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Fundamentals of an ATRP Reaction

  • Summary
  • Atom Transfer Radical Polymerization
  • ATRP in Protic Media
    • Homogeneous
    • Heterogeneous
      • Compartmentalization

Summary

Atom Transfer Radical Polymerization (ATRP) is a particularly successful CRP that has attracted commercial interest (1) because of its easy experimental setup, use of readily accessible and inexpensive catalysts (usually copper complexes formed with aliphatic amines or imines, or pyridine based ligands, many of which are commercially available), and simple commercially available or easily prepared initiators (often alkyl halides).

ATRP is probably the most robust and efficient CRP and well-defined polymers with controlled topology, composition and functionality can be prepared. Historically, the primary objection to commercialization of materials prepared by ATRP was the presence of a significant amount of the transition metal catalyst complex in the final product. This barrier to commercialization is continuing to be addressed within the Matyjaszewski group. Commercially viable systems with reduced concentration of the transition metal complex, low ppm levels, have been developed simplifying purification of the final product.


As noted on the introductory page, one of the primary objectives of the research conducted in the Matyjaszewski group is the development of an understanding of the mechanistic features or structural parameters that influence transition metal catalyzed living/controlled radical polymerization. ATRP and numerous improvements to the basic ATRP process, remains the subject of an extensive intellectual property (IP) program at Carnegie Mellon University. The patent portfolio also covers the composition of many materials first prepared by ATRP. Indeed, because ATRP was the first robust CRP process, and RAFT and second generation NMP mediators were not developed until later than 1995, many materials disclosed in these patents are materials prepared for the first time by any CRP process. The patents covers polymerizations conducted with the four fundamental components listed below and ATRP conducted in biphasic media, including a full spectrum of heterogeneous aqueous media, and grafting from initiators tethered to solid surfaces.

Atom Transfer Radical Polymerization (ATRP)

ATRP is mechanistically closely related to another useful radical process, atom transfer radical addition (2) and indeed this relationship is the reason this polymerization process is named ATRP. (3) ATRP can be viewed as a very special case of ATRA, which requires the reactivation of the first formed alkyl halide adduct of the unsaturated compound (monomer) and the further reaction of the formed radical with monomer (propagation). The "livingness" of this polymerization process can be ascertained from a linear first-order kinetic plot, accompanied by a linear increase in polymer molecular weights with conversion, with a value of the number-average degree of polymerization (DPn) determined by the ratio of reacted monomer to initially introduced initiator (i.e., DPn = ^[M]/[RX]0).

Scheme 1. Mechanism of metal complex-mediated ATRA and ATRP

The normal schematic of the ATRP equilibrium which emphasizes the repetitive nature of activation and deactivation is shown below.

Scheme 2. Mechanism of metal complex-mediated ATRP.

Mechanistically, ATRP is based on an inner sphere electron transfer process, which involves a reversible (pseudo)halogen homolytic transfer between a dormant species, an added initiator or the propagating dormant chain end, (R-X) and a transition metal complex in the lower oxidation state (Mtm/Ln) resulting in the formation of propagating radicals (R*) (4) and the metal complex in the higher oxidation state with a coordinated halide ligand (e.g. X-Mtm+1/Ln). The active radicals form at a rate of activation (kact), subsequently propagate with a rate (kp) and reversibly deactivate (kdeact), but also terminate (kt). As the reaction progresses radical termination is diminished as a result of the persistent radical effect, (PRE), (5) chain length (6) and the equilibrium is strongly shifted towards the dormant species (kact << kdeact). (7)

The higher oxidation state transition metal (complex), the equivalent of the persistent radical in an ATRP, can be added directly to a reaction prior to initiation to increase the efficiency of initiation by reducing the fraction of low molecular weight termination reactions initially required to generate the PRE, (8) or can be formed in situ by reaction with dissolved oxygen. (9) Addition of the PRE is of particular utility when conducting a "grafting from" reaction with a multifunctional initiator or grafting from a surface. It is also strongly recommended when ATRP is carried out in protic, particularly homogeneous aqueous media.

ATRP is in many ways a complex reaction, which includes one or more (co)monomers, a transition metal complex in two or more oxidation states, (10) which can comprise various counterions and ligands, an initiator with one or more radically transferable atoms or groups and can additionally include an optional solvent, suspending media and various additives. All of the components present in the reaction medium can, and often do, affect the ATRP equilibrium. (11, 12) The initiator is most frequently an alkyl (pseudo)halide which can be either a low or high molar mass compound or even a part of an insoluble material, such as when initiators are tethered to the surface of modified particles, flat wafers, or even fibers, etc.

A series of starting points for conducting an ATRP for a range on monomers in different media is provided elsewhere on this site.

In most of the following discussion we will use copper (13) as an exemplary transition metal but a wide range of other metals can be employed in an ATRP including Ti (14), Mo (15-17), Re (18-19), Fe (20-24), Ru (25-28), Os (29), Rh (30, 31) Co (32), Ni (33-36), and Pd (37). There are additional references in a recent review article which also addresses the environmental issues associated with industrial scale ATRP. (38) Copper has proven by far to be the transition metal of choice, as determined by the successful application of a spectrum of copper complexes as catalysts, for the ATRP of a broad range of monomers in diverse media by many research groups. However iron may eventually prove to be the transition metal of choice for environmental reasons unless industrially viable procedures for internal reuse of the copper complexes are adopted. It should also be noted that Ru and Os have certain advantages as a consequence of its high halidophilicity that may make it a good choice for use in protic media.

