WO2007025310A1 - Polymerization process with catalyst reactivation - Google Patents

Polymerization process with catalyst reactivation Download PDF

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Publication number
WO2007025310A1
WO2007025310A1 PCT/US2006/033792 US2006033792W WO2007025310A1 WO 2007025310 A1 WO2007025310 A1 WO 2007025310A1 US 2006033792 W US2006033792 W US 2006033792W WO 2007025310 A1 WO2007025310 A1 WO 2007025310A1
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Prior art keywords
polymerization
transition metal
polymerization process
atrp
reaction
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PCT/US2006/033792
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French (fr)
Inventor
Krzysztof Matyjaszewski
Wojciech Jakubowski
James Spanswick
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Carnegie Mellon University
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Priority to US11/990,841 priority Critical patent/US7893173B2/en
Priority to EP06813937A priority patent/EP1943278B1/en
Priority to CN2006800404028A priority patent/CN101379091B/en
Priority to DE602006017416T priority patent/DE602006017416D1/en
Publication of WO2007025310A1 publication Critical patent/WO2007025310A1/en
Priority to US12/949,466 priority patent/US20110065875A1/en

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2/00—Processes of polymerisation
    • C08F2/38—Polymerisation using regulators, e.g. chain terminating agents, e.g. telomerisation
    • C08F2/40—Polymerisation using regulators, e.g. chain terminating agents, e.g. telomerisation using retarding agents
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
    • C08F212/02—Monomers containing only one unsaturated aliphatic radical
    • C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
    • C08F212/06—Hydrocarbons
    • C08F212/08—Styrene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
    • C08F212/02—Monomers containing only one unsaturated aliphatic radical
    • C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
    • C08F212/06—Hydrocarbons
    • C08F212/08—Styrene
    • C08F212/10—Styrene with nitriles
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F4/00—Polymerisation catalysts
    • C08F4/04—Azo-compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F4/00—Polymerisation catalysts
    • C08F4/40—Redox systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Definitions

  • the present invention is directed to an atom transfer radical polymerization process where the catalyst in the activator state, or catalytic transfer agent, is continuously regenerated.
  • CRP controlled radical polymerization
  • CRP processes typically, but not necessarily, comprise a relatively low stationary concentration of propagating chain ends in relation to dormant chain ends.
  • a dormant chain end comprises a transferable atom or group.
  • the dormant chain end may be converted to a propagating chain end by loss of the transferable atom or group to the transition metal complex in the lower oxidation state.
  • the low concentration of propagating chain ends present during the polymerization process reduces the probability of bimolecular termination reactions, leading to radical polymerization processes that behave as a "living" polymerization process.
  • the ATRP equilibrium (characterized by KATRP) most frequently involves homolytic cleavage of an alkyl (pseudo)halide bond R-X by a transition metal complex activator Mf /L which (reversibly) generates an active propagating alkyl radical R * and the corresponding higher oxidation state metal halide deactivator Mf +1 XfL in a redox reaction Scheme 1.
  • the active R" may then propagate with a vinyl monomer (M), be deactivated in this equilibrium reaction by Mt n+1 X/L, or terminate by either coupling or disproportionation with another R".
  • Mt n+1 X/L vinyl monomer
  • Such termination results in an increase in the amount of deactivator, Mt n+1 X/L, by two equivalents resulting in an increase in concentration of dormant species as a result of the persistent radical effect.
  • polymer refers to a macromolecule formed by the chemical union of monomers, typically rive or more monomers.
  • polymer includes homopolymers and copolymers including random copolymers, statistical copolymers, alternating copolymers, gradient copolymers, periodic copolymers, telechelic polymers and polymers of any topology or architecture including block copolymers, graft polymers, star polymers, bottle-brush polymers, comb polymers, branched or hyperbranched polymers, and such polymers tethered to particle surfaces or flat surfaces as well as other polymer structures.
  • ATRP is the most frequently used CRP technique with a significant commercial potential for many specialty materials including coatings, sealants, adhesives, dispersants but also materials for health and beauty products, electronics and biomedical applications.
  • the most frequently used ATRP process comprises a reversible halogen atom transfer catalyzed by redox active transition metal compounds, most frequently copper based.
  • ATRP transition metal catalysts typically comprise a transition metal complexed with a ligand.
  • radically polymerizable monomers are polymerized in the presence of a transition metal catalyst.
  • transition metal catalyst participates in a redox reaction with at least one of an ATRP initiator and a dormant polymer chain, see Scheme 1.
  • Suitable transition metal catalysts comprise a transition metal and a ligand coordinated to the transition metal.
  • the transition metal catalyst participates in a reversible redox reaction with at least one of an ATRP initiator and a dormant polymer chain.
  • Suitable transition metal catalysts comprise a transition metal and, optionally, at least one ligand coordinated to the transition metal. The activity of the transition metal catalyst depends on the composition of the transition metal and the ligand.
  • the transition metal To function as an ATRP transition metal catalyst, the transition metal must have at least two readily accessible oxidation states separated by one electron, a higher oxidation state and a lower oxidation state.
  • the reversible redox reaction results in the transition metal catalyst cycling between the higher oxidation state (the "deactivator state”) and a lower oxidation state (the “activator state”) while the polymer chains cycle between having propagating chain ends and dormant chain ends.
  • the transition metal is one of copper, iron, rhodium, nickel, cobalt, palladium, molybdenum, manganese, rhenium, or ruthenium.
  • the transition metal catalyst comprises a copper halide, and preferably the copper halide is one of Cu(I)Br or
  • Living/controlled polymerizations typically, but not necessarily, comprise a relatively low stationary concentration of polymers comprising propagating chain ends in relation to polymers having dormant chain ends.
  • the chain end comprises the transferable atom or group.
  • the dormant chain end may be converted to a propagating chain F" end by transfer of the transferable atom or group to the transition metal catalyst.
  • the description of the mechanism of an ATRP is provided for explanation and is not intended to limit the invention.
  • the disclosed mechanism is generally accepted, but different transition metal catalyst may result in different mechanisms.
  • the ligand affects the structure of the catalyst, the solubilizing effect, and 5 catalyst activity. See Catalyst Development www.chem.cmuedu/groups/maty/about/research/OS.html, hereby incorporated by reference.
  • ATRP is considered to be one of the most successful CRP and has been thoroughly described in a series of co-assigned U.S Patents and Applications, such as U. S. Patent Nos. 5,763,548; 5,807,937; 5,789,487; 5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882;
  • transition metal ligand combinations 20 transition metal ligand combinations and the manner in which an ATRP equilibrium can be adjusted for more or less reactive monomers.
  • Embodiments of ATRP processes provide advantages over other CRP processes, including the availability wide variety of initiators and macroinitiators, including wafers, inorganic colloids, glass, paper, and bio-active molecules including proteins, DNA, carbohydrates and many
  • 25 commercial polymers may be simply synthesized as initiators; many polymers produced by ATRP allow facile functionalization or transformation of the end groups by replacing terminal halogens with azides, amines, phosphines and other functionalities via nucleophilic substitution, radical addition or other radical combination reactions; an abundance of monomers are polymerizable by ATRP.
  • Such monomers include, but are not limited to, styrenics, (meth)acrylates, acrylonitrile,
  • ATRP acrylamides, vinyl chlorides, and other monomers.
  • Embodiments of ATRP allow the production of macromolecules with complex topology such as stars, combs and dendrimers, coupled with the ability to control composition and hence functionality in block, gradient, periodic copolymers etc. and even control polymer tacticity.
  • ATRP may be carried out in bulk, or in the presence of organic solvents or in water under homogeneous or heterogeneous conditions, in ionic liquids, and in supercritical CO 2 . .
  • transition metal catalyst in an ATRP medium may be desired.
  • Several methods have been developed to remove or reduce the amount of transition metals in the process, but these processes may add additional cost to the preparation of polymers by ATRP.
  • Such methods include performing an ATRP process with highly active catalyst that may require a lower concentration of catalyst to maintain the desired polymerization rate, for example, CuBr complexed by Me 6 TREN is ⁇ 10,000 more active than CuBr complexed by bipyridine ligands; immobilizing the catalysts on solids such as a hybrid catalyst system comprising both immobilized catalyst complexes interacting with small concentrations of soluble catalysts ( ⁇ 10-20 ppm); and several post polymerization methods developed to recover and regenerate catalysts, including separating the catalyst by filtration, adsorption, precipitation or extraction.
  • CuBr/PMDETA complex may be oxidized to Cu(II) species by exposure to air and quantitatively extracted from toluene to water, resulting, in some cases, with less than 1 ppm of catalyst remaining in the polymer.
  • concentration of catalyst in the active polymerization media while maintaining polymer reaction rate and retaining control over MW and PDI.
  • the most attractive route may be just a simple decrease of the amount of the catalyst, providing that it has a sufficient reactivity.
  • ATRP processes comprising CuBr/Me 6 TREN complexes may be carried out at room temperature with much lower concentrations of the copper based catalyst.
  • the amount of transition metal catalyst such a Cu(I) may not simply be reduced 10,000 fold. Radical termination reactions result in an increase in the concentration of the transition metal catalyst in the deactivator state and irreversible consumption of the catalyst activators.
  • the polymerization may stop if the amount of Cu(I) present in the reaction is below 10% of the initiator (as, 1 ⁇ 10% of chains are terminated).
  • the amount of terminated chains depends on the concentration of propagating radicals and rate constant of termination according to equation 1, which describes the number of terminated chains (or loss of Cu(I) activator) in an ATRP.
  • Equation 2 The ATRP rate law (Equation 2) indicates that the polymerization rate depends on the ratio of Cu(I) to X-Cu(II) concentration but does NOT depend on the absolute concentration of copper complexes. Thus, in principle, the amount of copper may be reduced without affecting polymerization rate as long as the ratio of activator to deactivator is maintained.
  • Some amount of the deactivation species (i.e. X-Cu(II)) is also needed in the system for a well-controlled polymerization because molecular weight distribution and initial molecular weight depend on the ratio of propagation and deactivation rate constants and concentration of deactivator, according to Equation 4.
  • RAFT polymerization process termination reactions are suppressed through the addition of a suitable thiocarbonylthio compound, also known as a dithioester, to an otherwise conventional free radical polymerization; i.e. there is a continuous slow generation of radicals by decomposition of a standard radical initiator in order to drive the reaction forward.
  • Control in such a RAFT process is thought to be achieved through a degenerative chain transfer mechanism in which a propagating radical reacts with the thiocarbonylthio compound to produce an intermediate radical species. This process decreases the instantaneous number of free radicals available for termination reactions that require two free radicals.
  • RAFT (co)polymerization reactions have been discussed in U. S. Patents, 6,153,705; 6,380,355; 6,642,318 and 6,855,840.
  • Polymerization processes of the present invention comprise low catalyst concentration.
  • Embodiments include a polymerization process comprising polymerizing free radically (co)polymerizable monomers in a polymerization medium comprising one or more 5 radically (co)polymerizable monomers, a transition metal catalyst complex capable of participating in a one electron redox reaction with an ATRP initiator; a free radical initiator; and an ATRP initiator; (wherein the concentration of transition metal catalyst complex in the polymerization medium is less than 100 ppm).
