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This chapter traces the early history of nitroxide-mediated polymerization (NMP) during the first ∼15 years. It begins with a short prehistory of observations, made during studies on defining initiation mechanisms using nitroxide radical trapping that can be seen to have inspired the initial experiments. The main part of the chapter is devoted to an account of the discovery of NMP in the early 1980s and research carried out in the period through to 1993, which saw most aspects of the polymerization mechanism defined and the process exploited at CSIRO mainly in the synthesis of acrylic block copolymers. We also provide a brief summary of developments in both the patent and open literature during the period 1993–2000 when the process came to the attention of the wider polymer community mainly for the controlled radical polymerization of styrenics. The end of this period saw the discovery of nitroxides such as SG1 and TIPNO, which provided improved utility and versatility to NMP.

This chapter traces the early history of nitroxide-mediated polymerization (NMP) during its first ∼15 years. It begins with a short prehistory of observations made during studies on defining initiation mechanisms using nitroxide radical trapping that can be seen to have inspired the initial experiments. The main part of the chapter is devoted to an account of the discovery of NMP in the early 1980s and research carried out in the period through to 1993, which saw most aspects of the mechanism defined and the process exploited at CSIRO, mainly in the synthesis of acrylic block copolymers. Many nitroxides for NMP were evaluated, including TEMPO (1.1). However, those found to be more effective and which were most used were 1,1,3,3-tetraethylisoindolin-N-oxyl (1.2) and di-t-butyl nitroxide (1.3) (Figure 1.1). We also provide a brief summary of developments in both the patent and open literature during the period 1993–2000 when the process came to the attention of the wider polymer community, mainly for the TEMPO-mediated polymerization of styrenics. The end of this period saw the discovery of nitroxides such as SG1 (1.4) and TIPNO (1.5) (Figure 1.2), which provided utility and versatility to NMP.

Figure 1.1

Structures of nitroxides favored in early studies of nitroxide-mediated polymerization.

Figure 1.1

Structures of nitroxides favored in early studies of nitroxide-mediated polymerization.

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Figure 1.2

Structures of α-hydrido nitroxides commonly known as SG1 and TIPNO.

Figure 1.2

Structures of α-hydrido nitroxides commonly known as SG1 and TIPNO.

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The term “nitroxide” is discouraged in IUPAC nomenclature, which instead recommends the term “aminoxyl”. The IUPAC recommended term for “nitroxide-mediated polymerization” (NMP) is “aminoxyl-mediated radical polymerization” (AMRP).1  However, in keeping with the historical context, the terms in common use are used throughout this chapter.

Over the past 20 years, radical polymerization has proved to be one of the most active and fertile fields for research into polymer synthesis. The growth of interest in radical polymerization over this period can be largely attributed to the development of techniques for reversible deactivation radical polymerization (RDRP),1  which impart living character to the process. These techniques include nitroxide-mediated polymerization (NMP—vide infra), atom transfer radical polymerization (ATRP),2–5  reversible addition-fragmentation chain transfer (RAFT),6–13  and tellurium-mediated radical polymerization (TERP).14  Papers on these methods now account for more than two-thirds of all papers on radical polymerization.15 

NMP was discovered at CSIRO, in the then Division of Applied Organic Chemistry, and lodged as an Australian patent application Alkoxyamines useful as initiators in 1984. The first publication on NMP was a European patent application, Free radical polymerization and the produced polymers, which appeared in 1985.16  In these documents, the process was described as a method for controlled-growth radical polymerization. The introduction16  states “The present invention relates generally to improved processes for free radical polymerization, particularly to improved processes in which it is possible to control the growth steps of the polymerization to produce relatively short chain length homopolymers and copolymers, including block and graft copolymers, and further relates to new initiators which find particular application in the improved processes,” and goes on to define suitable alkoxyamine initiators. The process was said to have living character and be particularly suited for the preparation of well-defined short-chain or oligomeric chains with Mn in the range 500–5000. However, the preparation of higher molecular weight polymers was also outlined.

NMP was briefly described in our review entitled Other initiating systems, which appeared in Comprehensive Polymer Science in 1989.17  However, the origins of the process at CSIRO are given little mention in most reviews of NMP.18–29  Some details of the discovery are revealed in articles by Solomon30  and Rizzardo and Solomon.7 

In the 1980s, radical polymerization was possibly the most widely used processes for the commercial production of high molecular weight polymers.15  Radical polymerization provides the ability to polymerize a vast array of monomers. This versatility can be attributed to the technique's tolerance of unprotected functionality in monomer and solvent, its compatibility with a variety of reaction conditions, and the relative simplicity and low cost of implementation. However, use of the conventional process imposes severe limitations on the degree of control that can be asserted over features such as molecular weight distribution, copolymer compositions and macromolecular architecture.

Conventional radical polymerization is a chain reaction (Scheme 1.1).31  Chains are initiated by radicals, formed from an initiator, adding to monomer. These chains propagate by sequential addition of monomer units. Chain termination occurs when the propagating radicals self-react by combination or disproportionation. Continuous initiation and termination provides a steady-state radical concentration of only ∼10−7 M and the lifetimes of individual chains are typically ∼5–10 seconds within a reaction span that may be many hours. In the absence of chain transfer, the lengths of the chains formed during the early stages of polymerization are high. The breadth of the molecular weight distribution is governed by statistical factors. The dispersity (Ð), the ratio of weight to number average molecular weights (Mw/Mn), is ideally 2.0 if termination is by disproportionation or chain transfer, or 1.5 if termination is by combination.31 

Scheme 1.1

Ideal reaction scheme for conventional radical polymerization.

Scheme 1.1

Ideal reaction scheme for conventional radical polymerization.

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In marked contrast, in a living polymerization, all chains are initiated at the beginning of the process, grow at a similar rate and all survive the polymerization (Scheme 1.2). By definition, there is no termination or irreversible chain transfer.32–34  If initiation is rapid with respect to propagation, the molar mass distributions should be very narrow, approaching a Poisson distribution. In a living polymerization, chains can be extended indefinitely with the provision of monomer and conditions to support polymerization. In a conventional radical polymerization, the propensity of radicals to undergo self-termination means that all chains cannot be simultaneously active.

Scheme 1.2

Reaction scheme for living anionic polymerization.

Scheme 1.2

Reaction scheme for living anionic polymerization.

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The first examples of what we now recognize as stable radical-mediated polymerization (SRMP) mediated by dithiocarbamyl radicals were reported by Otsu35,36  in 1956–1957. Further examples of what may be considered SRMP mediated by diarylmethyl radicals were described by Braun and colleagues in the period 1970–1990.37  Braun termed these processes “resuscitatable” radical polymerizations.

However, the concept of living radical polymerization (now known as RDRP)1  was only introduced by Otsu and coworkers in 1982.38–40  They recognized that radical polymerizations might display living attributes in the presence of reagents that are capable of reversibly deactivating active chains (propagating radicals, Pn˙) such that the majority of living chains are maintained in a dormant form (Pn-X). A further requirement is reaction conditions that support an equilibrium between active and dormant chains that is rapid with respect to propagation. The terms “initer” (for initiator-terminator) and “iniferter” (for initiater-transfer agent-terminator) were introduced to describe the reagents used. A similar terminology [“inifer” (for initiater-transfer agent)] had already been used by Kennedy41,42  in describing cationic polymerizations with reversible deactivation.

Even though there are clear differences in the mechanism of radical (Scheme 1.1) and other processes for chain polymerization, for example, anionic polymerization (Scheme 1.2), polymers formed are usually represented by the same structure (Figure 1.3). This structure defines only the dominant repeat unit and ignores connectivity, end-groups and side reactions during propagation.

Figure 1.3

Generic polymer structure.

Figure 1.3

Generic polymer structure.

