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Reducing the Concentration of Catalyst in an ATRP Reaction and Removal/recycle of Residual Catalyst

  • Catalyst Removal
  • Catalyst Reduction
  • ARGET and ICAR
  • Biphasic Systems
  • A hybrid catalyst System
  • A "soluble" hybrid catalyst system
  • Mixed Solvent Polymerization
  • Liquid/liquid biphasic polymerization

The rapid development of Atom Transfer Radical Polymerization that has occurred over the past 12 years, summarized on this site, has not yet resulted in its wide spread industrial scale implementation for the preparation of large volume materials, although smaller volume higher value applications have been commercialized. (1) For industrial viability, particularly for larger volume applications, there has to be one or more economic, environmentally viable, approaches to reduce the concentration of the catalyst in the final material.

Two general approaches have been pursued to overcome this problem; one is increasing the activity of the catalyst complex, so that less catalyst is required for a homogeneous polymerization and then take steps to remove the residual catalyst from the final product. The other is to support, recover and recycle the catalyst complex.

In the past three years significant progress has been made on both approaches including:

  • improved processes for catalyst removal;
  • catalyst reduction by preparation of catalyst complexes with increased activity and development of ARGET ATRP;
  • immobilization methodology, including understanding how ligand support structure affects catalyst polymerization performance, regeneration, and recyclability;
  • development of bi-phasic systems for catalyst separation by commercially viable liquid/liquid separation or solid/liquid separation methods; and
  • use of ligands with reactive substituents to aid in catalyst separation by physical or chemical methods.

These procedures are scaleable, indeed using the procedures described on this site it is now possible to prepare polymers with low ppm levels of residual catalyst, levels so low the polymers are colorless. Nevertheless for historical record and as a summary that may offer further opportunities for improvement the historical course to low catalyst ATRP is summarized.

The concentration of the residual transition metals in the initially formed polymers is below the levels allowed in oral drug products. (2)

  • A weekly dose of multi-vitamin tablets (left). Total Cu = 14 mg
  • 4.4 g of unpurified polystyrene prepared by ATRP (DP target = 200) (right). Total Cu = 14 mg

This image shows that while low levels of copper are not a health hazard there was a strong incentive to remove the catalyst complex from polymers, since many applications for polymers do not require a green color.

Catalyst Removal:

As discussed on the Mechanisms and Catalyst Development page, the foundation of ATRP is the reversible homolytic transfer of a radically transferable atom, or group, typically a halogen atom, from a monomeric or polymeric alkyl (pseudo)halide, to a transition metal complex initially in a lower oxidation state, forming an active organic radical and a transition metal complex in a higher oxidation state. Transition metal complexes therefore play a key role in ATRP, and have been the subject of several advances including development of catalyst systems based on new metals [3-8] and ligands resulting in the development of catalyst systems over 10,000 times more active than our initial bpy based systems. [9-18]

When ATRP was initially developed, the concentration of catalyst complex used in a typical polymerization was equivalent to the moles of initiator employed for the reaction i.e. [I]:[Cu]:[L] = 1:1:3 with bpy as ligand in order to achieve sustainable reaction rates. Therefore, catalyst removal or catalyst reduction was, and remains, a critical step in the preparation of pure copolymers, particularly since catalyst removal and recycle may cause environmental problems and imparts economic costs that commercial manufacturers would have to address.

In the laboratory, the transition metal compounds were initially removed from the reaction medium by passing a solution containing the product and oxidized catalyst through a column or pad of acidic or neutral alumina, silica and/or clay. (19) If one is concerned about chain end functionality neutral alumina should be used. The range of media that could be used in this catalyst removal step was later expanded to include ion exchange resins with acidic groups which would allow recovery and recycle of the transition metal. (20, 21) The rate of catalyst removal was found to be dependent on the polarity of the solvent and generally increased as the solvent polarity increased, increased as temperature increased, and was also dependent upon the size of the copper complex and the type of ion exchange resin. Dowex MCS-1 macroporous 20-50 mesh resin was the most efficient resin examined, with Cu/PMDETA and Cu/Me6TREN the fastest complexes to be adsorbed. Other agents that have been reported to be successful at removing copper catalyst complexes include carbon black, carbon filters, kaolin, hydrotalcite, acidic clays, and Mg silicate.

