Amine oxides hydroxylamines

B. Reduction The enzymology of reduction is not as well as characterized as for oxidation but, for example, reductive reactions can be catalyzed by cytochrome P-450 and P-450 reductase and soluble enzymes such as DT-diaphorase (EC 1.6.99.2) Many compounds including azo-and nitro-compounds, epoxides, heterocycles and halogenated hydrocarbons Sources of reducing equivalents for the reactions include NAD PH and NADH. Chemical groups modified include nitro, nitroso, tertiary amine oxide, hydroxylamine, azo, quinone, nitroso, alkylhalide... 

Primary amino groups are oxidized stepwise by ozone to hydroxylamine, nitroso, and nitro (54,58) tertiary amines are oxidized to amine oxides. 

Rearrangement, Aliphatic amine oxides without an ahphatic hydrogen atom P to the nitrogen undergo Meisenheimer s rearrangement when heated to give trisubstituted hydroxylamines. 

Elimination. Ahphatic amine oxides having an ahphatic hydrogen P to the nitrogen form olefins and diaLkyl hydroxylamines when heated. This reaction is known as the Cope elimination (17)... 

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

As shown in Fig. 6.4, primary amines are converted to oximes, secondary amines to hydroxylamines, and tertiary amines to N-oxides.34... 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

The actual oxidant may be peroxyseleninic acid, H0Se(0)00H, which is known to oxidize secondary amines to hydroxylamines. 

Tertiary Amines to Amine Oxides and Hydroxylamines to Nitrones... 

SCHEME 150. Ti-catalyzed oxidation of primary amines to hydroxylamines or oximes... 

In the reaction of pyridazine 26 with perfIuoro-(2-butyl-3-propyloxaziridine) 38 both pyridazin-1-oxide 39 and T-(perf1uorobutanoyl)pyridazinium-l-aminide 40 were formed (Equation 9) <1996J(P1)2517>. In CHEC(1984) <1984CHEC(2)1> and CHEC-II(1996) <1996CHEC-11(6)1>, the N-amination with hydroxylamine-O-sulfonic acid and derivatives was covered. 

Murray Singh Synth. Commun. 1989, 19. 3509. This reagent also oxidizes primary amines to hydroxylamines Wittman Halcomb Danishefsky/. Org. Chem. 1990,55, 1981. 

Tertiary amine oxides and hydroxy la mines are also reduced by cytochromes P-450. Hydroxylamines, as well as being reduced by cytochromes P-450, are also reduced by a flavoprotein, which is part of a system, which requires NADH and includes NADH cytochrome b5 reductase and cytochrome b5. Quinones, such as the anticancer drug adriamycin (doxorubicin) and menadione, can undergo one-electron reduction catalyzed by NADPH cytochrome P-450 reductase. The semiquinone product may be oxidized back to the quinone with the concomitant production of superoxide anion radical, giving rise to redox cycling and potential cytotoxicity. This underlies the cardiac toxicity of adriamycin (see chap. 6). 

Cyclodextrin ketones have been used as powerful catalysts of amine oxidation in the presence of hydrogen peroxide as the stoichiometric oxidant. This oxidation follows Michaelis-Menten kinetics and depending on the substrate the oxidation rate is increased up to 1100-fold. It has been proposed that hydrogen peroxide reacts with the ketone to form a hydroperoxide adduct and this adduct is responsible for oxidizing the amine, bound in the cavity, to the hydroxylamine.189... 

The most studied kinds of explosives are nitroaromatic explosives and their metabolites. Therefore, the emphasis of this review is on properties of nitroaromatic explosives, rather than propellants, pyrotechnics, or munitions, and their interactions with soils. Nitroaromatic explosives are toxic, and their environmental transformation products, including arylamines, arylhydroxyl-amines, and condensed products such azoxy- and azo-compounds, are equally or more toxic than the parent nitroaromatic [3]. Aromatic amines and hydroxylamines are implicated as carcinogenic intermediates as a result of nitrenium ions formed by enzymatic oxidation [4], Aromatic nitro compounds... 

Secondary amines are easily oxidized to hydroxylamines. Side products are often formed, however, and the yields may be low. The mechanisms of amine oxidations are not well characterized, partly because many reaction paths (especially those involving free radicals) are available. 

A variation of the Hofmann elimination, where a tertiary amine oxide eliminates to an alkene with a hydroxylamine serving as the leaving group, (p. 907)... 

Microsomes contain, in addition to the two cytochrome reductases just discussed, a flavoprotein which catalyzes the mixed function oxidation of secondary and tertiary amines to the hydroxylamines and amine oxides, respectively (333, 334). This flavoprotein, which contains about 2 moles of phospholipid and 1 mole of FAD per 70,000 g of protein, is specific for NADPH (333, 334) The enzyme is also able to catalyze the further oxidation of the hydroxylamines to nitrones (336). The reactions... 

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