  • Further embodiments include a polymerization process, comprising polymerizing one or more radically (co)polymerizable monomers in the presence of at least one 10 transition metal catalyst complex; and an ATRP initiator;; and a reducing agent; wherein the transition metal catalyst complex is present at less than 10 "3 mole compared to the moles of radically transferable atoms or groups present on the ATRP initiator.
  • Figure 2 is a graph of the molecular weight and polydispersity of a polystryrene formed as a 20 function of conversion formed in the embodiment of Figure 1 ;
  • Figure 3 is a graph showing the evolution of molecular weight by GPC traces during the embodiment of the polymerization process of Figure 1 ;
  • Figure 5 is a graph of the evolution of molecular weight by GPC traces during the embodiment of the polymerization process of Figure 4;
  • Figure 6 is a graph of the GPC curves showing the presence of a small amount of terminated polymer chains which were initiated by radicals produced from thermal decomposition of AIBN at beginning of activation procedure before being overwhelmed by the bulk of the polymer prepared by CRP;
  • Figure 7 is a graph of showing the temperature dependence of the conditional stability constant of Cu 11 L ATRP catalysts with various ligands including TPMA, Me 6 TREN, and PMDETA;
  • Figure 9 is a graph of data from a Predici computer simulation of first order kinetic plot for embodiments of ICAR ATRP processes comprising styrene, various ligands including TPMA 5 PMDETA, or bpy, and 50 ppm of Cu;
  • Figure 10 is a graph of data from a Predici computer simulation of the molecular weight and polydisperisty evolution in embodiments of ICAR ATRP processes comprising styrene, various ligands including TPMA, PMDETA, or bpy, and 50 ppm of Cu;
  • Figure 11 is graph of the kinetic data from Predici computer simulations for embodiments of ICAR ATRP processes comprising styrene, various ligands including TPMA, PMDETA, or bpy, 50 ppm of Cu,and AIBN as the free radical initiator;
  • Figure 15 are graphs of the kinetic data of an embodiment of a CuCl 2 /TPMA mediated ARGET ATRP of BA, variable N 2 H 4 reducing agent.
  • [BA]o:[EtBrro]o:[CuCl 2 ]o:[TPMA]o:[N 2 H4]o 200 : 1.28 : 0.01 : 0.1 : 0.05 or 0.1;
  • [BA] 0 5.88 M; 60 0 C, 20% anisole by volume;
  • Figure 24 is graphs of the kinetic data, molecular weight and molecular weight distribution as a function of conversion for ARGET ATRP of styrene and acrylonitrile with 30
  • Figure 25 is graphs of the GPC traces for samples taken during the preparation of high molecular weight polyacrylonitrile.
  • the present invention is directed to a polymerization process that regenerate the transition metal in the activator state.
  • Embodiments could be considered to provide a new mechanism for Controlled Radical Polymerization.
  • Embodiments of the ATRP polymerization process comprise a transition metal complex catalyzed halogen transfer polymerization where the transition metal complex is continuously reactivated by reaction with radicals.
  • the radicals may be formed by the decomposition of a free radical initiator or by self initiation reactions.
  • the present invention could tie considered to be a new mechanism for continuous reactivation a transition metal complex catalyzed (pseudo)halogen transfer polymerization where the transition metal complex is continuously reactivated by reaction with formed radicals.
  • This mechanism comprises initiators for continuous activator regeneration (“ICAR”), see Scheme 2.
  • Embodiments of the present invention provide control over radical reactions that may be considered conceptually to combine aspects of ATRP and RAFT.
  • RAFT a chain transfer agent is employed to reversibly transfer a labile dithioester end group among propagating radical chains.
  • ICAR ATRP process may be considered to be similar, wherein the role ' of the dithioester transfer agent in RAFT is replaced in ICAR by the initiator or growing polymer chain end in the presence of low concentrations, ppm amounts, of an ATRP catalyst complex and there is a continuous slow generation of radicals by decomposition of a standard radical initiator in order to drive the reaction forward.
  • ATRP process over a RAFT polymerization
  • monofunctional and multifunctional ATRP initiators as disclosed in other patents and patent applications with Matyjaszewski as inventor
  • the exchange reaction in an ATRP process is WSk If with a small molecule, (Mt(II)X) 5 not with a polymeric chain end as in RAFT; and the dormant chain end can be readily modified to provide the desired tele-fiinctional groups.
  • ATRP process may comprise any radically transferable atom or group and 5 transition metal such as, for example, environmentally friendly iron complexes.
  • Embodiments of the polymerization process of the present invention are directed towards polymerizing free radically (co)polymerizable monomers in the presence of a polymerization medium comprising at least one transition metal catalyst, or precursor of the active catalytic species, at least one of a free radical initiator and a reducing agent, and an ATRP initiator
  • ATRP initiators include molecules comprising at least one radically transferable atom or group, including small molecule initiators, polymeric initiators, and polymers in the polymerization medium comprising a dormant chain end that may be reinitiated or reactivated.
  • the polymerization medium may initially comprise a free radical initiator or a reducing agent or the free radical initiator or reducing agent may be added after initiation of the polymerization. After initiation of the
  • the ATRP process comprises polymerizing free radically polymerizable monomers in a polymerization medium comprising radically polymerizable monomers, a transition metal catalyst, an ATRP initiator, a free radical initiator, wherein the
  • the polymerization medium may further comprise a solvent, or water forming either a homogeneous or heterogeneous polymerization medium.
  • the free radical initiator may be any molecule that may be induced to form free radicals, such as a molecule that forms radicals by thermal, photoiniated or other decomposition process. Free radical initiators include peroxides, azo
  • free radical initiators include acyl peroxides, acyl peroxides, benzoyl peroxides, alkyl peroxides, cumyl peroxides, tributyl peroxides, hydroperoxides, cumyl hydroperoxide, tibutyl hydroperoxide, peresters, tibutyl perbenzoate, akyl sulfonyl peroxides, dialkyl peroxydicarbonates, diperoxyketals, ketone peroxides, 2, 2' azobisisobutyronitrile ("AIBN”), 2, 2' azobis (2,4- dimethyl pertanenitrile), and 1, 1' azobis
  • the monomer of the polymerization process may also act as the free radical initiator or reducing agent in embodiments of low catalyst ATRP processes.
  • Free radical initiators decompose to form radicals at different rates based on the decomposition n > stimulus, such as temperature.
  • the free radical initiator may be soluble in the polymerization medium.
  • the free radical initiator is selected such that at the - temperature of the polymerization reaction the free radical initiator decomposes at a rate that is substantially the same as the rate of termination in the polymerization.
  • the free radical initiator forms free radicals, or the equivalent of free radicals in the reaction medium. See Table 1 for half lives of free radical initiators at various temperatures.
  • 10 b t 1 A values are for benezene or toluene solutions of the initiators.
  • the system therefore behaves essentially as a conventional RP with similar kinetics but with the ATRP initiator acting as a combination "transfer agent" - initiator present at 50 ppm or less, in some polymerization processes less than 10 ppm, Mt(II) or Mt(I) as a transfer catalyst.
  • the polymerization process comprises polymerizing free radically polymerizable monomers in a polymerization medium comprising radically polymerizable monomers, a transition metal catalyst, an ATRP initiator, and a reducing agent.
  • the polymerization medium may further comprise a solvent, or water, hi such an embodiment, the transition metal complex may be initially in the oxidatively stable higher oxidation state, such as Cu n , and reduced
  • the reducing agent may be any reducing agent capable of reducing the transition metal catalyst from a higher oxidation state to a lower oxidation state, thereby reforming the catalyst activator state.
  • reducing agents include, but are not limited to, SO 2 , sulfites,
  • the reducing agent may further be capable of complexing with the transition metal, thereby becoming a ligand.
  • the reducing agent does not produce an acid after reducing the transition metal complex from the higher oxidation state to the lower oxidation state, such as hydrazine and phenyl hydrazine.
  • the products of oxidation are either nitrogen gas or organic in nature, compared to previous exemplified ARGET systems which predominately employed metal reducing agents for the reduction process in bulk media.
  • the reducing agent may also scavenge oxidants in the polymerization medium.
  • the amount of reducing agent will be determined by the total concentration of the oxidants in the polymerization medium, if any; the amount of termination reactions in the polymerization; and the desired rate of the redox reaction.
  • the reducing agent will be present in the polymerization medium such that the molar ratio of reducing agent to ATRP initiator is less than 0.1, or in certain embodiments, less than 0.05.
  • the stability of the complexes depends very strongly upon the basicity of the ligands.
  • a ligand that is not very basic may be advantageous.
  • the basicity/nucleophilicity of the reducing agent such as N 2 H 4 and PhNHNH 2 may be an issue, particularly in the ARGET ATRP of styrene.
  • the alkyl halide chain end may react with bases resulting in both in a loss of functionality and a consumption of reducing agent.
  • the dynamics of the redox process between the Cu complexes and reducing agents (and ultimately attainable control) will likely depend upon the ligand used to form the complex with the catalyst (and value of KA TRP ) that is employed.
  • the reducing agent may be select for a particular polymerization process such that at the polymerization temperature the reducing agent reduces a sufficient quantity of transition metal catalyst in the higher oxidation state to transition metal catalyst in the lower oxidation state to substantially maintain the polymerization rate. For example, at the polymerization temperature the reducing agent reduces the additional amount of transition metal catalyst in the higher oxidation state to substantially maintain the ratio of transition metal catalyst in the higher oxidation state to transition metal catalyst in the lower oxidation state. To substantially maintain such ratio means that the ratio does not vary greater than 20% after initiation of the polymerization.
  • the concentration of the transition metal catalyst must be present in the polymerization medium and may be less than 100 ppm, less than 50 ppm, or even less than 10 ppm.
  • the reducing agents do not initiate a new polymer chain after reducing the transition metal catalyst in the higher oxidation state.
  • the atom or group transfer transition metal complex may be an efficient deactivator, i.e. efficiently donate the (X) atom or group to the growing active chain.
  • the process will be initially exemplified by the use of a very small amount of Cu, ⁇ 10 ppm complexed with a ligand that forms an active ATRP catalyst and is also an effective deactivator, such as tris[2-(dimethylamino)ethyl]amine (“Me 6 TREN”), tris[(2- pyridyl)methyl]amine (“TPMA”), and H 6 TREN.
  • ligands forming less active catalysts such as N,N, ⁇ N",N"-pentamemyldiemyleneMamine (PMDETA), 4,4'-di-(5- nonyl)-2,2'-dipyridyl (dNbpy) andN-(n-octyl)-2-pyridylmethanimine.
  • PMDETA N,N, ⁇ N",N"-pentamemyldiemyleneMamine
  • dNbpy 4,4'-di-(5- nonyl)-2,2'-dipyridyl
  • dNbpy 4,4'-di-(5- nonyl)-2,2'-dipyridyl
  • N-(n-octyl)-2-pyridylmethanimine N,N, ⁇ N",N"-pentamemyldiemyleneMamine
  • the use of low concentrations of catalyst in an ATRP reaction reduces the impact of catalyst based side reactions that limited the ability to prepare high molecular weight materials in some embodiments.
