Oxidation nitrosoalkanes

Hindered di-t-alkylamines RNHBu1 (R = t-Bu, t-octyl or 1-adamantyl) have been synthesized from t-alkylamines as follows. Reaction with peracetic acid gave the nitrosoalkanes RNO, which were treated with t-butyl radicals, generated from t-butylhydrazine and lead(IV) oxide, to yield t-butyloxyhydroxylamines. Reduction with sodium naphthalide in THF gave the products (equation 12). The di-t-alkyl-amines are inert to methyl iodide and dimethyl sulphate but can be alkylated by methyl fluorosulphonate42. 

Carbazole oxidized by nickel peroxide in the absence of light and in the presence of 2-methyl-2-nitrosopropane gave the radical 71, an observation taken as additional evidence for the intermediacy of radical cations, trapped in this case by the nitrosoalkane, in oxidative dimerization of carbazoles (see Section II,A,2). 

Insertion of coordinated NO into one of the metal alkyls would yield a nitrosoalkane, which could dissociate and in turn react with the starting material via 0-atom transfer. The independent observation that PhNO reacted with Cp W(NO)(CH2SiMe3)2 to form Cp W(0)2(CH2SiMe3) in low yield supports the role of the nitrosoalkane as an alternative oxidant. 

Complexes involving oxime ligands display a variety of reactivity modes that lead to unusual types of chemical compounds. As far as the oxime chemistry of platinum is concerned, these complexes are involved in facile deprotonation of the OH group with formation of oximato complexes, reduction of Pt(IV) species, Pt(II)-assisted reactions with coordinated allene," alkylation by ketones, oxime-ligand-supported stabilization of Pt(III)—Pt(III) compounds, oxidative conversion into rare nitrosoalkane platinum(II) species, and coupling with organocyanamides. ... 

At low concentrations of chlorine, dimeric nitrosoalkanes free from chlorine are produced when alkanes are treated also with nitric oxide. Under these circumstances, molecular chlorine is first converted into atomic chlorine which attacks the alkane to form alkyl radicals and hydrogen chloride. The alkyl radicals, in turn, form nitrosoalkanes with nitric oxide. This reaction is most effectively carried out when the ultraviolet radiation is between 380 and 420 mp. [43, 56],... 

From a preparative point of view one ef the more Important oxazwaue reactions is their oxidation te nitrosoalkanes. This is eon-... 

Although nitric oxide is frequently used as an inhibitor in free radical reactions, its role is not fully understood. Presumably alkyl radicals first combine with the nitric oxide to form the nitrosoalkane ... 

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). 

MCPBA has been regarded as the reagent of choice for the conversion of primary aliphatic amines into the corresponding nitro compounds. The peroxy acid must be used in excess to minimize formation of dimers of the intermediate nitroso compounds, llie yield of nitroalkane is also increased if the reaction is carried out at elevated temperature, since this favors the monomeric rather than the dimeric foim of the intermediate nitrosoalkane and allows it to be oxidized further. For example, cyclohexylamine gave the dimer of nitrosocyclohexane (43%) when oxidized by MCPBA at 23 C, but at 83 C (in boiling 1,2-di-chloroethane) the only product was nitrocyclohexane (86%). 

Attempted nitration of dichloro(phenyl)phosphine under mild conditions results only in oxidation at phosphorus.The phosphinate esters (95) have been isolated from the reactions of chlorodialkylphosphines with 1,l-dichloro-l-nitrosoalkanes. 

Metabolite intermediate complexation of CYP450. In this case the drug is acted upon by the enzyme to form an oxidised derivative with a high affinity for the iron at the active site. Examples of this type of inhibition include alkylamine drugs that undergo oxidation to nitrosoalkane derivatives. Inhibition of this type renders the enzyme unavailable for further oxidation and synthesis of new enzyme is required to restore CYP450 activity. 

The probable reaction course to the nitroalkane (XI), after the formation of the amine-ozone adduct (Reaction 1), is shown by Reactions 7 to 9 and summed up in Reaction 10. A primary amine oxide would not be expected to be stable and should rearrange to the hydroxylamine (IX, Reaction 7). A similar set of reactions (Reaction 8) should result in the nitrosoalkane (X), which should then be converted to the nitroalkane (XI) as shown in Reaction 9. Evidence for this series of reactions was the observation of the blue color of the nitrosoalkane (X) throughout the ozonation and the demonstration, in separate experiments, that the hydroxylamine (IX) reacts with two mole equivalents of ozone and the nitrosoalkane (X) with one mole equivalent of ozone, each to give the nitroalkane (XI). 

Nitrosoalkanes condense with diethyl phosphoramidate in the presence of Bu OCl, A/ -bromosuccinimide, or more particularly, of dibromoisocyanurate, to give (diethoxyphosphinoyl)diazene oxides it is thought that this reaction proceeds through the... 

Nitrogen Compounds. The aqueous Oxone-acetone combination has been developed for the transformation of certain anilines to the corresponding nitrobenzene derivatives, as exemplified in eq 15. This process involves sequential oxidation steps proceeding by way of an intermediate nitroso compound. In the case of primary aliphatic amines, other reactions of the nitrosoalkane species compete with the second oxidation step (for example, dimerization and tautomerization to the isomeric oxime), thereby limiting the synthetic generality of these oxidations. An overwhelming excess of aqueous Oxone has been used to convert cyclohexylamine to nitrocyclohexane (eq 16)P... 

It has been shown by isotopic labelling that the exchange reaction of nitrosoalkanes with nitric oxide occurs via oxygen atom transfer, and not by a displacement mechanism (Scheme 132). 

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