Polymers prepared by other polymerization processes can be functionalized at the termini or along the backbone and incorporated into an ATRP as a macromonomer or macroinitiator, or simultaneously through use of both macroinitiator and macromonomer to improve incorporation of the macromonomer into the polymer, (39) leading to well defined block and graft copolymers. There may be one or multiple initiating sites, leading to chain growth in several directions. The initiator may carry a special functionality, in addition to a radically transferable atom or group, to yield telechelic materials. (40)

The transition metal complex has to be at least partially soluble in the reaction medium and reactions can be run under homogeneous or heterogeneous conditions, the former generally provides better control since the concentration of activator and deactivator can be controlled. (41) Reaction temperatures typically range from room temperature to 150 0C, but can be correspondingly altered. The reaction can be run under vacuum or pressure. Reactions can not only be conducted in the presence of moisture but even in the presence of water under homogeneous (42) or heterogeneous (micro-emulsion -> suspension) conditions. (43

Oxygen should be removed, but a limited amount of oxygen can be tolerated particularly in the presence of an added reducing agent e.g. Cu(0), Sn(EH2) or ascorbic acid. (10, 44-47) The order of addition of reagents may vary but most often the initiator is added last to a preformed solution of the catalyst in the monomer/solvent. An important parameter may be the addition or formation of a small amount of Cu(II) species at the beginning of the reaction since it enables the deactivation process to occur immediately without requiring its spontaneous formation by termination reactions, thereby providing both higher initiator efficiency and instantaneous control. (48)

Understanding, and controlling the equilibrium, and hence the dynamics of the atom transfer process, are basic prerequisites for running a successful ATRP. Therefore it is a very important objective within the Matyjaszewski group to correlate structure with reactivity for each of the involved reagents, the oxidation states of the transition metal complex, radicals and dormant species, in addition to solvent effects and reaction temperature in order to provide that fundamental understanding required for the selection of optimum conditions to conduct the desired reaction. (10, 49, 50)


The ATRP equilibrium, (KATRP in the scheme above), is expressed as a combination of several contributing reversible reactions, including a combination of C-X bond homolysis of the alkyl halide (R-X), (other transferable atoms or groups can participate in an ATRP (51) but the most frequently employed radically transferable atoms are halogens and will be used to exemplify ATRP throughout most of following discussions) two redox processes, and heterolytic cleavage of the CuII-X bond. Therefore KATRP can be expressed as the product of the equilibrium constants for electron transfer between metal complexes (KET), electron affinity of the halogen (KEA), bond dissociation energy of the alkyl halide (KBD) and the equilibrium constant for the heterolytic cleavage of the Mtn+1-X bond (KX), which measures the "halidophilicity" of the deactivator. This means that for a given alkyl halide, R-X, the activity of a catalyst in an ATRP reaction depends not only on the redox potential, but also on the halidophilicity of the transition metal complex. For complexes that have similar halidophilicity, the redox potential can be used as a measure of catalyst activity in the ATRP. This was demonstrated by the linear correlation between KATRP and E1/2, ( ie. KET), for a series of CuI complexes with nitrogen based ligands. (52-54)


It can also be concluded that for a given catalytic system in the same solvent (where KET, KEA, and KX are essentially constant), KATRP should depend upon the energy required for alkyl halide bond homolysis, or KBD. Indeed, when the alkyl halide bond dissociation energies were calculated recently for a series of ATRP monomers/initiators, they were found to correlate well with measured values of KATRP. (52, 55)

It was proposed that such calculations could also be used to predict equilibrium constants for unreactive monomers. Knowing KBD as well as the rate constants of propagation for a given monomer, the rates of polymerization could be calculated for different monomers in ATRP under comparable conditions (same catalyst, constant KET, KEA, and KX). For example, if the ATRP of acrylonitrile reached 90% conversion in 1 second, methyl acrylate 2 hours, styrene 22 hours and vinyl acetate 30 years under the same conditions. (52) This calculation merely serves to demonstrate the necessity of choosing an appropriate catalyst and appropriate reaction conditions for each monomer.

Determination of the equilibrium rate constant is crucial in order to understand the kinetics of an ATRP. Assuming steady-state kinetics, the rate of polymerization is given by:

This equation means that the rate of polymerization is controlled by the ratio of CuI to CuII and not the absolute amount of catalyst present in the reaction medium. Understanding the implications of this equation was critical to the development of ARGET ATRP. (56) Experimentally, the values of KATRP can be determined by direct analysis of the polymerization mixture (by EPR, NMR, GC, GPC, IR...) or by the study of low molecular weight model compounds. Furthermore, while some side reactions (thermal-initiation of monomer, elimination reactions, transfer reactions, degradation of the catalyst...) and some physical parameters (viscosity, inhomogeneity...) may have an important effect on the kinetics of CRP the influence of these parameters may also be investigated by model studies or by computer simulation. (6, 57-60)


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

(2) "Free-radical additions to olefins in the presence of redox systems," Minisci, F. Accounts of Chemical Research 1975, 8, 165-171.

(3) "Controlled/\"living\" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes," Wang, J.-S.; Matyjaszewski, K. J. Am. Chem. Soc. 1995, 117, 5614-5615.

(4) "Isotope Effects and the Mechanism of Atom Transfer Radical Polymerization," Singleton, D. A.; Nowlan, D. T., III; Jahed, N.; Matyjaszewski, K., Macromolecules 2003, 36, 8609-8616.