  • One possible explanation of this limitation may be that the radicals interacted with the catalyst complex.
  • the polystyryl radical may be oxidized to a cation by the Cu species, thereby limiting formation of well-defined high molecular weight polystyrenes by
  • excess ligand may be added to the polymerization. Excess ligand is present when the quantity of ligand present in the polymerization medium exceeds the amount of ligand required to complex with the transition metal to form the transition metal catalyst.
  • the amount of excess ligand, or ligand surrogate such as free amine may be as much as ten times the require amount of ligand.
  • the transition metal catalyst may complex with the monomer.
  • the ligand may complex with the monomer such as styrene with other components of the polymerization medium. For example, if tin is used as a reducing agent, sufficient ligand should be added to allow for complex formation with both the reducing agent and the transition metal of the catalyst.
  • the present invention is also directed to polymers comprising high molecular weight.
  • Embodiments include polystyrene comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000 and polyacrylonitrile comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000.
  • the initiator is of the formula R-X, where X is the radically transferable atom or group. After polymerization, a typical polymer formed by ATRP will have the R group on one end and the X group on the other end.
  • the definitions of R and X are defined in United States patents that are incorporated by reference.
  • the free radical initiator or the reducing agent controls the rate of polymerization by regenerating the activator catalyst complex while allowing sufficient amounts of the catalyst complex efficiently deactivates the growing chains to remain, hi such embodiments, controlled synthesis (M w /M n ⁇ 1.2) of polystyrene and poly(alkyl (meth)acrylates) can be performed with catalyst concentrations between 1 and 50 ppm. At such concentrations, catalyst removal or recycling may be unnecessary for many industrial applications, since the color of products are not significantly affected by the such low concentrations of catalysts.
  • Embodiments of the ICAR ATRP and ARGET ATRP process comprise initial use of the oxidatively stable catalyst precursors that can be prepared, stored, and shipped for use in ATRP.
  • the transition metal complex in the activator state may be generated in situ from free radical initiators, a reducing agent, an in situ formed peroxide in the case of acrylate polymerization, or a combination thereof [Acar, A. E.; Yagci, M. B.; Mathias, L. J.
  • the oxidatively stable transition metal catalyst for example Cu 11 or Fe 11 .
  • the quantity of ligand present in the polymerization medium exceeds the amount of ligand required to complex with the transition metal to form the transition metal catalyst.
  • One - si ⁇ Hed in the art would understand ' ⁇ he coordination characteristics of each transition metal complex.
  • the amount of excess ligand, or ligand surrogate such as free amine may be as much as ten times the require amount of ligand. In some polymerization processes lower amounts of ligand may lead to polymers with higher polydispersities. At reduced quantities of ligand the transition metal catalyst may complex with the monomer.
  • the ligand may complex with the monomer such as styrene with other components of the polymerization medium.
  • the monomer such as styrene
  • tin is used as a reducing agent
  • sufficient ligand should be added to allow for complex formation with both the reducing agent and the transition metal of the catalyst.
  • the present invention is also directed to polymers comprising high molecular weight.
  • Embodiments include polystyrene comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000 and polyacrylonitrile comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000.
  • the initiator is of the formula R-X, where X is the radically transferable atom or group. After polymerization, a typical polymer formed by ATRP will have the R group on one end and the X group on the other end.
  • the definitions of R and X are defined in United States patents that are incorporated by reference.
  • the free radical initiator or the reducing agent controls the rate of polymerization by regenerating the activator catalyst complex while allowing sufficient amounts of the catalyst complex efficiently deactivates the growing chains to remain.
  • controlled synthesis M w /M ⁇ ⁇ 1.2
  • catalyst concentrations between 1 and 50 ppm. At such concentrations, catalyst removal or recycling may be unnecessary for many industrial applications, since the color of products are not significantly affected by the such low concentrations of catalysts.
  • Embodiments of the ICAR ATRP and ARGET ATRP process comprise initial use of the oxidatively stable catalyst precursors that can be prepared, stored, and shipped for use in ATRP.
  • the transition metal complex in the activator state may be generated in situ from free radical initiators, a reducing agent, an in situ formed peroxide in the case of acrylate polymerization, or a combination thereof [Acar, A. E.; Yagci, M. B.; Mathias, L. J.
  • the free radical initiator slowly and continuously decomposes to prevent the build up of the persistent .radical, or higher oxidation state transition " metaTcbmpTex, formed by termination reactions.
  • This decomposition of the free radical initiator may be used to maintain a substantially constant rate of polymerization; i.e. keep the ratio of transition metal in the low oxidation state (activator state) to transition metal in the higher oxidation state (deactivator state) relatively constant.
  • the free radical initiator or reducing agent may be used to increase or decrease the polymerization rate.
  • the ATRP polymerization process comprises two different free radical initiators.
  • one free radical initiator may quickly activate the catalyst complex to ensure rapid initiation of the polymerization and the other may slowly act throughout the reaction to reactivate the complex, for example.
  • the self-formed free radical initiator such as present in nitroxide mediated polymerizations with styrene and TEMPO may also be used.
  • Free radical initiators may be used in coordination with reducing agents, also.
  • the following examples exemplify the broad applicability of this novel CRP. In order to obtain consistent kinetics the reagents used in most of the examples were purified however as detailed in some examples this is not a requirement and the reaction can be conducted directly with industrial grade monomers and in the presence of low concentrations of oxygen.
  • Styrene (St) Aldrich, 99%
  • raBA n-butyl acrylate
  • Me 6 TREN Tris(2-(dimethylamino)ethyl)amine
  • Ethyl 2-bromoisobutyrate (EtBrIB) (Acros, 98%), copper(II) chloride (Acros, 99%), tin(II) 2-ethylhexanoate (Sn(EH)f) (Aldrich), anisole (Aldrich, 99%) were used as received.
  • Conversion of styrene were determined using a Shimadzu GC 14-A gas chromatograph equipped with a FID detector using a J&W Scientific 30 m DB WAX Megabore column and anisole as an internal standard. Injector and detector temperatures were kept constant at 250 0 C. Analysis was carried out is ⁇ thermally " at 60 0 C for 2 min followed by an increase of temperature to 140 0 C at a heating rate of 40 °C/min and holding at 140 0 C for 2 min. Conversion was calculated by detecting the decrease of the monomer peak area relative to the peak areas of the standards.
  • Table 2 is shows typical ratio's of reagents used various ATRP processes and in a RAFT polymerization process. Table 2. Typical molar ratios of reagents used in various ATRP processes and a RAFT process
  • AGET ATRP 200 1 0.2 0.2 0.18 -
  • ARGET ATRP 200 1 ⁇ 0.01 0.1 0.1 -
  • transition metal complex is typically comprised in ARGET ATRP and ICAR ATRP processes than the other listed ATRP process. While similar reagents are used in simultaneous reverse and normal initiation ("SR&NI") ATRP as in ICAR ATRP, ICAR ATRP allows the advantage of the use of much lower concentrations of transition metal catalysts. For more description of SR&NI ATRP, see United States Patent No. 6,759,491.
  • Example 1 General procedure for Activators ReGenerated by Electron Transfer (“ARGET”) ATRP of styrene (with number average degree of polymerization (DP n ) of 200 and at 50 ppm of Cu).
  • ARGET Electron Transfer
  • Styrene (5.0 ml, 44 mmol) and anisole (1.5 ml) were added to open Schlenk flask.
  • CuCl 2 (0.29 mg, 0.22x10 '2 mmol)/Me 6 TREN (0.57 ⁇ l, 0.22x10 '2 mmol) complex in anisole (0.5 ml) was added.
  • Mixture was stirred for 10 minutes and then solution Of Sn(EH) 2 (7.0 ⁇ l, 2.2x10 "2 mmol) and Me 6 TREN (1.7 ⁇ l, 0.7x10 "2 mmol) in anisole (0.5 ml) was added.
  • Sn(EH) 2 7.0 ⁇ l, 2.2x10 "2 mmol
  • Me 6 TREN 1.7 ⁇ l, 0.7x10 "2 mmol
  • Example 3 Preparation of block copolymers: PS-PnBA and PnBA-PS An embodiment of ARGET ATRP was used for preparation of block copolymers.
  • Copolymers PS-PnBA styrene and PwBA-PS were synthesized using previously specified conditions for polymerization of styrene (WJ-03-27) and n-butyl acrylate (WJ-03-53) in the presence of reducing agent Sn(EH) 2 .
  • the conditions and results for all the reactions are presented in Table 3.
  • the polystyrene macroinitiator was prepared (WJ-03-55) by polymerization of styrene in the presence of 15 ppm of Cu.
  • WJ-03-27 a well controlled polymerization was observed demonstrating that results are reproducible.
  • WJ-03-05 200 1 0.1 0.1 0.1 500 1020 67 14000 17000 , 1.12j : i i
  • WJ-03-08 200 1 0.01 0.1 0.1 50 460 59 12300 12700 ; l. ⁇ ;
  • Figure 1 is a kinetic plot of data obtained during the ATRP polymerization process comprising polymerizing styrene in the presence of 15 ppm of a copper/Me 6 TREN catalyst and a reducing agent Sn(EH) 2 , and an ATRP initiator, EtBrIB, wherein the SN(EH) 2 corresponds to 10% of the ATRP initiator (Table 3, entry WJ-03-27).
  • Figure 1 shows that the rate of polymerization was constant with only a slight decrease after 500 minutes.
  • the molecular weight and PDl curves in Figure 2 indicates excellent control over the polymerization process.
  • Figure 3 shows smooth shift of entire molecular weight distribution towards higher molecular weights.
  • WJ-03-06 200 1 0.01 0.01 0.1 50 1000 44 9200 oligomers
  • Lewis acids may also destroy the active Cu/Me ⁇ TREN species by direct complexation with the ligand.
  • a small excess of ligand, or ligand surrogate, should be used.
  • Cu(II) species can be still regenerated to Cu(I) state by the action of a reducing agent, such as Sn(EH) 2 .
  • a reducing agent such as Sn(EH) 2 .
  • WJ-03-08 a 200 1 0.01 0.1 0.1 50 460 59 12300 12700 i;.ii
  • the amount of transition metal catalyst complex species in ATRP can be reduced down to a few ppm without losing control of polymerization, if an appropriate amount of reducing
  • Reducing agent may also be involved in atom transfer process (this would generate dual catalytic system, e.g. bimetallic catalysis), however, the sufficient amount of quickly deactivation species (i.e., X-Cu(II) ) is needed for control.
  • the concentration of reducing agent should account for [Cu(II)] sufficient amount of transition metal species to be activated, amount of air or some other radical traps present in the system, and the amount of terminated chains.
  • Sn(EH) 2 species are used as the reducing agent this concentration is ⁇ 50 ppm but depends on the particular reaction conditions.