A recent independent review (22) examining removal of copper from crude amino-functionalized polymethacrylate chains has confirmed these observations through a series of high-throughput experiments applied to ATRP which focused automated optimization of the copper catalysts removal from polymers. (23) Zhu reported that if certain linear amine ligands are used for the ATRP adding additional Cu(II) halide at the end of a polymerization can cause precipitation of the soluble copper complex and the solid can be removed by microfiltration. (24) A reusable and environmentally friendly ionic trinuclear iron complex catalyst for atom transfer radical polymerization has also been developed. (25)

Nevertheless, it remains a desirable objective to identify additional methods to reduce the amount of transition metal used in the process and develop procedures to remove and potentially recycle the metal complex after the polymerization is complete to provide options for corporations who wish to consider ATRP as a method for preparation of designed materials for a particular application.

In aqueous biphasic systems when copper based ATRP catalysts are exposed to air they are oxidized to Cu(II) and in the presence of an appropriate ligand migrate to the aqueous phase of an emulsion or miniemulsion system. The catalyst complex can be adsorbed onto an ion exchange resin, or given time, they precipitate out as a solid. The catalyst can readily be recycled using AGET or ARGET ATRP initiation procedures.

1. "Controlled/living radical polymerization," Matyjaszewski, K.; Spanswick, J. Materials Today 2005, 8, 26-33.

2. "Removing Impurities", Ann Thayer C&ENews Sept 5, 2005 55-58.

3. "Controlled/\"Living\" Radical Polymerization of Styrene and Methyl Methacrylate Catalyzed by Iron Complexes", Matyjaszewski, K.; Wei, M.; Xia, J.; McDermott, N. E. Macromolecules 1997, 30, 8161.

4. "Iron(II) Chloride Complex for Living Radical Polymerization of Methyl Methacrylate," Ando, T.; Kamigaito, M.; Sawamoto, M. Macromolecules 1997, 30, 4507.

5. "Design of Highly Active Iron-Based Catalysts for Atom Transfer Radical Polymerization: Tridentate Salicylaldiminato Ligands Affording near Ideal Nernstian Behavior." O'Reilly, R. K.; Gibson, V. C.; White, A. J. P.; Williams, D. J. Journal of the American Chemical Society 2003, 125, 8450-8451.

6. "Controlled Radical Polymerization of Methacrylic Monomers in the Presence of a Bis(ortho-chelated) Arylnickel(II) Complex and Different Activated Alkyl Halides." Granel, C.; Dubois, P.; Jerome, R.; Teyssie, P. Macromolecules 1996, 29, 8576.

7. "Nickel-Mediated Living Radical Polymerization of Methyl Methacrylate." Uegaki, H.; Kotani, Y.; Kamigaito, M.; Sawamoto, M. Macromolecules 1997, 30, 2249.

8. "Osmium-Mediated Radical Polymerization." Braunecker, W. A.; Itami, Y.; Matyjaszewski, K. Macromolecules 2005, 38, 9402-9404.

9. "Polymers with very low polydispersities from atom transfer radical polymerization." Patten, T. E.; Xia, J.; Abernathy, T.; Matyjaszewski, K. Science 1996, 272, 866.\

10. "Controlled/\"Living\" Radical Polymerization. Kinetics of the Homogeneous Atom Transfer Radical Polymerization of Styrene." Matyjaszewski, K.; Patten, T. E.; Xia, J. J. Am. Chem. Soc. 1997, 119, 674.

11. "Controlled/\"Living\" Radical Polymerization. Atom Transfer Radical Polymerization using Multidentate Amine Ligands." Xia, J.; Matyjaszewski, K. Macromolecules 1997, 30, 7697.

12. "Controlled/\"Living\" Radical Polymerization. Atom Transfer Radical Polymerization of Acrylates at Ambient Temperature." Xia, J.; Gaynor, S. G.; Matyjaszewski, K. Macromolecules 1998, 31, 5958.

13. "4,4',4''-tris(5-nonyl)-2,2':6',2''-terpyridine as ligand in atom transfer radical polymerization (ATRP)." Kickelbick, G.; Matyjaszewski, K. Macromol. Rapid Commun. 1999, 20, 341-34.

14. "The effect of ligands on copper-mediated atom transfer radical polymerization." Xia, J.; Zhang, X.; Matyjaszewski, K. ACS Symp. Ser. 2000, 760, 207-223.

15. "Tridentate nitrogen based ligands in Cu-based ATRP. A structure-activity study." Matyjaszewski, K.; Gobelt, B.; Paik, H.-j.; Horwitz, C. P. Macromolecules 2001, 34, 430.

16. "Simultaneous Reverse and Normal Initiation in Atom Transfer Radical Polymerization." Gromada, J.; Matyjaszewski, K. Macromolecules 2001, 34, 7664-7671.

