TEMPO stable radical

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). 

FIGURE 10.3 The structure of TEMPO. The compound 2,2,6,6-tetramethylpiperidine-l-oxyl is a stable radical. 

Nitroxide attached to macromolecules also induces the living radical polymerization of St. Yoshida and Sugita [252] prepared a polymeric stable radical by the reaction of the living end of the polytetrahydrofuran prepared by cationic polymerization with 4-hydroxy-TEMPO and studied the living radical polymerization of St with the nitroxide-bearing polytetrahydrofuran chain. The nitroxides attached to the dendrimer have been synthesized (Eq. 69) to yield block copolymers consisting of a dendrimer and a linear polymer [250,253]. 

Various stable radicals such as nitroxide, triazolinyl, trityl, and dithiocarbamate have been used as the mediating or persistent radical (deactivator) for SFRP. Nitroxides are generally more efficient than the others. Cyclic nitroxide radicals such as 2,2,6,6-tetramethyl-l-piper-idinoxyl (TEMPO) have been extensively studied. SFRP with nitroxides is called nitroxide-mediated polymerization (NMP). Polymerization is carried out by two methods that parallel those used in ATRP [Bertin et al., 1998 Georges, 1993 Flawker, 1997 Flawker et al., 2001], One method involves the thermal decomposition of an alkoxyamine such as... 

The ease of the synthesis maybe disclosed by the experimental procedure. An evacuated 100-mL flask was filled with N2O4/NO2 to a pressure of ca. 650 mbar (296 mg, 6.4 mmol NO2). The sampling flask was connected to an evacuated 1-L flask, which was then connected to an evacuated 10-mL flask that was cooled to 5 °C and contained the nitroxyl 4a or 4b, or the nitroxyl precursor to 7 (500 mg, 2.70 mmol). After 1 h, the cooling bath was removed and excess NO2 and NO were condensed in a cold trap at 77 K for further use. The yield was 665 mg (100%) of pure 6a, 6b, or 7 [19]. Similarly, 2-g quantities of tetra-methylpiperidine-AT-oxyl (TEMPO) or 0.2 g of the ferromagnetic 2-fluoro-phenyl-tetramethylnitronyl nitroxide stable radical [21] were reacted at -10 °C (initial pressure of NO2 0.03 bar) or 5 °C (0.3 bar NO2) in 12 h with a quantitative yield of pure 8 or 9, respectively [19]. 

The 2,2,6,6-tetramethylpiperidinoxyl radical (TEMPO) was first prepared in 1960 by Lebedev and Kazarnovskii by oxidation of its piperidine precursor.18 The steric hindrance of the NO bond in TEMPO makes it a highly stable radical species, resistant to air and moisture. Paramagnetic TEMPO radicals can be employed as powerful spin probes for elucidating the structure and dynamics of both synthetic and biopolymers (e.g., proteins and DNA) by ESR spectroscopy.19 Unlike solid-phase 1H-NMR where magic angle spinning is required in order to reduce the anisotropic effects in the solid-phase environment, solid-phase ESR spectroscopy can be conducted without specialized equipment. Thus, we conducted comparative ESR studies of various polymers with persistent radical labels, and we also determined rotational correlation times as a function of... 

The direct oxidation of hydroxyls on inulin allows the potential introduction of carbonyl and carboxyl groups, altering the properties of the polysaccharide and opening additional commercial applications (Bragd et al., 2004). The primary hydroxyl in the C-6 position on the fructofuranoside subunits can be selectively oxidized using 2,2,6,6-tetramethyl-l-piperidinyloxy (TEMPO). This forms a stable radical that can be oxidized by hypobromite, or similar reagent, to give a nitrosonium... 

In a stable free-radical polymerization (SFRP), the initiated polymer chains are reversibly capped by a stable radical, for example, the 2,2,6,6-tetra-methylpyridin-l-oxyl radical (TEMPO). Stable PS dispersions via miniemulsion polymerization were prepared by MacLeod et al. with an optimized ratio... 

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. 

Other functional core moieties include stable TEMPO-based radicals for controlled radical polymerization,342 crown ethers,343 344 hexacyclenes,170 poly-(quarternary ammonium) cations,345 ethylene thio-lates,346,347 calixarenes,348-352 cyclodextrins,178 inorganic clusters,93-95 340 353,354 dichalcogenides,355 and silses-quioxanes.356... 