  • the minimal amount of active ATRP catalyst also depends on the particular system, for styrene polymerization the transition metal catalyst may be to a few ppm, significantly lower than in any other reported ATRP process.
  • the examples of ARGET ATRP detailed herein demonstrate a significant improvement over traditional ATRP, since it can be carried out with drastically reduced amount of Cu species and FDA approved Sn(EH) 2 or other environmentally sound reducing agents (sugars, ascorbic acid).
  • Example 4 Development of Initiators for Continuous Activator Regeneration (ICAR) ATRP.
  • IIR Continuous Activator Regeneration
  • the polymerization medium comprises a significantly lower catalyst concentration, for example many times less than the total number of polymer chains formed in the polymerization, in order that the reaction can continue the radical initiator has to continuously generate radicals at a rate comparable to radicals consumed by termination reactions.
  • the radicals can be formed by any reaction mechanisms. Indeed, as shown below, in the case of styrene polymerization this is the mechanism that actually operates, but it was analysis of the above results that led to this unexpected recognition.
  • the relatively uncontrolled character of the polymerization could be due to too low a concentration of ligand, which allows the copper to be complexed by monomer leading to loss of active metal catalyst complex (Cu(I)/ligand), as the ligand was involved in side reactions. Consequently, in next two reactions (WJ-03-36, 37) amount of ligand was increased.
  • Styrene was polymerized in the presence of 50 and 5 ppm of Cu species respectively.
  • CuCl 2 ZMe 6 TREN was used as catalyst complex and ratio of In/Cu/ligand was 1/0.01/0.1 and 1/0.001/0.1.
  • ATRP with low catalyst concentration was performed without the presence of added reducing agent.
  • the regeneration of Cu(I) species which can be lost due to termination 0 reactions (e.g. radical coupling), was performed by generation of radicals by thermal decomposition of AEBN (polymerization at 60 0 C). In this case, radicals are produced slowly through whole reaction time and are able to reduce Cu(II) to Cu(I), so that active complex can be regenerated.
  • the conditions and results for all the reactions are presented in Table 9. 1 P
  • WJ-03-35 1 15 0.003 0.003 0.01 - 4570 0.19 3560 37200 1.40
  • WJ-03-38 15 0.003 0.1 0.01 - 7200 0.26 5200 3800 1.51 WJ-03-39 15 0.003 0.1 0.05 - 7200 0.28 5500 5100 1.44
  • WJ-03-62 1 50 0.01 0.01 0.1 2760 0.44 8700 7900 1.12
  • Cu(I) is generated at the beginning stage of the reaction and high molecular weight polymers are obtained, since there is not enough Cu(II) in the system to deactivate growing chains, (ii) Cu(I) is more soluble than Cu(II) with Me 6 TREN ligand, thus during the transfer of active complex froni preparation flask to the Schenk flask some of Cu(II) species which are not fully soluble in the transfer medium are lost. Therefore the real value of Cu species in the reaction
  • 25 medium can be different, higher when Cu(I) is used.
  • Example 6 Synthesis of a PSt-ft-PnBA block Copolymer by ICAR and ARGET ATRP.
  • a clean shift in molecular weight indicates successful chain extension of the PS- macroinitiator prepared by ICAR and formation of a block copolymer and thereby confirms the "livingness" of the macroinitiator prepared by an embodiment of ICAR ATRP. 0
  • control over molecular weight distributions in ATRP is at least in part dependent upon absolute deactivator concentration.
  • the rate constant of deactivation of a given catalyst can be calculated from equation 4.
  • the polymerization process may comprise complexes with high values of K A TRP (resulting in sufficiently high concentrations of Cu 11 in solution) and relatively fast deactivation rates, (i.e. above 10 "8 or even 0 preferably above 10 "7 ; [Tang, W., Tsarevsky, N. V. & Matyjaszewski, K.; J. Am. Chem. Soc. 128, 1598-1604.])
  • the polymerization process may comprise the catalyst that does not dissociate appreciably under the polymerization conditions.
  • the dissociation problem may be compounded by competitive complexation between the s ErSfc- l ⁇ l monomer and the ligand to the metal, as the monomer is present in very large excess compared to the catalyst in these reactions.
  • ICAR ATRP of St was first conducted at low temperature (60 0 C) where organic radicals were produced solely by the slow decomposition of azobisisobutyronitrile (AIBN) (0.1 eq vs. ethyl 2-bromoisobutyrate (EtBrIB) initiator) in the presence of 50 ppm of CuCl 2 /L complexes (entries
  • the rates of polymerization differ by less than a factor of two among reactions catalyzed by CuCl 2 complexes OfMe 6 TREN 5 TPMA, and PMDETA (entries 1-3, Table 10), suggesting KATRP may not play a significant role in determining polymerization rate.
  • control over molecular weight distribution was significantly lower in the polymerization mediated by CuC ⁇ /PMDETA. This behavior can be rationalized based on the stability of these complexes towards dissociation at high dilution.
  • the fraction of non-dissociated Cu complex can be calculated from equation (5) knowing the stability constant ( ⁇ J ) and total concentration of the complex ([CuVL]o, where j is the Cu oxidation state and L is the ligand).
  • the catalyst should have a stability constant larger than 10 8 . This should be true for both the Cu 1 and Cu 11 states of the catalyst. From this perspective, ligands such as PMDETA displaying a value of ⁇ ⁇ 10 8 at room temperature [Navon, N.; et al; Inorg. Chem. 1999, 38, 3484] are not suitable for ICAR or ARGET ATRP if narrow molecular weight distribution is desired. However this can be relaxed if broader molecular weight distribution is acceptable or even desired for certain applications.
  • thermochemistry of polyamine complexes of metal ions, including Cu 11 has been extensively studied.
  • the Predici program (version 6.3.1) was used for all kinetic modeling. It employs an adaptive Rothe methoU as a ⁇ u ⁇ e ⁇ cal sj ⁇ afegy " fo ⁇ "tin ⁇ e:3iscrifizatiori. The be followed with time. Each actual calculation took 3-5 min to complete on a personal computer. The modeling was conducted in order to obtain a clear picture of the kinetics of ICAR ATRP and determine whether the rate of polymerization in ICAR is governed by K A T RP or by the rate of AIBN decomposition. (AIBN is being used herein as an exemplary free radical initiator and it is believed that any free radical initiator can be used.
  • k & the deactivation rate constant for free radical with X-Cu" species, estimated from k ⁇ cacl for ATRP (10 "5 ⁇ 10 '8 M “1 0 s "1 ) [Matyjaszewski, K., Paik, H.-j., Zhou, P. & Diamanti, S. J. (2001) Macromolecules 34, 5125.]
  • Auand k a the rate constant for addition of radicals from EBIB (Aii) and AIBN (k ⁇ ) to styrene. Values are calculated at 60
  • Equation (7) shows how the radical concentration (and hence, the polymerization rate) under steady state conditions is primarily dependent on the AIBN decomposition rate constant, its , concentration, and the radical termination rate constant. Radical concentration should therefore not be governed by the choice of ATRP catalyst, KA TRP , or the initial concentration of Cu 11 species. This further suggests that polymerization rates can be adjusted with the choice of an appropriate free radical initiator. These predictions are in relatively good agreement with experimental observations, where apparent rates of polymerization in CuCVMe 6 TREN, TPMA and PMDETA mediated polymerizations (entries 1, 2, & 3, Table 10) are very similar.
  • the Cu catalyst formed with bpy is the least active among the three complexes in this discussion, with .KA T R P ( ⁇ 3.6X10 '9 ) and a relatively small k ⁇ (8.3x10 6 M “1 s "1 ).
  • the concentration of Cu 11 species present at quasi-steady state can be estimated from the ATRP equilibrium.
  • ICAR ATRP and ARGET processes comprise a halogen exchange process.
  • Halogen exchange processes comprise switching the radically transferable atom or group in a polymerization process to another radically transferable atom or group.
  • the catalyst employed for the second step of a block polymerization is chlorine based while that employed for the first polymerization step was bromine based.
  • the halogen on the growing chain end was converted to a chlorine soon after the macroinitiator was activated thereby, in the case of bromine to chlorine, slowing down the rate of propagation of the second polymerization to more closely to match the rate of initiation, for example. This cannot be accomplished when the ratio of catalyst to end group on the macroinitiator is significantly less than 1 : 1 and certainly not when less than 10%.
  • Another approach was a copolymerization process for either ICAR ATRP or ARGET ATRP comprising forming the second block with a different monomer, such as, for example, styrene which and in the end group on the dormant growing polymer chain predominately comprised a styrene unit then the macromolecule could be controllably reactivated.
  • An embodiment of ARGET ATRP process comprised adding acrylonitrile to the polymerization of acrylate.
  • Example 11 Expanding Range of Exemplified Reducing Agents.
  • Stability was quantitatively determined by both the value of ⁇ J and the basicity of the ligand L.
  • the stability of the complex decreases by a factor of OC L (taking into account the amount of protonation or other side reactions of L) to a new value, termed the conditional stability constant ⁇ ' * .
  • A any of the reaction components (monomer, solvent, polymer, reducing agent or the product of its oxidation, designated by A) reacts with the copper ions
  • the stability of CuVL decreases additionally by a factor of ⁇ cu taking into account these side reactions with A (characterized by stability constants ⁇ J cu J Am), according to eq (5).
  • Figure 11 illustrates the pH dependence of the stability of the Cu 11 complexes of PMDETA, Me 6 TREN, and TPMA, calculated from equation 5 (knowing the protonation constants which are available in literature) and shows that the complexes of basic ligands are very much destabilized in acidic media, especially when their stability constants in the absence of protonation (Figure 12) are relatively low (e.g., the Cu 11 complex of PMDETA).
  • Figure 12 also illustrates why PMDETA is less applicable for ARGET ATRP than the other ligands.
  • the complex of the basic Me 6 TREN is markedly more destabilized in acidic media than that of the less basic ligand TPMA. From the point of view of temperature and pH stability, TPMA appears a preferred ligand for ARGET reactions where one of the byproducts of the reducing reaction is an acid.
  • Reducing agents such as glucose were also examined.
  • the polymerization process with glucose as the reducing agent stopped after 500 minutes or so.
  • the kinetic plots and the molecular weight curves showed that each time ATRP stopped at 8-9 hours and then thermal initiated conventional radical polymerization of styrene took place, see 0 Figure 10.
  • Addition of a base can potentially extend the conversion of a polymerization with glucose as a reducing agent by diminishing the protonation of ligand and in fact triethylamine was effective, hi addition, increasing the concentration of ligand also resulted in higher conversion.
  • Another base, 1,4-di-tert-butyl-pyridine was probably to weak to affect protonation and the polymerization but the polymerization process still stopped prior to high conversion.
  • ARGET ATRP processes comprising methyl methacrylate (MMA) and styrene.