(5) "The Persistent Radical Effect: A Principle for Selective Radical Reactions and Living Radical Polymerizations," Fischer, H., Chem. Rev. 2001, 101, 3581-3610.

(6) "Easy access to chain-length-dependent termination rate coefficients using RAFT polymerization," Vana, P.; Davis, T. P.; Barner-Kowollik, C. Macromolecular Rapid Communications 2002, 23, 952-956.

(7) "Determination of Equilibrium Constants for Atom Transfer Radical Polymerization," Tang, W.; Tsarevsky, N. V.; Matyjaszewski, K. Journal of the American Chemical Society 2006, 128, 1598-1604.

(8) "Effect of [CuII] on the Rate of Activation in ATRP"; Matyjaszewski, K.; Nanda, A. K.; Tang, W. Macromolecules 2005, 38, 2015-2018.

(9) Matyjaszewski, K., et al; U.S.: 5,807,937, 1998.

(10) "Controlled Radical Polymerization in the Presence of Oxygen," Matyjaszewski, K.; Coca, S.; Gaynor, S. G.; Wei, M.; Woodworth, B. E. Macromolecules 1998, 31, 5967-5969.

(11) "Controlled/living radical polymerization: Features, developments, and perspectives," Braunecker, W. A.; Matyjaszewski, K. Progress in Polymer Science 2007, 32, 93-146.

(12) "Electron transfer reactions relevant to atom transfer radical polymerization,"Tsarevsky, N. V.; Braunecker, W. A.; Matyjaszewski, K. Journal of Organometallic Chemistry 2007, 692, 3212-3222.

(13) "Atom Transfer Radical Polymerization." Matyjaszewski, K., Xia, J.: Chem. Rev. 2001, 101: 2921-2990.

(14) "Atom Transfer Radical Polymerization with Ti(III) Halides and Alkoxides;" Kabachii, Y. A.; Kochev, S. Y.; Bronstein, L. M.; Blagodatskikh, I. B.; Valetsky, P. M. Polym. Bull. 2003, 50, 271-278.

(15) "Controlled radical polymerization of styrene in the presence of lithium molybdate(v) complexes and benzylic halides;" Brandts, J. A. M.; van de Geijn, P.; van Faassen, E. E.; Boersma, J.; Van Koten, G. J. Organomet. Chem. 1999, 584, 246-253.

(16) "Radical Polymerization of Styrene Controlled by Half-Sandwich Mo(III)/Mo(IV) Couples: All Basic Mechanisms Are Possible"; Le Grognec, E.; Claverie, J.; Poli, R. J. Am. Chem. Soc. 2001, 123, 9513-9524.

(17) "The Radical Trap in Atom Transfer Radical Polymerization Need Not Be Thermodynamically Stable. A Study of the MoX3(PMe3)3 Catalysts;" Maria, S.; Stoffelbach, F.; Mata, J.; Daran, J.-C.; Richard, P.; Poli, R. J. Am. Chem. Soc. 2005, 127, 5946-5956.

(18) "Living radical polymerization of acrylates with rhenium(V)-based initiating systems: ReO2I(PPh3)2/Alkyl Iodide, Uegaki, H.; Kotani, Y.; Kamigaito, M.; Sawamoto, M. ACS Symp. Ser. 2000, 760, 196.

(19) "Living Radical Polymerization of Para-Substituted Styrenes and Synthesis of Styrene-Based Copolymers with Rhenium and Iron Complex Catalysts," Kotani, Y.; Kamigaito, M.; Sawamoto, M. Macromolecules 2000, 33, 6746.

(20) "FeCp(CO)2I: a phosphine-free half-metallocene-type iron(II) catalyst for living radical polymerization of styrene"; Kotani, Y.; Kamigaito, M.; Sawamoto, M. Macromolecules 1999, 32, 2420-2424.

(21) "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, 8161-8164.

(22) "Iron(II) Chloride Complex for Living Radical Polymerization of Methyl Methacrylate"; Ando, T.; Kamigaito, M.; Sawamoto, M. Macromolecules 1997, 30, 4507-4510.

(23) "Five-coordinate iron(II) complexes bearing tridentate nitrogen donor ligands as catalysts for atom transfer radical polymerization"; O'Reilly, R. K.; Gibson, V. C.; White, A. J. P.; Williams, D. J. Polyhedron 2004, 23, 2921-2928.

(24) "Halide Anions as Ligands in Iron-Mediated Atom Transfer Radical Polymerization"; Teodorescu, M.; Gaynor, S. G.; Matyjaszewski, K. Macromolecules 2000, 33, 2335-2339.

(25) "Polymerization of Methyl Methacrylate with the Carbon Tetrachloride/Dichlorotris- (triphenylphosphine)ruthenium(II)/Methylaluminum Bis(2,6-di-tert-butylphenoxide) Initiating System: Possibility of Living Radical Polymerization"; Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura, T. Macromolecules 1995, 28, 1721-1723.

(26) "A New Ruthenium Complex with an Electron-Donating Aminoindenyl Ligand for Fast Metal-Mediated Living Radical Polymerizations," Kamigaito, M.; Watanabe, Y.; Ando, T.; Sawamoto, M. J. Am. Chem. Soc. 2002, 124, 9994.

(27) "Highly efficient ruthenium-based catalytic systems for the controlled free-radical polymerization of vinyl monomers"; Simal, F.; Demonceau, A.; Noels, A. F. Angew. Chem., Int. Ed. 1999, 38, 538-540.