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This idealized structure has deficiencies when it comes to rationalizing certain polymer properties. For example, poly(methyl methacrylate) (PMMA) synthesized by anionic polymerization can be more stable than the (apparently) same polymer made by radical polymerization.43  The stability of PMMA made by radical polymerization depends on the initiator used and other details of its preparation. Similar observations have been made for other polymers, including poly(vinyl chloride) (PVC) and polystyrene (PSt).44  These observations led to a recognition that chain polymers contain structural irregularities, which include the structures formed by chain initiation and termination (Scheme 1.1).45–47 

At CSIRO, these issues prompted the application and development of methods for probing the detailed chemistry of initiation of radical polymerization. Amongst these was the radical-trapping method making use of nitroxides [the IUPAC recommended term for nitroxide is aminoxyl].48  A now well-known feature of the chemistry of nitroxides (e.g.1.11.8) is that they combine with carbon-centred radicals to give alkoxyamines at close to diffusion controlled rates.49–53  This property led to the use of nitroxides in the so-called inhibitor method for the determination of initiator efficiency54  and was the basis of the radical-trapping method.

The radical trapping method using nitroxides had been developed at CSIRO in the late 1970s in response to a need to be able to quantitatively characterize radical reactions.48  The use of spin-trapping using nitroso-compounds and nitrones had already been explored by several research groups in this context55  and had been used to study the initiation of polymerization.56–61  However, that method was not generally regarded as quantitative due to the complication of various side reactions. One side reaction is the formation of stable alkoxyamines by the further reaction of the nitroxides formed to scavenge carbon-centred radicals.55  There was other literature to indicate that the nitroxides were able to selectively scavenge carbon-centred radicals62  and limited kinetic data to indicate that the rate of reaction was extremely rapid (kc 107–109 M−1 s−1).63  Nitroxides were also known to be effective inhibitors of radical polymerization.62  Thus a stable nitroxide, in particular 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO, 1.1) (Figure 1.4), was explored as a radical trap initially to study initiation pathways in methyl acrylate (MA) polymerization.48  This and subsequent studies confirmed that nitroxides selectively scavenge carbon-centred radicals to yield stable alkoxyamines (under the conditions used and when isolated) while oxygen-centred radicals either did not react or reacted reversibly with the nitroxide.

Figure 1.4

Nitroxides used in radical trapping experiments.

Figure 1.4

Nitroxides used in radical trapping experiments.

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Largely over the period 1979–2000, the radical trapping technique was successfully used to define the initiation pathways for the reactions of mainly oxygen-centred (t-butoxy, 48,64–81  cumyloxy,82  other t-alkoxy,83–87  isopropoxy,88,89  ethoxy,89  benzoyloxy,70–72,77,79,90–92  isopropoxycarbonyloxy,70  hydroxy,93,94 ), more reactive carbon-centred radicals (methyl,81 t-butyl,81,95  phenyl71,72,77,78,92 ) and cyanoisopropyl radicals85,96  with a range of monomers. The nitroxides used in these studies included 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO, 1.1) and its derivatives (1.6,71 1.773 ), and the isoindoline nitroxide, 1,1,3,3-tetramethylisoindolin-2-oxyl (1.8).71,97  The nitroxides 1.61.8 (Figure 1.4) possess a UV chromophore facilitating chromatographic detection.

A number of observations were made when applying the radical-trapping method with nitroxides that led to the development of NMP (note that most of the references cited below postdate the invention of on NMP—the original observations were not published or were published later).

  • Certain alkoxyamines appeared unstable during isolation or subsequent handling.77,98  This was sometimes indicated by color development or the appearance of the characteristic absorbance of the corresponding nitroxide.

  • Certain alkoxyamines were observed to equilibrate to a mixture of isomers on heating or on standing for prolonged periods. For example, the isolated “styrene dimer” alkoxyamines shown in Scheme 1.3,99  undergo cis–trans isomerization to form the same mixture of isomers on heating. The allylic alkoxyamines shown in Scheme 1.4 isomerize with a 1,3-shift of the nitroxide functionality.100  In both examples, the findings can be understood if the alkoxyamines undergo reversible homolytic dissociation as shown.

  • In some trapping experiments, the formation of small amounts of oligomers was observed.72,82,92  This was attributed to the rate of trapping of the initiating radical being slow with respect to propagation. The yield of propagation products was consistent with the known kinetics of propagation and trapping, and this remains the likely explanation. NMP was unlikely under the conditions used for the trapping experiments because of the nitroxide used (1.1 or 1.8), the significant excess of nitroxide (∼10% at complete initiator consumption), and the low reaction temperatures used (60 °C). Nonetheless, the observations led us to consider other possibilities.

Scheme 1.3

Mechanism of cistrans isomerization of “styrene dimer” alkoxyamines.

Scheme 1.3

Mechanism of cistrans isomerization of “styrene dimer” alkoxyamines.

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Scheme 1.4

Mechanism of isomerization of allylic alkoxyamines.

Scheme 1.4

Mechanism of isomerization of allylic alkoxyamines.

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These and similar observations suggested that the alkoxyamines formed were thermally labile, perhaps undergoing reversible dissociation as shown in Scheme 1.5. This in turn suggested the possibility of a method for controlled-growth radical polymerization based on alkoxyamine chemistry with the potential to open the door to structures that were not readily approached by conventional radical polymerization.

Scheme 1.5

Activation–deactivation equilibrium in nitroxide-mediated polymerization.

Scheme 1.5

Activation–deactivation equilibrium in nitroxide-mediated polymerization.

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The concept of NMP as a method for living radical polymerization was first disclosed in a Plenary lecture by Ezio Rizzardo at the 14th Australian Polymer Symposium, which was held in Ballarat in February 1984101  only a few days after the first patent application had been lodged.

The alkoxyamines based on the nitroxides used in the trapping work (1.1 and 1.61.8) were not very effective in NMP and required the use of relatively high reaction temperatures for homolysis, particularly, with acrylates and styrene. It was reasoned that the rate of homolysis should be lowered by steric congestion. Therefore, the first successful NMP experiment (Scheme 1.6) made use of the tetraethylisoindoline nitroxide 1.2, an analog of the tetramethylisoindoline nitroxide 1.8 that had been used in the trapping experiments. The patent102  generically covered the use of nitroxides of general structure 1.9 in NMP with specific examples being 1.11.3 (Figure 1.1) and 1.101.13 (Figure 1.5).

Scheme 1.6

Nitroxide-mediated polymerization of methyl acrylate (MA). Example 23 of the original patent application.102 

Scheme 1.6

Nitroxide-mediated polymerization of methyl acrylate (MA). Example 23 of the original patent application.102 

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Figure 1.5

Nitroxides used in nitroxide-mediated polymerization (NMP).

Figure 1.5

Nitroxides used in nitroxide-mediated polymerization (NMP).

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The first successful NMP experiment carried out in 1982, detailed as Example 23 of the original patent application,102  is summarized in Scheme 1.6. It was found that heating the alkoxyamine 1.19 with MA in benzene (50% v/v) solution at 80 °C provided complete conversion of the alkoxyamine to the single-unit monomer insertion product 1.20). When the same alkoxyamine 1.19 was heated at 80 °C in bulk MA, ∼7 units of MA were inserted to give the heptamer 1.21. In both cases, no further reaction (oligomerization) was observed when the mixtures were heated at 80 °C for longer times.

These observations are explained as follows. At 80 °C, the alkoxyamine 1.19 dissociates and MA units add; the number is dictated by the relative concentrations of MA and nitroxide. Combination of the propagating species with nitroxide gives alkoxyamine 1.20 or 1.21. These insertion products 1.20 and 1.21 are stable at 80 °C, so no NMP was observed.

NMP required higher reaction temperatures, sufficient to allow reversible dissociation of the alkoxyamine products. When the heptamer 1.21 was heated at 100 °C, slow NMP was observed such that a 14-mer was obtained after 1.5 h. Faster NMP took place at 120 °C providing a 70-mer after 1.5 h. NMP of styrene (Scheme 1.7) was also successful at 100 °C. A 4.5-mer macro-alkoxyamine was obtained after 1 h and a 12-mer after 2 h at 100 °C. The mechanism proposed for NMP is shown in Scheme 1.8.