  • ARGET ATRP processes comprising MMA initiated by EtBrIB at 60 0 C resulted in observed molecular weights higher than theoretical values with M w /M n ⁇ 1.6 (entries 1 & 2, Table 12a). Better control was observed in the ARGET ATRP of MMA employing Sn(EH) 2 as a reducing agent. Polymerization of St was initiated by EtBnB at 9O 0 C (where thermal initiation should not be significant) in the presence of a 10 fold excess OfPhNHNH 2 and ligand to 50 ppm of Cu. These reactions were fairly well controlled (M w /M n ⁇ 1.3, entries 3 & 4, Figure 12a).
  • ARGET ATRP process comprising MAO as a reducing reagent
  • Anisole was used as an internal standard (10 vol.% of BA)
  • Control Run Copolymerization of styrene and acrylonitrile by ATRP (amounts entry 2 in Figure 13a).
  • a preferred ATRP catalyst possesses a low affinity for alkyl radicals and hydrogen atoms on alkyl groups in order to suppress the contribution of side reactions in the transition metal mediated polymerization.
  • copper-mediated ATRP of styrene loss of terminal 5 halogen functionality by elimination of HX results in loss of chain functionality and consequently loss of control over the reaction.
  • ARGET ATRP The main advantage of ARGET ATRP is that the system comprises continuous reactivation of a small amount of catalyst to maintain control. In most systems this means that catalyst solubility problems and purification issues are easily overcome.
  • ARGET ATRP of styrene and acrylonitrile was conducted with ethyl 2-bromoisobutyrate (EBiB) as an initiator and Me ⁇ TREN/Cu as the catalyst.
  • EBI ethyl 2-bromoisobutyrate
  • Me ⁇ TREN/Cu the catalyst.
  • Experimental conditions and properties of the SAN copolymers prepared by ARGET ATRP are shown in Figure 13b. In order to optimize the amount of copper three different concentrations of catalyst were evaluated: 10, 30 and 50 ppm versus monomer ( Figure 13b, entries 3-5). The amount of the reducing agent, Sn(EH) 2 was kept constant at 50 mol% of the initiator.
  • FIG. 17 presents the kinetic plots for the copolymerization of styrene and acrylonitrile with 30 ppm of copper versus monomer, as well as the molecular weight and polydispersities of the polymers formed in this system.
  • the kinetic plot showed a very small deviation from linear characteristics and the molecular weight was only slightly different from theoretical, a constant increase of molecular weight distribution with conversion was observed.
  • the increase in polydispersity was visible on the SEC traces with tailing to the low molecular weight species which means formation of dead chains from various termination reactions cannot be completely neglected and high monomer conversion cannot be attained with good control over polymerization under these conditions.
  • the high molecular weight SAN copolymer was obtained in a controlled radical polymerization, which leads to the conclusion that the very low concentration of catalyst used in this example significantly suppresses the side reactions of growing radicals with copper species leading to the preparation of well defined high molecular weight linear copolymers.
  • a macroinitiator was also used for the copolymerization of styrene and acrylonitrile.
  • the macroinitiator used was a poly(ethylene oxide) based macroinitiator containing a terminal 2-bromoisobutyrate group.
  • the reaction conditions are shown in Figure 13b, entry 13.
  • the linear character of the kinetic plot indicates a constant number of growing species in the reaction medium, up to 20% of monomer conversion after which the rate of monomer consumption was reduced. Slight discrepancies between theoretical molecular weight and that determined by GPC was observed only the early stage of the polymerization, due to the presence
  • reaction conditions developed using a monomfunctional initiator (EtBriBu) and PEO-macroinitiator were employed in a series of reactions with multifunctional initiators. Identical concentrations of catalyst and initiator were used in each system which should provide
  • ARGET ATRP allows a significant reduction in the amount of catalyst complex employed in the reaction and it was possible to synthesize high molecular weight polymer due to significant suppression of side reactions through reduction of the absolute concentration of the copper species in the system. Side reactions between the growing radicals and the catalyst were avoided to a significant extent.
  • the amount of copper species present in the system can be as low as 10 ppm without loss of control making this process very useful for industrial scale production.
  • Polymerization with mono-, di- and trifunctional initiators low molecular weight initiators and a macroinitiator resulted in the formation of well-defined polymers with controlled architecture. Synthesis Of SiO 2 -PSAN:
  • mini emulsion ATRP allows for compartmentalization of multifunctional initiators in the well dispersed droplets and reduces crosslinking as a consequence of low instantaneous concentration of radicals in a given droplet.
  • HEMA-TMS high molecular weight polymer suitable as a backbone for a grafting from polymerization
  • p(HEMA-TMS) RAFT very high molecular weight RAFT
  • the ratio of monomer to initiator was 10,000 to 1 and the amount of catalyst, tin and solvent were varied to find the best conditions.
  • PAN is not soluble in monomer and most organic solvents such as THF, anisole, methanol, acetone.
  • organic solvents such as THF, anisole, methanol, acetone.
  • THF trifluoride
  • anisole methanol
  • acetone a non-linear first order kinetic plot of monomer consumption
  • DMF GPC
  • AMPSA based block copolymers are desired as templating agents for the preparation of flexible conductive polymers however their preparation by standard ATRP techniques have met with a limitation on the MW of the AMPSA block.
  • the following example was run under conditions developed for the preparation OfAMPSA 27 BA 46 SAMPSA 27 in a standard ATRP reaction.
  • the conditions for this AGET ATRP are similar to those used in the 'regular' ATRP polymerization of AMPSA, with the addition of a proportion of ascorbic acid in addition to the other components.
  • the role of the added reducing agent is to reactivate any excess Cu 11 formed by termination reactions.
  • AMPSA (16.6 g) was added to a Schlenk flask, along with 8.2 g of PBA macroinitiator (MW 60,000g/mol) and degassed for 30 minutes. Degassed tributylamine (19.2 mL) and degassed DMF (48 mL) were then added, followed by stirring until the AMPSA and PBA dissolved, then another 20 minutes of degassing. Copper chloride (79.2 mg), ascorbic acid (47 mg) and bpy (87.6 mg) were added to a separate Schlenk flask, and oxygen was removed by 3 cycles of vacuum pumping and nitrogen purging.
  • TPMA has been found to be an effective ligand for AGET ATRP of NIPAAm in water when using a solvent such as 2-propanol.
  • the polymerization can be driven to >90% conversion and low polydispersity polymers can be obtained.
  • NIPAAm 200
  • Table 13a AGET ATRP of OEOMA 475 in water at 30 0 C.
  • Table 15b AGET ATRP of OEOMA 475 in water at 3O 0 C.
  • Table 15c AGET ATRP of OEOMA 475 in water at 30 0 C.
  • Sequential or gradual addition of the reducing agent therefore does allow one to control the rate of reduction and hence the ratio of Cu 1 to Cu 11 throughout the reaction and attain higher molecular weight materials.
  • the main goal of this example is to define and demonstrate a very simple procedure for grafting from flat surfaces with different monomers.
  • the initial target was to perform AGET or ARGET ATRP at room temperature in the presence of a limited amount of air in a dish (e.g. Petri dish) which can be just simply covered and insulated with parafilm.
  • a dish e.g. Petri dish
  • the polymerization did not occur even after degassing all the reagents with N 2 and adding a higher amount of reducing agent Sn(EH) 2 .
  • the next set of experiments were performed in a weighing dish, which is equipped with ground cover and is deeper than a Petri dish.
  • Solvent anisole/acetone 0.05/0.05 volume equivalents vs. M. 1.5 equivalents Of Sn(EH) 2 was added after 49.5 h.
  • Example 15 Each opening of the reactor in Example 15 resulted in addition of air, which can consume catalyst and reducing agent, however, the molecular weight of the polymer moved to higher molecular weight without any sign of tailing.
  • the polymerizations were well controlled, molecular weights were close to theoretical values and low PDI (1.28) was observed.
  • This example does show that an ATRP can be conducted from a solid flat surface and that the initial presence of a small amount of air can be compensated for by addition of excess reducing agent.

Abstract

Polymerization processes of the present invention comprise low catalyst concentration. Embodiments include a polymerization process comprising polymerizing free radically (co)polymerizable monomers in a polymerization medium comprising one or more radically (co)polymerizable monomers, a transition metal catalyst complex capable of participating in a one electron redox reaction with an ATRP initiator; a free radical initiator; and an ATRP initiator; (wherein the concentration of transition metal catalyst complex in the polymerization medium is less than 100 ppm). Further embodiments include a polymerization process, comprising polymerizing one or more radically (co)polymerizable monomers in the presence of at least one transition metal catalyst complex; and an ATRP initiator;; and a reducing agent; wherein the transition metal catalyst complex is present at less than 10'3 mole compared to the moles of radically transferable atoms or groups present on the ATRP initiator.

Description

TJTLE:--
Polymerizatiόh Process with Catalyst Reactivation .
INVENTOR Krzysztof Matyjaszewski, Wojciech Jakubowski, and James Spanswick
TECHNICAL FIELD OF THE INVENTION
The present invention is directed to an atom transfer radical polymerization process where the catalyst in the activator state, or catalytic transfer agent, is continuously regenerated.
BACKGROUND OF THE INVENTION
Since their discovery controlled radical polymerization ("CRP") processes have gained increasing research and industrial attention. CRP processes couple the capability of conventional free radical polymerization ("RP") to (co)polymerize a wide range of monomers with the ability to synthesize polymeric materials with predetermined molecular weight ("MW"), low polydispersity ("PDI"), controlled composition, site specific functionality, selected chain topology, and incorporation of biological or inorganic species into the final product.
The three most studied methods- of CRP processes are nitroxide mediated polymerization ("NMP"), atom transfer radical polymerization ("ATRP"), and degenerative transfer with dithioesters via reversible addition-fragmentation chain transfer polymerization ("RAFT"). CRP processes typically, but not necessarily, comprise a relatively low stationary concentration of propagating chain ends in relation to dormant chain ends. A dormant chain end comprises a transferable atom or group. The dormant chain end may be converted to a propagating chain end by loss of the transferable atom or group to the transition metal complex in the lower oxidation state. The low concentration of propagating chain ends present during the polymerization process reduces the probability of bimolecular termination reactions, leading to radical polymerization processes that behave as a "living" polymerization process.
The ATRP equilibrium (characterized by KATRP) most frequently involves homolytic cleavage of an alkyl (pseudo)halide bond R-X by a transition metal complex activator Mf /L which (reversibly) generates an active propagating alkyl radical R* and the corresponding higher oxidation state metal halide deactivator Mf+1XfL in a redox reaction Scheme 1. No
Scheme 1. Representation of the equilibrium for an embodiment of an ATRP process.
The active R" may then propagate with a vinyl monomer (M), be deactivated in this equilibrium reaction by Mtn+1X/L, or terminate by either coupling or disproportionation with another R". Such termination results in an increase in the amount of deactivator, Mtn+1X/L, by two equivalents resulting in an increase in concentration of dormant species as a result of the persistent radical effect. [Fischer, H. Chem. Rev. 2001, 101, 3581-3610.] In some embodiments of CRP processes, a fast rate of initiation ("Ri")? relative to the rate of propagation ("Rp")> (For example, where from a process where Rj « Rp to a process where Ri ~ Rp) contributes to control of the molecular weight, degree of polymerization ("DPn") and molecular weight distribution. As used herein, DPn ~ [M]/[I]o, where [M] is the moles of monomer polymerized and [I]0 is the initial concentration of the added initiator. Termination reactions will tend to reduce the control over such properties and since CRP processes are radical based polymerization processes, some termination reactions during a CRP process are unavoidable.