(28) "A bimetallic ruthenium complex as a catalyst precursor for the atom transfer radical polymerization of methacrylates at ambient temperature," Haas, M.; Solari, E.; Nguyen, Q. T.; Gautier, S.; Scopelliti, R.; Severin, K. Adv. Synth. Catal. 2006, 348, 439.

(29) "Osmium catalyzed radical polymerization"; Braunecker, W. A.; Itami, Y.; Matyjaszewski, K. Macromolecules 2005, 38, 9402-9404.

(30) "Metal-Catalyzed \"Living\" Radical Polymerization of Styrene Initiated with Arenesulfonyl Chlorides. From Heterogeneous to Homogeneous Catalysis"; Percec, V.; Barboiu, B.; Neumann, A.; Ronda, J. C.; Zhao, M. Macromolecules 1996, 29, 3665-3668.

(31) "Controlled Radical Polymerization of Methyl Methacrylate Initiated by an Alkyl Halide in the Presence of the Wilkinson Catalyst," Moineau, G.; Granel, C.; Dubois, P.; Jerome, R.; Teyssie, P. Macromolecules 1998, 31, 542.

(32) "Controlled/\"Living\" Radical Polymerization of MMA Catalyzed by Cobaltocene"; Wang, B.; Zhuang, Y.; Luo, X.; Xu, S.; Zhou, X. Macromolecules 2003, 36, 9684-9686.

(33) "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, 8576-8582.

(34) "Nickel-Mediated Living Radical Polymerization of Methyl Methacrylate"; Uegaki, H.; Kotani, Y.; Kamigaito, M.; Sawamoto, M. Macromolecules 1997, 30, 2249-2253.

(35) " Living radical polymerization of methyl methacrylate with a zerovalent nickel complex, Ni(PPh3)4," Uegaki, H.; Kamigaito, M.; Sawamoto, M. J. Polym. Sci.: Part A: Polym. Chem. 1999, 37, 3003.

(36) "Controlled Radical Polymerization of (Meth)acrylates by ATRP with NiBr2(PPh3)2 as Catalyst," Moineau, G.; Minet, M.; Dubois, P.; Teyssie, P.; Senninger, T.; Jerome, R. Macromolecules 1999, 32, 27.

(37) "Controlled Radical Polymerization of Methyl Methacrylate in the Presence of Palladium Acetate, Triphenylphosphine, and Carbon Tetrachloride"; Lecomte, P.; Drapier, I.; Dubois, P.; Teyssie, P.; Jerome, R. Macromolecules 1997, 30, 7631-7633.

(38) "\"Green\" Atom Transfer Radical Polymerization: From Process Design to Preparation of Well-Defined Environmentally Friendly Polymeric Materials," Tsarevsky, N. V.; Matyjaszewski, K. Chemical Reviews (Washington, DC, United States) 2007, 107, 2270-2299.

(39) "Structural Control of Poly(methyl methacrylate)-g-poly(dimethylsiloxane) Copolymers Using Controlled Radical Polymerization: Effect of the Molecular Structure on Morphology and Mechanical Properties." Shinoda, H., Matyjaszewski, K., Okrasa, L., Mierzwa, M., Pakula, T.: Macromolecules, 2003, 36: 4772-4778.

(40) "How to make polymer chains of various shapes, compositions, and functionalities by atom transfer radical polymerization." Gaynor, S. G., Matyjaszewski, K.: ACS Symp. Ser. 1998, 685: 396,.

(41) "Polymers with very low polydispersities from atom transfer radical polymerization," Patten, T. E.; Xia, J.; Abernathy, T.; Matyjaszewski, K. Science, 1996, 272, 866-868.

(42) "Polymerization of acrylates by atom transfer radical polymerization. Homopolymerization of 2-hydroxyethyl acrylate," Coca, S.; Jasieczek, C. B.; Beers, K. L.; Matyjaszewski, K. J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 1417-1424.

(43) "Controlled/living radical polymerization in aqueous media: homogeneous and heterogeneous systems," Qiu, J.; Charleux, B.; Matyjaszewski, K. Prog. Polym. Sci. 2001, 26, 2083-2134.

(44) "Controlled atom or group-transfer radical polymerization, coupling of molecules, multifunctional polymerization initiators, and formation of telechelic functional material." Matyjaszewski, K., Gaynor, S. G., Coca, S.: PCT Int. Appl.: 9840415, 1998.

(45) "Controlled/living radical polymerization in the undergraduate laboratories. 2. Using ATRP in limited amounts of air to prepare block and statistical copolymers of n-butyl acrylate and styrene," Matyjaszewski, K.; Beers, K. L.; Woodworth, B.; Metzner, Z. J. Chem. Educ. 2001, 78, 547-550.

(46) "Jakubowski, W., Matyjaszewski, K.: Activator Generated by Electron Transfer for Atom Transfer Radical Polymerization." Macromolecules, 2005, 38: 4139-4146.

(47) "Preparation of Homopolymers and Block Copolymers in Miniemulsion by ATRP Using Activators Generated by Electron Transfer (AGET)." Min, K., Gao, H., Matyjaszewski, K.: J. Am. Chem. Ssoc., 2005 127: 3825-3830.

(48) "Mechanistic aspects of atom transfer radical polymerization." Matyjaszewski, K.: ACS Symp. Ser. 685: 1998, 258-283.