17. "Highly Active Copper-Based Catalyst for Atom Transfer Radical Polymerization," Tang, H.; Arulsamy, N.; Radosz, M.; Shen, Y.; Tsarevsky, N. V.; Braunecker, W. A.; Tang, W.; Matyjaszewski, K. Journal of the American Chemical Society 2006, 128, 16277-16285.

18. "Copper-based ATRP catalysts of very high activity derived from dimethyl cross-bridged cyclam," Tsarevsky, N. V.; Braunecker, W. A.; Tang, W.; Brooks, S. J.; Matyjaszewski, K.; Weisman, G. R.; Wong, E. H. Journal of Molecular Catalysis A: Chemical 2006, 257, 132-140.

19. "Improved processes based on atom (or group) transfer radical polymerization and novel (co)polymers having useful structures and properties." Matyjaszewski, K., Coca, S., Gaynor, S. G., Greszta, D., Patten, T. E., Wang, J.-s., Xia, J.: PCT Int. Appl.: 9718247, 1997.

20. "Removal of Copper-Based Catalyst in Atom Transfer Radical Polymerization Using Ion Exchange Resins." Matyjaszewski, K., Pintauer, T., Gaynor, S.: Macromolecules, 2000, 33: 1476-1478.

21. Matyjaszewski, K.; Gaynor, S. G.; Paik, H.-j.; Pintauer, T.; Pyun, J.; Qiu, J.; Teodorescu, M.; Xia, J.; Zhang, X. In PCT Int. Appl.; (Carnegie Mellon University, USA). WO 0056795, 2000.

22. "Removal of copper-based catalyst in atom transfer radical polymerization using different extraction techniques." Ydens, I., Moins, S., Botteman, F., Degee, P., Dubois, P.: e-Polymers, 2004 no 39.

23. "High-throughput experimentation applied to atom transfer radical polymerization: automated optimization of the copper catalysts removal from polymers," Zhang, H.; Abeln, C. H.; Fijten, M. W. M.; Schubert, U. S. e-Polymers 2006,

24. "Facile and Effective Purification of Polymers Produced by Atom Transfer Radical Polymerization via Simple Catalyst Precipitation and Microfiltration." Faucher, S.; Okrutny, P.; Zhu, S. Macromolecules, 2006, 39, 3-5.

25. "Reusable and environmentally friendly ionic trinuclear iron complex catalyst for atom transfer radical polymerization," Niibayashi, S.; Hayakawa, H.; Jin, R.-H.; Nagashima, H. Chemical Communications, 2007, 1855-1857.

Catalyst Reduction

ARGET and ICAR: As shown in the figure displaying relative catalyst activity for copper based catalysts at the end of the page on Catalyst Development {link} catalysts have been developed that show a broad range of activity. It is possible, therefore, to select an active catalyst and run the reaction with lower levels of catalyst. (26, 27) In the page on "Procedures for Initiation of an ATRP Reaction" we cover much of the background on the development of this low catalyst concentration ATRP. Indeed with an extension of the concept of AGET ATRP (28, 29) to include continuous regeneration of the transition metal complex throughout the reaction, ARGET ATRP (27-32), it is possible to reduce the level of catalyst below that of natural termination reactions and ATRP can be conducted with ppm levels of catalyst. ARGET ATRP arose when we considered the implications of the convenient procedure for initiating an ATRP system described in AGET ATRP, where the activators are generated by electron transfer (AGET) ATRP. We realized it should be possible to use the reducing agents to constantly regenerate the ATRP activator, the Cu(I) species, from the Cu(II) species, formed during termination process, without directly or indirectly producing initiating species that generate new chains. (28) A detailed examination of the ATRP rate law shows that the polymerization rate depends only on the ratio of the concentration of Cu(I) to X-Cu(II), and does NOT depend on the absolute concentration of the copper complexes, therefore in principle, one could reduce the absolute amount of copper complex to ppm levels without affecting the polymerization rate.

However, a residual amount of deactivating species (i.e. X-Cu(II)) is required for a well-controlled polymerization since both, molecular weight distribution and initial molecular weight, depend on the ratio of the propagation and deactivation rate constants and the concentration of deactivator.

This means that in order to obtain polystyrene with Mw/Mn~1.2, when targeting a DP~200 and 90% conversion at ~100 0C, the actual amount of X-Cu(II) species required to conduct a controlled reaction is ~2 ppm (kp~103 M-1s-1 and kda~107 M-1s-1), meaning that it could be reduced over 1,000 times from the level typically used in the initial ATRP of styrene. Unfortunately, if the amount of Cu(I) is reduced 1,000 fold, unavoidable radical-radical termination reactions irreversibly consume all of the activators present in the reaction media and the reactions stops; i.e. if the amount of Cu(I) initially added to the system was below 10 mole% of the initiator (i.e., all Cu(I) would be consumed if "10% of chains terminate). However, this situation could be overcome if there was constant regeneration of the Cu(I) activator species by environmentally acceptable reducing agents to compensate for any loss of Cu(I) by termination.