In all radical polymerizations, biradical termination occurs with a rate of termination ("kt") which is dependent on the concentration of radicals ("[P*]") to the power two (Rt= kt[P*]2). Therefore, it may be assumed that at the same rate of propagation (the same concentration of radicals), generally the same number of chains would terminate, regardless whether the polymerization process is a RP or a CRP. However, this assumption ignores the diffusion effect of the macromolecule radicals in a CRP. In a RP most chains are terminated by the reaction of a small radical with a growing polymer radical. In the case of SFRP, or ATRP, these initial termination reactions result in an increase in the concentration of dormant species as a result of the persistent radical effect, [Fischer, H. Chem. Rev. 2001, 101, 3581-3610.]
In an RP, all polymer chains are eventually terminated, whereas in CRP the terminated chains constitute only small fraction of all chains (~1 to 10%) while most polymer chains are in the dormant state. The majority of polymer chains in a CRP in the dormant state are capable of reactivation which allows continuation of the polymerization, functionalization, chain extension to form block copolymers, etc. Thus, a CRP behaves as a "living" polymerization process. [Greszta, D. et. al. Macromolecules 1994, 27, 638.] As used herein, "polymer" refers to a macromolecule formed by the chemical union of monomers, typically rive or more monomers. The term polymer includes homopolymers and copolymers including random copolymers, statistical copolymers, alternating copolymers, gradient copolymers, periodic copolymers, telechelic polymers and polymers of any topology or architecture including block copolymers, graft polymers, star polymers, bottle-brush polymers, comb polymers, branched or hyperbranched polymers, and such polymers tethered to particle surfaces or flat surfaces as well as other polymer structures.
ATRP is the most frequently used CRP technique with a significant commercial potential for many specialty materials including coatings, sealants, adhesives, dispersants but also materials for health and beauty products, electronics and biomedical applications. The most frequently used ATRP process comprises a reversible halogen atom transfer catalyzed by redox active transition metal compounds, most frequently copper based. ATRP transition metal catalysts typically comprise a transition metal complexed with a ligand. In ATRP, radically polymerizable monomers are polymerized in the presence of a transition metal catalyst. For a list of radically polymerizable monomers, see U.S. Patent No. 5,763,548, hereby incorporated by reference. It is believed that the transition metal catalyst participates in a redox reaction with at least one of an ATRP initiator and a dormant polymer chain, see Scheme 1. Suitable transition metal catalysts comprise a transition metal and a ligand coordinated to the transition metal. The transition metal catalyst participates in a reversible redox reaction with at least one of an ATRP initiator and a dormant polymer chain. Suitable transition metal catalysts comprise a transition metal and, optionally, at least one ligand coordinated to the transition metal. The activity of the transition metal catalyst depends on the composition of the transition metal and the ligand.
To function as an ATRP transition metal catalyst, the transition metal must have at least two readily accessible oxidation states separated by one electron, a higher oxidation state and a lower oxidation state. The reversible redox reaction results in the transition metal catalyst cycling between the higher oxidation state (the "deactivator state") and a lower oxidation state (the "activator state") while the polymer chains cycle between having propagating chain ends and dormant chain ends. Typically, the transition metal is one of copper, iron, rhodium, nickel, cobalt, palladium, molybdenum, manganese, rhenium, or ruthenium. In some embodiments, the transition metal catalyst comprises a copper halide, and preferably the copper halide is one of Cu(I)Br or
Cu(I)Cl. Living/controlled polymerizations typically, but not necessarily, comprise a relatively low stationary concentration of polymers comprising propagating chain ends in relation to polymers having dormant chain ends. When the polymer has a dormant chain end, the chain end comprises the transferable atom or group. The dormant chain end may be converted to a propagating chain F" end by transfer of the transferable atom or group to the transition metal catalyst. The description of the mechanism of an ATRP is provided for explanation and is not intended to limit the invention. The disclosed mechanism is generally accepted, but different transition metal catalyst may result in different mechanisms. The ligand affects the structure of the catalyst, the solubilizing effect, and 5 catalyst activity. See Catalyst Development www.chem.cmuedu/groups/maty/about/research/OS.html, hereby incorporated by reference.
ATRP is considered to be one of the most successful CRP and has been thoroughly described in a series of co-assigned U.S Patents and Applications, such as U. S. Patent Nos. 5,763,548; 5,807,937; 5,789,487; 5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882;
10 6,407,187; 6,512,060; 6,538,091; 6,541,580; 6,624,262; 6,624,263; 6,627,314; 6,759,491; and U.S. Patent Applications 09/534,827; 09/972,056; 10/034,908; 10/269,556; 10/289,545; 10/638,584; 10/860,807; 10/684,137; 10/781,061 and 10/992,249 all of which are herein incorporated by reference. ATRP has also been discussed in numerous publications with Matyjaszewski as coauthor and reviewed in several book chapters. [ACS Symp. Ser., 1998, 685; ACS Symp. Sen, 2000;
15 768; Chem. Rev. 2001, 101, 2921-2990; ACS Symp. Ser., 2003; 854; ACS Symp. Ser., 2006; 944.} Within these publications similar polymerization processes may be referred to by different names, such as transition metal mediated polymerization or atom transfer polymerization, but the processes may be similar and if involve reaction mechanism of Scheme 1 will be referred to herein as "ATRP". Such publications describe ATRP catalysts including the reducing power of several
20 transition metal ligand combinations and the manner in which an ATRP equilibrium can be adjusted for more or less reactive monomers.
Embodiments of ATRP processes provide advantages over other CRP processes, including the availability wide variety of initiators and macroinitiators, including wafers, inorganic colloids, glass, paper, and bio-active molecules including proteins, DNA, carbohydrates and many
25 commercial polymers may be simply synthesized as initiators; many polymers produced by ATRP allow facile functionalization or transformation of the end groups by replacing terminal halogens with azides, amines, phosphines and other functionalities via nucleophilic substitution, radical addition or other radical combination reactions; an abundance of monomers are polymerizable by ATRP. Such monomers include, but are not limited to, styrenics, (meth)acrylates, acrylonitrile,
30 acrylamides, vinyl chlorides, and other monomers. Embodiments of ATRP allow the production of macromolecules with complex topology such as stars, combs and dendrimers, coupled with the ability to control composition and hence functionality in block, gradient, periodic copolymers etc. and even control polymer tacticity. ATRP may be carried out in bulk, or in the presence of organic solvents or in water under homogeneous or heterogeneous conditions, in ionic liquids, and in supercritical CO2. .
However, for certain applications and economic considerations, a low concentration of transition metal catalyst in an ATRP medium may be desired. Several methods have been developed to remove or reduce the amount of transition metals in the process, but these processes may add additional cost to the preparation of polymers by ATRP.
Several methods may be used to provide polymers by ATRP processes with low concentrations of catalysts. Such methods include performing an ATRP process with highly active catalyst that may require a lower concentration of catalyst to maintain the desired polymerization rate, for example, CuBr complexed by Me6TREN is ~ 10,000 more active than CuBr complexed by bipyridine ligands; immobilizing the catalysts on solids such as a hybrid catalyst system comprising both immobilized catalyst complexes interacting with small concentrations of soluble catalysts (~10-20 ppm); and several post polymerization methods developed to recover and regenerate catalysts, including separating the catalyst by filtration, adsorption, precipitation or extraction. For example, CuBr/PMDETA complex may be oxidized to Cu(II) species by exposure to air and quantitatively extracted from toluene to water, resulting, in some cases, with less than 1 ppm of catalyst remaining in the polymer. In spite of these advances, there remains a need to reduce the concentration of catalyst in the active polymerization media while maintaining polymer reaction rate and retaining control over MW and PDI. The most attractive route may be just a simple decrease of the amount of the catalyst, providing that it has a sufficient reactivity. For example, ATRP processes comprising CuBr/Me6TREN complexes may be carried out at room temperature with much lower concentrations of the copper based catalyst. Regrettably, the amount of transition metal catalyst, such a Cu(I), may not simply be reduced 10,000 fold. Radical termination reactions result in an increase in the concentration of the transition metal catalyst in the deactivator state and irreversible consumption of the catalyst activators. In certain embodiments with certain monomers, the polymerization may stop if the amount of Cu(I) present in the reaction is below 10% of the initiator (as, 1 ~ 10% of chains are terminated). The amount of terminated chains depends on the concentration of propagating radicals and rate constant of termination according to equation 1, which describes the number of terminated chains (or loss of Cu(I) activator) in an ATRP.
Figure imgf000007_0001
The ATRP rate law (Equation 2) indicates that the polymerization rate depends on the ratio of Cu(I) to X-Cu(II) concentration but does NOT depend on the absolute concentration of copper complexes. Thus, in principle, the amount of copper may be reduced without affecting polymerization rate as long as the ratio of activator to deactivator is maintained.
Rp = MM][P'] = *P[MKJI]O L (2)
Unfortunately, as the reaction progresses the ratio of Cu(I) to X-Cu(II) is reduced through termination reactions and the polymerization rate decreases and eventually, in the absence of a sufficient concentration of the catalyst activator ATRP stops. See Equation 3. Thus, the amount of copper catalyst complexes that have generally been added to an ATRP reaction has exceed that of the expected number of terminated chains (i.e. > 10% [I]0) in order to drive the reaction to completion.
-A[Cu1 /L] = Δ[Cu"X/L] = Δ[Pdead] = kt J[F ]2dt (3)
Some amount of the deactivation species (i.e. X-Cu(II)) is also needed in the system for a well-controlled polymerization because molecular weight distribution and initial molecular weight depend on the ratio of propagation and deactivation rate constants and concentration of deactivator, according to Equation 4.
Figure imgf000008_0001
In a RAFT polymerization process termination reactions are suppressed through the addition of a suitable thiocarbonylthio compound, also known as a dithioester, to an otherwise conventional free radical polymerization; i.e. there is a continuous slow generation of radicals by decomposition of a standard radical initiator in order to drive the reaction forward. Control in such a RAFT process is thought to be achieved through a degenerative chain transfer mechanism in which a propagating radical reacts with the thiocarbonylthio compound to produce an intermediate radical species. This process decreases the instantaneous number of free radicals available for termination reactions that require two free radicals. RAFT (co)polymerization reactions have been discussed in U. S. Patents, 6,153,705; 6,380,355; 6,642,318 and 6,855,840.
