The oxidation of amines

This replacement is achieved by the decomposition of the aryldiazonium fluoroborate with aqueous sodium nitrite in the presence of copper powder and is described in Expt 6.78. This procedure gives better yields and thus replaces the former method of reacting an acidic aryldiazonium salt solution with nitrous acid in the presence of copper(i) oxide. 

CAUTION This reaction should be carried out in a fume cupboard behind a safety screen. Adequate precautions should be observed in handling the hydrogen peroxide solution (Expt 5.190, Note (7)). 

The compounds described and discussed below are those in which the halogen is directly attached to the aromatic nucleus (e.g. C6H5C1, or PhCl, chlorobenzene) and those in which the halogen is substituted into an alkyl side chain (e.g. C6H5-CH2C1, or Ph-CH2C1, benzyl chloride). 

---

The oxidation of amines by mercuric acetate is an old reaction (54) which up until recent years was employed primarily to modify alkaloid structures (55). A systemic study of the oxidizing action of mercuric acetate by Leonard and co-workers led to the development of a general method for the synthesis of enamines from cyclic tertiary amines. An observation made after a large number of compounds were oxidized, but which is worth noting at the onset, is that a tertiary hydrogen alpha to the nitrogen atom is removed preferentially to a secondary a-hydrogen. 

Conversely, the use of elevated temperatures will be most advantageous when the current is determined by the rate of a preceding chemical reaction or when the electron transfer occurs via an indirect route involving a rate-determining chemical process. An example of the latter is the oxidation of amines at a nickel anode where the limiting current shows marked temperature dependence (Fleischmann et al., 1972a). The complete anodic oxidation of organic compounds to carbon dioxide is favoured by an increase in temperature and much fuel cell research has been carried out at temperatures up to 700°C. 

Kinetic analysis of the results of ketone oxidation in the presence of amine II reveals that the velocity constant of the oxidation of amines by acyl per-oxy radicals must be greater (by a factor of 2 - 3) than that of the interaction of these radicals with the nitroxide-i. In this reaction, acyl peroxy radicals are captured and destroyed by amines. 

Also in the case of a polymer therefore, provided the acyl peroxy radicals are formed by ketone photolysis in the presence of oxygen, the oxidation of amines by these radicals would make a significantly greater contribution to stabilization than the nit-roxide. The latter is in any case present in only very small amount as secondary producti - -. 

Hydroperoxides oxidize aromatic amines more readily than analogous phenols. Thus, at 368 K cumyl hydroperoxide oxidizes a-naphthylamine and a-naphthol with ku = 1.4 x 10 4 and 1.7 x 10 5L mol-1 s 1, respectively [115,118], The oxidation of amines with hydroperoxides occurs apparently by chain mechanism, since the step of free radical generation proceeds much more slowly. This was proved in experiments on amines oxidation by cumyl hydroperoxide in the presence of /V,/V -diphcnyl-l, 4-phcnylcnediamine (QH2) as a radical acceptor [125]. The following reactions were supposed to occur in solution (80% decane and 20% chlorobenzene) ... 

It has been proposed that Ru plays an important role in the oxidation of amines coordinated to ruthenium. A ruthenium(IV) amido species, [Ru(sar-H)] ", characterized by UV-vis spectroscopy, has been generated by two-electron oxidation of [Ru(sar)] " " (sar = 3,6,10,13,16,19-hexa-azabicyclo[6.6.6]eicosane)." This species is short lived and is rapidly transformed into a Ru(II) imine species. 

This group of enzymes catalyzes the oxidation of amines. Amine oxidase [EC 1.4.3.4], a flavin-containing enzyme (also known as monoamine oxidase, tyramine oxidase, tyraminase, or adrenalin oxidase) catalyzes the reaction of an organic amine R—CH2—NH2) with dioxygen... 

While it is well established that HO—ONO can be involved in such two-electron processes as alkene epoxidation and the oxidation of amines, sulfides and phosphines, the controversy remains concerning the mechanism of HO-ONO oxidation of saturated hydrocarbons. Rank and coworkers advanced the hypothesis that the reactive species in hydrocarbon oxidations by peroxynitrous acid, and in lipid peroxidation in the presence of air, is the discrete hydroxyl radical formed in the homolysis of HO—ONO. The HO—ONO oxidation of methane (equation 7) on the restricted surface with the B3LYP and QCISD methods gave about the same activation energy (31 3 kcalmol" ) irrespective of basis set size . ... 

VII. OXYGEN ATOM TRANSFER FROM SELECTED HYDROPEROXIDES A. The Oxidation of Amines... 

It is not surprising that the proton relay for sulfide oxidation (Figure 34) can be extended to the involvement of both HO—OH and RO—OH dimers in the oxidation of amines ". The dimeric forms of the hydroperoxides can reduce the activation barriers as evidenced by the HO—OH and CH3O—OH dimeric oxidation of TMA (Figure 35). The activation barrier for TMA oxidation with dimeric HO—OH is effectively reduced by 12.1 kcalmoU relative to the same oxidation of TMA with monomeric HO—OH (25.8 kcalmoU, Figure 30). 

