Nitroxide compounds

Since the reported synthesis [1] of stable 2-phenyl-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide, NitPh, considerable effort has been spent in the physical characterization of nitronyl nitroxide compounds. Their general formula is presented in Figure 1 A. These compounds carry a delocalized, S = 1/2, unpaired electron. Among them, some derivatives were found to be paramagnetic at low temperature (NitPh, [1]), others were found to exhibit an antiferromagnetic or a ferromagnetic behavior [2-7]. 

The most critical point of all CRP techniques is to gain absolute control over the activation and deactivation of the reactive chain end. This can be simply controlled by altering the polymerization temperature or increasing the deactivator concentration. Thus, additional stable free-nitroxide compounds can be added to the... 

Andrews and co-workers have used the matrix reaction between lithium atoms and some inorganic compounds to produce species of spectroscopic interest. Reaction of lithium with molecular oxygen [301] produces, in addition to the molecule Li02, the molecule LiO and a dimer Li2 02. Reaction with nitric oxide produced a nitroxide compound [302], but analysis of the infrared spectrum indicated that in this compound the lithium atom was bound to the oxygen atom (LiON), rather than to the nitrogen atom (LiNO), as would be expected by analogy with the known compounds HNO and RNO. The matrix deposition of lithium and nitrous oxide [303] leads to the formation of LiO and LijO. The other alkali metals have also been reacted in the same way with nitrous oxide [304]. Potassium, rubidium and caesium all led to the formation of the compounds MO and M2O. No sodium oxides were produced when sodium and nitrous oxide were co-deposited. This is to be compared with the mechanism advanced for the sodium-catalysed gas-phase reaction between N2O and CO, where sodium is assumed to react with N2O, (Section 4, ref. 

Magnetism of metal-nitroxide compounds involving bis-chelating imidazole and benzimidazole substituted nitronyl nitroxide free radicals 05CCR(249)2591. 

Another type of controlled radical polymerization employs a reversible termination with a nitroxide compound [21]. Rosenfeld et al. [22] reported details of the nitroxide-mediated radical polymerization of styrene and butyl acrylate at 140 °C in a 2.9 m tubular micro-reactor with an inner diameter of 900 gm. Whereas, for the low-heat-producing monomer, styrene, the differences between a batch process and the microtubular reaction were small, in the case of butyl acrylate the difference was high. This situation, which may have been due to the Trommsdorff effect in the batch reaction (Figure 14.11), indicated that the polymerization was no longer under control. By contrast, no such effect was observed in the tubular micro-reactor, and the degree of conversion remained quite low under the applied conditions. 

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. 

Generation of free radicals from a conventional free-radical initiator (eg, azo compound or peroxide), addition of one or a few monomer units, followed by trapping of the carbon-centered radical by the nitroxide compound (1). The trapping reaction produces an alkoxy amine, which contains a thermally labile C—0 bond (44). 

Jousset, S., Hammouch, S. O., and Catala, J. M. (1997). Kinetic studies of the polymerization of p-tert-butylstyrene and its block copolymerization with styrene through living radical polymerization mediated by a nitroxide compound. Macromolecules, 50(21) ... 

Fig. 8 Schematic of n-doping and p-doping mechanism of nitroxide compounds. Reprinted from Ref. [22] with permission from WILEY-VCH...

More recently, new nitroxide compounds have been developed that permit a broader range of monomers to be used. By fine-tuning the stability of the radical and the... 

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). 

Nitrones arc generally more stable than nitroso-compounds and arc therefore easier to handle. However, the nitroxides formed by reaction with nitrones [e.g. phenyl /-butyl nitrone (109)]483 484 have the radical center one carbon removed from the trapped radical (Scheme 3.86). The LPR spectra are therefore less sensitive to the nature of that radical and there is greater difficulty in resolving and assigning signals. Nitrones are generally less efficient traps than nitroso-compounds.476... 

The efficiency of these inhibitors may depend on reaction conditions. For example the reaction of radicals with stable radicals (e.g. nitroxides) may be reversible at elevated temperatures (Section 7.5.3) triphenylmethyl may initiate polymerizations (Section 7.5.2). A further complication is that the products may be capable of undergoing further radical chemistry. In the case of DPPH (22) this is attributed to the fact that the product is an aromatic nitro-compound (Section 5.3.7). Certain adducts may undergo induced decomposition to form a stable radical which can then scavenge further. 

Many nitrones and nitroso-compounds have been exploited as spin traps in elucidating radical reaction mechanisms by EPR spectroscopy (Section 3.5.2.1). The initial adducts are nitroxides which can trap further radicals (Scheme 5.17). 

Aromatic nitro-compounds have also seen use as inhibitors in polymerization and as additives in radical reactions. The reactions of these compounds with radicals are very complex and may involve nitroso-compounds and nitroxide intermediates.20" 206 In this case, up to four moles of radicals may be consumed per mole of nitro-compound. The overall mechanism in the case of nitrobenzene has been written as shown in Scheme 5.18. The alkoxyamiuc 40 can be isolated in... 

