Alkoxyamine

Compounds of the type R NH—OR are named (1) as alkoxyamino derivatives of compound R H, (2) as A, 0-substituted hydroxylamines, (3) as alkoxyamines (even if R is hydrogen), or (4) by the prefix aminooxy- when another substituent has priority for parent name. Examples of each type are... 

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

Reaction of the enantiomerically pure alkoxyamines 3, prepared from L-ephedrine or norephedrine derivatives 1 with acetaldehyde, isobutyraldehyde or benzaldehyde using ethanol as the solvent, afford the corresponding oxime ethers 4 as mixtures of E/Z-stereoisomers11. 

Table 5. Addition of Organolithium Reagents R2Li to Oxime Ethers 4 and Reduction of the Resulting Alkoxyamines 5 to Amines 6"...

Obviously, racemization occurred during the reduction step. For this benzylic alkoxyamine. racemization may occur by initial elimination of a metal alkoxide followed by reduction of the resulting achiral imine. 

The reaction of radicals with nitroxides is reversible. 09 This means that the highest temperature that the technique can reasonably be employed at is ca 80 °C for tertiary propagating species and ca 120 °C for secondary propagating species.22 These maximum temperatures are only guidelines. The stability of alkoxyamines is also dependent on solvent (polar solvents favor decomposition) and the structure of the trapped species. This chemistry has led to certain alkoxyamines being useful as initiators of living polymerization (Section 9.3.6). At elevated temperatures nitroxides are observed to add to monomer albeit slowly. 3IS 5" 523... 

The initiator or iniferter determines the number of growing chains. Several methods of initiation are used. Only three will be considered here. The first involves direct use of a species 1-X (e.g. a dilhiocarbamale ester - Section 9.3.2 or an alkoxyamine - Section 9.3.6) as shown in Scheme 9.4. Ideally, the degree of polymerization is given by eq. I and the molecular weight by eq. 2. 

Prior to the development of NMP, nitroxides were well known as inhibitors of polymerization (Section 5.3.1). They and various derivatives were (and still are) widely used in polymer stabilization. Both applications are based on the property of nitroxides to efficiently scavenge carbon-centered radicals by combining with them at near diffusion-controlled rates to form alkoxyamines. This property also saw nitroxides exploited as trapping agents to define initiation mechanisms (Section 3.5.2.4). 

A wide range of nitroxidcs and derived alkoxyamincs has now been explored for application in NMP. Experimental work and theoretical studies have been carried out to establish structure-property correlations and provide further understanding of the kinetics and mechanism. Important parameters are the value of the activation-deactivation equilibrium constant K and the values of kaa and (Scheme 9.17), the combination disproportionation ratio for the reaction of the nilroxide with Ihe propagating radical (Section 9.3.6.3) and the intrinsic stability of the nitroxide and the alkoxyamine under the polymerization conditions (Section 9.3.6.4). The values of K, k3Cl and ktieact are influenced by several factors.11-1 "7-"9 ... 

Two basic strategics have been applied to initiate NMP. In the first method, the initiator is a low molecular weight alkoxyamine (Scheme 9.4). This approach was used in the original work of Solomon and coworkers,111-113 Later, Hawker and coworkers141X165 also exploited this method and coined the term Tinimer to describe these initiators. 

In the second approach, the alkoxyamine is fonned in situ typically from the nitroxide and radicals generated using a conventional initiator (Scheme 9.5). The initiator used in the early work of Georges et was BPO (Scheme 9.18). The yield of alkoxyamine based on BPO is not quantitative and various side reactions are known to accompany alkoxyamine formation (Section 3.5.2.4). When the... 