Since TEMPO is only a regulator, not an initiator, radicals must be generated from another source the required amount of TEMPO depends on the initiator efficiency. Application of alkoxyamines (i.e., unimolecular initiators) allows for stoichiometric amounts of the initiating and mediating species to be incorporated and enables the use of multifunctional initiators, growing chains in several directions [61]. Numerous advances have been made in both the synthesis of different types of unimolecular initiators (alkoxyamines) that can be used not only for the polymerization of St-based monomers, but other monomers as well [62-69]. Most recently, the use of more reactive alkoxyamines and less reactive nitroxides has expanded the range of polymerizable monomers to acrylates, dienes, and acrylamides [70-73]. An important issue is the stability of nitroxides and other stable radicals. Apparently, slow self-destruction of the PRE helps control the polymerization [39]. Specific details about use of stable free radicals for the synthesis of copolymers can be found in later sections. 

Keywords solid-solid reaction, ball milling, stable radicals, TEMPO, TEMPO-nitrosonium salts, TEMPO-nitrosonium salts, triphenylverdazylium salts... 

Stable radicals, such as nitroxides hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPO) [8,156], can be added to the polymerization medium to terminate all polymer radicals produced. For styrenes and acrylates [157], this mainly occurs through combination. Chambard et al. [157] showed this technique allows for the modification of poly( -butyl acrylate)-Br in the presence of an excess of hydroxy-TEMPO, resulting in hydroxy-functional poly( -butyl acrylate) with good functionality (f> 95%). This process is not desirable, because the polymer produced is thermally unstable (carbon nitroxide) and cannot be used at high temperature. 

These radicals (DPPII, 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 lennination agents (in living radical polymerization - Section 9.3). 

An inhibitor is used to completely stop the conversion of monomer to polymer produced by accidental initiation during storage. To induce the inhibition, some stable radicals are mixed with the monomer. Such radicals are incapable for initiation the polymerization, but they are very effective in combining with any propagating radical. Diphenylpicryl-hydrazyl and tetramethylpiperidinyloxy (TEMPO) are two examples of radicals used to inhibit the radical polymerization. The chemical reactions of the inhibition produced by these compounds are shown in Scheme 4.8. 

The supramolecular chemistry of radicals has been widely investigated, especially with stable radicals like TEMPO or benzyl f-butyl nitroxide. This is because radicals can be observed by EPR spectroscopy, a method particularly suitable to obtain kinetic information about the association and dissociation processes in the time range between 10 and 10 seconds, i.e., for complexes displaying fast exchange on the NMR time scale. 

A similar reaction of siiyi ether 472 with iodosylbenzene/TMSNs at lower temperatures and in the presence of catalytic amounts of the stable radical TEMPO stereoselectively affords vicinal frany-diazides 473 as the major products (Scheme 3.187) [562]. The effect of TEMPO on the outcome of this reaction has been explained by a change of mechanism from ionic dehydrogenation to a radical addition process in the presence of TEMPO [562],... 

FIGURE 3.19 General concept of NMRP highlighted using TEMPO as stable radical and some examples for advanced stable nitroxide radicals and Hawker adducts. 

The thermal lability of the R—C—O—N bond system controls the reversibility of the chain termination and limits also the use of NMRP. SFRP of styrene at about 130°C is studied intensively. In this case, high control and high molar mass products could be achieved. It was found that the thermal autopolymerization of the styrene monomer plays an important role in the mechanism of the reaction. Therefore, first experiments using different monomers in the presence of TEMPO and a radical initiator failed with regard to the control. However, new nitroxide adducts with a different R—O—N bond stabiUty have been developed, for example, by Hawker [14], which work also for styrene derivatives as well as for acrylates. End group functionalization in NMRP can be achieved by using a functional radical initiator in combination with a stable radical or functionalized nitroxide adducts. 

TEMPO is a stable radical that can be used for a wide variety of oxidation reactions in organic chemistry. Softwood and hardwood... 

We chose this as our first case study due to the many special features of the TEMPO compound(s) and also that the studies made are thorough and exemplifies the level of accuracy that has been reached for predicting the electrochemical stability of additives. There are also a number of delicate computational issues that we do not find described elsewhere for these types of additives. The core TEMPO molecule is a stable radical, with a sterically protected nitroxide. In 2006 only BDB and TEMPO had shown the required stability to act as an overcharge protecting redox shuttle [90]. 

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