Scheme 1.7

Nitroxide-mediated polymerization of styrene (St). Example 15, St unimer preparation, and Example 27 of the original patent application.102 

Scheme 1.7

Nitroxide-mediated polymerization of styrene (St). Example 15, St unimer preparation, and Example 27 of the original patent application.102 

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Scheme 1.8

Mechanism for nitroxide-mediated polymerization (NMP) proposed in the CSIRO patent application.102 

Scheme 1.8

Mechanism for nitroxide-mediated polymerization (NMP) proposed in the CSIRO patent application.102 

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NMP of methyl methacrylate (MMA) provided a low dispersity macromonomer rather than a macro-alkoxyamine as the isolated product (Scheme 1.9, Scheme 1.10). Two explanations for this finding were proposed:102  (a) that the tertiary alkoxyamine underwent thermal elimination to provide the macromonomer and hydroxylamine and/or (b) that the PMMA propagating species gave some disproportionation with nitroxide to give the same products (Scheme 1.11).

Scheme 1.9

Nitroxide-mediated polymerization of methyl methacrylate (MMA). Example 13, α-methylstyrene (AMS) unimer preparation, and Example 33 of the original patent application.102 

Scheme 1.9

Nitroxide-mediated polymerization of methyl methacrylate (MMA). Example 13, α-methylstyrene (AMS) unimer preparation, and Example 33 of the original patent application.102 

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Scheme 1.10

Nitroxide-mediated polymerization of methyl methacrylate (MMA). Example 34 of the original patent application.102 

Scheme 1.10

Nitroxide-mediated polymerization of methyl methacrylate (MMA). Example 34 of the original patent application.102 

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Scheme 1.11

Possible mechanisms for end-group loss during NMP of α-methyl vinyl monomers.102 

Scheme 1.11

Possible mechanisms for end-group loss during NMP of α-methyl vinyl monomers.102 

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A MMA-based macro-alkoxyamine was prepared by NMP of MMA in the presence of styrene (Scheme 1.12). Since the macro-alkoxyamine with a terminal styrene is stable at 60 °C, under these reaction conditions, the molecular weight is determined by the styrene concentration and the monomer reactivity ratios. Nitroxide-mediated copolymerization of MMA and EA was also successful in providing a macro-alkoxyamine with a terminal EA unit (Scheme 1.13).

Scheme 1.12

Nitroxide-mediated polymerization of methyl methacrylate (MMA) in the presence of styrene. Example 13, α-methylstyrene (AMS) unimer preparation, and Example 31 of the original patent application.102 

Scheme 1.12

Nitroxide-mediated polymerization of methyl methacrylate (MMA) in the presence of styrene. Example 13, α-methylstyrene (AMS) unimer preparation, and Example 31 of the original patent application.102 

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Scheme 1.13

Nitroxide-mediated copolymerization of ethyl acrylate (EA) and methyl methacrylate (MMA). Example 32 of the original patent application.102 

Scheme 1.13

Nitroxide-mediated copolymerization of ethyl acrylate (EA) and methyl methacrylate (MMA). Example 32 of the original patent application.102 

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In later work,103,104  a comparative study of a series of nitroxides in controlling MMA polymerization at 90 °C was performed in experiments where the alkoxyamine was formed in situ.103,104  Azobis(2,4-dimethyl-2-pentanenitrile) was used as the initiator since it has a very short half-life at 90 °C (<20 sec).105  The results (conversions, dispersities, molecular weights) obtained in these experiments are summarized in Table 1.1. The lowest dispersities, in the range 1.4–1.7, were obtained with the 5-membered ring nitroxides. These dispersities are not exceptional but compare very favorably with the values in the range 3.1–4.1 obtained with the 6-membered ring nitroxides, TEMPO (1.1) and its 4-oxo derivative 1.12, or the open chain nitroxide 1.14. In these experiments, polymerization ceased after less than one hour reaction time. Best conversions (up to 38%) were obtained with the imidazolidinone nitroxide 1.17. All other experiments in the series gave monomer conversions <20%.

Table 1.1

Molecular weight/conversion data for polymerizations (90 °C, bulk) of methyl methacrylate in the presence of various nitroxides and with azobis(2,4-dimethyl-2-pentanenitrile) as initiator.a,103,104 

NitroxideMnbÐConv. %[nitroxide] MMn(calc)c
1.15 35 700 1.57 38 0.0077 36 800 
33 800 1.65 36 0.0069 34 500 
20 400d 1.70 19 0.0077 18 500 
1.17 31 021 1.63 17 0.0077 18 200 
1.16e 6500 1.44 0.0077 6100 
1.18e 28 800 1.89 21 0.0077 22 500 
1.2 18 300 1.71 18 0.0079 17 400 
5600 1.68 0.0115 5900 
1.8 10 500 2.24 11 0.0076 10 800 
1.12 17 000 3.30 18 0.0077 16 900 
1.1 22 100 3.11 14 0.0076 13 800 
1.14 19 200 4.10 18 0.0076 17 200 
NitroxideMnbÐConv. %[nitroxide] MMn(calc)c
1.15 35 700 1.57 38 0.0077 36 800 
33 800 1.65 36 0.0069 34 500 
20 400d 1.70 19 0.0077 18 500 
1.17 31 021 1.63 17 0.0077 18 200 
1.16e 6500 1.44 0.0077 6100 
1.18e 28 800 1.89 21 0.0077 22 500 
1.2 18 300 1.71 18 0.0079 17 400 
5600 1.68 0.0115 5900 
1.8 10 500 2.24 11 0.0076 10 800 
1.12 17 000 3.30 18 0.0077 16 900 
1.1 22 100 3.11 14 0.0076 13 800 
1.14 19 200 4.10 18 0.0076 17 200 
a

[Initiator] 0.0054 M.

b

Number average molecular weight in polySt equivalents.

c

Calculated molecular weight based on an initiator efficiency of 90%. Values shown have been rounded to the nearest hundred.

d

Reaction temperature 100 °C.

e

[initiator] 0.0049 M.

The findings are consistent with NMP of MMA proceeding only until the nitroxide concentration builds to a level so as to inhibit further polymerization. After this time, reversible dissociation of the alkoxyamine continues but little propagation occurs and the propagating radicals ultimately disproportionate with nitroxide. Kinetic simulations103  supported this hypothesis and indicated that the dependence on nitroxide type could be attributed to the combination:disproportionation ratio for the reaction the MMA propagating species and nitroxide, which is lower in the case of the 5-membered ring nitroxides than it is with 6-membered ring or open chain nitroxides. The ‘worst case’ combination:disproportionation ratio consistent with the experimental results was <0.01.103 

It is worth noting that macromonomers have wide utility in the synthesis of graft copolymers,106  as transfer agents,107  and as so-called macromonomer RAFT agents.108,109 

The molecular weight dispersities achieved in most of the examples of NMP in the patent are high with respect to what we have come to expect from effective RDRP. In part, this can be attributed to the polymerization conditions and to the relatively low molecular weights that were targeted. Nonetheless, the patent contains an example of polyMMA with Ð of 1.15 and several polymers with Ð<1.5. The dispersity of chains formed by conventional radical polymerization under ideal conditions with termination by disproportionation is 2.0.

The experiments shown in demonstrated that the NMP had living characteristics in that chain extension, by re-subjecting the macro-alkoxyamine to the polymerization conditions, was possible. Nonetheless, it was important to provide further evidence and demonstrate block copolymer synthesis. In the patent, this was exemplified with the synthesis of polyEA-block-polyMA (Scheme 1.14) and polyMA-block-polyEA-block-polyMMA (Scheme 1.15). Note that the polyMMA block must be made last since the end-group is lost during NMP and the product is a macromonomer.