Catala and coworkers167JuiS made the discovery that the rate of TEMPO-mediated polymerization of S is independent of the concentration of the alkoxyamine. This initially surprising result was soon confirmed by others.23 69 Gretza and Matyjaszewski169 showed that the rate of NMP is controlled by the rate of thermal initiation. With faster decomposing alkoxyamines (those based on the open-chain nitroxides) at lower polymerization temperatures, the rate of thermal initiation is lower such that the rate of polymerization becomes dependent on the alkoxyamine concentration, Irrespective of whether the alkoxyamine initiator is preformed or formed in situ, low dispersities require that the alkoxyamine initiator should have a short lifetime. The rate of initiation should be as fast as or faster than propagation under the polymerization conditions and lifetimes of the alkoxyamine initiators should be as short as or shorter than individual polymeric alkoxyamines. 

Various methods have been used to form low molecular weight alkoxyamine initiators for NMP. Most involve forming an appropriate carbon-centered radical in the presence of a nitroxide. Initiators that generate carbon-ccntcrcd radicals may be thermally decomposed in the presence of a nitroxide. For example, alkoxyamine 100 is formed by decomposition of AIBN in the presence of TEMPO (Scheme 9.19). 1,1 Carbon-centered radicals may also be generated photochemically. 70... 

ATRP catalysts may be used to generate radicals and thus alkoxyamines can be produced from alkyl halides in high yield (Scheme 9.21).174 The alkoxyaminc 102 was obtained in 92% yield 174 whereas reaction of TEMPO with PMMA under ATRP conditions is reported to provide a macromonomer (Section 9.7.2.1). 

The Manganese(V) catalyzed oxidation of S derivatives in the presence of a nitroxide provides excellent yields of phenylethyl alkoxyamines (Scheme 9.22).175,176 Alkoxyamines can also be prepared from acrylates by... 

The thermal decomposition of the phenylelhyl alkoxyamine with TEMPO and the fraction of living ends in TEMPO-mediated S polymerization has been studied by Priddy and coworkers.143 179 They concluded that to achieve >90% living ends conversions and/or nitroxide concentrations should be chosen to give V/ less than 10000.143 However, disproportionation or elimination is most important during polymerizations of methacrylates and accounts for NMP being less successful with... 

Alkoxyamine C-O bond homolysis rates have been shown to increase where propagating radical is 2 118... 

NMP with acrylates and acrylamides with TEMPO provides only very low conversions. Very low limiting conversions and broad dispersities were reported.2 Better results were obtained with DTBN (83),111 151 imidazoline (61-64)I3S and isoindoline (59) nitroxides.111 However, limiting conversions were still observed. The self-regulation provided in S polymerization by thermal initiation is absent and, as a consequence, polymerization proceeds until inhibited by the buildup of nitroxide. The final product is an alkoxyamine and NMP can be continued... 

Successful NMP in emulsion requires use of conditions where there is no discrete monomer droplet phase and a mechanism to remove any excess nitroxide formed in the particle phase as a consequence of the persistent radical effect. Szkurhan and Georges"18 precipitated an acetone solution of a low molecular weight TEMPO-tcrminated PS into an aqueous solution of PVA to form emulsion particles. These were swollen with monomer and polymerized at 135 °C to yield very low dispersity PS and a stable latex. Nicolas et at.219 performed emulsion NMP of BA at 90 °C making use of the water-soluble alkoxyamine 110 or the corresponding sodium salt both of which are based on the open-chain nitroxide 89. They obtained PBA with narrow molecular weight distribution as a stable latex at a relatively high solids level (26%). A low dispersity PBA-WocA-PS was also prepared,... 

Various initiation strategies and surfactant/cosurfactant systems have been used. Early work involved in situ alkoxyamine formation with either oil soluble (BPO) or water soluble initiators (persulfate) and traditional surfactant and hydrophobic cosurfactants. Later work established that preformed polymer could perform the role of the cosurfactant and surfactant-free systems with persulfate initiation were also developed, l90 222,2i3 Oil soluble (PS capped with TEMPO,221 111,224 PBA capped with 89) and water soluble alkoxyamines (110, sodium salt""4) have also been used as initiators. Addition of ascorbic acid, which reduces the nitroxide which exits the particles to the corresponding hydroxylamine, gave enhanced rates and improved conversions in miniemulsion polymerization with TEMPO.225 Ascorbic acid is localized in the aqueous phase by solubility. 

