2,2,6,6-tetramethylpiperidine A-oxyl TEMPO

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

U sing TR ESR, a model reaction between the free radicals of Pis and stable nitroxyl radicals of 2,2,6,6-tetramethylpiperidine-A-oxyl (TEMPO) family was studied. We will abbreviate the TEMPO fragment further as N. Nitroxyl biradicals (N-O-N), had radical termini in proximity to each other (see Scheme 12.12). 

Vinyl Compounds. Photorefractive polymers can be prepared by living radical polymerization. 4-Vinyl-triphenylamine can be polymerized by a conventional radical catalyst or a 2,2,6,6-tetramethylpiperidine-A-oxyl (TEMPO) like catalyst, such as A-(a-methyl-benzyloxy)-2,2,6,6-tetramethylpiperidine [167]. 

In the 1990s the groups of Rizzardo and Georges reported a stable free radical polymerization process (SFRP) allowing the preparation of polystyrene with a narrow polydispersity. In the presence of stable free radicals, such as the mainly used 2,2,6,6-tetramethylpiperidine-A-oxyl (TEMPO), macromolecules based on styrene and styrene derivatives with well defined structures were synthesized [263,264],... 

In other cases, organic modification of the sol gel cages markedly protects the entrapped molecular dopant from degradation by external reactants, as shown for instance by the entrapment of the radical 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO). This is a highly active catalyst which in the NaOCl oxidation of alcohols to carbonyls in a CH2CI2-H20 biphasic system becomes highly stabilized upon sol gel entrapment in an ORMOSIL matrix it progressively loses it activity when entrapped at the external surface of commercial silica.25... 

Laser flash photolysis at wavelengths within the charge-transfer absorption bands of 2,2,6,6-tetramethylpiperidine-./V-oxyl (TEMPO) and carbon tetrachloride yields theoxoam-monium chloride of TEMPO 291 (Xmax = 460 nm) and the trichloromethyl radical in an essentially instantaneous 18 ps) process152. The primary photochemical reaction is an electron transfer from TEMPO to carbon tetrachloride followed by immediate decomposition of the carbon tetrachloride anion radical to chloride and trichloromethyl radical (equation 140). The laser flash photolysis of TEMPO and of other nitroxides in a variety of halogenated solvents have confirmed the generality of these photoreactions152. 

Reaction of the Ru macrocyclic complex [RuLCy (L= 1,5,9,13-tetramethyl-l,5,9,13-tetraaza-cyclohexadecane) with N02 results in a disproportionation of the initial [Ru °LCl(N02)], the final products being traTO-[Ru L(0)Cl]" " and [Ru L(OH)(NO)] " "." The reaction between [Ru(OEP)Me] (H2OEP = octaethylporphyrin) and 2,2,6,6,-tetramethylpiperidine-l-oxyl (TEMPO) produces [Ru(OEP)CO]. There is clear evidence that the CO ligand is derived from the axially bound CH3 group, making this reaction an important example of CH3 to CO transformation." ... 

A convenient procedure for the oxidation of primary and secondary alcohols was reported by Anelli and co-workers (8,9). The oxidation was carried out in CH2CI2 with an aqueous buffer at pH 8.5-9.5 utilizing 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO, 1) as the catalyst and KBr as a co-catalyst. The terminal oxidant in this system was NaOCl. The major disadvantage of using sodium hypochlorite or any other hypohalite as a stoichiometric oxidant is that for each mole of alcohol oxidized during the reaction one mole of halogenated salt is formed. Furthermore,... 

We wish to report here on a new and highly efficient catalyst composition for the aerobic oxidation of alcohols to carbonyl derivatives (Scheme 1). The catalyst system is based on 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO), Mg(N03)2 (MNT) and N-Bromosuccinimide (NBS), utilizes ecologically friendly solvents and does not require any transition metal co-catalyst. It has been shown, that the described process represents a highly effective catalytic oxidation protocol that can easily and safely be scaled up and transferred to technical scale. 

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. 

The anionic methylruthenium(II) species was autoxidized to a Ru(III) compound, RuMe(OEP). The methyl group of this compound was accidentally transformed into a coordinated carbon monoxide molecule by an excess of 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) [158] on an attempt to use TEMPO as a radical trap for the measurement of the Ru-C bond energy in solution. This was the first transformation of a methyl group to carbon monoxide to be observed in the proximity of a metal. 

Figure 7.2.12 shows the principal set-up for this experiment. The column, containing the immobilized free radicals consists of an adapted PEEK tube, which fits into the flow probe below the detection cell. Figure 7.2.13 depicts a spectrum of d-n-butylphthalate recorded under the influence of a ( free-radical ) column filled with 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO), immobilized with an aminopropyl spacer on silica. The spectrum is taken from an on-line separation of a two-compound mixture. The line width is of the same order as... 

Our group have developed 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO)-functionalized PEG for biomimetic oxidation of alcohols together with CuCl in compressed C02, through a so-called mono-phase reaction, two-phase separation process to recover the catalyst, thus leading to conducting a homogeneous catalysis in a continuous mode [62]. 

Direct 1,2-bis azidation of triisopropylsilyl enol ethers was possible when catalytic amounts of 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO) were used, at - 45°C. The reaction under these conditions was often highly stereoselective, since only one (trans) adduct was obtained. In contrast to the other bis azidations of alkenes, which proceed ionically or through cycloaddition, this addition is a free radical process [98], A radical pathway occurred also when cyclohexene was treated with PhIO-Me3SiN3-TEMPO the yield of 1,2-bis azide was doubled (80%) in relation to the system PhIO-AcOH-NaN3 (in both cases the trans adduct prevailed). 

