Ketone nitroxide

Sodium hydrogen telluride, (NaTeH), prepared in situ from the reaction of tellurium powder with an aqueous ethanol solution of sodium borohydride, is an effective reducing reagent for many functionalities, such as azide, sulfoxide, disulfide, activated C=C bonds, nitroxide, and so forth. Water is a convenient solvent for these transformations.28 A variety of functional groups including aldehydes, ketones, olefins, nitroxides, and azides are also reduced by sodium hypophosphite buffer solution.29... 

In the presence of the nitroxide I, DiPK photolysis yields - in amounts equivalent to the loss of ketone -the two combination products of nitroxyl with the isopropyl and isobutyryl radical respectively (Fig. 3, reaction (6)) ... 

As can be seen from Figure 3, the ratio of the isopropyl ether to isobutyrate is about 1 1. It is clear that after a-cleavage of the ketone the two radicals primarily formed are captured directly by nitroxide. This takes place without decarbonylation of the acyl radical (reaction (7)) ... 

In the presence of nitroxide I, diisopropyl ketone photooxidation takes a course differing considerably from that without this additive (Fig. 5). In this case high yields of isobutyric acid and acetone were obtained, presumably as products arising from the postulated peroxy radicals c and d. On the other hand, the formation of isopropanol is almost completely suppressed. 

Irradiation of diisopropyl ketone under oxygen in the presence of the hindered piperidine II likewise results in formation of isobutyric acid, acetone and small amounts of isopropanol. At the same time the amine is quantitatively oxidized to the corresponding nitroxide I (Fig. 7, reaction (17)) ... 

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. 

Separate experiments in which tert.-butoxy radicals were produced thermally in benzene from di-tert.-butyl peroxyoxalate failed to reveal any direct reaction of these radicals with amine II. Even at higher temperatures (A/ 150°C, dichlorobenzene, +00+ decomposition), the +0 radicals attacked neither amine II nor nitroxide I. The earlier described experiments of ketone photooxidation showed additionally that amine II displays no specially marked reactivity towards peroxy radicals. 

Nitrone cycloaddition reactions with alkynes have been widely used for the synthesis of imidazolidine nitroxides (736) and (737), containing chelating enam-ino ketone groups (821). Different heterocyclic systems were obtained, such as 3-(2-oxygenated alkyl)piperazin-2-ones (738) (822), also compounds containing the isoxazolo[3,2-i]indole ring system (739) (823) and a new class of ene-hydroxylamino ketones- (l )-2-( 1-hydroxy-4,4,5,5-tetraalkylimidazolidin-2-ylidene)ethanones (740) (824) (Fig. 2.46). 

During the 70 s, Celia et al. treated the hindered secondary amine 52 with / -chloroperbenzoic acid, with the intention of transforming it into the nitroxide 53.1 Unexpectedly, the oxidation of the amine functionality was accompanied by the transformation of the alcohol moiety into a ketone, resulting in the formation of compound 54. 

As peracids react very sluggishly with alcohols, it was apparent that the presence of a nitroxide was playing an important role in the oxidation of the alcohol into a ketone. This seminal serendipitous observation led to the development of the first description of the oxidation of alcohols mediated by catalytic 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) (55), published almost simultaneously by Celia et al and Ganem.3 These authors presented two papers with remarkably similar contents, in which alcohols were oxidized by treatment with MCPBA in CH2CI2 at room temperature in the presence of a catalytic amount of TEMPO (55). In both papers, a plausible mechanism is presented, whereby m-chloroperbenzoic acid oxidizes TEMPO (55) to an oxoammonium salt 56. This oxoammonium salt 56, as detailed in Ganem s paper, can react with the alcohol producing an intermediate 57, which can deliver a carbonyl compound by a Cope-like elimination. 

An alternative approach to the oxidation of alcohols to ketones was also reported by Shea et al., who incorporated a nitroxide catalyst into a polymeric matrix [56], A polymerisable 2,2,6,6-tetramethylpiperidine (90) was derivatised as /V-allyl-amine (91), which was removed after polymerisation, leaving a catalytically active nitroxide (92) able to form stable free radicals, thereby efficiently catalysing the reaction of oxidation with yields ranging from 55 to 88%. 

The dimer of (74) is isolated as one of the products. In the flow ESR spectra, nitroxides (76) and (77) can be recognized. These are proposed to arise by H-abstraction from (74) by a cyclobutoxy radical, giving (75), which either reacts with a further molecule of (74), yielding (76), or undergoes, 5-exo ring closure to (77). The steroidal nitrite (78) (Scheme 17) yields 50% of the ketone (79) and 16% of the alcohol (80) when photolysed in the solid state (X > 300 nm), but only 5% of (79) and 52% of the Barton-type product (81) when photolysed in toluene solution. It is usual for ketones to be produced only in low yields from photoreactions of nitrites in solution, and so the promotion of this reaction pathway in solid-state photolysis is of considerable interest. Similar results were obtained for the solid-state photolyses of a number of other steroidal nitrites, but nitrites prepared from acyclic alcohols showed much less selectivity in favour of the corresponding ketones. 

Treatment of nitroxides with strong acids such as toluenesulfonic acid or perchloric acid facilitates disproportionation to form one oxoammonium salt in situ for every two equivalents of starting nitroxide. Under strongly acidic conditions, secondary alcohols are efficiently oxidized to ketones, whereas primary alcohols are much slower to react [33]. The reaction mechanism [31] is most likely that shown in Scheme 15. A kinetic isotope effect [kn/ku = 3.1) supports deprotonation of the alpha hydrogen as the rate limiting step [34]. The use of an additional oxidant such as bleach (NaOCl) or hypobromous acid (HOBr) or hypochlorous acid (HOCl) generated in situ from bromide or chloride ion [35] can facilitate the reaction by rapidly reforming the oxoammonium species under the reaction conditions. This allows the nitroxide to be utilized in catalytic amounts. Recently, Bobbitt [36] has... 

Oxammonium salts such as 81 are new and powerful oxidizing agents for the selective oxidation of alcohols to aldehydes or ketones. 28 Such salts can be generated catalytically from small amounts of a nitro-xide in the presence of a secondary oxidation procedure, either chemical or electrochemical,. 29 or with two equivalents of acid and 2 equivalents of a nitroxide. When 81 was mixed with acetylenic alcohol 82 in dichloromethane, aldehyde 83 was isolated in 93% yield. The reaction can be monitored as the initial yellow slurry changes to a white slurry and the presence of unreacted oxidant can be checked with starch. 3l It is not necessary to use anhydrous conditions, and it was discovered that the rate of reaction was enhanced by the presence of silica gel. This reagent is compatible for the mild oxidation of many alcohols, including aliphatic primary and secondary as well as allylic and benzylic alcohols. 

Tetrafluoroallene reacts with two moles of bistrifluoromethyl nitroxide at ambient temperature. The initial adduct (134) reacts further with the radical to give a ketone (135a) and the bistrifiuoromethylamino-radical, which may attack the allene at the central carbon atom since the enamine (136) is isolated in substantial yield. Alternatively, the enamine (136) may arise by reaction of the allene with perfluoro-(2,4-dimethyl-3-oxa-2,4-diazapentane) (135b), because the N—O—N compound was shown to react in this way with the allene at room temperature. The yield of the ketone rose to 89%, accompanied by an equimolar proportion of the N—O—compound, when the allene was treated with a six-fold excess of the nitroxide, further justifying the proposed reaction scheme (Scheme 29). 

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