(49) "Tsarevsky, N. V.; Tang, W.; Brooks, S. J.; Matyjaszewski, K. "Factors Determining the Performance of Copper-Based ATRP Catalysts and Criteria for Rational Catalyst Selection" ACS Symp. Ser. 2006, 944, 56.

(50) "Competitive equilibria in atom transfer radical polymerization," Tsarevsky, N. V.; Braunecker, W. A.; Vacca, A.; Gans, P.; Matyjaszewski, K. Macromolecular Symposia 2007, 248, 60-70.

(51) "Effect of (Pseudo)halide Initiators and Copper Complexes with Non-halogen Anions on the ATRP," Davis, K. A.; Matyjaszewski, K. Journal of Macromolecular Science, Pure and Applied Chemistry 2004, 41, 449-465.

(52) "A DFT Study of R-X Bond Dissociation Enthalpies of Relevance to the Initiation Process of Atom Transfer Radical Polymerization," Gillies, M. B.; Matyjaszewski, K.; Norrby, P.-O.; Pintauer, T.; Poli, R.; Richard, P. Macromolecules 2003, 36, 8551-8559.

(53) "Tridentate Nitrogen-Based Ligands in Cu-Based ATRP: A Structure-Activity Study," Matyjaszewski, K.; Goebelt, B.; Paik, H.-j.; Horwitz, C. P. Macromolecules 2001, 34, 430-440.

(54) "Toward structural and mechanistic understanding of transition metal-catalyzed atom transfer radical processes," Pintauer, T.; McKenzie, B.; Matyjaszewski, K. ACS Symposium Series 2003, 854, 130-147.

(55) "Effects of Initiator Structure on Activation Rate Constants in ATRP," Tang, W.; Matyjaszewski, K. Macromolecules 2007, 40, 1858-1863.

(56) "Atom transfer radical polymerization in the presence of a reducing agent" Matyjaszewski, K.; Bombalski, L.; Jakubowski, W.; Min, K.; Spanswick, J.; Tsarevsky, N. In PCT Int. Appl.; (Carnegie Mellon University, USA). WO 2005087819, p 96 pp.

(57) "Characterization of Cu(II) Bipyridine Complexes in Halogen Atom Transfer Reactions by Electron Spin Resonance," Knuehl, B.; Pintauer, T.; Kajiwara, A.; Fischer, H.; Matyjaszewski, K. Macromolecules 2003, 36, 8291-8296.

(58) "Kinetic analysis of controlled/\"living\" radical polymerizations by simulations. 1. The importance of diffusion-controlled reactions," Shipp, D. A.; Matyjaszewski, K. Macromolecules 1999, 32, 2948-2955.

(59) "Kinetic Analysis of Controlled/\"Living\" Radical Polymerizations by Simulations. 2. Apparent External Orders of Reactants in Atom Transfer Radical Polymerization," Shipp, D. A.; Matyjaszewski, K. Macromolecules 2000, 33, 1553-1559.

(60) "Determination of Rate Constants for the Activation Step in Atom Transfer Radical Polymerization Using the Stopped-Flow Technique," Pintauer, T.; Braunecker, W.; Collange, E.; Poli, R.; Matyjaszewski, K. Macromolecules 2004, 37, 2679-2682.

ATRP in Protic Media

One limitation on the scope of ATRP, as the process was initially being defined, were side reactions involving the catalyst in polar media. However it has become increasingly desirable to conduct ATRP in protic media because it allows a significant expansion of the range of monomers that can be controllable polymerized. Therefore it became of primary importance to understand the side reactions. Predominately theses side reactions affected deactivation efficiency, resulting in decreased level of control over an ATRP in protic solvents. Many of these issues have now been addressed.(61) Both the rate of polymerization and the degree of control over the polymerization, (evaluated from the polydispersity index, PDI = Mw/Mn) depend on the concentration of the deactivator actually present in the system, which in turn depends upon the value of the solvent-sensitive electron affinity (KEH) and halogenophilicity (KX). The values of KEA are expected to be relatively high in protic solvents as halide anions formed in KEA are stabilized. KX will likewise be affected by changes in solvent polarity and by selective solvation of ions.

In the above equation, kp is the propagation rate constant for the monomer M. Thus the values of KAE affect the rate of as well as the level of control over a polymerization. The addition of halide salts can largely suppress the dissociation of the ATRP deactivator, while the addition of complex-forming agents or co-solvents that stabilize the CuI state of the catalyst relative to CuII can suppress disproportionation. (20, 38) All side reactions have been quantitatively described (52, 55) which should make it possible to predict the reaction conditions required for optimal results in specific controlled radical polymerizations of a variety of water soluble monomers in water-based solvents.

All CRP processes, in particular ATRP, can be applied to the entire range of water-borne systems: from solution to suspension.

Water is an inexpensive environmentally friendly solvent with high thermal capacity, which makes it an attractive medium for exothermic radical copolymerization reactions, particularly since both solution polymerization of water-soluble polymers and biphasic polymerization of hydrophobic monomers in latexes have found direct application in various practical fields. In heterogeneous media it is possible to prepare particles with a wide range of size using different polymerization systems

Although many monomers have been successfully polymerized in water-based media using ATRP, (62-66) as noted above, there is an ongoing research effort to clarify the mechanisms of the interactions of water with the catalyst, initiator, and monomer in both homogeneous and heterogeneous systems in order to understand the multiplicity of interactions that can take place in the presence of polar monomers and solvents.