Scheme 1.14

Sequential nitroxide-mediated polymerization of ethyl acrylate (EA) and methyl acrylate (MA) to form a diblock copolymer. Examples 29 and 38 of the original patent application.102 

Scheme 1.14

Sequential nitroxide-mediated polymerization of ethyl acrylate (EA) and methyl acrylate (MA) to form a diblock copolymer. Examples 29 and 38 of the original patent application.102 

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Scheme 1.15

Sequential nitroxide-mediated polymerization of methyl acrylate (MA), ethyl acrylate (EA) and methyl methacrylate (MMA) to form a triblock copolymer. Examples 26, 36 and 39 of the original patent application.102 

Scheme 1.15

Sequential nitroxide-mediated polymerization of methyl acrylate (MA), ethyl acrylate (EA) and methyl methacrylate (MMA) to form a triblock copolymer. Examples 26, 36 and 39 of the original patent application.102 

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A major application interest for NMP at CSIRO, dictated in part by our commercial partners, lay with the synthesis of low molecular weight acrylic acid–alkyl acrylate block copolymers. This research was briefly reported in two papers.110,111  The methodology was applied in the multi-gram synthesis of block copolymers useful as pigment dispersants. For example, poly(BA-co-MA)-block-polyAA, as shown in Scheme 1.16.112 

Scheme 1.16

Sequential nitroxide-mediated copolymerization of methyl acrylate (MA) and n-butyl acrylate (BA) followed by polymerization of t-butyl acrylate (tBA) to form a diblock copolymer. The tBA units were converted to acrylic acid units by heating with formic acid. The end-groups X in the final polymer were not determined.112 

Scheme 1.16

Sequential nitroxide-mediated copolymerization of methyl acrylate (MA) and n-butyl acrylate (BA) followed by polymerization of t-butyl acrylate (tBA) to form a diblock copolymer. The tBA units were converted to acrylic acid units by heating with formic acid. The end-groups X in the final polymer were not determined.112 

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The CSIRO patent also demonstrated the utility of NMP in forming branched or graft copolymers from copolymers containing alkoxyamine functionality. The latter polymers could be formed in various ways, of which two were exemplified: (a) copolymerization of an appropriate functional monomer, and (b) trapping radicals formed on a polymer substrate. The process (a) is illustrated in Scheme 1.17.

Scheme 1.17

Synthesis of alkoxyamine functional methyl methacylate (MMA) copolymer by conventional radical copolymerization at low temperature initiated by di-t-butyl peroxyoxalate (DBPOX) and nitroxide-mediated graft copolymerization of styrene (St). Examples 21 and 44 of the original patent application.102 

Scheme 1.17

Synthesis of alkoxyamine functional methyl methacylate (MMA) copolymer by conventional radical copolymerization at low temperature initiated by di-t-butyl peroxyoxalate (DBPOX) and nitroxide-mediated graft copolymerization of styrene (St). Examples 21 and 44 of the original patent application.102 

Close modal

Following the success of the experiments shown in Scheme 1.6, much early work revolved around ascertaining the dependence of NMP on nitroxide structure. In 1995,113  we reported a study on the kinetics of alkoxyamine decomposition based in large part on the experimental data from the patent102  and two earlier papers.114,115  The half-lives of alkoxyamines formed between various nitroxides and radicals were measured by a nitroxide-exchange process that involved following the rate of consumption of the alkoxyamine (or appearance of product) when it was heated in the presence an excess of nitroxide 1.1 or 1.8 in ethyl acetate solution (Scheme 1.18, Table 1.2).102,113  The reaction between the carbon-centred radicals and 1.1 or 1.8 is essentially irreversible under the measurement conditions such that the exchange could be conveniently followed by HPLC. The concentration of nitroxides 1.1 or 1.8 was chosen to be in excess such that the rate of disappearance of alkoxyamine is a direct measure of the homolysis rate constant (i.e. there was no significant likelihood of recombination to form the original alkoxyamine). It was later found that similar data could be obtained simply by heating the alkoxyamines in air when the released radicals were scavenged by oxygen.

Scheme 1.18

Nitroxide exchange experiment used to determine alkoxyamine half-lives.

Scheme 1.18

Nitroxide exchange experiment used to determine alkoxyamine half-lives.

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Table 1.2

Half-lives (min) of alkoxyaminesa (R–X) in ethyl acetate solution.102,113 

R
X60 °C60 °C80 °C90 °C60 °C60 °C
1.10 280 — — — — — 
1.8 780 — — — — — 
1.2 33 75 >1000 — 55 123 
1.11 31 — — — — — 
1.1 65 — — — — — 
1.13 — 10 400 — — — 
1.3 <2b ∼2c 70d 105 — — 
1.14297  — — 25 — — — 
1.15297  — — 180e — — — 
R
X60 °C60 °C80 °C90 °C60 °C60 °C
1.10 280 — — — — — 
1.8 780 — — — — — 
1.2 33 75 >1000 — 55 123 
1.11 31 — — — — — 
1.1 65 — — — — — 
1.13 — 10 400 — — — 
1.3 <2b ∼2c 70d 105 — — 
1.14297  — — 25 — — — 
1.15297  — — 180e — — — 
a

Alkoxyamines (R–X) formed between nitroxide (X) and radical (R) indicated.

b

Half-life 8.5 min at 40 °C.

c

Half-life is 18 min at 40 °C.

d

Half-life is 22 min at 90 °C.

e

At 110 °C.

The first NMP experiments showed that homolysis rates increased with an increase in steric bulk of the substituents α to the nitroxide nitrogen. The nitroxide exchange experiments confirmed this hypothesis. The experiments also showed that alkoxyamine homolysis rates increased with increasing ring size, for the cyclic nitroxides, and that alkoxyamines based on the open chain nitroxide (1.3) offered the fastest homolysis rates amongst those studied at the time. These findings were in accord with bond dissociation energies and activation energies for C–O bond homolysis estimated with molecular orbital calculations. Later work showed that rates for combination exhibit the inverse trend, i.e., 5-membered ring>6-membered ring>open chain, but are somewhat smaller.53 

The effect of alkyl group structure on homolysis rates was also examined.113  Alkoxyamines based on tertiary radicals with an α-methyl substituent gave substantially faster homolysis rates than analogous secondary radicals (Figure 1.6).

Figure 1.6

Effect of alkyl group structure on homolysis rates.

Figure 1.6

Effect of alkyl group structure on homolysis rates.

Close modal

The reaction medium was also found to have a significant effect on the rate constant for C–O bond homolysis. Half-life data at 60 °C for the alkoxyamine formed between nitroxide 1.2 and the cyanoisopropyl radical determined by the radical exchange method are presented in Table 1.3.113  Rate constants for C–O bond homolysis (kH) estimated on the basis of these half-lives and rate constants for the reverse trapping reaction (kT)116  are also provided. Clear trends for an increase in alkoxyamine dissociation rate (decrease in half-life) and increase in association or trapping with increasing solvent polarity were apparent. Significantly higher alkoxyamine dissociation rates were observed for NMP in acidic media (acetic acid in methanol).

Table 1.3

Solvent dependence of homolysis and trapping reactions.

SolventHalf-lifea (min)kHb (s−1)kT/107c (M−1 s−1)
Hexane 38 0.00062 48 
Ethyl acetate 33 0.00071 17 
Acetonitrile 22 0.00107 9.5 
Dimethylformamide 20 0.00118 — 
Methanol 17 0.00139 13 
10% (v/v) Water in methanol 16 0.00147 — 
10% (v/v) Acetic acid in methanol 15 0.00157 — 
SolventHalf-lifea (min)kHb (s−1)kT/107c (M−1 s−1)
Hexane 38 0.00062 48 
Ethyl acetate 33 0.00071 17 
Acetonitrile 22 0.00107 9.5 
Dimethylformamide 20 0.00118 — 
Methanol 17 0.00139 13 
10% (v/v) Water in methanol 16 0.00147 — 
10% (v/v) Acetic acid in methanol 15 0.00157 — 
a

Half-life of alkoxyamine 1.19 formed between 2-cyanoprop-2-yl and nitroxide 1.2 at 60 °C.113 

b

Rate constant for alkoxyamine homolysis at 60 °C derived from half-life value.

c

Rate constant for trapping of benzyl radical at 18 °C with TEMPO (1.1).116 

The first full paper from CSIRO on NMP, published in 1990,117  dealt with kinetic simulation of NMP of acrylates. The paper showed that high molecular weight polymers with very low dispersities were feasible and indicated some of the conditions that should be met to achieve this. The paper described the persistent radical effect, but did not attach a name to the phenomenon or associate it with the theory that had been previously expounded by Fischer. Fischer had described the persistent radical effect in radical reactions in a non-polymerization context in 1986.118  A full description of the persistent radical effect in RDRP, in particular NMP, was not published by Fischer until 1997.119  The kinetics of NMP will not be described in this chapter since they are detailed in another chapter of this volume.

