Peracids, amine oxidation

Owiag to the lower basicity of the parent amines, aromatic amine oxides cannot be formed directiy by hydrogen peroxide oxidation. These compounds may be obtained by oxidation of the corresponding amine with a peracid perbenzoic, monoperphthaUc, and monopermaleic acids have been employed. 

Direct oxidation of primary amines with peroxide oxidants does not provide appreciable yield of hydroxylamines. As was mentioned above, oxidation of secondary amines usually proceeds smoothly giving moderate to good yields of iV,iV-disubstituted hydroxylamines. Oxidation of sterically hindered secondary amines such as 125 (equation 88) can also be done with peracids . Further oxidation of the resulting Af,A-disubstituted hydroxylamines 126 with an excess of m-chloroperbenzoic acid is known to end up with the corresponding nitroxyl radicals of type 127 (equation 88) ° although the reaction can be stopped at the hydroxylamine stage. 

Thietes can be prepared by elimination from appropriately substituted thietanes. 2,4-Diarylthiete 1,1-dioxides (146 and 147) were produced in good yields by peracid oxidation and intramolecular amine oxide elimination of 3-dimethylaminothietane 1,1-dioxides (Eq. 23). 

Tertiary amines can be converted to amine oxides by oxidation. Hydrogen peroxide is often used, but peracids are also important reagents for this purpose. Pyridine and its derivatives are oxidized only by peracids.421 In the attack by hydrogen peroxide there is first formed a trialkylammonium peroxide, a hydrogen-bonded complex represented as R,NH202, which can be isolated.422 The decomposition of this complex probably involves an attack by the... 

This mechanism is the same as that of 9-24 the products differ only because tertiary amine oxides cannot be further oxidized. The mechanism with other peracids is probably the same. Racemic p-hydroxy tertary amines have been resolved by oxidizing them with /-BuOOH and a chiral catalyst—one enantiomer reacts faster than the other.424 This kinetic resolution gives products with enantiomeric excesses of >90%. 

It is well known that other non-metal oxides can react with hydrogen peroxide to form similar compounds which can be viewed as inorganic peracids. Such species include boron(III), arsenic(III) and selenium(IV). For example, selenium dioxide can be used as a catalyst for epoxidations or amine oxidations through perselenous acid (Figure 2.29).86... 

The highly acidic conditions required to generate peracids in situ from carboxylic acids and hydrogen peroxide are usually not conducive to efficient amine oxidation. In situ generation from anhydrides in neutral solution or other acylated agents in alkali can be employed. In situ perphthalic or permaleic have been reported for pyrimidine oxidation.332... 

Aqueous or alcohol solutions of amine oxides are normally obtained by oxidizing tertiary amines with either hydrogen peroxide or a peracid.4 For example, N,N-dimethyldodecyl-amine oxide has been prepared by treating N,N-dimethyl-dodecylamine with aqueous hydrogen peroxide.5 The procedure illustrated in this preparation permits the oxidation of tertiary amines with /-butyl hydroperoxide in organic solvents under relatively anhydrous conditions.6 In this procedure the reaction time is short and the method is as convenient as the use of aqueous hydrogen peroxide or a peracid as the oxidant. Furthermore, isolation of the anhydrous amine oxide is often relatively simple. 

Sulfoxides, prepared by the oxidation of sulfides with NaI04 or peracid, undergo elimination to give the alkenes at temperatures similar to the amine oxides (Scheme 4.12). 

Peroxy propionic acid (C2H5CO3H) [340], peroxylauric acid (C11H23CO3H) [174], and other aliphatic peroxy acids [341] are used rarely, and the results do not differ appreciably from those obtained from more common peracids. The same is true of peroxypentafluorobenzoic acid, C FjCOjH, which is obtained from pentafluorobenzaldehyde and ozone and is used for epoxidations the Baeyer-Villiger reaction and the preparation of amine oxides, sulfoxides, and sulfones [342]. 

Triacetonamine and 2,2,6,6-tetramethyl-4-piperidinol are oxidized by the hydrogen peroxide-sodium carbonate system very selectively, giving practically a quantitative yield (45). For amine oxidation, the hydrogen peroxide-acetonitrile system is often effective enough (46,47), while for hindered piperidine oxidation, peracids can be also used. 

Several other oxidizing agents can be made from hydrogen peroxide and thus be derived indirectly from oxygen. These include sodium perborate, sodium percarbonate, urea peroxide, peracids, potassium peroxymonosulfate, amine oxides, dioxiranes, and iodosobenzene (4.24). 

Molecules containing reduced oxygen species, e.g. alkyl hydroperoxides, peracids, periodate, hypochlorite, hydrogen peroxide, amine oxides, and iodosoarenes, are also capable of reducing dioxygen in the presence of P450. It is this that gave the impetus to the development of models based on simple porphyrin systems. 

Study the reaction shown in the following. Don t worry for the present about the protecting groups on the oxygen atoms we will meet these in detail later (Chapter 20), and they don t participate in this reaction. The peracid oxidizes the amine to an amine oxide. Write a mechanism for the elimination process and explain why it shows the regiochemistry observed ... 

Amine oxides are prepared by the oxidation of tertiary amines with peroxides or peracids to yield materials that, while possessing a formal charge separation on the nitrogen and oxygen atoms, behave as nonelectrolytes ... 

Commercially, pure ozonides generally are not isolated or handled because of the explosive nature of lower molecular weight species. Ozonides can be hydrolyzed or reduced (eg, by Zn/CH COOH) to aldehydes and/or ketones. Hydrolysis of the cycHc bisperoxide (8) gives similar products. Catalytic (Pt/excess H2) or hydride (eg, LiAlH reduction of (7) provides alcohols. Oxidation (O2, H2O2, peracids) leads to ketones and/or carboxyUc acids. Ozonides also can be catalyticaHy converted to amines by NH and H2. Reaction with an alcohol and anhydrous HCl gives carboxyUc esters. 

It is interesting to note that the oxidation of sulphoxides by peracids is faster in alkaline than in acidic solution. This is in contrast to the oxidation of sulphides and amines with the same reagents " . The oxidation rate of ortho-substituted aryl alkyl sulphoxides with aromatic peracids is less than the corresponding meta- and para-substituted species due to steric hindrance of the incoming peracid anion nucleophiles . Steric bulk in the alkyl group also has some effect . Such hindrance is not nearly so important in the oxidation reaction carried out under acidic conditions . 

To avoid overoxidation, primary amines (e.g. 128, equation 89) can be converted into Schiff bases with an aromatic aldehyde. Subsequent oxidation of the resultant imines 129 with an excess of peracids produces oxaziridines 130 and/or nitrones 131. Both of them produce hydroxylamines 132 (equation 89) upon hydrolysis in moderate to good overall yields. Yields of hydroxylamines are considerably better if anisaldehyde instead of benzaldehyde is used for the protection . ... 

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