), and condensation with aromatic amines gives azo compounds, e.g. (774) — (775). Nitroso compounds are oxidized by ozone or sodium hypochlorite to the corresponding nitro compounds. 5-Nitrosopyrimidines can be reduced to the 5-amino derivatives or condensed with activated methylene groups. 

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

Catalytic reduction of aromatic nitro compounds to the amines is highly exothermic (AH = —548 12 kJ/mol) and has high potential for hazard in the event of cooling- or other process-failure. The total reaction proceeds via nitroso and hydroxylamino intermediates, both of which are reactive and may undergo undesired condensation or disproportionation reactions, and the thermochemistry of all these possibilities was investigated. The reduction or disproportionation of the hydroxylamino intermediate (which is of low thermal stability) is identified as the fastest and most exothermic step (despite which it can frequently be concentrated or trapped) implications for process safety are considered in detail and verified by experiment with typical compounds and intermediates [1]. A calorimetric study of the hazards inherent in hydrogenation of nitroaromatics was made, using nitrobenzene as model compound [2]. Individual incidents of this type are ... 

The submitters reported that successive 2.5-1. portions of distillate were filtered, and the following weights of product were obtained 14.5, 10.7, 9.0, and 2 g., or 36.2 g. in 10 1. From one run the checkers obtained 19, 12, 6, and 2 g., or 39 g. In some runs it was necessary to collect 15-30 1. of distillate in order to obtain a 30-g. yield. The submitters report that unchanged amine, if present during the steam distillation, condenses with the nitroso compound, giving tarry products, and the yield of nitroso compound is reduced. 

N-Nitrosoamines, decomposition, 741 reduction to hydrazines, 734 Nitrosoanilines, hydrolysis, 680 Nitroso compounds, condensation with amines, 765 oxidation, 751 preparation, 739... 

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. 

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. 

The formation of a dinitrone - in contrast to the ozonation of DOPPD - is inhibited most probably just by the stabilizing effect of the N-phenyl group. The same structural moiety stabilizes aromatic nitro and nitroso compounds formed via the amine oxide pathway no Bandrowski bases were detected in the ozonation product of HPPD. The authors (40) favor the N-alkyl side reactivity in HPPD also in the interpretation of the formation of N-phenyl-N -acyl-l,4-PD, i.e. in the condensation with aliphatic aldehydes. 

The Timmis synthesis is a versatile reaction and a range of 2,6-substituted 5-nitrosopyrim-idin-4-amines can be condensed with a variety of a-oxomethylene compounds as well as a-methylenenitriles. Generally, the products have unambiguous structures as it is the nitroso group which condenses with the methylene group, and the amine with the carbonyl group. However, the yields which are obtained are often rather poor. 

Like 2-aminopyridines and 2-aminopyrimidine, 2-aminopyrazine (39) (Scheme 29) has been converted into the nitroso compound (121) by reaction with dimethyl sulfide and NCS followed by deprotonation of the resulting sulfonium salt with sodium methoxide to the 5, 5-dimethylsulfilimine and then oxidation with MCPBA <82JOC552>. The extremely reactive nitrosopyrazine (121) condenses with 1,3-dienes to give 3,6-dihydro-1,2-oxazines and with aromatic amines in the presence of acid to gives azo compounds, and is smoothly oxidized with ozone or sodium hypochlorite to 2-nitropyrazine (122). Methyl 3-aminopyrazinecarboxylate reacts with thiophosgene to produce the... 

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]. 

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). 

Oxidation of primary amines with DMD or other oxidants leads to the formation of a complex mixture of nitroso, oximes, and nitro compounds (76). Utilization of DMD in acetone affords dimethyl nitrone (22). This is likely to be a result of the initial oxidation of primary amine (19) to hydroxylamine (20) with the subsequent condensation of acetone and oxidation of imine (21) (Scheme 2.9) (77). 

This route to the a-nitroso derivatives of the 7r-deficient heterocycles has permitted an exploration of their chemistry. They are extremely reactive and condense readily with 1,3-dienes to give 3,6-dihydro-l,2-oxazines (e.g. 99), and with aromatic amines in the presence of acid to give azo compounds (Scheme 86). This latter reaction is particularly useful in view of the instability of the corresponding 2-pyridinediazonium salts referred to above, which limits conventional access. The a-nitroso heterocycles are oxidized by ozone or sodium hypochlorite to the a-nitro compounds (Scheme 86) (82JOC553). 

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