Three processes for end-group removal from macro-alkoxyamines were described in the original CSIRO patent application102  and are summarized in Scheme 1.19. The first simply involves heating the macro-alkoxyamine in an α-methylvinyl monomer, such as MMA, to convert the macro-alkoxyamine to a macromonomer and a hydroxylamine. While the hydroxylamine is a good hydrogen atom donor, its low concentration dictates that it is inert under normal reaction conditions for NMP. The hydroxylamine is isolable but it is converted to the nitroxide on exposure to air. This process also provides for a relatively simple method of nitroxide recycling. For an example of the chemistry, see Scheme 1.10.102 

Scheme 1.19

Processes for end-group transformation of macro-alkoxyamines described in the CSIRO patent.102 

Scheme 1.19

Processes for end-group transformation of macro-alkoxyamines described in the CSIRO patent.102 

Close modal

A second method for end-group removal involves heating the macro-alkoxyamine in the presence of an excess of a good hydrogen atom-donor. An excess of the hydrogen atom-donor is required so that hydrogen atom-transfer can compete with other processes (Scheme 1.20)

Scheme 1.20

Conversion of alkoxyamine end-group (of polymer shown in Scheme 1.6) to hydrogen end-group by heating in the presence of a thiol. Example 48 of original patent application.102 

Scheme 1.20

Conversion of alkoxyamine end-group (of polymer shown in Scheme 1.6) to hydrogen end-group by heating in the presence of a thiol. Example 48 of original patent application.102 

Close modal

The third method of end-group transformation involves reduction with zinc in acetic acid to provide a polymer with a hydroxyl chain end (Scheme 1.21).

Scheme 1.21

Conversion of alkoxyamine end-group (of polymer shown in Scheme 1.6) to hydroxy end-group by zinc–acetic acid reduction. Example 48 of original patent application.102 

Scheme 1.21

Conversion of alkoxyamine end-group (of polymer shown in Scheme 1.6) to hydroxy end-group by zinc–acetic acid reduction. Example 48 of original patent application.102 

Close modal

In this section, we describe developments in NMP produced by various research groups over the period 1993–2000. We focus on reports in the open literature. However, it is informative to also examine the patent literature of the period. In Table 1.4, we provide a summary of 77 granted US Patents relating to NMP that were first filed during the period 1983–2000. The patents are listed in chronological order with respect to priority date. It will be seen that many publications in the open literature were preceded by patent filings. The list includes patents assigned to Xerox (28),120–147  Elf Atochem/Atofina (8),148–155  BASF (5),156–160  Ciba (7),161–167  Symyx (5),168–172  Lubrizol (4),173–176  IBM (3),177–179  Bayer (3),180–182  CSIRO/DuPont (2),102,183  Carnegie-Mellon University (2),184,185  Dow (2),186,187  Melbourne University (2),188,189  and others (BF Goodrich,190  Kaneka,191  Kansai Paint,192  Shipley,193  Sumitomo194 ; 1 each). There are additional patents in the field that were not filed in the US.

Table 1.4

US patents relating to nitroxide-mediated polymerization 1983–2000 (patents are listed in chronological order with respect to priority date).

