TEMPO oxidation

Fig. 6. Specific oxidation of the 6-hydroxyl of starch usiag bromide—hypochlorite and tetramethylpiperidine oxide (TEMPO).

A planar BLM cannot be investigated by means of the molecular spectroscopical methods because of the small amount of substance in an individual BLM. This disadvantage is removed for liposomes as they can form quite concentrated suspensions. For example, in the application of electron spin resonance (ESR) a spin-labelled phospholipid is incorporated into the liposome membrane this substance can be a phospholipid with, for example, a 2,2,6,6-tetramethylpiperidyl-A-oxide (TEMPO) group ... 

In presence of 3 equivalents of oxidant, TEMPO mediates then the rapid conversion into ketomalonic acid. The pH of the reaction medium is critical at pH 7 no reaction occurs, while at high alkalinity TEMPO+ undergoes basic dismuta-tion. At pH 10, even the immobilized catalyst is stable and can be used during several subsequent reactions [95]. 

Figure 13.15 Synthesis of 2,2,6,6-tetramethylpiperidine A-oxide (TEMPO) functionalized dendrimers.

Figure 13.16 Stackplot of electron paramagnetic resonance (EPR) spectra of 2,2,6,6-tetramethylpiperidine A -oxide (TEMPO)-functionalized dendrimers with 5, 10, 25, 50, 75, 90, and 95% TEMPO.

Figure 13.17 Graph of line-broadening effects for 2,2,6,6-tetramethylpiperidine A -oxide (TEMPO) and R-4-isothiocyanato (R-NCS) functionalized dendrimers from Figure 13.15. NCS-TEMPO was added first half of the time and R-NCS was added first half of the time.

Figure 13.19 Affinity chromatography with 2,2,6,6-tetiamethylpiperidine A-oxide (TEMPO)-/ mannose-functionalized dendrimers. Electron paramagnetic resonance spectra for one TEMPO/mannose experiment are shown.

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

The reaction of triplet carbenes with a persistent nitroxide such as 2,2,6,6-tetra-methylpiperidine A -oxide (TEMPO, 84) to form benzophenone would be spin allowed and >100-kcal/mol exothermic (Scheme 9.26). The reaction has a few parallels in free radical chemistry, such as the reaction of tert-butoxyl with carbon monoxide (to yield CO2) or with phosphorus (111) substrates to yield P(V) products. " ... 

Other organic mediators act as hydride atom-abstracting agents. This is true, for example, with 2,2-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and the oxoammonium ion which is anodically accessible from 2,2,6,6-tetramethylpiperidyl oxide (TEMPO). DDQ has been electrochemically regenerated either externally or internally The in situ electrochemical oxidation, of TEMPO to the active oxoammonium ion is performed in lutidine-containing acetonitrile. Thus, primary alcohols can be oxidized to the aldehydes, while secondary ones are stable Primary amines are transformed to nitriles. If water is present, the amines are cleaved via the Schiff bases to the corresponding carbonyl compounds... 

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. 

Among common alcohol oxidants, TEMPO-mediated oxidations have been the subject of a close scrutiny, aimed at finding optimum conditions for the selective oxidation of primary alcohols. In fact, TEMPO-mediated oxidations, that is oxidations in which an oxoammonium salt acts as a primary oxidant, have a great tendency to operate quicker with primary alcohols, regardless of the secondary oxidant employed and the exact experimental conditions. 

The need to better control surface-initiated polymerization recently led to the development of controlled radical polymerization techniques. The trick is to keep the concentration of free radicals low in order to decrease the number of side reactions. This is achieved by introducing a dormant species in equilibrium with the active free radical. Important reactions are the living radical polymerization with 2,2,4,4-methylpiperidine N-oxide (TEMPO) [439], reversible addition fragment chain transfer (RAFT) which utilizes so-called iniferters (a word formed from initiator, chain transfer and terminator) [440], and atom transfer radical polymerization (ATRP) [441-443]. The latter forms radicals by added metal complexes as copper halogenides which exhibit reversible reduction-oxidation processes. 

First, one had to check that the mechanism of action was correct. The product of co-ozonlysis of O-methyl-2-adamantanone oxime with 1,4-cyclohexanedione afforded on treatment with ferrous acetate a secondary carbon-centered free radical that was trapped with the usual spin trap, 2,2,6,6-tetramethylpiperidine-Ar-oxide (TEMPO), and involved a /3-scission of the adamantane fragment, thus proving that the attack of the Fe(ll) species occurred on the less-hindered peroxide bond oxygen atom (Scheme 85) <2004NAT900, 2005JOC513>. 

