Hydroxylamine reaction with nitroso compounds

Schenk et al. have used the a-chloro nitroso compound 93 for the reaction with cyclopentene 98 in order to solve the problem with the instability of the allyl amine product formed from the reaction with nitroso compounds [56c]. The product formed, 99, rearranges to the stable nitrone hydrochloride salt 100, which is easily hydrolyzed to the hydroxylamine 101 (Eq. (23)). 

The oxidants dimethyl sulfoxide and nitroso compounds react easily with oL-bromo ketones and convert them into a-dicarbonyl compounds. The reaction with nitroso compounds is usually carried out in the presence of pyridine and proceeds through a nitrone stage. Phenacyl bromide (a-bromoacetophenone) is thus transformed first into phenacylpyridinium bromide and further, with nitrosobenzene, into a-ketoaldonitrone, which is subsequently treated with hydroxylamine to give phenylglyoxal monoxime or with phenylhydrazine to give phenylglyoxal osazone [985] (equation 411). 

Nitroaromatic Reduction Nitroaromatics constitute an important class of potential environmental contaminants, because of their wide use in agrochemicals, textile dyes, munitions, and other classes of industrial chemicals. Reduction of nitroaromatics produces amines, throngh a series of electron transfer reactions with nitroso and hydroxylamines as intermediates (Fig. 13.1). Compared to the parent nitroaromatic compound, all intermediates typically reduce readily (Larson and Weber 1994). 

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]. 

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). 

Functionalization of rubbers with nitroso compounds (174) involves two reaction steps [233] formation of a hydroxylamine derivative 175 and its... 

N-Allylhydroxylamines can be prepared from nitrone hydrochlorides, which are produced by the reaction of nitroso compounds with alkenes, in an ene-type mechanism (Scheme 188). Analogues of potent dopaminomimetic ergot derivatives have been prepared, in which of a (5R,8S,10R)-6-allylergoline N -oxide was converted into a substituted hydroxylamine function. The key step is a Meisenheimer [3,2] sigmatropic rearrangement of the N6-oxide (Scheme 189). 413... 

Ruthenium and iridium catalysts have also been shown to promote the reaction of nitroso compounds with simple ene substrates. In this example, hydrogen peroxide acted as the oxidant to convert the hydroxylamine into the nitroso compound in situ. Ru- or Ir-catalyzed reaction with 2-Me-2-butene (85) then provides a mixture of regioisomers. The metal utilized greatly influences the ratio of products Ru was proven to be more twix selective giving an 8 1 ratio of 156 and 157. ... 

The reaction of alkenes with nitroso compounds gives hydroxylamine products [47]. The process was thought to occur by either a one-step ene reaction (Eq. 4.56, below) or a two-step reaction via a transient aziridine oxide intermediate (Eq. 4.57). The following deuterium isotope effects were measured for the reaction of 2,3-dimethyl-2-butene and pentafluoronitrosobenzene. Explain the similarities and differences among these results in terms of one of these mechanisms. Use the results to exclude one mechanism. The first three cases are intramolecular competitions where is the rate of formation of the C=CH2 product and is the rate of formation of the = 0 alternative product. The last case is an intermolecular competition. The results were determined by H NMR analysis of the products. 

In a reaction similar to 12-50, azoxy compounds can be prepared by the condensation of a nitroso compound with a hydroxylamine. The position of the oxygen in the final product is determined by the nature of the R groups, not by which R groups came from which starting compound. Both R and R can be alkyl or aryl, but when two different aryl groups are involved, mixtures of azoxy compounds (ArNONAr, ArNONAr, and Ar NONAr ) are obtained and the unsymmetrical product (ArNONAr ) is likely to be formed in the smallest amount. This behavior is probably caused by an equilibration between the starting compounds prior to the actual reaction (ArNO -I- Ar NHOH Ar NO - - ArNHOH). The mechanism has been investigated in the presence of base. Under these conditions both reactants are converted to radical anions, which couple ... 

Most reactions of nitroso intermediates are however too slow to compete with further reduction. In these cases it is necessary to carry out the tandem reduction to the hydroxylamine stage and then oxidation back to the nitroso compounds using the type of double-cell sketched in Fig. 11.2. The intermediate is then allowed to... 