Generally, it is desirable to add an excess of the ligands compared to the transition metal complex, in order to compensate for competitive complexation by monomer/solvent/reducing agent all present in excess compared to the transition metal. (29-32) For example, styrene was polymerized by the addition of 5 ppm of CuCl2/Me6TREN and 500 ppm of Sn(EH)2 to the reaction resulting in a polystyrene with Mn=12,500 (Mn,th = 12,600) and Mw/Mn = 1.28.

An added advantage of using low levels of catalyst is that catalyst induced side reactions are reduced and it is possible to prepare high molecular weight copolymers (33, 34) and conduct the reaction in the presence of limited amounts of oxygen. (35) However ARGET is not the answer to all problems since the impact of the by products of the reduction reaction have to be considered.

26. "Preparation of Homopolymers and Block Copolymers in Miniemulsion by ATRP Using Activators Generated by Electron Transfer (AGET)"; Min, K.; Gao, H.; Matyjaszewski, K. Journal of the American Chemical Society 2005, 127, 3825-3830.

27. "Activator Generated by Electron Transfer for Atom Transfer Radical Polymerization." Jakubowski, W.; Matyjaszewski, K. Macromolecules 2005, 38, 4139-4146.

28. "Atom transfer radical polymerization in the presence of a reducing agent" PCT/US05/007265 filed March 2004; published as WO 2005087819, 96 pp.

29. "Activators Regenerated by Electron Transfer for Atom Transfer Radical Polymerization of Styrene." Jakubowski, W.; Min, K.; Matyjaszewski, K. Macromolecules, 2006, 39, 39-45.

30. "Activators regenerated by electron transfer for atom-transfer radical polymerization of (meth)acrylates and related block copolymers," Jakubowski, W.; Matyjaszewski, K. Angewandte Chemie, International Edition 2006, 45, 4482-4486.

31. "Diminishing catalyst concentration in atom transfer radical polymerization with reducing agents" K. Matyjaszewski, W. Jakubowski, K. Min, W. Tang, J. Huang, W. A. Braunecker, N. V. Tsarevsky, PNAS 2006, 103, 15309-15314.

32. "Use of Ascorbic Acid as Reducing Agent for Synthesis of Well-Defined Polymers by ARGET ATRP," Min, K.; Gao, H.; Matyjaszewski, K. Macromolecules, 2007, 40, 1789-1791

33. "Synthesis of High Molecular Weight Poly(styrene-co-acrylonitrile) Copolymers with Controlled Architecture," Pietrasik, J.; Dong, H.; Matyjaszewski, K. Macromolecules 2006, 39(19), 6384-6390.

34. "Well-Defined High-Molecular-Weight Polyacrylonitrile via Activators Regenerated by Electron Transfer ATRP," Dong, H.; Tang, W.; Matyjaszewski, K. Macromolecules 2007, 40, 2974-2977.

35. "Grafting from Surfaces for \"Everyone\": ARGET ATRP in the Presence of Air ," Matyjaszewski, K.; Dong, H.; Jakubowski, W.; Pietrasik, J.; Kusumo, A. Langmuir 2007, 23, 4528-4531.

Biphasic Catalyst Systems:

Prior to the development of ARGET and ICAR several other procedures had been examined for reduction and removal of catalyst complexes from an ATRP reaction. They are included herein for education and further development since ppm levels of catalyst may still be undesirable for certain applications. Since waste or discarded catalyst increases the cost of the final product, one of the first approaches to reducing catalyst concentration in the final polymer was development of heterogeneous catalyst systems. Surface-immobilized catalysts offered a convenient method for catalyst recovery, after the reaction had been completed. Catalyst recovery and reuse are important when residual transition metal complex is not desired in the final product. There was a great deal of interest in immobilizing the homogeneous transition metal polymerization catalysts on solid supports for the purpose of recovery and reuse. In a batch polymerization process, the catalyst from such a heterogeneous system can be removed by simple decantation, filtration, or centrifugation and provides a route for efficient catalyst separation with a possibility to reuse the catalyst after reactivation.