The objective is to expand the utility of homogeneous and heterogeneous aqueous ATRP

Homogeneous

An understanding of the complex interactions that can occur in aqueous ATRP (shown below for the case of homogeneous aqueous solutions) is important in order to find the reaction conditions that will allow preparation of new well-defined polymeric materials. (61, 63-65)

The following schematic shows that several complex equilibrium compete when ATRP is being conducted in protic solvents such as


alcohols or water, leading to:

  • disproportionation of the Cu(I) complex (the ATRP activator ) (Kdisp)
  • reduction in the concentration of the copper(II)-based deactivator (CuIILmX) via dissociation of the halide ligand (KX)
  • complexation of the dissociated complex or ligand with the solvent and/or the polar monomers (KCu,aq or KX,aq,j), or
  • disproportionation or hydrolysis of the initiator or dormant chain end.

The addition of appropriate complex-forming agents or co-solvents that stabilize the CuI state of the catalyst relative to CuII can suppress disproportionation; e.g. Kdisp, of CuI can be suppressed by more than 10 orders of magnitude in the presence of 1 M pyridine. (61) Using pyridine as a co-solvent allows the successful ATRP of several ionic monomers, which otherwise stabilized CuII relative to CuI in pure water.

Another ATRP side reaction that occurs to a significant extent in water is hydrolysis of the CuII-halide complex. Because H2O solvates Br- ions much better than organic solvents reversible dissociation of the halide anion from the higher oxidation state metal complex will be much more significant in aqueous media. This dissociation, which is presumably followed by coordination of water to CuII, ultimately lowers the concentration of deactivator available during an aqueous ATRP. This is consistent with the observation that ATRP reactions are typically much faster and less controlled in aqueous and protic media. However, deactivator solvolysis can be suppressed, and control over the polymerization of hydrophilic polymers achieved, by addition of extra halide salts to the reaction. (61)

Therefore it is possible to predict the reaction conditions leading to optimal results in the controlled radical polymerization of variety of water soluble monomers in water-based solvents including neutral 2-hydroxyethyl methacrylate, (HEMA) and cationic 2-(N,N,N-trimethylammonio)ethyl methacrylate triflate, (TMATf) and 2-(N,N,N-dimethylethylammonio)ethyl methacrylate bromide (DMEABr). Polar monomers with nucleophilic groups (4VP, DMAEMA) can displace the chain end by nucleophilic substitution, which can be minimized by using alkyl chloride initiators and/or chloride-based catalysts. (61) Optimization of ATRP of neutral 2-hydroxyethyl methacrylate, (HEMA) and cationic 2-(N,N,N-trimethylammonio)ethyl methacrylate triflate, (TMATf) and 2-(N,N,N-dimethylethylammonio)ethyl methacrylate bromide (DMEABr) ammonium salts in protic/aqueous solvents is described in reference 53 and work by Armes (65) and Dubois. (66)

A general review describing all side reactions in protic media and catalyst optimization is provided in a recent Chemical Review paper. (38)


(61) "Deactivation Efficiency and Degree of Control over Polymerization in ATRP in Protic Solvents," Tsarevsky, N. V ;. Pintauer, T.; Matyjaszewski, K., Macromolecules 2004, 37, 9768-9778.

(62) "Stabilization of transition metal complexes for catalysis in diverse environments." Matyjaszewski, K., Tsarevsky, N.: U.S. Pat. Appl. Publ.: 2004122189.

(63) "ATRP synthesis of amphiphilic random, gradient, and block copolymers of 2-(dimethylamino)ethyl methacrylate and n-butyl methacrylate in aqueous media," Lee, S. B.; Russell, A. J.; Matyjaszewski, K. Biomacromolecules 2003, 4, 1386-1393.

(64) "Rational Selection of Initiating/Catalytic Systems for the Copper-Mediated Atom Transfer Radical Polymerization of Basic Monomers in Protic Media: ATRP of 4-Vinylpyridine"; Tsarevsky, N. V.; Braunecker, W. A.; Brooks, S. J.; Matyjaszewski, K.; Macromolecules, 2006, 39, 6817.

(65) "Direct Synthesis of Well-Defined Quaternized Homopolymers and Diblock Copolymers via ATRP in Protic Media, Li, Y.;" Armes, S. P.; Jin, X.; Zhu, S. Macromolecules 2003, 36, 8268-8275.

(66) "Preparation of well-defined poly[(ethylene oxide)-block-(sodium 2-acrylamido-2-methyl-1-propane sulfonate)] diblock copolymers by water-based atom transfer radical polymerization," Paneva, D.; Mespouille, L.; Manolova, N.; Degee, P.; Rashkov, I.; Dubois, P. Macromolecular Rapid Communications 2006, 27, 1489-1494.

Heterogeneous

Selection of a suitable ligand is a critical first step in order to conduct a controlled ATRP in any aqueous system. The choice of surfactant is also important in all heterogeneous emulsion systems. However ligand selection remains of primary importance since the ligand determines the solubility of the metal complex in the monomer phase and the partitioning of the metal complexes between the different phases.