Nitrenium ions can be viewed as products from two-electron oxidation of amines (Fig. 13.13) followed by loss of a proton. Thus they need to be considered as intermediates in the oxidation of amines. In two early studies, diarylnitrenium ions were shown to have formed in the oxidation of diarylamines. Svanholm and Parker carried out cyclic voltammetry on A,A-di-(2,4-methoxyphenyl)amine (25) in acetonitrile with alumina added to suppress any adventitious nucleophiles. The voltam-mogram revealed two sequential oxidation processes (1) formation of the cation radical 26, and (2) either the nitrenium ion 27 or its conjugate acid. In strongly acidic solution the latter was sufficiently stable that its absorption spectrum could be recorded. 

Mercuric acetate has been used for the oxidation of amine groups to give modified alkaloid structures [105-120]. 

The Oxidation of Amines and Alcohols The Disproportionation of Hydroxylamine Miscellaneous Reactions... 

Oxidative dehydrogenation reactions of alcohols and amines are widespread in enzymatic biochemistry, and are of potential importance with regard to the operation of fuel cells based on simple alcohols such as methanol. The nature of products, and their rates of formation, may vary depending on the reaction conditions, and a role of metal ions has been recognized. The oxidation of amines may lead to a variety of products (nitriles, nitro species, etc.) although dehydrogenated diimine products are obtained quantitatively when the oxidation of the amine occurs via coordination to metal centers. A review is available on the mechanisms of oxidative dehydrogenations of coordinated amines and alcohols (93). 

For reviews on the oxidation of amines, see Rosenblatt Burrows, in Patai The Chemistry of Functional Groups, Supplement F, pt. 2 Wiley New York, 1982, pp. 1085-1149 Challis Butler, in Patai The Chemistry of the Amino Group Wiley New York, 1968, pp. 320-338. For reviews confined to primary aromatic amines, sec Hcdayalullah Bull. Soc. Chim. Fr. 1972, 2957 Surville Jozefowicz Buvet Ann. Chem. (Paris) 1967, [14] 2, 149-157. 

Amine oxidation. As well as the microsomal enzymes involved in the oxidation of amines, there are a number of other amine oxidase enzymes, which have a different subcellular distribution. The most important are the monoamine oxidases and the diamine oxidases. The monoamine oxidases are located in the mitochondria within the cell and are found in the liver and also other organs such as the heart and central nervous system and in vascular tissue. They are a group of flavoprotein enzymes with overlapping substrate specificities. Although primarily of importance in the metabolism of endogenous compounds such as 5-hydroxy try pt-amine, they may be involved in the metabolism of foreign compounds. 

Monoamine oxidase (MAO) serves as a marker enzyme for outer membrane. There is some MAO activity in the inner membrane and therefore also in SMPs however, a high level of monoamine oxidase in the SMP preparation indicates a large contamination by outer membrane. Mitochondrial monoamine oxidase is an FAD-dependent enzyme that catalyzes the oxidation of amines to aldehydes (Equation E10.2). A convenient assay for this enzyme uses benzylamine as substrate and monitors the rate of ben-zaldehyde production at 250 nm. 

Another method which should prove suitable is that of flash-photolysis (Norrish and Thrush, 1956) coupled with a similar flow system. However, oxidation in situ at low temperature may often be sufficient, and stabilizing substituents suitably located in the aromatic rings may increase the lifetime sufficiently for detection without the use of a flow technique. An interesting example of a class of neutral radicals which have only recently been studied systematically, and which appear to be important and relatively stable intermediates in the oxidation of amines, are the radicals R2NO, which are isoelectronic with the better known ketyls. 

Figure 14.22 Arrhenius plot for amide growth in the oxidation of amine crosslinked epoxy films.

Amine Oxidases. The most important function of amine oxidases appears to be the oxidation of amines formed during normal processes. Two types of amine oxidases are concerned with oxidative deamination of both endogenous and exogenous amines. Typical substrates are shown in Figure 7.10. 

Amine oxidases catalyze the oxidation of amines, diamines, and polyamines. According to their ability to recognize one of those substrates preferentially, amine oxidases may be divided into monoamine oxidases, diamine oxidases, and polyamine oxidases, respectively. Several different enzymes fall into the amine oxidase class, and the classification of some of them still remains ambiguous. The term monoamine oxidase (flavin-containing, EC 1.4.3.4) was introduced to contrast with copper-containing amine oxidases (EC 1.4.3.6). 

The oxidation of amines is very well documented in the scientific literature. Little work has been done in this area in industry (patent literature) over the past few years, however. One reason for this is certainly the frequently unsatisfactory yields in these reactions. 

Today, many stable radicals are known, as shown in Figures 1.11 and 1.12. However, most of them are nitroxyl radicals like NO or N02. Standard generation methods of nitroxyl radicals are as follows. One is the oxidation of amines or hydroxyamines by Pb02, or by less toxic oxidants such as oxone, Cu(OAc)2, mCPBA (eqs. 1.13 and 1.14). Another one is the reaction of nitro compounds with Grignard reagents (eq. 1.15) [9-14]. 

Fig. 22 Reactivity of oxometal (Ru) versus peroxometal (W) species in the oxidation of amines...

---