However initial comparison of these methods to traditional ATRP showed that surface-immobilized catalysts often provide products with higher molecular weights than predicted and broader molecular weight distributions, and sometimes requiring longer reaction times. (36-41) The level of control over the polymerization was improved by introduction of soluble spacer groups between the support and the ligand. (38) These approaches offered limited control over the polymerization due to diffusion limitations, primarily the result of slow deactivation. The implication of this observation was immediately seen in the preparation of polymers exhibiting higher molecular weight and broader molecular weight distribution. This phenomenon of slow deactivation is shown in the first animation. Activation occurs readily when the initiator containing a radically transferable atom, most often a halide, diffuses to the immobilized catalyst on the surface of a separable particle, the halide is transferred from the polymer chain end to the immobilized catalyst and initiation of polymerization occurs. Note, however, that deactivation does not occur until the active chain diffuses back to the surface of the particle and encounters a tethered higher oxidation state transition metal complex.

A Hybrid Catalyst System:

A "hybrid" catalyst system can overcome one aspect of this difficulty. Our hybrid catalyst is composed of an immobilized catalyst working in conjunction with a small amount of soluble catalyst, predominately present in the deactivator oxidation state. (42) Therefore, controlled polymerization of vinyl monomers over a ligand supported catalyst was achieved through use of a small amount of soluble catalyst preferentially present in the higher oxidation state that accelerates the rate of deactivation of the growing radical. The major fraction of the activator state of transition metal complex is immobilized on solid carriers. When used in a batch polymerization, the catalyst was successfully removed by simple filtration after the polymerization, resulting in low ppm concentration of residual transition metal in the polymer. (43) The role of the soluble deactivator, which is selected to display a different (higher) redox potential than the supported catalyst complex, is shown in the second animation. After deactivating the growing radical the soluble Cu(I) species diffuses to the supported catalyst complex, without a significant diffusion barrier, since it is a low molecular weight species and, due to the different redox potential, the soluble catalyst is rapidly reconverted to the deactivator, the Cu(II) species, through a halogen exchange reaction with the immobilized catalyst. In this way a very low concentration of a soluble catalyst acts to shuttle the deactivator from the supported catalyst to the active growing polymer chain.

In a full scale commercial operation there would be a slow accumulation of Cu(II) on the tethered catalyst and this would have to be reactivated in situ by measured addition of a reducing agent. Initially reactivation of the supported catalyst was conducted with a standard free radical initiator, or a transition metal in the zero oxidation state. With the current state of knowledge based on application of ARGET ATRP, another non-radical forming reducing agent could be selected. Selection of a reducing agent that does not completely reduce the soluble Cu(II) species would allow continuous activation and continuous polymerization to occur simultaneously.

The feasibility of supported catalysts used in ATRP to facilitate catalyst recovery and recycling was recently reviewed by Zhu. (44) He noted that historically these catalysts consist of catalytic sites that are covalently tethered to larger supporting particles. It was generally believed that non-hybrid supported ATRP systems was a surface-mediated polymerization process; i.e., both activation and deactivation reactions take place at the surface of the particles. However, recent experiments had shown that this may not be the case. A theoretical analysis testing the concept of surface-mediated ATRP that showed that deactivation at the surface is unlikely. The topological/geographic isolation of catalytic sites, rather than polymer diffusivity limitation, was primarily responsible for this infeasibility. A trace amount of free catalyst in solution that minimizes the physical isolation is essential for mediating supported ATRP. This analysis suggests that many successful reports of controlled polymerization using a supported catalyst actually depended on formation of a fortuitous "hybrid" catalyst system.

Use of a ligand with a reactive substituent allows adsorption of the most of the soluble catalyst complex onto a short silica column. (45) The catalyst can be adsorbed onto an ion exchange resin then recovered during regeneration. In order to demonstrate the full utility of this hybrid catalyst system we have prepared polymers with high chain end functionality and complex polymeric architectures such as block, graft or gradient copolymers using this hybrid catalyst concept. (46, 47)

Other research groups have also addressed this problem and developed other approaches to reduce catalyst concentrations and/or improve control in an ATRP reaction. Jandel resins that provide better access to the supported catalyst for polymer chain for the catalyst have been examined. (48) Brittain also examined the use of a polyethylene-ligand system which was soluble at the reaction temperature but separated out at lower temperature. (49) An extension of this concept is the use of precipitons to induce the precipitation of the catalyst after the polymerization was complete. (50-52)

Shen and Zhu have examined continuous polymerization systems (53-56) employing silica supported catalysts and more recently a reversible system using hydrogen mediated self assembly. (54) They also provided an excellent summary of extensive efforts to reduce the concentration of the transition metal in the final polymer and reported that fine silica particles can be used as an example of a concept that provides a homogeneous system for catalysis but is heterogeneous for separation/recovery. The system has been demonstrated to provide a viable recyclable polymerization catalyst. (56)

