Oxidation of tertiary amines

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. 

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 ... 

Enamines via Mercuric Acetate Oxidation of Tertiary Amines. 

The preceding section described the preparation of enamines by mercuric acetate oxidation of tertiary amines. The initial product in these oxidations is the ternary iminium salt, which is converted to the enamine or mixture of enamines by reaetion with base. Thus iminium salts synthesized by methods other than the oxidation of tertiary amines or the protonation of enamines are potential enamine sources. 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

The key step in syntheses of if/-quebrachamine (122-127) and if/-dihydro-cleavamine (12S) is the oxidation of tertiary amines with mercuric acetate to cyclic imonium salts, which give rise to an intramolecular electrophilic attack on an indole. 

While the oxidation of tertiary amines has been used extensively for the generation of enamines, an example of overoxidation with formation of an acetoxyimonium salt has been reported (484). 

Rosenblatt etal have examined the effect of structure and isotopic substitution upon the permanganate oxidation of some alky famines (Table 4). The isotope effect of 1.84 is considered to be sufficiently low to be compatible with aminium radical-cation formation, and it is felt that, while C-H cleavage is significant for oxidation of primary amines, the dominant mode of oxidation of tertiary amines is electron-transfer, e.g. 

The use of m-CPBA allows the formation of nitrones in the oxidation of tertiary amines. The resulting amines A-oxides are subject to either Cope or Meisenheimer rearrangements, providing formation of nitrones. Thus, the generated corresponding nitrones in the oxidation of bicyclic aziridines give nitrones as a result of a Meisenheimer rearrangement (Scheme 2.14) (93). 

Oxidation of tertiary amines. Early investigations have shown that tertiary amines are oxidized by C102 to iminium ions, and this oxidation can be used to effect cyclization of 2-aminoethanols or 3-aminopropanols to bicyclic oxazolidines or tetrahydro-l,3-oxazines. 

The direct oxidation of tertiary amines leads to the formation of an iminium... 

Ottolina, G., Bianchi, S., Belloni, B., Carrea, G. and Danieli, B., First asymmetric oxidation of tertiary amines by cyclohexanone monooxygenase. Tetrahedron Lett., 1999, 40, 8483. 

Recently, Choudary et al. reported the first example of catalytic N-oxidation of tertiary amines by tungstate-exchanged Mg/Al LDHs in water [113], and the halodecarboxylation of Q ,/l-unsaturated aromatic carboxylic acids to /1-bromostyrenes has also been achieved for the first time, using a molybdate-exchanged Mg/Al LDH catalyst [114] this latter catalyst was active for selective oxidation [ 115,116]. 

The direct oxidation of an amino group to a nitro group is a desirable route to nitro compounds. The oxidation of tertiary amines with potassium permanganate has been known for some... 

SCHEME 152. V- and Mo-catalyzed oxidation of tertiary amines to A-oxides with hydroperoxides... 

Oxidation of organonitrogen compounds is an important process from both industrial and synthetic viewpoints . N-oxides are obtained by oxidation of tertiary amines (equation 52), which in some cases may undergo further reactions like Cope elimination and Meisenheimer rearrangement . The oxygenation products of secondary amines are generally hydroxylamines, nitroxides and nitrones (equation 53), while oxidation of primary amines usually afforded oxime, nitro, nitroso derivatives and azo and azoxy compounds through coupling, as shown in Scheme 17. Product composition depends on the oxidant, catalyst and reaction conditions employed. 

A similar mechanism was invoked by Ohshima and Kawabata (2) to account for their results in the nitrosation of tertiary amines and amine oxides. In applying these concepts to the nitrosative dealkylation of tetraalkyltetrazenes, Michejda al. 5) introduced an interesting variant by suggesting that immonium ions could be formed in two successive one-electron oxidation steps (for example by ferric ion oxidation of tertiary amine to the radical cation followed by radical abstraction of a hydrogen atom from the alpha position), rather than exclusively through the one-step removal of a hydride ion as nitroxyl. The resulting immonium ion was again considered to react directly with nitrite to produce the N-nitroso derivative. These reactions are summarized in Fig. 2b. 

The mercury(II) acetate oxidation of tertiary amines is a reaction which can be used to introduce unsaturation /3 to the nitrogen atom (equation 123). 

Although the Pt/02 reaction has been used for oxidation of primary and secondary alcohols [67], hydroxylation of 12a-deoxytetracyclines [68], oxygenation of cholesterol [69], and oxidation of tertiary amines [5f], this... 

Oxidation of Tertiary Amines to Amine Oxides /V-Oxygen-attachment... 

Alkyl hydroperoxides can oxidize a variety of other nucleophilic substrates in the presence of d° metal catalysts. Thus molybdenum and vanadium catalysts have been used for the selective oxidation of tertiary amines to the corresponding JV-oxides (equations 79 and 80).225,254... 

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