There is a need for a transition metal catalyzed chain transfer polymerization process for free radically (co)polymerizable monomers that uses low concentrations of catalysts. βfc
SUMMARY
Polymerization processes of the present invention comprise low catalyst concentration. Embodiments include a polymerization process comprising polymerizing free radically (co)polymerizable monomers in a polymerization medium comprising one or more 5 radically (co)polymerizable monomers, a transition metal catalyst complex capable of participating in a one electron redox reaction with an ATRP initiator; a free radical initiator; and an ATRP initiator; (wherein the concentration of transition metal catalyst complex in the polymerization medium is less than 100 ppm). Further embodiments include a polymerization process, comprising polymerizing one or more radically (co)polymerizable monomers in the presence of at least one 10 transition metal catalyst complex; and an ATRP initiator;; and a reducing agent; wherein the transition metal catalyst complex is present at less than 10"3 mole compared to the moles of radically transferable atoms or groups present on the ATRP initiator.
BRIEF DESCRIPTION OF THE FIGURES 15 Figure 1 is a graph of the kinetic data for an embodiment of a polymerization process comprising polymerizing styrene in the presence of 15 ppm of copper with a polymerization medium having the following components, ratios, and conditions: StZEtBrIBZCu(II)ZMe6TRENZSn(EH)2 =
200Z1Z0.003Z0.1Z0.1; [St]0=5.82 M, T=I 100C, in anisole (0.5 equivalents vs. monomer);
Figure 2. is a graph of the molecular weight and polydispersity of a polystryrene formed as a 20 function of conversion formed in the embodiment of Figure 1 ;
Figure 3 is a graph showing the evolution of molecular weight by GPC traces during the embodiment of the polymerization process of Figure 1 ;
Figure 4 is a graph of the evolution of molecular weight and polydispersity of polystyrene as a function of conversion in an ARGET ATRP process comprising polymerizing styrene in the 25 presence of 10 ppm of copper with a polymerization medium having the following components, ratios, and conditions: StZEtBrIBZCu(II)ZMe6TRENZSn(EH)2 = 1000/1/0.003/0.1/0.1; [St]0=5.82 M,
T=IlO 0C, in anisole (0.5 equivalents vs. monomer);
Figure 5. is a graph of the evolution of molecular weight by GPC traces during the embodiment of the polymerization process of Figure 4; 30 Figure 6 is a graph of the GPC curves showing the presence of a small amount of terminated polymer chains which were initiated by radicals produced from thermal decomposition of AIBN at beginning of activation procedure before being overwhelmed by the bulk of the polymer prepared by CRP; Figure 7 is a graph of showing the temperature dependence of the conditional stability constant of Cu11L ATRP catalysts with various ligands including TPMA, Me6TREN, and PMDETA; Figure 8 is graphs of the kinetic data and molecular weight and~Mw/Mn data as a function of conversion in an embodiment of ICAR ATRP process comprising styrene with 50 ppm and 1 ppm of Cu and the following reaction conditions: St/EtBrIB/CuCl2/Me6TREN/AIBN =
200/1/0.01/0.01/0.1; St/Effirm/CuCl2/TPMA/AIBN = 200/1/0.0002/0.1/0.1 [St]0=5.82 M, 600C, 50% anisole by volume (entries 1 & 10, Table 4);
Figure 9 is a graph of data from a Predici computer simulation of first order kinetic plot for embodiments of ICAR ATRP processes comprising styrene, various ligands including TPMA5 PMDETA, or bpy, and 50 ppm of Cu;
Figure 10 is a graph of data from a Predici computer simulation of the molecular weight and polydisperisty evolution in embodiments of ICAR ATRP processes comprising styrene, various ligands including TPMA, PMDETA, or bpy, and 50 ppm of Cu; Figure 11 is graph of the kinetic data from Predici computer simulations for embodiments of ICAR ATRP processes comprising styrene, various ligands including TPMA, PMDETA, or bpy, 50 ppm of Cu,and AIBN as the free radical initiator;
Figure 12 are graphs of data from Predici compuer simulations of the ICAR ATRP homopolymerization process comprising MMA (6E-20 of St) with the following polymerization conditions: Monomer: Initiator: CuII: AIBN = 200 : 1 : 0.01 : 0.1, [Monomer] = 6 M; Figure 13 are graphs of data from Predici compuer simulations of the ICAR ATRP homopolymerization process comprising MMA and 20% styrene under the following polymerization conditions: Monomer: Initiator: CuII: ABBN = 200 : 1 : 0.01 : 0.1, [Monomer] = 6 M; Figure 14 is a graph of the pH Dependence of the conditional stability constant of Cu11L ATRP catalysts;
Figure 15 are graphs of the kinetic data of an embodiment of a CuCl2/TPMA mediated ARGET ATRP of BA, variable N2H4 reducing agent. [BA]o:[EtBrro]o:[CuCl2]o:[TPMA]o:[N2H4]o = 200 : 1.28 : 0.01 : 0.1 : 0.05 or 0.1; [BA]0=5.88 M; 60 0C, 20% anisole by volume; Figure 16 are graphs of the kinetic data of two embodiments of a polymerization process wherein (Left) CuCl2/TPMA and (Right) CuCl2/Me6TREN are transition metal catalysts in ARGET ATRP of BA with N2H4 as the reducing agent in different concentrations nder the following polymerization conditions [BA]o:[EtBrIB]o:[CuCl2]o:[Ligand]o:[N2H4]o = 2OO : 1 : 0.01 : 0.1 : 0.05, 0.1 or 1.0; [BA]0=5.88 M; 60 0C, 20% anisole by volume; Figure 17 are semilogarithmic kinetic plots (a) and a graph of the dependence of molecular weights (closed symbols) and molecular weight distributions (open symbols) (b) for ATRP of styrene and acrylonitrile;
Figure 18 Evolution of SEC traces for ATRP of styrene and acrylonitrile with Me6TREN as a ligand (Table 7a, entry 1);
Figure 19 are graphs of the kinetic data for an embodiment of an ARGET ATRP of styrene and acrylonitrile with 10 ppm, 30 ppm, and 50 ppm of copper, under the foolowing polymerizatoin conditions St/AN/EBiB/Me6TREN/Sn(EH)2 = 600/390/1/0.5/0.5, in anisole at 80 0C; Figure 20 is a graph of the molecular weight and molecular weight distribution as a function of conversion in ARGET ATRP of styrene and acrylonitrile with 10 ppm, 30 ppm, and 50 ppm of copper, under the following polymerization conditions St/AN/EBiB/Me6TREN/Sn(EH)2 == 600/390/1/0.5/0.5, in anisole at 800C;
Figure 21 is a graph of the evolution of molecular weight distribution during ARGET ATRP of styrene and acrylonitrile with 30 ppm of copper, under the following polmerization conditions: St/AN/EBiB/CuCl2/Me6TREN/Sn(EH)2 = 600/390/1/0.03/0.5/0.5, in anisole at 800C;
Figure 22 is graphs of the kinetic data and molecular weight and molecular weight distribution as a function of conversion for ARGET ATRP of styrene and acrylonitrile with 30 ppm of copper, under the following polymerization conditions: StZANZEBiBZCuCl2ZMe6TRENZSn(EH)2 = 1000Z650Z1Z0.05Z0.5Z0.5, in anisole; Figure 23 is a graph of the evolution of molecular weight distribution during ARGET ATRP of styrene and acrylonitrile with 30 ppm of copper, under the following polymerization conditions: SIyANZEBiBZCuCl2ZMe6TRENZSn(EH)2 = 600Z390Z1Z0.03Z0.5Z0.5, in anisole at 80 0C; Figure 24 is graphs of the kinetic data, molecular weight and molecular weight distribution as a function of conversion for ARGET ATRP of styrene and acrylonitrile with 30 ppm of copper, under the following polymerization conditions: StZANZEBiB/CuCl2ZMe6TRENZSn(EH)2 = 1000Z650Z1Z0.05Z0.5Z0.5, in anisole; and
Figure 25 is graphs of the GPC traces for samples taken during the preparation of high molecular weight polyacrylonitrile.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
The present invention is directed to a polymerization process that regenerate the transition metal in the activator state. Embodiments could be considered to provide a new mechanism for Controlled Radical Polymerization. Embodiments of the ATRP polymerization process comprise a transition metal complex catalyzed halogen transfer polymerization where the transition metal complex is continuously reactivated by reaction with radicals. The radicals may be formed by the decomposition of a free radical initiator or by self initiation reactions.
In one embodiment the present invention could tie considered to be a new mechanism for continuous reactivation a transition metal complex catalyzed (pseudo)halogen transfer polymerization where the transition metal complex is continuously reactivated by reaction with formed radicals. This mechanism comprises initiators for continuous activator regeneration ("ICAR"), see Scheme 2.
Figure imgf000012_0001
th e rm a l)
Scheme 2. A General Representation of an embodiment of the equilibrium for ICAR ATRP.
Embodiments of the present invention provide control over radical reactions that may be considered conceptually to combine aspects of ATRP and RAFT. In RAFT, a chain transfer agent is employed to reversibly transfer a labile dithioester end group among propagating radical chains. Embodiments of ICAR ATRP process may be considered to be similar, wherein the role'of the dithioester transfer agent in RAFT is replaced in ICAR by the initiator or growing polymer chain end in the presence of low concentrations, ppm amounts, of an ATRP catalyst complex and there is a continuous slow generation of radicals by decomposition of a standard radical initiator in order to drive the reaction forward. Control in a RAFT process is thought to be achieved through a degenerative chain transfer mechanism in which a propagating radical reacts with the thiocarbonylthio compound to produce an intermediate radical species. This process decreases the instantaneous number of free radicals available for termination reactions that require two free radicals. RAFT (co)polymerization reactions have been discussed in U. S. Patents, 6,153,705; 6,380,355; 6,642,318 and 6,855,840. This process may be correlated to the process of scheme 2, where the transfer of a radically transferable atom is catalyzed by a transition metal complex and the reaction is driven by the presence of radicals formed by decomposition of a free radical initiator.
The advantage of an ATRP process over a RAFT polymerization include the availability of monofunctional and multifunctional ATRP initiators as disclosed in other patents and patent applications with Matyjaszewski as inventor; the exchange reaction in an ATRP process is WSk If with a small molecule, (Mt(II)X)5 not with a polymeric chain end as in RAFT; and the dormant chain end can be readily modified to provide the desired tele-fiinctional groups. Although the invention is exemplified with a halogen a transferable atom or group and copper based transition metal complexes, ATRP process may comprise any radically transferable atom or group and 5 transition metal such as, for example, environmentally friendly iron complexes.
Embodiments of the polymerization process of the present invention are directed towards polymerizing free radically (co)polymerizable monomers in the presence of a polymerization medium comprising at least one transition metal catalyst, or precursor of the active catalytic species, at least one of a free radical initiator and a reducing agent, and an ATRP initiator
10 (RX). ATRP initiators include molecules comprising at least one radically transferable atom or group, including small molecule initiators, polymeric initiators, and polymers in the polymerization medium comprising a dormant chain end that may be reinitiated or reactivated. The polymerization medium may initially comprise a free radical initiator or a reducing agent or the free radical initiator or reducing agent may be added after initiation of the polymerization. After initiation of the
15 polymerization of the radically (co)polymerizable monomers, free radical initiators or reducing agent may be added continuously, sequentially, or all at once into the reaction medium.