Jones (57) has also examined CuBr/bpy catalyst complexes supported on very small particles for ATRP of MMA and found that the mobile covalently tethered catalyst complexes provided good control with MW close to theoretical and narrow PDI. The catalyst was reactivated by using AIBN as reductant. However, the work on AGET ATRP reported elsewhere on these pages indicates that other reducing agents, potentially lower cost agents, have now been identified for catalyst reactivation. Jones" results indicated that not all of the Cu(II) species was reduced to Cu(I) and this was the reason for slower rates of polymerization during reuse; not catalyst leaching. Leaching experiments indicate that the tethered systems result in no detectable soluble copper species and that the majority of the catalytic transformations occur with sites tethered to the surface. In contrast, use of the physisorbed catalyst results in a substantial amount of leached copper species.

Other approaches to systems that provide homogeneous reaction systems for catalysis but heterogeneous systems for separation/recovery resulting in low absolute concentrations of the catalyst in the final product were described by Zhu. [53] The low absolute concentration of the catalyst in the reaction medium was attained by physical desorption of a low concentration of catalyst (21 ppm) from the silica support. This work has been summarized in a paper describing the fundamentals and development of high-efficiency supported catalyst systems for atom transfer radical polymerization. (59)

Shen recently examined another approach to supported dispersible/recyclable catalyst through the use of magnetic nanoparticles which were used to support an ATRP catalyst for polymerization of MMA. The nanoparticle-supported catalyst mediated a living/controlled radical polymerization of MMA as effectively as unsupported catalysts particularly after the addition of 22 mol % of CuBr2. The polymer MW was well-controlled with an initiator efficiency of 0.85 and polydispersity lower than 1.2. The supported catalysts could be easily separated/isolated using an external magnetic field. The activity of the recycled catalyst was regenerated by copper metal or in-situ regeneration using reducing agents such as alkylamine or tin(II) compdounds. Chain extension confirmed the livingness of the system and it was concluded that nanosized supports had reduced adverse effects of tethered catalysts. (60)

Now that some well-behaved immobilized ATRP catalyst systems have been reported, a shift in focus towards improving and optimizing current systems, and developing protocols for catalyst recycling should take precedence, hopefully leading to eventual widespread industrial practice.

36. "Immobilization of the Copper Catalyst in Atom Transfer Radical Polymerization." Kickelbick, G., Paik, H.-j., Matyjaszewski, K.: Macromolecules, 1999, 32: 2941-2947.

37. "3-Aminopropyl Silica Supported Living Radical Polymerization of Methyl Methacrylate: Dichlorotris(triphenylphosphine)ruthenium(II) Mediated Atom Transfer Polymerization." Haddleton, D. M., Duncalf, D. J., Kukulj, D., Radigue, A. P.: Macromolecules, 1999, 32: 4769-4775.

38. "Atom Transfer Radical Polymerization of Methyl Methacrylate by Silica Gel Supported Copper Bromide/Multidentate Amine." Shen, Y.; Zhu, S.; Zeng, F.; Pelton, R. H. Macromolecules 2000, 33, 5427.

39. "Effect of Ligand Spacer on Silica Gel Supported Atom Transfer Radical Polymerization of Methyl Methacrylate." Shen, Y., Zhu, S., Pelton, R.: Macromolecules, 2001, 34: 5812-5818.

40. "Packed column reactor for continuous atom transfer radical polymerization: methyl methacrylate polymerization using silica gel supported catalyst." Shen, Y.; Zhu, S.; Pelton, R. Macromol. Rapid Commun. 2000, 21, 956.

41. "Synthesis of methacrylate macromonomers using silica gel supported atom transfer radical polymerization." Shen, Y.; Zhu, S.; Zeng, F.; Pelton, R. Macromol. Chem. Phys. 2000, 201, 1387.

42. "An Immobilized/Soluble Hybrid Catalyst System for Atom Transfer Radical Polymerization." Hong, S. C.; Paik, H.-J.; Matyjaszewski, K. Macromolecules 2001, 34, 5099.

43. "Fundamentals of Supported Catalysts for Atom Transfer Radical Polymerization (ATRP) and Application of an Immobilized/Soluble Hybrid Catalyst System to ATRP" Hong, S. C.; Matyjaszewski, K. Macromolecules 2002, 35, 7592.

44. "Feasibility Analysis of Surface Mediation in Supported Atom Transfer Radical Polymerization," Faucher, S.; Zhu, S. Macromolecules 2006, 39, 4690-4695.