Patent No.AssigneePriority dateUS Patent Publication dateComment
US4581429A102  CSIRO 11 Jul 1983 8 Apr 1986 Original CSIRO NMP patent 
US5322912A120  Xerox 16 Nov 1992 21 Jun 1994 First Xerox NMP patent (BPO TEMPO in bulk or suspension) 
US5401804A121  Xerox 16 Nov 1992 28 Mar 1995 First Xerox NMP patent divisional 
US5549998AA127  Xerox 16 Nov 1992 27 Aug 1996 Xerox NMP patent divisional on toner compositions 
US5412047A122  Xerox 13 May 1994 2 May 1995 Acrylate polymerization with 4-oxo-TEMPO 
US6087451A140  Xerox 18 Aug 1994 11 Jul 2000 NMP with bis-alkoxyamines in for synthesis of telechelics 
US6258911B1144  Xerox 18 Aug 1994 10 Jul 2001 Telechelics formed from use of bis-alkoxyamines in NMP 
US5545504A126  Xerox 3 Oct 1994 13 Aug 1996 Toner compositions 
US5714993A131  Xerox 3 Oct 1994 3 Feb 1998 Toner compositions for inkjet 
US6320007B1145  Xerox 18 Nov 1994 20 Nov 2001 NMP 
US5449724A123  Xerox 14 Dec 1994 12 Sep 1995 NMP of ethylene 
US5530079A125  Xerox 3 Jan 1995 25 Jun 1996 SRMP with phenoxy radical mediator 
US5610250A130  Xerox 3 Jan 1995 11 Mar 1997 Polymer from SRMP with phenoxy radical mediator 
US5610249A192  Kansai Paint 24 Jan 1995 11 Mar 1997 NMP of styrene in presence of a phosphorus compound 
US5498679A124  Xerox 30 Mar 1995 12 Mar 1996 NMP (multifunctional TEMPO alkoxyamines) to form star polymers 
US5608023A129  Xerox 30 Mar 1995 4 Mar 1997 Use of sulfonic acids to enhance the rate of NMP 
US5723554A194  Sumitomo 6 Sep 1995 3 Mar 1998 NMP of styrene 
US5627248A186  Dow 26 Sep 1995 6 May 1997 bis-nitroxides in NMP 
US5739229A136  Xerox 7 Nov 1995 14 Apr 1998 NMP with TEMPO plus an electron acceptor 
US5552502A128  Xerox 16 Nov 1995 3 Sep 1996 NMP in supercritical SO2 
US6239226B1156  BASF 25 Jan 1996 29 May 2001 Acrylic block copolymer by NMP. No examples. 
US5721320A187  Dow 29 Mar 1996 24 Feb 1998 NMP formation of polydiene block and graft polymers 
US5723511A132  Xerox 17 Jun 1996 3 Mar 1998 Synthesis of branched polymer from unsaturated polymer substrate and macroalkoxyamine 
US5919861A138  Xerox 17 Jun 1996 6 Jul 1999 Synthesis of branched polymer 
US6114499A141  Xerox 17 Jun 1996 5 Sep 2000 NMP synthesis of star polymer from unsaturated polymer substrate 
US5728747A133  Xerox 8 Aug 1996 17 Mar 1998 Photoinitiated NMP 
US5910549A184  Carnegie-Mellon University 22 Aug 1996 8 Jun 1999 Conversion of ATRP catalyst to alkoxyamine 
US6288186B1185  Carnegie-Mellon University 22 Aug 1996 11 Sep 2001 NMP rate enhancement with added initiator 
US6075105A139  Xerox 26 Aug 1996 13 Jun 2000 NMP crosslinking polymerization 
US6255422B1149  Elf Atochem 20 Nov 1996 3 Jul 2001 NMP with inifers 
US6271340B1183  CSIRO/DuPont 10 Jan 1997 7 Aug 2001 NMP with imidazolinone nitroxodes 
US6300443B1188  Melbourne University 15 Jan 1997 9 Oct 2001 Star microgel by NMP 
US5744560A134  Xerox 21 Jan 1997 28 Apr 1998 NMP with TEMPO plus metal complex (Lewis acid) 
US6281311B1190  BF Goodrich 31 Mar 1997 28 Aug 2001 Nitroxides for NMP 
US6262206B1161  Ciba 15 Jul 1997 17 Jul 2001 Alkoxyamines from open chain nitroxides for NMP 
US6111025A174  Lubrizol 24 Jun 1997 29 Aug 2000 Amphiphilic block copolymer by NMP 
US6696533B1160  BASF 27 Jun 1997 24 Feb 2004 NMP in emulsion 
US6156858A143  Xerox 25 Jun 1997 5 Dec 2000 NMP (BPO TEMPO) in presence of base 
US6121397A142  Xerox 14 Jul 1997 19 Sep 2000 NMP in miniemulsion (TEMPO alkoxyamine) 
US6365675B1146  Xerox 14 Jul 1997 2 Apr 2002 NMP in miniemulsion. Multiblock copolymer synthesis. 
US6472485B2147  Xerox 14 Jul 1997 29 Oct 2002 NMP in miniemulsion (TEMPO alkoxyamine) 
US6503983B1159  BASF 27 Jul 1997 7 Jan 2003 NMP in miniemulsion (TEMPO alkoxyamine) 
US5817824A135  Xerox 1 Aug 1997 6 Oct 1998 Synthesis of 4-oxoTEMPO 
US5891971A137  Xerox 15 Aug 1997 6 Apr 1999 NMP with reducing agent 
US6911511B1155  Elf Atochem 30 Dec 1997 28 Jun 2005 NMP with a small amount of nitroxide 
US6107425A193  Shipley 6 Feb 1998 22 Aug 2000 NMP of 4-acetoxystyrene 
US6353107B1162  Ciba 9 Mar 1998 5 Mar 2002 Multialkylpiperidine-N-oxyl derivatives for NMP (alkoxyamines) 
US6927295B2163  Ciba 9 Mar 1998 24 Apr 2003 Multialkylpiperidine-N-oxyl derivatives for NMP (alkoxyamines) 
US6683142B2165  Ciba 9 Mar 1998 27 Jan 2004 Multialkylpiperidine-N-oxyl derivatives for NMP (NMP) 
US7402639B2167  Ciba 9 Mar 1998 22 Jul 2008 Multialkylpiperidine-N-oxyl derivatives for NMP (NMP) 
US6531547B1176  Lubrizol 25 Mar 1998 11 Mar 2003 Vinyl aromatic-co-acrylic block copolymers by NMP 
US6545095B1189  Melbourne University 7 May 1998 8 Apr 2003 Star microgel by NMP and other RDRP 
US6353065B1148  Elf Atochem 10 Jul 1998 5 Mar 2002 NMP in emulsion (SG1 used) 
US6521710B1164  Ciba 3 Sep 1998 18 Feb 2003 Graft copolymers by NMP (in extruder) 
US6734269B1154  Atofina 6 Oct 1998 11 May 2004 NMP of ethylene 
US6369162B1175  Lubrizol 26 Oct 1998 9 Apr 2002 Star microgel by NMP 
US6479603B1157  BASF 16 Dec 1998 12 Nov 2002 Polymerizable nitroxides 
US6649701B1191  Kaneka 27 Mar 1998 18 Nov 2003 Chain-extending NMP with non-conjugated dienes (example is ATRP) 
US6538141B1150  Atofina 8 Jan 1999 25 Mar 2003 Preparation of SG1 (1.4) and related nitroxides 
US6569967B1151  Atofina 18 Feb 1999 27 May 2003 SG1 (1.4) and related nitroxides in NMP 
US6624322B1152  Atofina 8 Jan 1999 23 Sep 2003 Preparation of SG1 (1.4) and related nitroxides 
US6472486B2168  Symyx 9 Mar 1999 29 Oct 2002 NMP with “unstable” Nitroxides (TIPNO, 1.5), NMP in seeded emulsion 
US6559255B2169  Symyx 9 Mar 1999 6 May 2003 NMP in seeded emulsion 
US6355756B1177  IBM 18 May 1999 12 Mar 2002 Electroactive polymers 
US 6433115B2178  IBM 18 May 1999 13 Aug 2002 Devices from electroactive polymers 
US6512070B2,179  IBM 18 May 1999 28 Jan 2003 Electroactive polymers 
US6657043B1298  Atofina 19 May 1999 2 Dec 2003 Multi-alkoxyamines based on SG1 (1.4
US6716948B1170  Symyx 31 Jul 1999 6 Apr 2004 Multi-alkoxyamines in NMP 
US7259217B2172  Symyx 31 Jul 1999 21 Aug 2007 Multi-alkoxyamines in NMP 
US6639033B158  BASF 18 Aug 1999 28 Oct 2003 Nitroxides for NMP 
US6573346B1180  Bayer 7 Sep 1999 2 Jun 2003 NMP synthesis of end-functional polymers 
US6632895B1181  Bayer 7 Sep 1999 14 Oct 2003 Functional alkoxyamine synthesis 
US6800708B2182  Bayer 7 Sep 1999 5 Oct 2004 End-functional polymers made by NMP 
US6706832B2153  Atofina 26 Jan 2000 16 Mar 2004 NMP of ethylene 
US7067586B2171  Symyx 3 Oct 2000 27 Jun 2006 Blocks based on amphiphilic copolymer 
US6844405B2166  Ciba 13 Nov 2000 18 Jan 2005 NMP of vinyl chloride 
Patent No.AssigneePriority dateUS Patent Publication dateComment
US4581429A102  CSIRO 11 Jul 1983 8 Apr 1986 Original CSIRO NMP patent 
US5322912A120  Xerox 16 Nov 1992 21 Jun 1994 First Xerox NMP patent (BPO TEMPO in bulk or suspension) 
US5401804A121  Xerox 16 Nov 1992 28 Mar 1995 First Xerox NMP patent divisional 
US5549998AA127  Xerox 16 Nov 1992 27 Aug 1996 Xerox NMP patent divisional on toner compositions 
US5412047A122  Xerox 13 May 1994 2 May 1995 Acrylate polymerization with 4-oxo-TEMPO 
US6087451A140  Xerox 18 Aug 1994 11 Jul 2000 NMP with bis-alkoxyamines in for synthesis of telechelics 
US6258911B1144  Xerox 18 Aug 1994 10 Jul 2001 Telechelics formed from use of bis-alkoxyamines in NMP 
US5545504A126  Xerox 3 Oct 1994 13 Aug 1996 Toner compositions 
US5714993A131  Xerox 3 Oct 1994 3 Feb 1998 Toner compositions for inkjet 
US6320007B1145  Xerox 18 Nov 1994 20 Nov 2001 NMP 
US5449724A123  Xerox 14 Dec 1994 12 Sep 1995 NMP of ethylene 
US5530079A125  Xerox 3 Jan 1995 25 Jun 1996 SRMP with phenoxy radical mediator 
US5610250A130  Xerox 3 Jan 1995 11 Mar 1997 Polymer from SRMP with phenoxy radical mediator 
US5610249A192  Kansai Paint 24 Jan 1995 11 Mar 1997 NMP of styrene in presence of a phosphorus compound 
US5498679A124  Xerox 30 Mar 1995 12 Mar 1996 NMP (multifunctional TEMPO alkoxyamines) to form star polymers 
US5608023A129  Xerox 30 Mar 1995 4 Mar 1997 Use of sulfonic acids to enhance the rate of NMP 
US5723554A194  Sumitomo 6 Sep 1995 3 Mar 1998 NMP of styrene 
US5627248A186  Dow 26 Sep 1995 6 May 1997 bis-nitroxides in NMP 
US5739229A136  Xerox 7 Nov 1995 14 Apr 1998 NMP with TEMPO plus an electron acceptor 
US5552502A128  Xerox 16 Nov 1995 3 Sep 1996 NMP in supercritical SO2 
US6239226B1156  BASF 25 Jan 1996 29 May 2001 Acrylic block copolymer by NMP. No examples. 
US5721320A187  Dow 29 Mar 1996 24 Feb 1998 NMP formation of polydiene block and graft polymers 
US5723511A132  Xerox 17 Jun 1996 3 Mar 1998 Synthesis of branched polymer from unsaturated polymer substrate and macroalkoxyamine 
US5919861A138  Xerox 17 Jun 1996 6 Jul 1999 Synthesis of branched polymer 
US6114499A141  Xerox 17 Jun 1996 5 Sep 2000 NMP synthesis of star polymer from unsaturated polymer substrate 
US5728747A133  Xerox 8 Aug 1996 17 Mar 1998 Photoinitiated NMP 
US5910549A184  Carnegie-Mellon University 22 Aug 1996 8 Jun 1999 Conversion of ATRP catalyst to alkoxyamine 
US6288186B1185  Carnegie-Mellon University 22 Aug 1996 11 Sep 2001 NMP rate enhancement with added initiator 
US6075105A139  Xerox 26 Aug 1996 13 Jun 2000 NMP crosslinking polymerization 
US6255422B1149  Elf Atochem 20 Nov 1996 3 Jul 2001 NMP with inifers 
US6271340B1183  CSIRO/DuPont 10 Jan 1997 7 Aug 2001 NMP with imidazolinone nitroxodes 
US6300443B1188  Melbourne University 15 Jan 1997 9 Oct 2001 Star microgel by NMP 
US5744560A134  Xerox 21 Jan 1997 28 Apr 1998 NMP with TEMPO plus metal complex (Lewis acid) 
US6281311B1190  BF Goodrich 31 Mar 1997 28 Aug 2001 Nitroxides for NMP 
US6262206B1161  Ciba 15 Jul 1997 17 Jul 2001 Alkoxyamines from open chain nitroxides for NMP 
US6111025A174  Lubrizol 24 Jun 1997 29 Aug 2000 Amphiphilic block copolymer by NMP 
US6696533B1160  BASF 27 Jun 1997 24 Feb 2004 NMP in emulsion 
US6156858A143  Xerox 25 Jun 1997 5 Dec 2000 NMP (BPO TEMPO) in presence of base 
US6121397A142  Xerox 14 Jul 1997 19 Sep 2000 NMP in miniemulsion (TEMPO alkoxyamine) 
US6365675B1146  Xerox 14 Jul 1997 2 Apr 2002 NMP in miniemulsion. Multiblock copolymer synthesis. 
US6472485B2147  Xerox 14 Jul 1997 29 Oct 2002 NMP in miniemulsion (TEMPO alkoxyamine) 
US6503983B1159  BASF 27 Jul 1997 7 Jan 2003 NMP in miniemulsion (TEMPO alkoxyamine) 
US5817824A135  Xerox 1 Aug 1997 6 Oct 1998 Synthesis of 4-oxoTEMPO 
US5891971A137  Xerox 15 Aug 1997 6 Apr 1999 NMP with reducing agent 
US6911511B1155  Elf Atochem 30 Dec 1997 28 Jun 2005 NMP with a small amount of nitroxide 
US6107425A193  Shipley 6 Feb 1998 22 Aug 2000 NMP of 4-acetoxystyrene 
US6353107B1162  Ciba 9 Mar 1998 5 Mar 2002 Multialkylpiperidine-N-oxyl derivatives for NMP (alkoxyamines) 
US6927295B2163  Ciba 9 Mar 1998 24 Apr 2003 Multialkylpiperidine-N-oxyl derivatives for NMP (alkoxyamines) 
US6683142B2165  Ciba 9 Mar 1998 27 Jan 2004 Multialkylpiperidine-N-oxyl derivatives for NMP (NMP) 
US7402639B2167  Ciba 9 Mar 1998 22 Jul 2008 Multialkylpiperidine-N-oxyl derivatives for NMP (NMP) 
US6531547B1176  Lubrizol 25 Mar 1998 11 Mar 2003 Vinyl aromatic-co-acrylic block copolymers by NMP 
US6545095B1189  Melbourne University 7 May 1998 8 Apr 2003 Star microgel by NMP and other RDRP 
US6353065B1148  Elf Atochem 10 Jul 1998 5 Mar 2002 NMP in emulsion (SG1 used) 
US6521710B1164  Ciba 3 Sep 1998 18 Feb 2003 Graft copolymers by NMP (in extruder) 
US6734269B1154  Atofina 6 Oct 1998 11 May 2004 NMP of ethylene 
US6369162B1175  Lubrizol 26 Oct 1998 9 Apr 2002 Star microgel by NMP 
US6479603B1157  BASF 16 Dec 1998 12 Nov 2002 Polymerizable nitroxides 
US6649701B1191  Kaneka 27 Mar 1998 18 Nov 2003 Chain-extending NMP with non-conjugated dienes (example is ATRP) 
US6538141B1150  Atofina 8 Jan 1999 25 Mar 2003 Preparation of SG1 (1.4) and related nitroxides 
US6569967B1151  Atofina 18 Feb 1999 27 May 2003 SG1 (1.4) and related nitroxides in NMP 
US6624322B1152  Atofina 8 Jan 1999 23 Sep 2003 Preparation of SG1 (1.4) and related nitroxides 
US6472486B2168  Symyx 9 Mar 1999 29 Oct 2002 NMP with “unstable” Nitroxides (TIPNO, 1.5), NMP in seeded emulsion 
US6559255B2169  Symyx 9 Mar 1999 6 May 2003 NMP in seeded emulsion 
US6355756B1177  IBM 18 May 1999 12 Mar 2002 Electroactive polymers 
US 6433115B2178  IBM 18 May 1999 13 Aug 2002 Devices from electroactive polymers 
US6512070B2,179  IBM 18 May 1999 28 Jan 2003 Electroactive polymers 
US6657043B1298  Atofina 19 May 1999 2 Dec 2003 Multi-alkoxyamines based on SG1 (1.4
US6716948B1170  Symyx 31 Jul 1999 6 Apr 2004 Multi-alkoxyamines in NMP 
US7259217B2172  Symyx 31 Jul 1999 21 Aug 2007 Multi-alkoxyamines in NMP 
US6639033B158  BASF 18 Aug 1999 28 Oct 2003 Nitroxides for NMP 
US6573346B1180  Bayer 7 Sep 1999 2 Jun 2003 NMP synthesis of end-functional polymers 
US6632895B1181  Bayer 7 Sep 1999 14 Oct 2003 Functional alkoxyamine synthesis 
US6800708B2182  Bayer 7 Sep 1999 5 Oct 2004 End-functional polymers made by NMP 
US6706832B2153  Atofina 26 Jan 2000 16 Mar 2004 NMP of ethylene 
US7067586B2171  Symyx 3 Oct 2000 27 Jun 2006 Blocks based on amphiphilic copolymer 
US6844405B2166  Ciba 13 Nov 2000 18 Jan 2005 NMP of vinyl chloride 

