Oxidation of primary amines

Fig. 27. Oxidation of primary amines and hydrazo compounds with BTMA Br3...

Oxidation of Primary Amines, Oximes, Azides, Isocyanates, or Nitroso Compounds to Nitro Compounds... 

Oxidation of primary amines, oximes, azides, isocyanates, or nitroso... 

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. 

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). 

Oxidation of primary amines with DMD or other oxidants leads to the formation of a complex mixture of nitroso, oximes, and nitro compounds (76). Utilization of DMD in acetone affords dimethyl nitrone (22). This is likely to be a result of the initial oxidation of primary amine (19) to hydroxylamine (20) with the subsequent condensation of acetone and oxidation of imine (21) (Scheme 2.9) (77). 

Monoamine oxidase (MAO) is a mammalian flavin-containing enzyme that catalyzes oxidation of primary amines. While the neurotransmitter amines are... 

FIGURE 4.34 Postulated mechanisms for MAO-catalyzed oxidation of primary amines, (A) SET (B) HAT mechanism, and (C) polar mechanism. 

The first product in the oxidation of primary amines is a hydroxylamine as indicated in Figure 4.85. Hydroxylamines can be further oxidized to nitroso metabolites, which can be viewed as analogous to the oxidation of an alcohol to an aldehyde. If there is a hydrogen... 

FIGURE 4.85 Oxidation of primary amines leads to a hydroxylamine followed by a nitroso metabolite, which if there is a hydrogen on the a-carbon can rearrange to an oxime. Without such a hydrogen, as in the case of phentermine, no rearrangement is possible. 

Aromatic nitroso-compounds can also be obtained by oxidation of primary amines, but only one oxidising agent is known with which the process can satisfactorily be carried out. This reagent is monopersvl-phuric acid (Caro s acid) ... 

Indirect electro-oxidation of primary amines to nitriles is achieved using halogen ion as mediator [93]. The reaction is typically carried out in an undivided cell... 

Oxidation of primary amines at a nickel oxide results in the formation of a nitrile. Formation of the nickel oxide electrode was discussed on p, 270. The rate determining stage ss the reaction between electrochemically formed nickel(ni) ox-... 

Silver(ll) oxide, present on a silver anode in aqueous alkali, will also cany out the oxidation of primary amines to nitriles. Oxidation of the intermediate imine at the silver anode is however relatively slow so that hydrolysis to the aldehyde becomes an important side reaction [97], a-Amino acids give nitriles in good yields at the silver(li) oxide electrode. 

Nitroxyl mediated electro-oxidation of primary amines also leads to formation of the imine and the further oxidation to the nitrile. In anhydrous acetonitrile containing 2,6-lutidine as a base, the nitrile is formed. In aqueous acetonitrile, hydrolysis of the imine intermediate is fast and good yields of the aldehyde result... 

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. 

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

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. 

Using the selenobiphenol ligand HL mentioned in the previous paragraph, Chaudhuri and co-workers also isolated the trinuclear complex 22 and the dinuclear complex 23 (Scheme 9) [155]. The latter was shown to catalyze the selective aerial oxidation of primary amines with at least one... 

Table 14. Comparison of the oxidation of primary amines with the nickel hydroxide electrode and nickel peroxide...

Oxidation of hydroxylamines 9-24 Oxidation of primary amines 9-48 Reduction of nitro compounds... 

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