Monomers not amenable to direct homopolymerization using a particular reagent can sometimes be copolymcrizcd. For example, NMP often fails with methacrylates (e.g. MMA, BMA), yet copolymerizalions of these monomers with S are possible even when the monomer mix is predominantly composed of the methacrylate monomer,15j This is attributed to the facility of cross propagation and the relatively low steady state concentration of propagating radicals with a terminal MMA (Section 7.4.3.1). MMA can also be copolymerized with S or acrylates at low temperature (60 C).111 Under these conditions, only deactivation of propagating radicals with a terminal MMA unit is reversible, deactivation of chains with a terminal S or acrylate unit is irreversible. Molecular weights should then be controlled by the reactivity ratios and the comonomer concentration rather than by the nitroxide/alkoxyamine concentration. 

Heating an alkoxyamine in the presence of another nitroxide provides nitroxide exchange 1 and a process for co-functionalization.584 The product... 

Functional alkoxyamines used as initiators for NMP include 283-287. The functional alkoxyamines can be formed in situ by use of a functional azo compound or peroxide. NMP has been shown to be compatible with hydroxy, epoxy, amide and tertiary amine groups in the initiator. Carboxylic acid groups can cause problems but may be tolerated in some circumstances.106... 

Addition of TEMPO post-polymerization to a methacrylate polymerization provides an unsaturated chain end (Scheme 9.52)i07 sw presumably by disproportionation of the PMMA propagating radical with the nitroxide. For polymers based on monosubstituted monomers (PS,1 0" PBA59,[Pg.534]

Commercial end functional polymers have been converted to alkoxyamincs and used to prepare PKO-Worri-PS.040 The hydroxyl group of alkoxyamine 284 was used to initiate ring-opening polymerization of caprolactonc catalyzed by aluminum tris(isopropoxide) and the product subsequently was used to initiate S polymerization by NMP thus forming polycaprolactone-Wodr- P8.641 The alternate strategy of forming PS by NMP and using the hydroxyl chain end of the product to initiate polymerization of caprolactonc was also used. 

The arm-first synthesis of star microgels by initiating polymerization or copolymerization of a divinyl monomer such as diviny lbenzene or a bis-maleimide with a polystyryl alkoxyamine was pioneered by Solomon and coworkers.692 693 The general approach had previously been used in anionic polymerization. The method has now been exploited in conjunction with NMP,692 6 ATRP69 700 and RAFT.449 701 702 The product contains dormant functionality in the core. This can be used as a core for subsequent polymerization of a monoene monomer to yield a mikto-arm star (NMP ATRP704). 

Several techniques have been applied in attaching the appropriate functionality to the polymer surface. For example, copolymeri/ation of a monomer containing functionality (alkoxyamine e.g. 358 or 359,744 ATRP initiator, e.g. 352,734 RAFT... 

The monomer 359 has been formed in situ by decomposing the initiator (A1BN) in the presence of the corresponding nilroxide in a solution of S or 2-ethoxyethyl acrylate.744 The kinetics dictate that alkoxyamine formation, by coupling of the nitroxide with cyanoisopropyl radicals, will take place before eopolymerization. 

The very small number of growing polymer chains, when compared to the monomer concentration results in a very low overall concentration of free control agent and leads to inefficient capping of chain ends. One solution to this problem is the addition of a free or unbound control agent to the polymerization medium. This can take the form of a low molecular weight alkoxyamine, ATRP initiator, RAFT agent or, alternatively, free deactivator such as nitroxide or Cu(II). This species is often called a sacrificial agent. This solution also leads to the formation of free polymer that must ultimately be removed from the brush. 

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