TEMPO 2,2,6,6-Tetramethylpiperidine-N-oxyl

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. 

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. 

Pyridylbenzenes are directly ortfio-arylated with tetra-arylstannanes in the presence of a rhodium(I)-phosphine complex as catalyst [140]. A mechanistic pathway was proposed based on the oxidative addition of a rhodium] I) complex to the ortho position of the phenyl ring directed by the pyridine nitrogen, followed by arylation by the tetra-arylstannane. A somewhat related reaction of arylboronic acids was achieved with a [RhCl(C2H4)2]2/P[p-(CF3)QH4]3 catalyst system [141]. In this instance, the 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) radical was used as a stoichiometric oxidant. Arylboronic acids also arylate benzophenone imines in the presence of Rh(I) catalysts [142]. 

Polymerization was either carried out in solution (50 wt.-% toluene and styrene, each) or in microemulstion. In the latter case the polymerization mixture was prepared according to the recipe of Gan and cow-orker. The oil phase consisted again of 50 wt.-% toluene and styrene, each. For all experiments 2,2 -azoisobutyronitrile (AIBN) was used as a photoinitiator at a concentration of 5 10 moU for the polymerization in solution and 44 10 moir with respect to the oil phase. The polymerization mixture was purged with Argon (15 min) prior to polymerization. For the intermittant illumination a Nd Yag laser (Quanta Ray GCR-130-20) was used at different pulse frequencies. AH polymerizations were carried out at 7 =25°C to low conversions only (in order to avoid phase separation). Immediately after irradiation all radicals were deactivated by injecting a solution of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) in toluene. The polymers were precipitated in pure methanol and filtered. Detergent was removed by carefully washing with water and methanol several times. 

Recently, it has been reported that 4-vinylpyridine undergoes controlled radical polymerization in the presence of 2,2,6,6-tetramethylpiperidin-N-oxyl (TEMPO). In calorimetric experiments a polymerization behavior similar to that observed for the controlled living polymerization of styrene was found. Furthermore, the resulting polymers showed a small polydispersity compared to polymers obtained by free-radical polymerization [572]. 

Electronic Distribution and Solvatochromism Investigation of a Model Radical (2,2,6, 6-Tetramethylpiperidine N-oxyl tempo) through TD-DFT Calculations Including PCM Solvation. 

Oxidation of 50 (Scheme 10.8) with 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and bis[acetoxy(iodo)]benzene (BAIB) in a 1 1 mixture of acetonitrile and water [66], afforded acid 47 in good yields. The two amines 45 and 46 were synthesized from 49 and 50, respectively, via the corresponding azides (Scheme 10.8). Functionalization of44-47 with the m-alkyne linkers (Scheme 10.10) yielded the 11 linker-armed Gal fragments 54-64 used in the library. 

Although there is some confusion in the Hterature about the nomenclature, these are odd-electron species unrelated to the above N-oxides. Some of these radicals are endowed with an uncommon persistence, such as shown in the indefinite stabihty of many 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO, 7) derivatives. This has led to their widespread use as radical traps, particularly for carbon-centered radicals generated in thermal and photochemical reactions. ° N-oxyl radicals and their photochemical reactions are not discussed in this chapter. 

C ) with a 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) terminated polystyrene (PS) (M = 12000gmor M /M = 1.16) at 95°C in toluene [19]. In a similar reaction, but with 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as the stable counter radical, a di-adduct was formed in high yield even when a four-fold excess of Qo per PS-TEMPO was used [20]. The two chains are attached in the 1,4 positions on the same six-membered ring, only one double bond is opened and no TEMPO is present on the fullerene (Scheme 5.2). 

Nitroxyl radicals can be oxidized to N-oxo ammonium salts that are themselves useful oxidants for primary and secondary alcohols. Recently, the behavior of different nitroxides as catalysts for alcohol oxidation has been studied by quantum chemical calculations [105]. Generally, 2,2,6,6-tetramethylpiperidine Ai-oxyl (TEMPO) (80) is used for the... 