45. "Synthesis and ATRP activity of new TREN-based ligands." Gromada, J., Spanswick, J., Matyjaszewski, K.: Macromolecular Chemistry and Physics, 2004 205: 551-566.

46. "Use of an Immobilized/Soluble Hybrid ATRP Catalyst System for the Preparation of Block Copolymers, Random Copolymers and Materials with High Chain End Functionality" Hong, S. C.; Lutz, J.-F.; Inoue, Y.; Strissel, C.; Nuyken, O.; Matyjaszewski, K. Macromolecules 2003, 36, 1075-1082.

47. "Preparation of Segmented Copolymers in the Presence of an Immobilized/Soluble Hybrid ATRP Catalyst System"; Hong, S. C.; Neugebauer, D.; Inoue, Y.; Lutz, J.-F.; Matyjaszewski, K. Macromolecules 2003, 36, 27-35.

48. "Use of JandaJel Resins for Copper Removal in Atom Transfer Radical Polymerization." Honigfort, M. E., Brittain,. J.: Macromolecules 36, 2003, 3111-3114.

49. "Atom transfer radical polymerization of methyl methacrylate with polyethylene-functionalized ligands." Liou, S.; Rademacher, J. T.; Malaba, D.; Pallack, M. E.; Brittain, W. J. Macromolecules 2000, 33, 4295-4296.

50. "Use of Precipitons for Copper Removal in Atom Transfer Radical Polymerization." Honigfort, M. E., Brittain, W. J., Bosanac, T., Wilcox, C. S.: Macromolecules 35: 4849-4851, 2002.

51. "Copper removal in atom transfer radical polymerization." Honigfort, M. E.; Liou, S.; Rademacher, J.; Malaba, D.; Bosanac, T.; Wilcox, C. S.; Brittain, W. J. ACS Symposium Series 2003, 854, 250-266.

52. "Precipitons for copper removal in atom transfer radical polymerization: Reversible isomerization"; Ayres, N.; Honigfort, M. E.; Brittain, W. J.; Wilcox, C. S. Polymer Preprints, 2005, 46(2), 343-344.

53. "Packed column reactor for continuous atom transfer radical polymerization: methyl methacrylate polymerization using silica gel supported catalyst." Shen Y, Zhu S, Pelton R. Macromol Rapid Commun.; 2000, 1(14):956"9.

54. Packed column reactor for the continuous atom transfer radical polymerization of methyl methacrylate and its block copolymerization." Shen Y, Zhu S, Pelton R. AIChE J 2002; 48(11):2609"19.

55. "Reversible Catalyst Supporting via Hydrogen-Bonding-Mediated Self-Assembly for Atom Transfer Radical Polymerization of MMA." Yang, J., Ding, S., Radosz, M., Shen, Y.: Macromolecules, 2004 37: 1728-1734.

56. Shen, Y., Tang, H., Ding, S.: Catalyst separation in atom transfer radical polymerization. Progress in Polymer Science, 2004 29: 1053-1078.

57. "Recyclable polymerization catalysts: methyl methacrylate polymerization with silica-supported CuBr-bipyridine atom transfer radical polymerization catalysts." Nguyen, J. V., Jones, C. W.: Journal of Catalysis, 2005 232: 276-294.

58. "Heterogeneous Atom Transfer Radical Polymerization of Methyl Methacrylate at Low Metal Salt Concentrations." Faucher, S.; Zhu, S. Industrial & Engineering Chemistry Research; 2005, 44, 677-685.

59. Fundamentals and development of high-efficiency supported catalyst systems for atom transfer radical polymerization, Faucher, S.; Zhu, S. Journal of Polymer Science, Part A: Polymer Chemistry 2007, 45, 553-565.

60. Magnetic Nanoparticle Supported Catalyst for Atom Transfer Radical Polymerization, Ding, S.; Xing, Y.; Radosz, M.; Shen, Y. Macromolecules 2006, 39, 6399-6405.

A "soluble" hybrid catalyst system

When examining the catalytic activity of a "halogen free" neutral copper complex, it was determined that CuI-phenoxide, the Cu(I) species, activated the dormant chain but the CuII complex did not deactivate the growing chain. We took a page from the Hybrid Catalyst concept and added an efficient deactivator to the reaction. The CuI-phenoxide/(Me6TREN)CuIIBr2 system provides a highly active and controlled soluble hybrid catalytic system. (61)

61. "A Dual Catalyst System for ATRP Based on a Halogen-Free Neutral Cu(I) Complex"; Inoue, Y.; Matyjaszewski, K. Macromolecules 2003, 36, 7432.