Following on from the early CSIRO work, the next significant development in NMP stemmed from the publication in 1993 by Georges and coworkers195  on the use of NMP for the synthesis of poly(styrene-co-butadiene) and low dispersity polystyrene (Scheme 1.22). A brief overview of the history of the research in NMP conducted at Xerox is provided in the 2010 review of Szkurhan et al.23  The studies by Georges and co-workers focused narrowly on the use of TEMPO as nitroxide and benzoyl peroxide (BPO) as initiator with in situ generation of the alkoxyamine. The in situ production of alkoxyamine was an option that was mentioned in the text of the CSIRO patent102  but was not exemplified.

Scheme 1.22

Nitroxide-mediated polymerization of styrene with TEMPO as nitroxide, benzoyl peroxide (BPO) as initiator, and in situ generation of alkoxyamine.195 

Scheme 1.22

Nitroxide-mediated polymerization of styrene with TEMPO as nitroxide, benzoyl peroxide (BPO) as initiator, and in situ generation of alkoxyamine.195 

Close modal

A large number of papers18,195–219  and patents (see Table 1.4)120–147  from the Xerox group followed the initial report195  with topics over the period 1993–2000 including the mechanism of the reaction between BPO and TEMPO,196  aspects of the kinetics of NMP,198,202,203,207,208,212,214–217,219  the effect of added acid to accelerate NMP,198,208  other additives for accelerating NMP,201,211  the role of excess nitroxide in providing a controlled process,207,214  controlling NMP with small amounts of nitroxide,210  NMP of styrenesulfonic acid,200  chloromethylstyrene209  and n-butyl acrylate,204  styrene–butadiene block copolymers213  and NMP in miniemulsion.218 

Some attention was paid to nitroxides other than TEMPO for use in NMP. Semi-empirical MO calculations were used to rank nitroxides on the basis of predicted C–O bond dissociation energies.197,199  Use of di-t-butyl nitroxide (1.3) was found to give improved control and faster polymerization rates than TEMPO in the case of the Xerox study for styrene polymerization.199  However, this finding was not followed up.

The induced decomposition of BPO by TEMPO had been examined at CSIRO220  in the context of a study of the initiation of styrene polymerization by BPO using the radical trapping method. The mechanism proposed (Scheme 1.23)220  involved the nitroxide being transformed to the oxammonium benzoate or an equivalent covalent adduct with formation of an equivalent of benzoyloxy radicals. The oxammonium benzoate then decomposed to benzoic acid and an unsaturated nitroso-compound, which underwent an intramolecular ‘ene’ reaction to give the hydroxylamine, oxidation of which afforded the nitrone shown in Scheme 1.23.

