Nitroso compounds tautomerism

There are three possible products when NOCl is added to alkenes. The initial product is always the [3-halo nitroso compound, but these are stable only if the carbon bearing the nitrogen has no hydrogen. If it has, the nitroso compound tautomerizes to the oxime ... 

Primary and secondary nitroso compounds tautomerize to isonitroso compounds - oximes of aldehydes and ketones, respectively. Their reductions are dealt with in the sections on derivatives of carbonyl compounds (pp. 106,132). 

There are three possible products when NOCl is added to alkenes, a (3-halo nitro-so compound, an oxime, or a (3-halo nitro compound.The initial product is always the (3-halo nitroso compound, but these are stable only if the carbon bearing the nitrogen has no hydrogen. If it has, the nitroso compound tautomerizes to the oxime, H—C-N=0 C=N-OH. With some alkenes, the initial (3-halo nitroso compound is oxidized by the NOCl to a (3-halo nitro compound. Many functional groups can be present without interference (e.g., COOH, COOR, CN, OR). The mechanism in most cases is probably simple electrophilic addition, and the addition is usually anti, although syn addition has been reported in some cases.Markovnikov s mle is followed, the positive NO going to the carbon that has more hydrogens. 

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Synthesis. Almost without exception, azo dyes ate made by diazotization of a primary aromatic amine followed by coupling of the resultant diazonium salt with an electron-rich nucleophile. The diazotization reaction is carried out by treating the primary aromatic amine with nitrous acid, normally generated in situ with hydrochloric acid and sodium nitrite. The nitrous acid nitrosates the amine to generate the N-nitroso compound, which tautomerizes to the diazo hydroxide. 

Nitroso-oxime tautomerism was reported to occur in compounds 266-268 [76AHC(S1), pp. 436,443,452],... 

The structure of the intermediate obtained from 3-phenyl-5-amino-l,2,4-thiadi-azole (Goerdeler and Deselaers, 1958) was elucidated by UV- and IR-spectroscopy. The results are consistent with the nitrosoamine structure 3.18. Its UV spectrum (Fig. 3.4) is very similar to that of the A-methyl-TV-nitroso compound 3.19, but different from that of the isomeric compound 3.20 with a methyl group in the 4-position (Goerdeler and Deselaers, 1958). The spectrum of this 4-methyl derivative is expected to be similar to that of the nitrosoamine structure 3.21, which is obviously not present, at least not in detectable tautomeric equilibrium concentration. 

Nitroso-Oxime Tautomerism. This equilibrium lies far to the right, and as a rule nitroso compounds are stable only when there is not a hydrogen. 

The nitro form is much more stable than the aci form in sharp contrast to the parallel case of nitroso-oxime tautomerism, undoubtedly because the nitro form has resonance not found in the nitroso case. Aci forms of nitro compounds are also called nitronic acids and azinic acids. 

There appears to be little reported work on S-nitrosation reactions of simple thioke-tones. Thiocamphor when treated with /50-amyl nitrite in fact gives the oxime58 (formerly called a isonitroso compounds), presumably via the tautomeric form of the thione, i.e. the enethiol. In this respect the reaction is very similar to the reactions of ketones59 which give oximes or C-nitroso compounds via the enol intermediates60. 

Aliphatic nitro compounds exhibit rather different behavior from nitroaromatic compounds. Secondary and primary nitro compounds tend to produce oximes because the intermediate nitroso compound quickly tautomerizes to the oxime (equation 1). Under aprotic conditions the radical anions of primary and secondary nitro compounds are relatively stable those derived from tertiary nitro compounds, on the other hand, eject nitrite ion relatively readily (equation 2)8. 

Aliphatic nitro compounds with the nitro group on a tertiary carbon were reduced to amines with aluminum amalgam [146 or iron [559]. 2-Nitro-2-methylpropane afforded ferf-butylamine in 65-75% yield [146. Even some secondary nitroalkanes were hydrogenated to amines. fra s-l,4-Dinitrocy-clohexane was converted to frans-l,4-diaminocyclohexane with retention of configuration. This may be considered as an evidence that the intermediate nitroso compound is reduced directly and not after tautomerization to the isonitroso compound [560] (see Scheme 54). 

Nitroso compounds (e.g. 116, equation 85) that are unable to tautomerize to oximes undergo an ene reaction with aikenes 117 giving Af-aUylhydroxylamines 118 (equation 85). Both trifluoromethyl and aryl nitroso compounds react with aikenes although in many cases the resulting Af-allylhydroxylamines are prone to subsequent chemical transformations. If allylzinc compounds are used as the aikene components, the chemos-electivity of the reaction is reversed and O-allylation products are preferably formed . 

