Stable nitroxide radicals

Most studies on stable nitroxide radical-mediated poljmeiization are made with TEMPO or a substituted TEMPO, such as, 4-methoxy-2,2,6,6-tetramethyl-piperidine-l-oxy (MTEMPO) as the stable counter radical. However, the bond formed between the polymer radical and these nitroxides becomes labile around 120°C. This high temperature favors thermal polymerization as also side reactions, such as transfer or termination by dismutation between the growing chain and the stable radical (Jousset et al., 1997). To minimize these reactions, a more hindered radical, namely, di-ieri-butyl nitroxide (II), produced from the compound (III) can be used. 

Heated, the compound (III) leads to the formation of a di-teri-butyl rutroxide radical (II) and an alkyl radical, CeHsC (H)CH3, that exhibits a chemical structure similar to that of the styryl radical. The choice of (III) as the capping agent comes from its absence of reactivity toward alkenes and from the low strength of the bond formed with the active site (Catala et al., 1995). It allows free radical polymerization of styrene and substituted styrene monomers at 90°C with complete control of the molecular weight and monomer consumption (Joussel et al., 1997). 

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Figure Bl.16.16 shows an example of RTPM in which the radical species is TEMPO (10), a stable nitroxide radical, while the triplet state is produced by photoexcitation of benzophenone (11) [45].

N-Alkoxylamines 88 are a class of initiators in "living" radical polymerization (Scheme 14). A new methodology for their synthesis mediated by (TMSlsSiH has been developed. The method consists of the trapping of alkyl radicals generated in situ by stable nitroxide radicals. To accomplish this simple reaction sequence, an alkyl bromide or iodide 87 was treated with (TMSlsSiH in the presence of thermally generated f-BuO radicals. The reaction is not a radical chain process and stoichiometric quantities of the radical initiator are required. This method allows the generation of a variety of carbon-centered radicals such as primary, secondary, tertiary, benzylic, allylic, and a-carbonyl, which can be trapped with various nitroxides. 

The ESR spectra of unusually stable nitroxide radicals such as 19 have been described by Forrester and Ramasseul 47>. 

Samuni AM, Barenholz Y. Stable nitroxide radicals protect lipid acyl chains from radiation damage. Free Radicals Biol Med 1997 22 1165-1174. 

An interesting class of stable nitroxide radicals 482 and 484 (paramagnetic biomolecules) has been prepared from 1,4-dibromomethyl 481 <1999S973> and 1,4-dihydroxymethyl derivative 483 (Scheme 60) <2000S831>. 

The trapped nitric oxide becomes a stable nitroxide radical that is the same chemical moiety present in most common spin-trapping reagents. Nitric oxide production from activated macrophages has been directly assayed by this method (Korth et al., 1992). 

Since only free radicals give an esr spectrum, the method can be used to detect the presence of radicals and to determine their concentration. Furthermore, information concerning the electron distribution (and hence the structure) of free radicals can be obtained from the splitting pattern of the esr spectrum (esr peaks are split by nearby protons).141 Fortunately (for the existence of most free radicals is very short), it is not necessary for a radical to be persistent for an esr spectrum to be obtained. Esr spectra have been observed for radicals with lifetimes considerably less than 1 sec. Failure to observe an esr spectrum does not prove that radicals are not involved, since the concentration may be too low for direct observation. In such cases the spin trapping technique can be used.142 In this technique a compound is added that is able to combine with very reactive radicals to produce more persistent radicals the new radicals can be observed by esr. The most important spin-trapping compounds are nitroso compounds, which react with radicals to give fairly stable nitroxide radicals 143 RN=0 + R —> RR N—O. 

The photochemical transformation of the spirocyclic 4//-pyran derivative 622 shown in Eq. (47)333 resembles the reverse of the phototransformation 349->350. Upon reaction with Pb02 622 gave a stable nitroxide radical.454... 

Peracids can oxidize 2//-imidazoles to A -oxides and N,N -dioxides, and sometimes to imidazoli-nones. Lead dioxide in methanol converts 2//-imidazole 1,3-dioxides into stable nitroxide radicals (96CHEC-II(3)146). 

Oxidations Mediated by TEMPO and Related Stable Nitroxide Radicals (Anelli Oxidation)... 

Although TEMPO (55), which is very easy to prepare17 and quite cheap—specially considering that it is employed in very small quantities—, is the most commonly used stable nitroxide radical. Other TEMPO related nitroxide radicals, such as 4-MeO-TEMPO18 (59) and 4-AcHN-TEMP05d 12 (60) can also be employed. 

Stable nitroxide radicals represent SOD mimics with kcat values over 107m/s at pH 6 and, therefore, are capable of a strong influence on O2 concentration in cells and tissues. Thus, it provides for effective detoxication. 

Oxidation of 2,2,4,4-tetraalkyloxazolidines gives stable nitroxide radicals (265) which are used as spin labels for probing biomolecular structures (69ACR17, B-76MI41800). The stearic acid derivative 12-doxylstearic acid (266) is commercially available. 

An additional step in the cascade reaction scheme is the quenching of the sensitizer triplet state with relatively low-concentration radicals (Fig. 1.5) (Papper et al 1999, 2000 Papper and Likhtenshtein, 2001). The entire investigated reaction that is shown in Fig. 1.5 is the sequence of the four kinetic processes and serves as a basis for the spin-triplet-photochrome labeling technique. This technique combines the three types of biophysical probes stilbene photochrome probe, triplet probe and stable nitroxide-radical spin probe, which depresses the sensitiser exited triplet state. 

When a dormant species or alkoxyamine dissociates homolytically, a carbon-centered radical and a stable nitroxide radical are formed (Scheme 2). This is a reversible process and the reversible reaction is very fast - close to diffusion-controlled rates. With increasing temperature, the dissociation rate will increase, which will increase the concentration of the polymeric radicals (P ). These will have a chance to add to monomer before being trapped again, which allows growth of the polymer chains. The nitroxide is an ideal candidate for this process since it only reacts with carbon-centered radicals, is stable and does not dimerize, and in general couples nonspecifically with all types of carbon-centered radicals (at close to diffusion-controlled rates). 

A single diastereomer 3 was obtained after crystallization from the reaction mixture on cis addition to (—)-caryophyllene98 10°. The diastereomer 3 undergoes transannular radical addition on treatment with bromine or iodine to give a stable nitroxide radical 4 (X-ray)98,99. 

Further evidence for Type I cleavage has been obtained by the use of diamagnetic radical scavengers as spin traps for radicals produced on photolysis of benzoin and benzoin methyl ether (18). In both < ses PhCO and PhCHOR (R = H, Me) radicals were trapped and characterised from the e.s.r. spectra of the stable nitroxide radicals formed e.g. 

C. Berti, M. Colonna, L. Greci, and L. Marchetti, Stable nitroxide radicals from phenylisatogen and arylimino-derivatives with organo-metallic compounds, Tetrahedron 31, 1745-1753 (1975). 

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