Frechet and coworkers recently described how living free radical polymerization can be used to make dendrigrafts. Either 2,2,6,6-tetramethylpiperidine oxide (TEMPO) modified polymerization or atom transfer radical polymerization (ATRP) can be used [96] (see Scheme 10). The method requires two alternating steps. In each polymerization step a copolymer is formed that contains some benzyl chloride functionality introduced by copolymerization with a small amount of p-(4-chloromethylbenzyloxymethyl) styrene. This unit is transformed into a TEMPO derivative. The TEMPO derivative initiates the polymerization of the next generation monomer or comonomer mixture. Alternatively, the chloromethyl groups on the polymer initiate an ATRP polymerization in the presence of CulCl or CuICl-4,4T dipyridyl complex. This was shown to be the case for styrene and n-butylmethacrylate. SEC shows clearly the increase in molecu-... 

The use of 0.75 mol% Yb(fod)3 (27) at 50 °C offered more reproducible results (Scheme 6). A diastereomeric mixture (65 35) of cis-11 to trans-11 was isolated in 60-65% yields as racemic materials. This process, however, required an oxidation (TEMPO, NaOCl) followed by NaBH4 reduction, protection as acetate derivative and lipase resolution (PS-C, amino-I) to afford the bis-THF alcohol in 97-98% ee and 28-35% yields. 

Reactions of Germylenes with Stabilized Radicals. The stable germylene Ge[C4H4(SiMe3)4] reacts with 2 equivalents 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO, -ONR2) to... 

Benzeneselenol is an extremely fast reducing agent for alkyl radicals. The rate constant for benzeneselenol trapping of alkyl radicals is 1.2 x 10 s at 20 °C [99]. This is faster than the coupling reaction of alkyl radicals with 2,2,6,6-tetramethyl-piperidine-N-oxide (TEMPO) [100]. This exceptionally large rate constant makes benzeneselenol a very useful radical clock for the measurement of very fast radical processes [99]. 

The mechanistic details of these laccase/mediator catalyzed aerobic oxidations are still a matter of conjecture (51-54). However, experiments with a probe alcohol point towards one-electron oxidation of the mediator by the oxidized (cupric) form of the laccase followed by reaction of the oxidized mediator with the substrate, either via electron transfer (ET), e.g., with ABTS, or via hydrogen atom transfer (HAT), e.g., with N-hydroxy compounds which form N-oxy radicals (55). TEMPO and its derivatives form a unique case one-electron oxidation of TEMPO affords the oxoammonium cation which oxidizes the alcohol via a heterolytic pathway (Fig. 6), giving the carbonyl product and the hydroxylamine. The Tl copper center in fungal laccases has a redox potential of ca. 0.8 V vs. NHE. Consequently, fungal laccases can easily oxidize TEMPO to the corresponding oxoammonium cation, since the oxidation potential of the latter, which was first measured by Golubev and co-workers (55,57), is 0.75 V. This was confirmed by EPR measurements, which showed that laccase is reduced in the presence of TEMPO One equivalent of laccase could oxidize at least three equivalents of TEMPO within a few minutes under anaerobic conditions (58). 

Ramachandran and Balasubramanian used the method to monitor structural alterations caused in water by added solutes. They used the spin probe 2,2,6,6-tetramethyl piperid-4-one TV oxide (TEMPO) to study structural alterations caused in water by the addition of urea and sodium butyrate. They studied the variation of hydrogen hyperflne linewidth as a function of the solute concentration and extracted information on the reorientation time [36]. They conclude that urea disrupts water structure continuously and this effect is significant at low molarities. With sodium butyrate they see evidence for two different environments, one attached to the solute and the other far away from it. 

TEMPO is widely used as a radical trap, as a structural probe for biological systems in conjunction with EPR spectroscopy, as a reagent in organic synthesis, and as a mediator in controlled free radical polymerisation. As well as alcohol oxidation, TEMPO also finds use in the oxidation of other functional groups, including amines, phosphines, phenols, anilines, sulfides and organometallic compounds [144]. 

Dahn et. al. have shown that the redox potential of fluorinated 2,2,6,6-tetramethylpiperinyl-oxides (TEMPO) increases with the degree of fluorination [35]. It is well known that the substitution of an electron-withdrawing group such as F around the redox active site, -N-0 radical in the case of TEMPO, can reduce the electron density on the active site and increase the energy needed to withdraw one electron out of the active site (oxidation process). Therefore, substitution of electron withdrawing groups can be an effective way to increase the redox potential of aromatic redox shuttles for... 

Tetramethylpiperidine-N-oxide(Tempo) traps R but not the Co(IT) unit in a Costa-type model B12 system, and has been used by Finke s group to obtain kinetic parameters for reaction (17) for R = PhCH2 and Mc3CH2 (see Table 11.2). (Further data on the saloph, cobalamin, and... 

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