Hydroxylamines reaction with nitroso groups

In a similar reaction, 2-(o-nitrophenyl)ethylamine (100) may be reduced in an ammonia buffer to the hydroxylamine and oxidized to the nitroso derivative, which condenses with the amino group to a dihydrocinnoline.160,161 It is also possible to prepare dihydrobenzo-l,2,3-triazinones on reduction of o-nitrobenzhydrazide, followed by oxidation of the hydroxylamine to a nitroso group, and 3-phenyldihydrobenzo-l,2,3-triazine (101) from N-phenyl-(V-(o-nitrobenzyl)hydrazine (100) in an analogous way161 [Eq. (78)]. 

An example of the product distribution during hydrogenation is shown in Fig. 2.39. The main difference between hydrogenation of aromatic nitro and nitroso goups is that the nitroso group reacts rapidly with intermediate hydroxylamine to form side products (see Fig. 2.31), so their concentrations must be kept low to avoid this reaction.294... 

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]. 

Similarly, nitroarenes can also be lithiated (Scheme 5.43), but reactions of meta-lated nitroarenes with electrophiles only proceed cleanly if the metalation is performed in the presence of the electrophile [403], Otherwise, the metalated arene can reduce nitro groups to nitroso groups, which quickly react with additional organo-metallic reagent to yield hydroxylamines [404, 405], Nitroarylmagnesium halides can be prepared by iodine-magnesium exchange at -80 °C to -40 °C, and react with electrophiles in the expected way [6] (Scheme 5.43). 

Q The nitroso group exhibits similar behaviour to a carbonyl group. Predict the products from the reaction of nitrosobenzene with (a) malononilrile (propane-1,3-dinjtrile), (b) hydroxylamine and (c) aniline. Suggest a mechanism for the last reaction. 

Condensation reactions can be grouped into two categories. The first category involves pyrazol-3-ones with formyl, acyl, nitroso, a,jS-unsaturated oxo, 3-oxo-2-azobutyric acid ethyl ester or acetonitrile substituents at position 4 or formyl substituents at position 5 and their reaction with carbanions, heterocyclic methylcarbenium salts, primary and secondary amines, diamines, heterocyclic perchlorates, hydroxylamine, hydrazines, urea or thiosemicarbazide. The second category involves pyrazol-3-ones with amino, hydrazino, heteroaromatic amino, acetyl or acetonitiilo groups at position 4 and their reaction with aryl or heteroaromatic aldehydes or cyclic ketones. 

The study of reactions of polyfluorinated nitroso alkanes shows that nitroso groups actively accept NO with the formation of a nitroso-derivative of hydroxylamines. 

The nitroso functional group is readily reduced in a thermodynamically favored and kinetically facile reaction to the hydroxylamine state (1). The relatively rapid kinetics of nitroso reduction can be reasonably explained on the basis of probable stabilities of transition state intermediates produced via electron addition. Unlike the nitro group, for which addition of an electron disrupts the major resonance of the ground state, addition of an electron to the nitroso group yields transitional intermediates with structures quite similar to the major resonance forms of the ground state nitroso group (Fig. 3). 

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 ... 

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. 

In general, reduction of aromatic nitro groups occurs in three steps, via nitroso and hydroxylamine intermediates, to the amine. For nitrobenzene and simple substituted nitrobenzenes reacting with Fe° in batch model systems, the intermediates have been detected in solution, but the dissolved amine alone is usually sufficient for good mass balance [99-103], Thus, the net reaction is ... 

In principle, the nitroso, hydroxylamine, and/or amine products of nitro reduction might undergo coupling to form azoxy, azo, and/or hydrazo dimers, but no evidence for these products has been found under the conditions that have been studied to date. One reason that these dimers do not accumulate may be that they are rapidly reduced by Fe°. In fact, Fe° reduces azo groups to amines [Eq. (12)] very rapidly [111-113], and this reaction may prove to be useful in the remediation of wastewaters contaminated with azo dyes. 

In a reaction similar to 13-24, 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... 

The Baudisch reaction295 makes it possible simultaneously to introduce a nitroso and a hydroxyl group in the ortho-position to one another. In this reaction NOH radicals are produced by oxidation of hydroxylamine or reduction of nitrous acid these radicals, in conjunction with an oxidizing agent and in the presence of a copper salt as catalyst attack the aromatic nucleus. Yields are seldom very high, but few o-nitrosophenols are easily prepared in other ways. Cronheim296 has reported the first preparation of fifty mono-and di-substituted n-nitrosophenols by the Baudisch reaction. 

The reduction of the nitro group of 3-nitrophthalhydrazide (20) with dithio-nate is mechanistically complex, but a possible sequence of events is illustrated in Scheme 20.5, with ArN02 representing 20. The reaction presumably is initiated by transfer of an electron from dithionate to produce the anion radical 23. Subsequent steps involving protonation and addition of a second electron afford the N,N-dihydroxy intermediate 24, which can dehydrate to produce the nitroso compound 25. Further addition of electrons from dithionate, protonation, and loss of water from the hydroxylamine 26 leads to the reduced product 15. 

The nitroso functionality is a powerful dienophile and N-alkyl- and N-acylnitroso compounds give inter- and intrahetero Diels-Alder reactions easily. The cycloadditions also occur in aqueous medium although some nitroso compounds (i.e. N-acylnitroso derivative) are short-lived in the presence of water. The NO functionality is generated in situ by periodate oxidation of the hydroxylamine group and the cycloaddition with butadienes gives a 1,2-oxazine ring. Scheme 5.16 illustrates the utility of the nitroso Diels-Alder cycloaddition for the synthesis of (—l-swainsonine/ (—)-pumiliotoxin and BCX-1812... 

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