The earliest work directed at conducting a successful ATRP in an emulsion system required relatively low solids content and high surfactant levels {13% solids, 13.5 wt% surfactant based on monomer} (67, 68) for production of stable latexes. However by moving to a miniemulsion process, using reverse initiation (69, 70), we were able to increase the solids content of the system and significantly reduce the level of surfactant {30 % solids, 2.3 wt% surfactant based on monomer} in addition to starting with an oxidatively stable catalyst system. dNbpy, BMODA and tNtpy are sufficiently hydrophobic ligands to retain enough CuII in the monomer droplets dispersed in a miniemulsion polymerization to provide a controlled polymerization, while complexes formed with bpy, PMDETA and Me6TREN allow migration of CuII to the aqueous phase and control is lost. (55, 69, 70)

Suitable commercially available surfactants include CTAB, Brij 98 and Tween 80 whereas PEG 100, PEG 4600, Brij 97 and Tween 20 provided less stable emulsions.

While reverse initiation simplified setting up a miniemulsion ATRP it limited the range of materials that could be prepared and the number of catalysts that could be employed in the reaction. One cannot independently adjust catalyst level and DPtarget. Therefore a new initiation system was developed: Simultaneous Reverse and Normal Initiation (SR&NI). (71) SR&NI allowed the preparation of block and star copolymers in a miniemulsion with low levels of an active catalyst and low levels of surfactant. (72, 73) The use of SR&NI provided stable latexes with high solids content. As shown in the 2D-GPC plot below, only 4.5% of linear homopolystyrene was present in the final polymer when a tri-arm poly(methyl acrylate) macroinitiator was chain extended by styrene in a SR&NI miniemulsion process. The homopolymer results from use of a free radical initiator to activate the catalyst complex.

This particular 2D-GPC plot provided the incentive to work on a further improvement in the procedures used for initiation of an ATRP and led directly to the development of AGET (Activator Generated by Electron Transfer) ATRP. In an AGET ATRP miniemulsion polymerization process a water soluble reducing agent is used to activate the catalyst and control the fraction of deactivator present in the suspending medium. (74, 75) The following 2D-GPC plot shows the final result of an AGET ATRP using the same tri-arm macroinitiator

No homopolymer can be detected, however, as noted in reference 74, the amount and addition rate of the reducing agent affects the polymerization rate and the level of control attained in the polymerization. However, as the image shows, when the selection is made appropriately no homopolymers and no coupling product are detected.

A further advantage of AGET ATRP is that by adding an excess of reducing agent the reaction can be successfully carried out in the presence of air. (75)

Rapid progress continues to be made in the development of aqueous dispersed media ATRP which has recently been expanded to microemulsion. (76) The proper selection of ligand and surfactant remain keys to success. A hydrophobic ligand is preferred for mini- and micro-emulsion and selection of a non-ionic surfactant with suitable HLB value results in good colloidal stability and good control. This expansion of dispersed media ATRP to microemulsion and development of a process for addition of pure monomer to the system to increase the %solids in the reaction, which was employed to prepare a forced gradient copolymer, (77) resulted in the development of an ab initio emulsion polymerization process capable of preparing block copolymers. (78)

The critical requirement for these advances in dispersed media ATRP was the ability to encapsulate all agents required for an ATRP in the first formed micelles. This allowed pure monomer to be added to the reaction medium. The added monomer was then able diffuse to the active micelles allowing an increase in micelle size and concomitant increase in the percent solids and decrease in % surfactants in the system.

At the other end of the particle size spectrum, there is another heterogeneous process where particles > 1 um are prepared. Atom transfer radical dispersion polymerization of styrene in ethanol was successfully carried out using a "two-stage" polymerization technique, in which the first stage involves an FRP and the second an ATRP. (79) Polystyrene particles with size 1.5-3 um were obtained. The large particles, with narrow size distribution, contained polymers and relatively low dispersity (Mw/Mn=1.4-1.8, compared with Mw/Mn= 4-5 from conventional radical dispersion polymerization) indicating a high fraction of retained chain end functionality which can be readily employed for further modification.

(A) GPC data from "two stage" suspension polymerization and (B) articles formed in the reaction


Another extension of heterogeneous controlled polymerization is the preparation of nano-particles in an inverse miniemulsion ATRP. (80) Stable colloidal nanoparticles of well-controlled water-soluble poly(oligo(ethylene glycol) monomethyl ether methacrylate) (P(OEOMA)) homo- and copolymers were successfully synthesized by inverse miniemulsion atom transfer radical polymerization using activators generated by electron transfer (AGET ATRP) at ambient temperature, (30 C). An oil soluble surfactant (sorbitan monooleate (Span 80)) was employed in conjunction with ascorbic acid as a reducing agent. An oxidatively stable CuBr2/tris[(2-pyridyl)methyl]amine (TPMA) catalyst complex, and [initiator]0/[CuBr2/TPMA]0 = 1/0.5 were selected as the catalyst precursor/initiator for the controlled AGET ATRP inverse miniemulsion. The effect of reaction parameters on control over AGET ATRP and colloidal stability were explored. It was found that the use of water-soluble poly(ethylene oxide)-based bromoisobutyrate macroinitiators (PEO-Br) with long chain EO units, up to 90% ascorbic acid of Cu(II) complex, and appropriate amount of water resulted in the formation of stable colloidal particles with less than 200 nm diameter and well-controlled P(OEOMA) with Mw/Mn < 1.3. The addition of a long chain poly(ethylene glycol) monomethyl ether (PEO-OMe) as a costabilizer improved colloidal stability without interfering with the polymerization. A water-soluble CuBr2/bipyridine catalyst complex was also suitable for AGET ATRP of OEOMA in inverse miniemulsion. Finally, colloidal particles of well-controlled block copolymers of OEOMA with different sizes of OEO side chains (DP of EO = 5 and 9) were produced with relatively low polydispersity, 1.3 at 85% conversion

Compartmentalization

Miniemulsion ATRP has been demonstrated to be an efficient procedure for the preparation of block and graft copolymers from multifunctional macroinitiators. (52, 73) As detailed in the referenced papers, this is partially a result of compartmentalization of the multifunctional initiators in the well dispersed stable "oil" droplets. (81, 82) This is shown schematically below. Because there are fewer active radicals in each miniemulsion droplet than in a bulk polymerization there is less inter-particle termination and significant levels of crosslinking are avoided, allowing the reaction to be driven to higher conversion.