The primary alcohol of the diol 309 was selectively oxidized to the corresponding hydroxyaldehyde through a 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO)-catalyzed oxidation. The remaining secondary hydroxyl functionality was protected as an acetoxy group and the aldehyde was further oxidized to the acetate carboxylic acid. Treatment of... 

Electron paramagnetic resonance (EPR) and neutron diffraction can also be used to study molten salts. An example of the former is a study of the motion of large organics [2,2,6,6-tetramethylpiperidine-l-oxyl (tempo) and 4-amino tempo, or tem-pamine] dissolved in room-temperature molten salts, e.g., l-ethyl-3-methylimidazalo-... 

Fig. 19. Different ways to introduce oxyl radical reactivity nature employs metal bound tyrosyl radicals (19) or high-valent metal oxo fragments in many active sites (65,153). Nitroxyl radicals such as 2,2,6,6,-tetramethylpiperidin-l-oxyl (TEMPO, 20) are reactive species used in organocatalysis (154). The excited states of carbonyl functional groups (21) and metal oxo-fragments (22) display a radical pair character, which may become very attractive for biomimetic photoredox processes upon spectral sensitization (3,5).

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

As mentioned at the beginning of this section, Kirmse and coworkers (Bunse et al., 1992) found the first clear case of a homolytic aliphatic dediazoniation As shown in Scheme 7>24, the aqueous diazotization of 2>amino>2>methylpropane" nitrile (7.59) with two equivalents of NaN02 (or N2O4) yields products that are likely to be formed from the carbocation 7.60, namely 2>hydroxy-2-methylpropane-nitrile (7.62) and 2-methylprop-2-enenitrile (7.61), but also 2-methyl-2-nitropropane-nitrile (7.64), and the 7V,A-disubstituted 2>amino-2>methylpropanenitrile (7.66). The two last-mentioned products are probably formed via the radical 7.63. Direct evidence for this radical was found by experiments conducted in the presence of the radical scavenger 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO) to give 7.65 in good yield. In other experiments, dimerization and oxidation products of the radical 7.63 were identified. 

The stable, commercially available nitroxyl radical 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) 51 is an excellent catalyst, in conjunction with a co-oxidant, for the oxidation of alcohols. The most popular co-oxidant is buffered sodium hypochlorite (NaOCl). Oxidation of the nitroxyl radical gives the oxoammonium ion 52, which acts as the oxidant for the alcohol to form the carbonyl product. Primary alcohols are oxidized faster than secondary and it is often possible to obtain high chemoselectivity for the former. For example, oxidation of the triol 53 gave the aldehyde 54, with no oxidation of the secondary alcohols (6.44). The use of TEMPO is particularly convenient for the oxidation of primary alcohols in carbohydrates, avoiding the need for protection of the secondary alcohols. 

A good method for the direct conversion of alcohols to carboxylic acid uses 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO) 51, in conjunction with the co-oxidant sodium chlorite (NaC102) and sodium hypochlorite (NaOCl) as a catalyst. See M. Zhao, J. Li, E. Mano, Z. Song, D. M. Tschaen, E. J. J. Grabowski and P. J. Reider, J. Org. Chem., 64 (1999), 2564. 

At this juncture, the stereochemistry of the amine-substituted carbon required inversion to the correct configuration of the natural product. Toward this end, lactone 354 was treated with tetramethylguanidine and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) under an air atmosphere in THE. These conditions led to oxidation to yield enamine 355, which was subsequendy reduced with sodium cyanoborohydride to complete the epimerization process. These conditions were also sufficiently hydridic to reduce the ketone carbonyl. Heating in ethyl acetate then led to cycHza-tion to yield lactam 356. Oxidation using IBX next provided ketone 357, which was employed as a coupling partner for 2-iodoanihne in the key indolization step (Scheme 51). 

It was shown that the NFC may be obtained using an efficient process, where 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) oxidation was utilized as a pretreatment step prior to mechanical treatment (Lavoine et al., 2012 Saito et al.,... 

Highly efficient rhodium-catalyzed direct arylations were accomplished through the use of 2,2, 6,6 -tetramethylpiperidine-N-oxyl (TEMPO) as terminal oxidant [17]. Thereby, a variety of pyridine-substituted arenes was regioselectively functionalized with aromatic boronic acids (Scheme 9.5). However, in order for efficient catalysis to proceed, 4equiv. of TEMPO were required. The use of molecular oxygen as terminal oxidant yielded, unfortunately, only unsatisfactory results under otherwise identical reaction conditions. However, a variety of easily available boronic acids could be employed as arylating reagents. 

A spin label is a stable paramagnetic molecule that contains an atom or group of atoms with an unpaired electron spin that can be bonded to another molecule. In this way, one can detect molecules that otherwise would not give an ESR spectrum. Most spin labels are nitroxide compounds. For example, 2,2,6,6-tetramethylpiperidine-A-oxyl (known as TEMPO) is a common spin label with a characteristic three-line ESR spectrum, seen in Figure 3.87. 

The electrochemical behavior of tris(4-bromophenyl)amine (xxiii) and 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO, xxiv) was comparatively studied in [C4mim][CF3S03], [C4mim][BF4], and [C4mim][PF6] [18]. TEMPO showed a... 

The amorphous regions were studied using EPR spectroscopy, which allows the estimation of the molecular mobility in disordered regions [17], A stable nitroxyl radical, 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) was used as a paramagnetic probe. The radical was introduced into the films from vapor at a temperature of 30 C. The rotational mobility of the radical probe was determined by the correlation time The following formula is used to calculate Eq. (2) r ... 

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