Hydroxylamines are usually more accessible than the corresponding nitroso compounds, so only few examples of this reaction have been described in the literature. Aromatic nitroso compounds have been reduced into hydroxylamines with ascorbic acid, gly-oxylic acid and by NADH. It can be safely assumed that any reagent capable of reducing nitro compounds should reduce nitroso compounds as well. 

Tertiary and aromatic nitroso compounds react with aryl Grignard or aryl-lithium reagents giving the corresponding hydroxylamines . This reaction is useful for preparation of alkyl- and aiylhydroxylamines (e.g. 109, equation 80 and 110, equation 81) and can be considered as complementary to arylation of hydroxy lamines with activated aryl halides. It has been used for functionalization of cyclophanes with the hydroxy amino group. The main limitation of the reaction is the relatively restricted choice of available aliphatic nitroso components, so most of reactions were done with 2-nitroso-2-methylpropane. There is no literature data about the possibility of removal of the tert-butyl group from these compounds. 

Aliphatic and aromatic nitroso compounds are powerful dienophiles and react with a variety of acyclic, cychc and heterocyclic 1,3-dienes producing cyclic hydroxylamines. The reaction proceeds with a high regioselectivity at room temperature (equation 99 291-293 Asymmetric variation of the reaction with chiral copper-BINAP catalyst has been reported ". The cycloaddition is reversible and some amounts of diene and nitroso components may be observed in reaction products. 

Although electrochemical oxidation of Al-cyclohexyl-Al-hydroxylamine in the presence of pyridine afforded the corresponding dimeric nitroso compound with a low yield, A-hydroxy t-alkylamines were transformed into the corresponding nitroso compounds (equation 8) . Similarly, A-phenylhydroxylamine was transformed into nitrosobenzene under similar reaction conditions. ... 

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 ). 

One of the reactions which has been used to prepare azoxy compounds is the condensation of C-nitroso compounds with hydroxylamines. In the aliphatic series this reaction is quite general and permits the preparation of unsym-metrical azoxy compounds. In the case of aromatic compounds, however, only symmetrical azoxy compounds can be synthesized reliably. In the reaction of dissimilar aromatic nitroso compounds and aromatic hydroxylamines, a complex mixture of azoxy products is obtained. 

It is self-evident that one of the simpler methods of preparing unsymmetrically substituted azoxy compounds must involve the condensation of two distinctly different starting materials. In principle, the reaction of C-nitroso compounds with hydroxylamines meets this requirement (Eq. 1). 

The reduction of aromatic nitro compounds is believed to proceed to an intermediate mixture of nitroso compounds and substituted hydroxylamines which are not isolated but condense to form an azoxy compound which, in turn, is reduced to an azo compound. Contributing evidence to substantiate this mechanism is that the reduction of a mixture of two aromatic nitro compounds leads to a mixture of azo compounds consistent with that predicted if each of the nitro compounds were reduced to a nitroso compound and a hydroxylamine and these, in turn, reacted with each other in all possible combinations. This observation also implies that the bimolecular reduction of nitro compounds is practical only from the preparative standpoint for the production of symmetrically substituted azo compounds. Spectrophotometric studies of the reaction kinetics of the reduction of variously substituted nitro compounds may, however, uncover reasonable procedures for the synthesis of unsymmetrical azo compounds. 

A. Reaction of C-Nitroso Compounds with Hydroxylamines and Related Compounds. 347... 

In some cases in which the Caro s acid oxidation of amines was not satisfactory, the corresponding hydroxylamines have been oxidized with acidified dichromate solutions [42], Both aliphatic and aromatic nitroso compounds have been prepared by this method [17, 42, 82, 90]. Frequently the reaction mixture from the reduction of a nitro compound is treated directly with the oxidizing medium without the isolation of the intermediate hydroxylamine. The method has been called the nitro reduction oxidation technique, [82] a terminology we cannot condone. 

The most important synthetic methods involve condensation of hydrazine, hydroxylamine or hydrogen peroxide with a 1,4-oxygenated carbon chain, and these procedures are particularly useful for the preparation of pyridazines and 1,2-oxazines. Other methods include Diels-Alder reactions of a diene with an azo or nitroso compound. 

Hydroxylamines play a significant role in modern industrial chemistry. Their most important chemical properties include differential reactivity of the N and O termini, changes in reactivity with pH and solubility in both aqueous and organic solvents. Hence the study of reactions of hydroxylamine derivatives, especially their oxidation to nitroso compounds, constitutes an important area of investigation. 

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