The AFM images on the right show the lack of interparticle crosslinking in the nanocomposite structure formed in a "grafting from" surface active silica particles in a miniemulsion polymerization. One reaction was conducted using SR&NI initiation and the other AGET ATRP. The second image shows significantly less unattached polymer chains in the AGET system and a total absence of linked particles due to the added ability to control the concentration of the deactivator in the dispersed droplets.

The same principle holds true for an ATRP "grafting from" a soluble linear multifunctional macroinitiator. The following images show that bottle-brush copolymers can also be prepared in an AGET ATRP miniemulsion polymerization and that brush-brush crosslinking reactions are minimized in such a system. (83)

The images shown above are atomic force microscopy images of a bottle brush copolymer prepared by ARGET ATRP in miniemulsion with ascorbic acid as the reducing agent at an ascorbic acid to Cu(II) ratio of 1:4. They images clearly show that almost no crosslinking occurred and that no homopolymer was formed in the reaction.


(67) "Controlled/\"Living\" Radical Polymerization Applied to Water-Borne Systems," Gaynor, S. G.; Qiu, J.; Matyjaszewski, K. Macromolecules 1998, 31, 5951-5954.

(68) "Water-Borne Block and Statistical Copolymers Synthesized Using Atom Transfer Radical Polymerization;" Matyjaszewski, K.; Shipp, D. A.; Qiu, J.; Gaynor, S. G. Macromolecules 2000, 33, 2296-2298.

(69) "Reverse Atom Transfer Radical Polymerization in Miniemulsion;" Li, M.; Matyjaszewski, K. Macromolecules 2003, 36, 6028-6035.

(70) "Further progress in atom transfer radical polymerizations conducted in a waterborne system," Li, M.; Matyjaszewski, K. Journal of Polymer Science, Part A: Polymer Chemistry 2003, 41, 3606-3614.

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

(72) "Preparation of Linear and Star-Shaped Block Copolymers by ATRP Using Simultaneous Reverse and Normal Initiation Process in Bulk and Miniemulsion;" Li, M.; Jahed, N. M.; Min, K.; Matyjaszewski, K. Macromolecules 2004, 37, 2434-2441.

(73) "ATRP in Waterborne Miniemulsion via a Simultaneous Reverse and Normal Initiation Process;" Li, M.; Min, K.; Matyjaszewski, K. Macromolecules 2004, 37, 2106-2112.

(74) "Preparation of Homopolymers and Block Copolymers in Miniemulsion by ATRP Using Activators Generated by Electron Transfer (AGET)." Min, K., Gao, H., Matyjaszewski, K.: J. Am. Chem. Soc., 2005 127: 3825-3830.

(75) "AGET ATRP in the presence of air in miniemulsion and in bulk," Min, K.; Jakubowski, W.; Matyjaszewski, K. Macromolecular Rapid Communications 2006, 27, 594-598.

(76) "Atom Transfer Radical Polymerization in Microemulsion." Min, K.; Matyjaszewski, K. Macromolecules 2005, 38, 8131-8134.

(77) "Preparation of gradient copolymers via ATRP in miniemulsion. II. Forced gradient;" Min, K.; Oh, J. K.; Matyjaszewski, K. Journal of Polymer Science, Part A: Polymer Chemistry 2007, 45, 1413-1423.

(78) "Development of an ab Initio Emulsion Atom Transfer Radical Polymerization: From Microemulsion to Emulsion" Min, K.; Gao, H.; Matyjaszewski, K. J. Am. Chem. Soc. 2006, 128, 10521-10526.

(79) "Atom transfer radical dispersion polymerization of styrene in ethanol," Ke Min and Krzysztof Matyjaszewski ACS Polymer Preprints 2007, 48(2),260-261.

(80) "Preparation of Nanoparticles of Well-Controlled Water-Soluble Homopolymers and Block Copolymers Using an Inverse Miniemulsion ATRP," Oh, J. K.; Perineau, F.; Matyjaszewski, K. Macromolecules 2006, 39, 8003-8010.

(81) "AGET ATRP in miniemulsion from functionalized CdE (E=S,Se) q-dot's surfaces," Esteves, A. C. C.; Bombalski, L.; Cusick, B.; Barros-Timmons, A.; Matyjaszewski, K.; Trindade, T. Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) 2005, 46, 134-135.

(82) "Studies on suspension and emulsion: part CCLXXXI. Compartmentalization in atom transfer radical polymerization (ATRP) in dispersed systems," Kagawa, Y.; Zetterlund, P. B.; Minami, H.; Okubo, M. Macromolecular Theory and Simulations 2006, 15, 608-613.

(83) "High Yield Synthesis of Molecular Brushes via ATRP in Miniemulsion," Min, K.; Yu, S.; Lee, H.-i.; Mueller, L.; Sheiko, S. S.; Matyjaszewski, K. Macromolecules 2007, 40 6557 " 6563.

Click to go to section 04: Procedures for Initiation