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... 

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). 

TABLE 10.2 Addition Rate Constants kj of Various Radicals to Monomers Reaction Rate Constants kr of These Radicals with Oxygen, an Amine, a Stabilizer (HQME Hydroquinone-Methyl Ether) and a Spin Trap (TEMPO 2,2,6,6 Tetramethylpiperidine N-Oxyl). 

TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) as an important reagent in alcohol oxidation and its application in synthesis of natural products between 2000 and 2004 06MRO155. 

To a suspension of 3.5 g (10 mmol) crystalline 507 in 50 ml heptane are added, at 25°C and under N2, 90 mg (0.5 mmol) 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl (4-OH-TEMPO) in 1 ml EtOH. Then 3 g (11 mmol) 5 are added and, within 4 h, 5 ml of a 20% solution of NaOEt (12.8 mmol in EtOH) is added at 25-30°C. Stirring is continued for 1 h. The organic phase is washed with iM H2SO4 and 60% MeOH. Upon addition of MeOH the p-apo-8 -carotenoic acid ethyl ester (/) precipitates, is filtered off and washed twice with MeOH. After drying at 50°C in vacuo 3.9 g (84.7%) of 1 are obtained [5]. 

Since its discovery in 1993 [27], nitroxide-mediated polymerization (NMP) has been the most extensively studied technique from the dissociation-combination dass of LRP mechanisms (Scheme 13.7). This method is also commonly termed stable free radical polymerization (SFRP). NMP reactions are distinguished by the use of stable free radical nitroxide molecules (N ) as the controlling agent [e.g. 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO), (l-diethylphosphono-2,2-dimethyl)propyl nitroxide (DEPN)]. 

A combination of RuQaCPhjP) and the stable nitroxyl radical, 2, 6,6-tetramethylpiperidine-N-oxyl (TEMPO) is a remarkably effective catalyst for the aerobic oxidation of a variety of primary and secondary alcohols, giving the corresponding aldehydes and ketones, respectively, in >99% selectivity. The best results were obtained using lm% of RuCl2(Ph3P)3 and 3m% of TEMPO (Reaction 4). 

Figure 2.5 Experimental and calculated aN values of TEMPO-choline [4-(N, Ndimethyl-N-(2-hydroxyethyl))ammonium-2/2/6/6-tetramethylpiperidine-l-oxyl chloride] as a function of the solvent dielectric constant.

For grafting, the amines were purchased from Aldrich Chemical Co 4-amino 2,2,6,6-tetramethylpiperidine-l-oxyl radical (called 4-amino TEMPO), n-octylamine, /j-butylamine and 2-methoxyethylamine (Table 2). 

The mechanism of the aerobic oxidation of alcohols depends on the particular catalyst used. Two general mechanisms can be considered (1) the direct oxygenation of alcohols by 02 through a free-radical chain process initiated by the catalyst, and (2) the direct oxidation of the alcohol by the catalyst, which is then regenerated by 02. Both mechanisms are well illustrated [6] by the aerobic oxidations catalyzed by the persistent tetramethylpiperidine-N-oxyl (TEMPO) radical 1 and the nonpersis-tent phthalimide-N-oxyl (PINO) radical 2. 

The nitroxyls (a.k.a. nitroxides) are remarkably stable free radicals. Nitroxyls have two major resonance structures, one N-centered and one O-centered the lone electron may also be considered to be in the tt orbital of an N—O tt bond. Nitroxyls are thermodynamically stable because dimerization would give a very weak N—N, N—O, or O—N bond. TEMPO (2,2,6,6-tetramethylpiperidin-l-oxyl), a commercially available nitroxyl, is further stabilized by steric shielding, as shown here. Other thermodynamically stable free radicals include the small molecules O2 (a 1,2-diradical, best represented as -O—O ) and nitric oxide (NO), a messenger molecule in mammals that mediates smooth muscle contraction. 

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