Tertiary amines oxidation reactions

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 reaction of tertiary amine oxides with nitrous acid has also been shown to produce N-nitroso compounds. The mechanism for the amine oxides is similar to that for the tertiary amines (26). 

Tertiary amine oxides can be converted into TV-hydroxy secondary amines provided that one of the TV-substituents can be selectively eliminated. This procedure has been applied to the synthesis of secondary A-hydroxy-a-amino acids 34 from the corresponding secondary a-amino acids using the /V-cyanoethyl group for transient protection of the secondary amine (Scheme 10) J40l More recently, direct oxidation with 2,2-dimethyldioxirane of a primary amine has been described for H-L-Val-OMe (82% yield) and H-L-Phe-OMe (54% yield))13 The reaction proceeds smoothly without epimerization, but no experimental details have been reported. 

Deoxygenation of amine oxides. Trialkylamine N-oxides and dialkylarylam-ine N-oxides are converted to the tertiary amines on reaction with this anhydride in CH2C12 at 25°.1... 

Inclusion in the reaction of a cooxidant serves to return the osmium to the osmium tetroxide level of oxidation and allows for the use of osmium in catalytic amounts. Various cooxidants have been used for this purpose historically, the application of sodium or potassium chlorate in this regard was first reported by Hofmann [7]. Milas and co-workers [8,9] introduced the use of hydrogen peroxide in f-butyl alcohol as an alternative to the metal chlorates. Although catalytic cis dihydroxylation by using perchlorates or hydrogen peroxide usually gives good yields of diols, it is difficult to avoid overoxidation, which with some types of olefins becomes a serious limitation to the method. Superior cooxidants that minimize overoxidation are alkaline t-butylhydroperoxide, introduced by Sharpless and Akashi [10], and tertiary amine oxides such as A - rn e t h y I rn o r p h o I i n e - A - o x i d e (NMO), introduced by VanRheenen, Kelly, and Cha (the Upjohn process) [11], A new, important addition to this list of cooxidants is potassium ferricyanide, introduced by Minato, Yamamoto, and Tsuji in 1990 [12]. 

The following reaction mechanism was ruled out by the authors cited [4 + 2] cycloaddition of the diene with the nitrone to give tertiary amine oxide, 7-21, which then thermally rearranges to the product. (Thermal rearrangement of a tertiary amine oxide to an alkylated hydroxylamine is called a Meisenheimer rearrangement.)... 

The thermal decomposition of sulfoxides whose sulfur atom is attached to the a carbons of ketones or esters leads to a,(3-unsaturated ketones or esters, respectively, via a cis elimination. The reaction is reminiscent of alkene formation by Cope elimination of dialkylhydroxylamines from tertiary amine oxides (equation 567) [321]. 

Tertiary amine oxides fragment on heating to give an alkene and an N,N-dialkyIhydroxylamine (e.g. equations 1 and 2). This reaction was studied extensively by Cope, and is commonly referred to as the Cope elimination . ... 

Figure 4 Representative illustrations of primary amine oxidation (A), secondary amine oxidation (B), tertiary amine oxidation (C), and xenobiotics that undergo N-hydroxylation or oxidation reactions (D).

Reductive desulfurization of the dithioketals 5.14 and 5.15 is performed under the same conditions as for thioethers [G02] LAH in the presence of copper salts or borohydrides in the presence of nickel salts (Figure 5.8). The deoxygenation of tertiary amine-oxides such as 5.16 and 5.17 can be performed with borohydride exchange resin-copper sulfate in methanol at room temperature or under reflux. This reaction tolerates other functional groups such as carbon-carbon double bonds, chlorides, epoxides, esters, amides, nitriles, sulfoxides, and sulfones [SA4] (Figure 5.8). 

As the name suggests, the reverse Cope elimination reaction involves formation of a tertiary amine oxide from a hydroxylamine and olefin.17,18 For example, reaction of N-methylhydroxylamine (49) with 2,2-diphenyl-4-pentenal (50) in ethanol at room temperature gave amine oxide 51 in 51% yield, together with the expected nitrone 52. It has been suggested the mechanism of the reverse Cope reaction could be a radical chain reaction19,20 however, more recent studies have confirmed the mechanism is analogous to the concerted Cope elimination.17... 

Tertiary amine oxides have been shown to oxidize arenesulphinyl chlorides to sulphonic acids, albeit in low yields290,291. In this reaction other products, such as thiosulphonates, are also produced. 

Amine oxides undergo a reaction similar to the Hofmann elimination reaction, called a Cope elimination reaction. In a Cope elimination reaction, a tertiary amine oxide rather than a quaternary anunonium ion undergoes elimination. The Cope elimination reaction occurs under milder conditions than does a Hofmann elimination reaction. 

Elimination reactions of quaternary ammonium hydroxides or tertiary amine oxides (Sections 21.5 and 21.7). 

Allylamine will react with ethylbromide to form ethylallylamine this will be accompanied by loss of hydrogen bromide. An excess of allylamine must be used in order to avoid polyalkylation of the amine. Methyl iodide will react with an excess of ethylallylamine to form methylethyl-allylamine with loss of hydrogen iodide. Subsequent reaction of the tertiary amine with hydrogen peroxide will produce the tertiary amine oxide, methylethylallylamine oxide. The reaction sequence can be shown as ... 

Pyrolysis of tertiary amine oxides (the Cope elimination reaction) also offers relatively mild reaction conditions (100-200 °C). Oxidation of the tertiary amine... 

Related to these reactions is the oxidation of alkyl halides or tosylates to carbonyl compounds with dimethyl sulfoxide (or trimethylammonium A/-oxide). The reaction is effected simply by warming the halide (normally the iodide) or sulfonate in DMSO (or MeaNO), generally in the presence of a proton acceptor such as sodium hydrogen carbonate or a tertiary amine. Oxidation never proceeds beyond the carbonyl stage and other functional groups are unaffected. The reaction has been applied to benzyl halides, phenacyl halides, primary sulfonates and iodides and a limited number of secondary sulfonates. With substrates containing a secondary rather than primary halide or sulfonate elimination becomes an important side reaction and the oxidation is less useful with such compounds. 

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