There is some evidence in favor ° of the captodative effect, some of it is from ESR studies. However, there is also experimental and theoretical evidence against it. There is evidence that while FCH2 and p2CH are more stable than CH3, the radical Cp3- is less stable that is, the presence of the third F destabilizes the radical. " Certain radicals with the unpaired electron not on a carbon are akso very stable. Diphenylpicrylhydrazyl is a solid that can be kept for years. We have already mentioned nitroxide radicals. Compound 29 is a nitroxide radical so stable that reactions can be performed on it without affecting the unpaired electron (the same is true for some of the chlorinated triarylmethyl radicals mentioned above ). ot-Trichloromethylbenzyl(rer/-butyl)aminoxyl (30) is extremely stable. In... 

A molecular compound the antibonding wave function in an imino nitroxide free radical... 

Nitronyl and imino nitroxide free radicals are also among the most versatile spin carriers which are widely used in the design of molecular magnets. Their delocalised unpaired electrons make them convenient building blocks and ideal magnetic bridges between magnetic metals, to achieve new compounds with particular... 

Another chemically more interesting spin labeled B12 derivative involves coordinate attachment of the nitroxyl function to the cobalt atom of a cobinamide. Fig. 22 shows a reaction in which an alkyl cobin-amide is mixed with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. The nitroxide displaces water from the 6th coordination position very slowly and therefore this reaction is usually allowed to proceed for a few days with a large excess of nitroxide. From the properties of the coordinated nitroxide derivative discussed below, it is certain that the cobalt is coordinated by the N—O functional group. An analogous compound to that shown in Fig. 22 can be made with a similar nitroxide in which the 4-hydroxyl-group is missing. In this case the N—O-function is the only basic site on the molecule and therefore must be the position of attachment to the cobalt 119). 

The u.v.-visible spectrum of the 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl-methyl-cobinamide is very similar to methyl-cobin-amide itself and as a result this technique cannot be used to rigorously identify the spin labeled derivative. The spin labeled compound does show a spectral change with pH between pH 7.0 and pH 2.0 which methyl-cobinamide does not exhibit. Despite the similarities between methyl-cobinamide and nitroxylmethylcobinamide, the circular dichroism spectrum of the two derivatives are quite different. Fig. 23 shows the marked difference in C. D. spectra of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, methylcobinamide, and a methylcobinamide solution containing an equimolar amount of uncoordinated nitroxide. 

As with the nitroxalkylcobalamins (119) and cobinamides, the co-binamides in which nitroxide is coordinated show electron spin resonance spectra very similar to the spectrum of free nitroxide. The high field line is not broadened as much as in the spectrum of a nitroxalkyl-cobinamide. No hyperfine splitting from methyl protons in the 2 or 6 positions can be observed for the bound nitroxide. However, treatment of the coordinate spin labeled compounds with cyanide releases the nitroxide. When this happens, the proton hyperfine can be observed (Fig. 25). Thus treatment with cyanide simply displaces the nitroxide and a spectrum for free nitroxide is observed. 

Various hybrid compounds comprised of two types of nitroxide radicals and either a pentamethine (Cy5) or trimethine cyanine (Cy3) were synthesized by Sato and co-workers [32]. These compounds seem to be promising fluorescent chemo-sensors for the measurement of reducing species such as Fe2+, ascorbic acid, and hydroxyl radicals. 

Sato S, Tsunoda M, Suzuki M, Kutsuna M, Takido-uchi K, Shindo M, Mizuguchi H, Obara H, Ohya H (2009) Synthesis and spectral properties of polymethine-cyanine dye-nitroxide radical hybrid compounds for use as fluorescence probes to monitor reducing species and radicals. Spectrochim Acta A 71 2030-2039... 

Since Huisgen s definition of the general concepts of 1,3-dipolar cycloaddition, this class of reaction has been used extensively in organic synthesis. Nitro compounds can participate in 1,3-dipolar cycloaddition as sources of 1,3-dipoles such as nitronates or nitroxides. Because the reaction of nitrones can be compared with that of nitronates, recent development of nitrones in organic synthesis is briefly summarized. 1,3-Dipolar cycloadditions to a double bond or a triple bond lead to five-membered heterocyclic compounds (Scheme 8.12). There are many excellent reviews on 1,3-dipolar cycloaddition, in particular, the monograph by Torssell covers this topic comprehensively. This chapter describes only recent progress in this field. Many papers have appeared after the comprehensive monograph by Torssell. Here, the natural product synthesis and asymmetric 1,3-dipolar cycloaddition are emphasized.630 Synthesis of pyrrolidine and -izidine alkaloids based on cycloaddition reactions are also discussed in this chapter. 

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