Tertiary amine oxide

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

Tertiary phosphine oxides are stable. The temperatures required for thermal decomposition are approximately 300°C higher than the corresponding amine oxides (96). Trimethyl phosphine oxide is stable to 700°C. 

Amine oxides, known as A[-oxides of tertiary amines, are classified as aromatic or aliphatic, depending on whether the nitrogen is part of an aromatic ring system or not. This stmctural difference accounts for the difference in chemical and physical properties between the two types. 

However, when the temperature is increased to 120°C, the principal reaction is the elimination to olefin. The thermal decomposition of dimethyl dodecyl amine oxide at 125°C in a sealed system, as opposed to a vacuum used by Cope and others, produces 2-methyl-5-decyhsoxa2ohdine, dimethyl dodecyl amine, and olefin (23). The amine oxide oxidi2es XW-diaLkylhydroxylainine to the nitrone during the pyrolysis and is reduced to a tertiary amine in the process. 

Reduction. Just as aromatic amine oxides are resistant to the foregoing decomposition reactions, they are more resistant than ahphatic amine oxides to reduction. Ahphatic amine oxides are readily reduced to tertiary amines by sulfurous acid at room temperature in contrast, few aromatic amine oxides can be reduced under these conditions. The ahphatic amine oxides can also be reduced by catalytic hydrogenation (27), with 2inc in acid, or with staimous chloride (28). For the aromatic amine oxides, catalytic hydrogenation with Raney nickel is a fairly general means of deoxygenation (29). Iron in acetic acid (30), phosphoms trichloride (31), and titanium trichloride (32) are also widely used systems for deoxygenation of aromatic amine oxides. 

Amine oxides used in industry are prepared by oxidation of tertiary amines with hydrogen peroxide solution using either water or water and alcohol solution as a solvent. A typical industrial formulation is as follows ... 

Industrial specifications for aHphatic tertiary amine oxides generally requite an amine oxide content of 20—50%. These products may contain as much as 5% unreacted amine, although normally less than 2% is present. Residual hydrogen peroxide content is usually less than 0.5%. The most common solvent systems employed are water and aqueous isopropyl alcohol, although some amine oxides are available ia aoapolar solveats. Specificatioas for iadividual products are available from the producers. 

Analytical methods iaclude thin-layer chromatography (69), gas chromatography (70), and specific methods for determining amine oxides ia detergeats (71) and foods (72). Nuclear magnetic resonance (73—75) and mass spectrometry (76) have also been used. A frequentiy used procedure for iadustrial amine oxides (77) iavolves titratioa with hydrochloric acid before and after conversion of the amine to the quaternary ammonium salt by reaction with methyl iodide. A simple, rapid quaHty control procedure has been developed for the deterrniaation of amine oxide and unreacted tertiary amine (78). 

CH—NHOH) to oxime (C=NOH) and ultimately to the nitroalkane (CH—NO2). Hydrogen peroxide generates amine oxides from tertiary cycloaUphatic... 

Amine oxides, prepared to protect tertiary amines during methylation and to prevent their protonation in diazotized aminopyridines, can be cleaved by reduction (e.g., SO2/H2O, 1 h, 22°, 63% yield H2/Pd-C, AcOH, AC2O, 7 h, 91% yield Zn/HCl, 30% yield). Photolytic reduction of an aromatic amine oxide has been reported [i.e., 4-nitropyridine A-oxide, 300 nm, (MeO)3PO/CH2Cl2, 15 min, 85-95% yieldl. ... 

Tertiary amines can be oxidized to form amine oxides in which the amino nitrogen atom is linked to a single oxygen atom. The resulting compounds are basic dissolving in water thus ... 

Similarly the active oxygen of oxaziranes can be transferred to triphenylphosphine with the formation of ]ihosphine oxide and to tertiary amines yielding amine oxides. ... 

Amines are ammonia derivatives in which one or more hydrogen atoms have been replaced by an organic radical. Amines are sometimes called nitrogen bases. Basic chemistries include fatty amines (as primary, secondary, tertiary, and polyamines), amine salts, quaternary ammonium compounds, amine oxides, and amides. 