The nitrosation of aliphatic carbon atoms, particularly of carbon atoms activated by adjacent carbonyl, carboxyl, nitrile, or nitro groups, has been reviewed in great detail [2]. Judging from this review, with few exceptions, nitrosation of active methylene compounds leads to the formation of oximes (unfortunately termed isonitroso compounds in the older literature). The few exceptional cases cited in which true nitroso compounds (or their dimers) were formed involved tertiary carbon atoms in which no hydrogen atoms were available to permit tautomerism to the oxime or involved a reaction which was carried out under neither acidic nor basic conditions. 

The reduction of N-nitroso derivatives was discussed in Part I C-nitroso compounds are generally reduced to the hydroxylamine, which in alkaline solution may react with the nitroso compound to form an azoxy compound, possibly through an electron transfer from the hydroxylamine to the nitroso compound. Nitrosoquinoxaline (276) behaves as an a,/l-unsaturated nitroso compound on reduction the primarily formed hydroxylamine tautomerizes to an oxime427 [Eq. (143)]. 

A third pathway for oxime formation is given by tautomerization of nitroso compounds possessing an a-hydrogen (equation 9). Such a process involves an intramolecular redox reaction, in which the nitrogen undergoes a formal two-electron reduction, while the a-carbon is oxidized. Kinetic analysis of this conversion, as performed with a set of a-substituted 2-nitroso-l-phenylethane compounds, has revealed sensitivity toward both the bulkiness of the substituents and the initial concentration of the nitroso dimers128. For instance, tautomerization of 2-nitroso-l-phenylpropane to 28 has been proposed to play a role in the metabolism of methamphetamine by fortified rat liver tissue129. 

Benzonitrile oxide (C in Figure 15.44) is an isolable 1,3-dipole. It can be generated from benzaldoxime and anNaOH/Cl2 solution. Under these reaction conditions the oxime/nitroso anion (A B) is initially formed and chlorine disproportionates into Cl—O and chloride. An SN reaction of the negatively charged C atom of the anion A B at the Cl atom of Cl— O or of Cl—O—H affords the oc-chlorinated nitroso compound E, which tautomerizes to the hydroxamic acid chloride D. From that species, the nitrile oxide C is generated via a base mediated 1,3-elimination. Isoxazoles are formed in the reactions of C with alkynes (Figure 15.44), while isoxazolines would be formed in its reactions with alkenes. 

The nitroso compound is unstable because it can tautomerize with the transfer of a proton from carbon to the oxygen of the nitroso group. This process is exactly like enolization but uses an N=0 instead of a C-O group. It gives a more familiar functional group from Chapter 14, the oxime, as the stable enol . The second structure shows how the oxime s O-H can form an intramolecular hydrogen bond with the ketone carbonyl group. Hydrolysis of the oxime reveals the second ketone. 

Primary and secondary aliphatic nitroso compounds, with an a-hydrogen, are unstable and readily rearrange to or exist as the more stable tautomeric oximes. Therefore, these nitroso compounds can be understood to be hydrogenated in the form of the oximes. On the other hand, tertiary and aromatic nitroso compounds as well as (V-nitrosamines may be hydrogenated as the compounds with a true nitroso group. 

Photohomolysis of the weak N-0 bond of a nitrite ester A forms a pair of radicals B and NO. The oxy radical B abstracts a hydrogen atom from a nearby carbon and the resulting radical C and NO couples to give a nitroso compound D. Tautomerism of the nitroso product D followed by treatment with nitrous acid converts this to the carbonyl group (Scheme 2.41). 

Aliphatic primary and secondary nitroso compounds are not stable but tautomerize to oximes. In nitrosocyclohexane the special steric conditions favor a dimerization rather than a tautomerization. The dimer is reduced polarographically in a six-electron reaction to A, A -dicyclohexylhydrazine [71]. Aliphatic Miitro compounds are dimers in the solid state, but dissociates in solution to a degree depending on the solvent the monomer is easier reducible than the dimer [72]. Only the monomer reacts as a spin trap the rate constant for the dissociation in MeCN is 1.5 x 10" s" [72a]. 

Oximes are tautomeric with nitroso compounds. Oximes are generally reduced to amines in a reaction in which the NO bond is cleaved before the hydrogenation of the ON double bond occurs. In acid solution the reaction is as in Eq. 15 [60] ... 

Since oximes are reduced to imines with buffered aqueous TiCb, one can assume that reduction of nitronate anions might progress through a similar mechanism. With regard to the reduction of nitro compounds themselves, there is some evidence for the intermediacy of a nitroso compound (178 Scheme 43). Indeed, at low pH tautomerization of (178) to oxime (179) would be rapid, whereas with TiCb-NH4OAC at pH 6 the nitro group is trapped to give only pyrroline (183), due to slow tautomerism. 

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