Alkoxyamines dissociation

Scheme 10.9 Measuring an alkoxyamine dissociation rate by ESR using oxygen as the scavenger.

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). 

Another mechanism of nitroxyl radical regeneration was proposed and discussed in the literature [67-71]. The alkoxyamine AmOR is thermally unstable. At elevated temperatures it dissociates with cleavage of the R—O bond, which leads to the appearance of an [AmO + R ] radical pair in the cage of polymer. The disproportionation of this radical pair gives hydroxylamine and alkene. The peroxyl radical reacts rapidly with hydroxylamine thus... 

An alkyl radical and a nitroxide radical exist in an equlibrium with the corresponding alkoxyamine as their coupling product (Eq. 57). Moad and Rizzardo [213] and Kazmaier et al. [214] independently estimated the effects of the structure of the alkyl group and the nitroxide on the dissociation energy of various alkoxyamines into the radicals by semiempirical molecular orbital calculations. The bond dissociation energies determined are summarized in Table 5 ... 

Table 5. Radical Dissociation Energy for Alkoxyamines (unit in kJ/mol)a...

It was clarified that the dissociation energy of the alkoxyamine decreased in the following order ... 

Scheme 10.8 Measuring the alkoxyamine (R—T) dissociation rate using a nitroxide-exchange experiment where the scavenger S is TMIO.

Scheme 10.11 shows a PRE-mediated 5-exo-trig radical cyclisation in which the controlled thermal formation of active radicals from the dormant alkoxyamine 2 is facilitated by steric compression of the alkoxyamine C—O bond by the bulky N-alkyl and O-alkyl groups [8]. Intramolecular H-bonding between a —CH2—OH and the nitroxyl oxygen of the incipient nitroxide in a six-membered cyclic transition structure further facilitated the dissociation of 2. After cyclisation, the resultant primary cyclopentylmethyl radical was trapped by the free nitroxide to form the new dormant isomerised alkoxyamine 3, which is more stable than 2 since the O-alkyl is now primary. The same reaction using TEMPO as the nitroxide component did not work presumably because the C—O bond in the alkoxyamine precursor is much stronger. 

Scheme 2 Dissociation of a typical alkoxyamine into a carbon-centered radical (ethylbenzene radical) and a nitroxide (TEMPO)...

Variations of the initial alkoxyamine concentration [I]o and independently measured rate constants k,, k,, and ktR nicely confirmed that the system fulfills the conditions (20) and reproduced the value of the parameter combination taken from the experimental data. The same was found for other alkoxyamines.16-23 However, it must be mentioned that the observation of such kinetics requires precautions with respect to the purity of chemicals, solvents, and containers. This is necessary because even very minor side reactions may strongly interfere with the many cycles of dissociation and recoupling that are necessary to provide a clear kinetic manifestation of the effect. 

In 1985, Rizzardo et al.27 filed a patent for the use of alkoxyamines (Scheme 12) as regulating initiators for the living radical polymerization and block copolymerization of vinyl monomers. R is a group that upon dissociation (Scheme 10) forms a radical that adds to the monomer. The mechanism was disclosed shortly thereafter and involves the reversible dissociations shown in Scheme 11, with the nitroxide radical taking the role of X.28 In a later simulation, the group also revealed the reason for the remarkable absence of the usual terminations and rediscovered the principles of the persistent radical effect 29 As chains undergo termination transient radicals are removed from the system and the concentration of persistent species builds . Further, the authors noted correctly that, in contrast to normal radical polymer-... 

The first directed application of the phenomenon toward high-yielding organic synthesis is due to Studer.4-81 He employed the reversible dissociation of alkoxyamines for the generation of cyclized derivatives to avoid the usual use of tin—organic compounds in radical cyclizations. One example is shown in Scheme 23. 

Table 1 displays rate data for alkoxyamine-termi-nated polymers and low molecular model compounds and shows some important trends. At about the same temperature, the dissociation rate constants Ad of alkoxyamines (Schemes 12 and 30) with the same leaving radical (polystyryl, 1-phenylethyl) increase in the order 3 (TEMPO) < 6 < 8 (DEPN) < 1 (DBNO) by a factor of about 30. Acrylate radicals dissociate markedly slower than styryl radicals from 1 (DBNO), but there is no appreciable difference for 8 (DEPN). The dependence of Ad on the nitroxide structure has been addressed by Moad et al.104 They found the order five membered ring < six membered ring < open chain nitroxides and pointed out additional steric (compare 3 and 6) and polar effects. 

Table 1. Rate and Equilibrium Constants for the Reversible Dissociation of Polymeric Alkoxyamines and Low Molecular Model Compounds, Frequency Factors, and Activation Energies of Dissociations...

Various descriptions of different unitnolecular initiators can be found in the literature. A presence of a-methyl groups on the alkoxyamines appears to be essential [266]. These compounds yield, upon dissociation, both stable radicals and initiating ones and can be shown as follows [267]. 

Importantly in NMP, the decomposition of alkoxyamines can occur through the reaction in Scheme 5, in which the P-proton abstraction by a nitroxide is assumed to take place in the solvent cage in both dissociation and combination processes. In this scheme, the rate constant of decomposition fe ec (the rate=fedec[P-X]) wiU be proportional to fed imda the DC equilibrium and will take the relation... 

It was however quickly realized that the main problem with TEMPO was the low value of the dissociation rate constant, fed, of the corresponding alkoxyamine. Moad and Rizzardo showed that alkoxyamine homolysis rate is governed by a combination of polar, steric, and electronic factors the steric one being predominant (see Section 3.10.3.1 for details). Many variations in the nature of the alkyl groups linked to the carbon in the a-position to the aminoxyl function were then investigated. For example, Mannan et and Miura et developed many six-membered cyclic nitroxides with spiro stmctures (18-24), which could be either mono (19) or disubstituted (21). The increase of the steric hindrance due to the spiro stmcture increased the dissociation rate constant of the (macro) alkoxyamines and led to successful NMP of S at 70 °C and -butyl acrylate (nBA) at 120 °C using nitroxide... 

A drastic change of nitroxide stmcture was witnessed with the use of the commercially available DBNO (27). In particular, Moad and Rizzardo showed that the dissociation rate constant of a DBNO-based alkoxyamine was higher than any similar alkoxyamines based on cyclic nitroxides bearing tetra-methyl alkyl groups on the vicinity of the aminoxyl function. The first experimental studies were performed by the group of Catala where it was shown that the polymerization of styrene and substituted styrene monomers could be carried out at 90 ° C with all the criteria of control/livingness. However, the polymerization rate was independent of the alkoxyamine concentration and remained governed by the production of thermal radicals in the medium. The tert-butyl-tert-amyl nitroxide 28 was tested by Moad et to control the polymerization of MMA and appeared to be inefficient. 

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