Oxidation of the secondary amine

A second-order dependence on crotonic acid has been observed in its Os(VIII)-catalysed oxidation with CAT in alkaline solution. The reaction rate varied linearly with the concentration of Os(VIII). A mechanism has been proposed.140 The kinetics of the ruthenium(III)-catalysed oxidation of the secondary amines with CAT in acidic medium have been obtained and mechanisms have been postulated.141 Uncatalysed and Ru(III)-catalysed oxidation of ethylenediamine, diethylenetriamine, triethylenete-tramine, aminoethylpiperazine, and isophoronediamine with CAT in HC1 solution showed a fractional dependence on the amine, hydrogen ions, and Ru(III), and it is independent of CAT concentration. TSNH2CI has been postulated as the reactive species and a mechanism has been suggested.142... 

Oxidation of the 1-benzyltetrahydroisoquinoline (195) with VOCl3 (145) yielded the dienone (196) in 34% yield reaction of this with boron trifluoride etherate provided 197, and this was converted, as shown in Scheme 41, to 14-methoxyerysodienone (199). Oxidation of the secondary amine (200) gave (146) the methoxyerysodienone (201) in only 6% yield. The alternative mode of oxidation, leading to 202, was not observed. 

The ring system of the homoerythrina alkaloids has been prepared (149) by oxidative coupling of the 1-phenethyltetrahydroisoquinoline (206, R = COCF3) (Scheme 44). The diphenol (208) was obtained in 76% yield from 207, but all attempts to oxidize the A-trifluoroacetate of 208 to a dipheno-quinone failed—probably because the two aromatic rings are orthogonal to each other. However, oxidation of the secondary amine (208) itself with potassium ferricyanide gave a mixture of 209 (45% yield) and 210 (15%) ... 

PhenoUc oxidative coupling. Oxidation of the secondary amine (I) with potassium ferricyanide in the presence of sodium hydrogen carbonate in chloroform gives the dienone (2, norerylhrinadienone). ... 

The importance of fully or partially hydrogenated isoxazolo[2,3-a]pyridines as intermediates in the synthesis of stereochemically complex molecules, particularly alkaloids, has led to a continued high level of interest in their preparation. The route of choice remains the 1,3-dipolar cycloaddition reaction between a tetrahydropyridine A-oxide, that is a nitrone, and a dipolarophile. A number of methods for the production of the nitrone for in situ reaction have been developed. They include the oxidation of the secondary amine, piperidine, with hydrogen peroxide in the presence of... 

Tryptoquivalines appear to be tetrapeptides derived from tryptophan, an-thranilic acid, valine, and alanine (or methylalanine). Deoxynortryptoquivalone (FTN) may be the first metabolite formed in the pathway of tryptoquivaline biosynthesis. Oxidation of the secondary amine to the hydroxyamine would form nortryptoquivalone. If the isobutyl side chain from the above tryptoquivalones is lost by further oxidation, FTJ and FTE would result. On the other hand, if reduction of the carbonyl group following acetylation occurs on the side chain, nortryptoquivaline (FTD) or deoxynortryptoquivaline respectively, would be... 

Yamazaki et al. (221) have postulated that the tryptoquivalines may be biogenetically derived from four amino acids tryptophan, anthranilic acid, valine and alanine. Deoxynortryptoquivalone is thought to be the first compound formed in the biosynthesis of the tryptoquivaline series. Oxidation of the secondary amine in this compound to a hydroxylamine would result in nortryptoquivalone. Oxidative loss of the side-chain would lead to FTE or FTJ. Alternatively, reduction of the side-chain carbonyl group would afford nortryptoquivaline. The geminal dimethyl group at C-15 may result from incorporation of a Cj-unit into deoxynortryptoquivalone or from the direct participation of methylalanine rather than alanine in the initial step of the biosynthesis. 

It is worth noting that tungstateamine with hydrogen peroxide gives nitrone (46) (Eq. (7.54)) [104]. These two catalytic transformations of secondary amines (Eqs. (7.51) and (7.54)) are particularly useful for the introduction of a substituent at the a-position of the amines, because either imines or nitrones undergo diastereo and enantioselective reactions with nucleophiles to give chiral a-substituted amines highly efficiently [105]. 

Condensation of normeperidine (81) with 3-chloropropan-l-ol affords the compound possessing the alcohol side chain (88). The hydroxyl is then converted to chlorine by means of thionyl chloride (89) displacement of the halogen by aniline yields pimino-dine (90). ° Condensation of the secondary amine, 81, with styrene oxide affords the alcohol, 91 removal of the benzyllic hydroxyl group by hydrogenolysis leads to pheneridlne (92). ... 

The cyclic metabolite 11.169 was also a substrate in further biotransformations, being (V-demethylated to the corresponding endocyclic imine, and oxidized to phenolic metabolites. Very little if any of the secondary amine metabolite (11.168) appeared to undergo direct (V-demethylation to the primary amine, in contrast to many other tertiary amines, presumably due to very rapid cyclization of the secondary amine facilitated by steric and electronic factors. The possibility for the iminium cation (11.169 H+) to become deprotonated (a reaction impossible for the iminium 11.166 in Fig. 11.20) should also drive the cyclization reaction. 

Oxidation of cyclic secondary amines such as pyrrolidine (351) and piperidine (353) with iodosobenzene in water leads to lactams 352 and 354, respectively (88TL6913, 88TL6917) (Scheme 90). Similar oxidation of 2-piperidinecarboxylic acid and 2-pyrrolidinecarboxylic acid is accompanied by decarboxylation. Cyclic tertiary amines 355, 357, and 359 (Eq. 48) are likewise oxidized to the corresponding lactams. Other examples include phencyclidine (360) to A-(l-phenylcyclohexyl)piperidone (361), N-(cyanocyclohexyl)piperidine (362) to A-(l-cyanocyclohexyl)piperidone (363) (Scheme 91), and 1,2,3,4-tetrahydroisoquinoline to 1,2,3,4-tetrahy-droisoquinolinone (Eq. 49). 

Polyamine oxidase (amine oxygen oxidoreductase, deaminating, flavin-containing), is also a FAD-dependent enzyme and has many similarities to MAO. It is responsible for the oxidation of the secondary amino group in such substrates as A/-acetyl spermine and spermidine in the biosynthesis of spermidine and putrescine [1,12], This enzyme will not be covered in this chapter. 

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. 

Hiotochemically induced oxidation of one secondary amine in the presence of 1,4-dicyanommhtlialene allows the introduction of oxygen into the position adjacent to the nitrogen atom (equation 34). Secondary amines have b oxidized to imines by several routes. The nitrogen atom can be halogen-... 

The one-electron oxidation of a secondary amine results in the formation of a secondary aminium ion which on deprotonation gives an aminyl radical (Scheme 1). The nature of the final products derived from these intermediates dqiends very much on the structure of the substrate and the reaction conditions. If the amine has a hydrogen atom on the a-carbon atom the major products usually result from deprotonation at this a-position. With aromatic secondary amines, products can result from coupling of the delocalized radicals at a ring carbon atom. The formal dimerization of aminyl radicals shown in Scheme 21 is therefore not often a useful method of preparation of hydrazines. Nickel peroxide has been used to oxidize diphenylamine to tetraphenylhydrazine in moderate yield, and other secondary arylamines also give... 

Nitroxyl forms nitrous oxide, and the secondary amine reacts with more nitrous acid giving the nitrosamine. Based on the observed isotope effect, the rate-determining step was thought to be the loss of HNO. Nitrous oxide is believed to arise from elimination of nitroxyl in many other reactions. 

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