Tertiary amines can be converted to amine oxides by oxidation. Hydrogen peroxide is often used, but peroxyacids are also important reagents for this purpose. Pyridine and its derivatives are oxidized only by peroxyacids. In the attack by hydrogen peroxide there is first formed a trialkylammonium peroxide, a hydrogen-bonded complex represented as R3N-H202, which can be isolated. The decomposition of this complex probably involves an attack by the OH moiety of the H2O2. Oxidation with Caro s acid has been shown to proceed in this manner ... 

This mechanism is the same as that of 19-23 the products differ only because tertiary amine oxides cannot be further oxidized. The mechanism with other peroxyacids is probably the same. Racemic (3-hydroxy tertiary amines have been resolved by oxidizing them with t-BuOOH and a chiral catalyst one enantiomer reacts faster than the other.This kinetic resolution gives products with enantiomeric excesses of > 90%. 

One of the exciting results to come out of heterogeneous catalysis research since the early 1980s is the discovery and development of catalysts that employ hydrogen peroxide to selectively oxidize organic compounds at low temperatures in the liquid phase. These catalysts are based on titanium, and the important discovery was a way to isolate titanium in framework locations of the inner cavities of zeolites (molecular sieves). Thus, mild oxidations may be run in water or water-soluble solvents. Practicing organic chemists now have a way to catalytically oxidize benzene to phenols alkanes to alcohols and ketones primary alcohols to aldehydes, acids, esters, and acetals secondary alcohols to ketones primary amines to oximes secondary amines to hydroxyl-amines and tertiary amines to amine oxides. 

The reaction that is perhaps of the greatest synthetic utility—because it proceeds at relatively low temperatures—is the Cope reaction of tertiary amine oxides, e.g. (82) ... 

The mechanism of H02 formation from peroxyl radicals of primary and secondary amines is clear (see the kinetic scheme). The problem of H02 formation in oxidized tertiary amines is not yet solved. The analysis of peroxides formed during amine oxidation using catalase, Ti(TV) and by water extraction gave controversial results [17], The formed hydroperoxide appeared to be labile and is hydrolyzed with H202 formation. The analysis of hydroperoxides formed in co-oxidation of cumene and 2-propaneamine, 7V-bis(ethyl methyl) showed the formation of two peroxides, namely H202 and (Me2CH)2NC(OOH)Me2 [16]. There is no doubt that the two peroxyl radicals are acting H02 and a-aminoalkylperoxyl. The difficulty is to find experimentally the real proportion between them in oxidized amine and to clarify the way of hydroperoxyl radical formation. 

Amine oxides are readily reduced back to tertiary amines (Fig. 5.9). There are few drugs that are amine oxides, but there are many drugs that are tertiary amines and amine oxides are common metabolites. The amine oxide is often pharmacologically inactive however, because they are readily reduced back to tertiary amines, amine oxides can act as a buffer to the concentration of the tertiary amine. 

FIGURE 5.9 Reduction of tertiary amine oxides to tertiary amines. 

Cope Elimination oxidize 3° amine to tertiary ammonium oxide (R N -< V I. heat produces RHC=CH2... 

Few studies have systematically examined how chemical characteristics of organic reductants influence rates of reductive dissolution. Oxidation of aliphatic alcohols and amines by iron, cobalt, and nickel oxide-coated electrodes was examined by Fleischman et al. (38). Experiments revealed that reductant molecules adsorb to the oxide surface, and that electron transfer within the surface complex is the rate-limiting step. It was also found that (i) amines are oxidized more quickly than corresponding alcohols, (ii) primary alcohols and amines are oxidized more quickly than secondary and tertiary analogs, and (iii) increased chain length and branching inhibit the reaction (38). The three different transition metal oxide surfaces exhibited different behavior as well. Rates of amine oxidation by the oxides considered decreased in the order Ni > Co >... 

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