Mixed Solvent Polymerization

Liquid/liquid biphasic polymerization: Other mixed media systems, liquid/liquid biphasic systems, have been evaluated. The simplest is a mixed solvent/water polymerization medium. (62) A mixture of toluene and water was used as the reaction medium in the polymerization. This system was developed to take advantage of the higher solubility of water in toluene at higher temperatures and the preferential partitioning of copper halides into the aqueous phase in heterogeneous systems which results in almost complete migration of Cu(II) into the aqueous phase after the reaction is complete and catalyst deliberately oxidized. Understanding and application of this concept assisted with catalyst removal from a homogenous polymerization medium after polymerization was complete. After the reaction was complete the catalyst complex was exposed to air and the copper migrated to the aqueous phase that separated when the reaction medium was cooled to room temperature. The amount of residual copper in the organic phase, measured by inductively coupled plasma, was less than 1 ppm.

The oxidized CuII catalyst complex could potentially be transformed back to the activator CuI complex by a reducing agent, cf. AGET and ARGET ATRP.

The ATRP of styrene in water/toluene mixtures occurred with the preservation of Br at the polymer chain end, as confirmed by successful chain extension to form block copolymers. The inherent inability to reuse the oxidized catalyst, accepted as fact three years ago, has now been overcome with the development of AGET ATRP.

A biphasic catalyst system that was immediately reusable after separation from the first reaction medium was formed by preparation of a ligand that allowed the reaction to be conducted under fluorous biphasic conditions. (63) Another liquid/liquid system that has gained general attention is the use of ionic liquids (64-69) which, in addition to allowing ATRP in an ionic liquid, (64) ultimately allowed use of much smaller amounts of the catalyst permitting a relatively easy removal of the polymer and residual monomer from the ionic liquid and the catalytic system could be reused without further treatment. In a recent paper (68) it was reported that a CuBr/N,N,N'',N''-tetraethyldiethylenetriamine (TEDETA) anchored on an imidazolium-based ionic liquid formed a catalyst that was insoluble in the mixture of MMA and toluene but could be easily dispersed in the reaction media. The polymerization was well controlled at 60 0C producing polymers with high initiator efficiency and low polydispersity. Once the stirring was stopped, the catalyst easily settled on the bottom of the reactor as a thin liquid layer, and thus the catalyst was easily isolated from the polymer solution and after regeneration, the recycled catalysts catalyzed the second run polymerization with similar or even higher activity and improved control. The residual catalyst concentrations in the polymers were in the range 50-100 ppm. Addition of a small amount of silica gel to the polymer solution could further reduce the residual catalyst concentration.

62. "Atom Transfer Radical Polymerization of Styrene in Toluene-Water Mixtures", Traian Sarbu, Tomislav Pintauer, Blayne McKenzie and Krzysztof Matyjaszewski, J. Polym. Sci., Polym. Chem., 40, 3153, 2002.

63. "Copper(I)-Mediated Living Radical Polymerization under Fluorous Biphasic Conditions." Haddleton, D. M., Jackson, S. G., Bon, S. A. F.: J. Am. Chem. Soc. 122: 1542-1543, 2000.

64. "ATRP of methyl methacrylate in the presence of ionic liquids with ferrous and cuprous anions." Sarbu, T., Matyjaszewski, K.: Macromolecular Chemistry and Physics 202: 3379-3391, 2001.

65. "Atom-transfer radical polymerization of acrylates in an ionic liquid." Biedron, T., Kubisa, P.: Macromol. Rapid Commun. 22: 1237-1242, 2001.

66. "Atom transfer radical polymerization of acrylates in an ionic liquid: synthesis of block copolymers." Biedron, T., Kubisa, P.: Journal of Polymer Science, Part A: Polymer Chemistry 40: 2799-2809, 2002.

67. "Reverse atom transfer radical polymerization of methyl methacrylate in room-temperature ionic liquids." Ma, H., Wan, X., Chen, X., Zhou, Q.-F.: Journal of Polymer Science, Part A: Polymer Chemistry 41: 143-151, 2002.

68. "Ionic Liquid Catalyst for Biphasic Atom Transfer Radical Polymerization of Methyl Methacrylate." Ding, S., Radosz, M., Shen, Y.: Macromolecules 38: 5921-5928, 2005.

69. "Atom transfer radical polymerization of styrenic ionic liquid monomers and carbon dioxide absorption of the polymerized ionic liquids." Tang, H., Tang, J., Ding, S., Radosz, M., Shen, Y.: Journal of Polymer Science, Part A: Polymer Chemistry 43: 1432-1443, 2005.

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