Scheme 1.23

Mechanism of reaction between TEMPO and benzoyl peroxide (BPO).220 

Scheme 1.23

Mechanism of reaction between TEMPO and benzoyl peroxide (BPO).220 

Close modal

The research of Hawker and coworkers is detailed in the review by Hawker et al. published in 2001.20  The in situ method of alkoxyamine formation used by Xerox, while convenient, adds a degree of complexity and uncertainty to the process. In 1994, Hawker and colleagues published their first paper on NMP.221  Claiming to have been inspired by the Xerox work195  and being aware of the CSIRO patent,102  they re-examined NMP of styrene initiated by a preformed alkoxyamine based on TEMPO (Scheme 1.24), which they called a unimer. The alkoxyamine was prepared using the methodology developed by CSIRO.102  They demonstrated that alkoxyamine-initiated NMP could be used to form high molecular weight low dispersity polystyrene. Lower than anticipated molecular weights, when higher molecular weights were targeted (Scheme 1.24), can be understood in terms of the contribution of thermal initiation to the process.

Scheme 1.24

Nitroxide-mediated polymerization of styrene with TEMPO-based unimer as initiator.221  All experiments were carried out at 130 °C in bulk styrene for 72 h and gave ∼90% monomer conversion. Calculated molecular weights were based on the alkoxyamine concentration and the monomer conversion.

Scheme 1.24

Nitroxide-mediated polymerization of styrene with TEMPO-based unimer as initiator.221  All experiments were carried out at 130 °C in bulk styrene for 72 h and gave ∼90% monomer conversion. Calculated molecular weights were based on the alkoxyamine concentration and the monomer conversion.

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In subsequent work, Hawker and coworkers examined the relative merits of the unimer vs. the in situ “initiator plus nitroxide” method,221,222  methods for alkoxyamine synthesis,223  and aspects of the kinetics and mechanism of NMP.224,225  They also demonstrated the utility of NMP in preparing a variety of statistical copolymers,226  star, graft and hyperbranched copolymers,227–231  block copolymers232  and end functional polymers.19,228  In 1999, Benoit et al. published on the screening of various nitroxides for NMP. This study showed that alkoxyamines based on α-hydrido species such as TIPNO (1.5) provided very much improved outcomes in NMP (lower dispersities, faster rates of polymerization at lower temperatures).232–234  These alkoxyamines were also claimed in a patent filed by Symyx.168 

Fukuda and coworkers’ initial work focused on analyzing the kinetics and mechanism of NMP.235–245  They developed methods for determining homolysis (activation) rate constants based on GPC analysis.236,237,245  They also demonstrated the effect of added initiator to control the excess nitroxide in NMP238,246  and used this knowledge to obtain enhanced rates in butyl acrylate polymerization mediated by di-t-butyl nitroxide.246  NMP was exploited in block copolymer synthesis247,248  crosslinking polymerization,249  and in the preparation of glycopolymers.250–252 

The kinetics of NMP and other SRMP were studied by Fischer et al.,119,253,254  who demonstrated the applicability of what he termed the persistent radical effect to NMP. Fischer had first described the persistent radical effect in radical reactions in a non-polymerization context in 1986.118 

In the reversible deactivation processes, the transient and the persistent species are formed and disappear with equal rates. If reversible deactivation was the only reaction then the concentrations of the two species would increase equally with time to reach steady state values. However, transient radicals also decay by irreversible bimolecular self-termination. Hence, the concentration of the transient species will reach a maximum and decrease while the concentration of the persistent radical will steadily increase. The excess concentration must balance the self-termination loss of the transient species. No steady state will exist. As bimolecular self-termination occurs, the cross reaction will be increasingly favored.255,256  Bimolecular self-termination is self-suppressing.

In a 1994 publication on possibilities for living radical polymerization, Greszta et al.257  postulated an alternative mechanism for NMP based on degenerative chain transfer. This257,258  prompted work by several groups to prove (or disprove) the original mechanism.224,239 

Much effort was devoted to improving NMP, particularly with respect to increasing the rate of polymerization and enhancing end-group fidelity. Many studied the kinetics of NMP.259–262  Catala et al. showed that the rate of NMP of styrene at higher temperatures was independent of the concentration of alkoxyamine initiator.259  This result was soon confirmed and it was then shown that the rate of NMP of styrene with TEMPO at higher reaction temperatures was determined by the rate of thermal initiation by the Mayo mechanism.119,235,260,263 

Various rate accelerating additives were devised to facilitate, in particular, TEMPO-mediated NMP.255  These reagents include organic acids,208,264  acid salts,201,211  anhydrides,225,243,264  added initiator238,246,264–266  and reducing agents such as ascorbic acid.215  Many of these are thought to work by removing the excess of nitroxide that builds during the course of polymerization as a side effect of termination.

New nitroxides/alkoxyamines for use in NMP were also reported by those outside of the major groups. Mention should be made of the work of Yamada and coworkers,267  and Puts and Sogah.268  The latter authors also reported a multifunctional initiator suitable for both cationic ring-opening polymerization and NMP.269  However the most significant developments in this context were the reports of SG1 (1.4) and TIPNO (1.5) (Hawker Group), and related species (Figure 1.2). The discovery of SG1 (1.4) was reported in a series of papers in 1998–2000233,270–273  and appears in patents filed by Elf Atochem.148,150–152 

The initial reports of NMP in heterogeneous media appeared in the patent literature with filing in the period from Xerox,142,146,147  BASF,159,160  Symyx168,169  and Elf Atochem.148  The Early attempts at NMP emulsion,274  miniemulsion218,274,275  and dispersion polymerization276,277  were complicated by the high reaction temperatures then necessary for NMP making use of TEMPO derivatives and by poor colloidal stability. The development is summarized in reviews of RDRP in heterogeneous media.278,279 

Many were active in exploring synthesis of block copolymers, functional copolymers and other structures mainly using TEMPO-based NMP. For example:

  • Synthesis of a polybutadiene block copolymer based on transformation of anionic polymerization to NMP280–282  with TEMPO. Various approaches for transforming anionic polybutadiene to the macro-alkoxyamine were explored.

  • polySt-block-poly(para-chlorostyrene),283  polySt-block-poly(St-co-BMA).284  The polySt macro-alkoxyamine was formed by BPO-initiated NMP with TEMPO.

  • polySt-block-poly(EA, MA or BA).285  (The polySt TEMPO macro-alkoxyamine was formed anionic polymerization and end-group transformation)

  • Li et al.286  examined the mechanism of thermal decomposition of alkoxyamines. The end-group fidelity in TEMPO-mediated styrene polymerization appears >90% for low molecular weights but drops off rapidly for higher molecular weights (>10 000), both due to the contribution of autopolymerization (i.e. thermal initiation by the Mayo mechanism) and the poor thermal stability of the alkoxyamine chain end.287 

  • Blocks by a combination of conventional radical polymerization and NMP.288 

  • polySt-block-polyEA, polySt-block-polyMMA.289  The polySt macro-alkoxyamine was formed by AIBN-initiated NMP with TEMPO. Poor reinitiation efficiencies were observed, which were improved with addition of camphorsulfonic acid. This led to the development of alternative agents for SRMP290,291  and a proposal that inbuilt instability of the stable radical could be used as a process for regulating the formation of excess stable radical during SRMP.292,293 

  • polyTHF-block-PolySt.294  The polyTHF TEMPO macro-alkoxyamine was formed from a macro azoinitiatior.

  • PolySt-block-poly(4-methylstyrene)-block-polySt.295  Synthesis from a bis-alkoxyamine. Alkoxyamine synthesis based on hydrogen atom abstraction from an ethylbenzene in the presence of TEMPO.296 

  • Moroni et al.205  prepared a polymer with pendent phenylenevinylene units by TEMPO-mediated NMP.

The early CSIRO work demonstrated NMP as a viable method for controlled polymer synthesis by RDRP. The method allowed the synthesis of polymers of lowered dispersity and made available block and graft copolymers that were not previously possible by radical polymerization. However, little attention was paid to NMP by the wider polymer community until the publications of Georges, Hawker, Fukuda and others in 1993–1995, a decade after the original invention. The period 1993–2000 saw many papers on kinetics and mechanism, and the exploitation of the method mainly for polymerization of styrene and derivatives in a range of architectures. A step change in the versatility of NMP was realized following the discovery of SG1 (1.4) and TIPNO (1.5) (Figure 1.2) in 1998–2000, but that further development is outside the scope of this chapter.

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