In one embodiment, the ATRP process comprises polymerizing free radically polymerizable monomers in a polymerization medium comprising radically polymerizable monomers, a transition metal catalyst, an ATRP initiator, a free radical initiator, wherein the
20 concentration of the transition metal catalyst complex in the polymerization medium is less than 100 ppm. The polymerization medium may further comprise a solvent, or water forming either a homogeneous or heterogeneous polymerization medium. The free radical initiator may be any molecule that may be induced to form free radicals, such as a molecule that forms radicals by thermal, photoiniated or other decomposition process. Free radical initiators include peroxides, azo
25 compounds, disulfides, and tetrazines. More specifically, free radical initiators include acyl peroxides, acyl peroxides, benzoyl peroxides, alkyl peroxides, cumyl peroxides, tributyl peroxides, hydroperoxides, cumyl hydroperoxide, tibutyl hydroperoxide, peresters, tibutyl perbenzoate, akyl sulfonyl peroxides, dialkyl peroxydicarbonates, diperoxyketals, ketone peroxides, 2, 2' azobisisobutyronitrile ("AIBN"), 2, 2' azobis (2,4- dimethyl pertanenitrile), and 1, 1' azobis
30 (cyclohexane — carbonitrile). Additionally, some monomers may decompose to form radicals, such as styrene and styrene derivatives, therefore the monomer of the polymerization process may also act as the free radical initiator or reducing agent in embodiments of low catalyst ATRP processes. Free radical initiators decompose to form radicals at different rates based on the decomposition n> stimulus, such as temperature. In certain embodiments, the free radical initiator may be soluble in the polymerization medium.
"In certain embodiments, the free radical initiator is selected such that at the - temperature of the polymerization reaction the free radical initiator decomposes at a rate that is substantially the same as the rate of termination in the polymerization. The free radical initiator forms free radicals, or the equivalent of free radicals in the reaction medium. See Table 1 for half lives of free radical initiators at various temperatures.
Figure imgf000014_0001
"Data from Brandrup and Immergut [1989] and Huyser [1970].
10 bt 1A values are for benezene or toluene solutions of the initiators.
The system therefore behaves essentially as a conventional RP with similar kinetics but with the ATRP initiator acting as a combination "transfer agent" - initiator present at 50 ppm or less, in some polymerization processes less than 10 ppm, Mt(II) or Mt(I) as a transfer catalyst.
15 In another embodiment, the polymerization process comprises polymerizing free radically polymerizable monomers in a polymerization medium comprising radically polymerizable monomers, a transition metal catalyst, an ATRP initiator, and a reducing agent. The polymerization medium may further comprise a solvent, or water, hi such an embodiment, the transition metal complex may be initially in the oxidatively stable higher oxidation state, such as Cun, and reduced
20 to the activator state to initiate the polymerization process. Excess of reducing agent may be added to remove low concentrations oxygen from the system.
The reducing agent may be any reducing agent capable of reducing the transition metal catalyst from a higher oxidation state to a lower oxidation state, thereby reforming the catalyst activator state. Such reducing agents include, but are not limited to, SO2, sulfites,
25 bisulfites, thiosulfites, mercaptans, hydroxylamines, hydrazine (N2H4), phenylhydrazine (PhNHNH2), hydrazones, hydroquinone, food preservatives, fiavonoids, beta carotene, vitamin A, α-tocopherols, vitamin E, propyl gallate, octyl gallate, BHA, BHT, propionic acids, ascorbic acid, sorbates, reducing sugars, sugars comprising an aldehyde group, glucose, lactose, fructose, " dextrose, potassium tartrate, nitrites, nitrites, dextrin, aldehydes, glycine, and transition metal salts.
The reducing agent may further be capable of complexing with the transition metal, thereby becoming a ligand.
In a preferred embodiment, the reducing agent does not produce an acid after reducing the transition metal complex from the higher oxidation state to the lower oxidation state, such as hydrazine and phenyl hydrazine. With hydrazines, and substituted hydrazines, the products of oxidation are either nitrogen gas or organic in nature, compared to previous exemplified ARGET systems which predominately employed metal reducing agents for the reduction process in bulk media. [Jakubowski, W.; Min, K.; Matyjaszewski, K. Macromolecules 2006, 39, 39-45.] The reducing agent may also scavenge oxidants in the polymerization medium. In certain embodiments, the amount of reducing agent will be determined by the total concentration of the oxidants in the polymerization medium, if any; the amount of termination reactions in the polymerization; and the desired rate of the redox reaction. Typically, the reducing agent will be present in the polymerization medium such that the molar ratio of reducing agent to ATRP initiator is less than 0.1, or in certain embodiments, less than 0.05.
As noted above similar rules for catalyst selection exist in ARGET ATRP as did in " Several factors should be considered for catalyst selection in ARGET ATRP. First, the release of acid during the oxidation of certain reducing agents (as is the case with many organic reducing agents that can be employed in ARGET ATRP, including sugars, phenols or thiophenols, ascorbic acid, etc.) can destabilize copper-based ATRP catalysts derived from amines. Therefore the addition of excess base, or excess ligand or reducing agent acting as a base, will likely be required to trap the acid. The addition of a base may modify the reducing power of the reducing agent. Of course, in the presence of acidic compounds (i.e., in some embodiments of ARGET ATRP), the stability of the complexes depends very strongly upon the basicity of the ligands. A ligand that is not very basic (such as some of the heterodonor ligands) may be advantageous.
Second, the basicity/nucleophilicity of the reducing agent such as N2H4 and PhNHNH2 may be an issue, particularly in the ARGET ATRP of styrene. The alkyl halide chain end may react with bases resulting in both in a loss of functionality and a consumption of reducing agent. Third, the dynamics of the redox process between the Cu complexes and reducing agents (and ultimately attainable control) will likely depend upon the ligand used to form the complex with the catalyst (and value of KATRP) that is employed.
In certain embodiments, the reducing agent may be select for a particular polymerization process such that at the polymerization temperature the reducing agent reduces a sufficient quantity of transition metal catalyst in the higher oxidation state to transition metal catalyst in the lower oxidation state to substantially maintain the polymerization rate. For example, at the polymerization temperature the reducing agent reduces the additional amount of transition metal catalyst in the higher oxidation state to substantially maintain the ratio of transition metal catalyst in the higher oxidation state to transition metal catalyst in the lower oxidation state. To substantially maintain such ratio means that the ratio does not vary greater than 20% after initiation of the polymerization.
In embodiments of the polymerization process, such as ICAR ATRP and ARGET ATRP polymerization processes, the concentration of the transition metal catalyst must be present in the polymerization medium and may be less than 100 ppm, less than 50 ppm, or even less than 10 ppm. In contrast to the free radical initiators, the reducing agents do not initiate a new polymer chain after reducing the transition metal catalyst in the higher oxidation state.
In embodiments of the ATRP process, the atom or group transfer transition metal complex may be an efficient deactivator, i.e. efficiently donate the (X) atom or group to the growing active chain. The process will be initially exemplified by the use of a very small amount of Cu, ~ 10 ppm complexed with a ligand that forms an active ATRP catalyst and is also an effective deactivator, such as tris[2-(dimethylamino)ethyl]amine ("Me6TREN"), tris[(2- pyridyl)methyl]amine ("TPMA"), and H6TREN. Other embodiments include ligands forming less active catalysts such as N,N,^N",N"-pentamemyldiemyleneMamine (PMDETA), 4,4'-di-(5- nonyl)-2,2'-dipyridyl (dNbpy) andN-(n-octyl)-2-pyridylmethanimine.
The use of low concentrations of catalyst in an ATRP reaction reduces the impact of catalyst based side reactions that limited the ability to prepare high molecular weight materials in some embodiments. One possible explanation of this limitation may be that the radicals interacted with the catalyst complex. For example, the polystyryl radical may be oxidized to a cation by the Cu species, thereby limiting formation of well-defined high molecular weight polystyrenes by
ATRP. However, since this ICAR ATRP and ARGET ATRP may comprise very small amounts of transition metal in the deactivator state, the synthesis of high molecular weight polymers for all monomers are now much more feasible. In certain embodiments of the polymerization processes of the present invention, excess ligand may be added to the polymerization. Excess ligand is present when the quantity of ligand present in the polymerization medium exceeds the amount of ligand required to complex with the transition metal to form the transition metal catalyst. One skilled in the art would understand the coordination characteristics of each transition metal complex. The amount of excess ligand, or ligand surrogate such as free amine, may be as much as ten times the require amount of ligand. In some polymerization processes lower amounts of ligand may lead to polymers with higher polydispersities. At reduced quantities of ligand the transition metal catalyst may complex with the monomer. The ligand may complex with the monomer such as styrene with other components of the polymerization medium. For example, if tin is used as a reducing agent, sufficient ligand should be added to allow for complex formation with both the reducing agent and the transition metal of the catalyst.
The present invention is also directed to polymers comprising high molecular weight. Embodiments include polystyrene comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000 and polyacrylonitrile comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000. In ATRP processes, the initiator is of the formula R-X, where X is the radically transferable atom or group. After polymerization, a typical polymer formed by ATRP will have the R group on one end and the X group on the other end. The definitions of R and X are defined in United States patents that are incorporated by reference.
In certain embodiments of an ICAR ATRP or ARGET ATRP process, the free radical initiator or the reducing agent controls the rate of polymerization by regenerating the activator catalyst complex while allowing sufficient amounts of the catalyst complex efficiently deactivates the growing chains to remain, hi such embodiments, controlled synthesis (Mw/Mn < 1.2) of polystyrene and poly(alkyl (meth)acrylates) can be performed with catalyst concentrations between 1 and 50 ppm. At such concentrations, catalyst removal or recycling may be unnecessary for many industrial applications, since the color of products are not significantly affected by the such low concentrations of catalysts.
Furthermore, because some of the components of the ATRP equilibrium are not oxidatively stable, special handling procedures are often required to remove all oxidants from the system. Embodiments of the ICAR ATRP and ARGET ATRP process comprise initial use of the oxidatively stable catalyst precursors that can be prepared, stored, and shipped for use in ATRP. The transition metal complex in the activator state may be generated in situ from free radical initiators, a reducing agent, an in situ formed peroxide in the case of acrylate polymerization, or a combination thereof [Acar, A. E.; Yagci, M. B.; Mathias, L. J. Macromolecules 2000, 33, 7700- 7706] and the oxidatively stable transition metal catalyst, for example Cu11 or Fe11. present when the quantity of ligand present in the polymerization medium exceeds the amount of ligand required to complex with the transition metal to form the transition metal catalyst. One - siαHed in the art would understand'ϊhe coordination characteristics of each transition metal complex. The amount of excess ligand, or ligand surrogate such as free amine, may be as much as ten times the require amount of ligand. In some polymerization processes lower amounts of ligand may lead to polymers with higher polydispersities. At reduced quantities of ligand the transition metal catalyst may complex with the monomer. The ligand may complex with the monomer such as styrene with other components of the polymerization medium. For example, if tin is used as a reducing agent, sufficient ligand should be added to allow for complex formation with both the reducing agent and the transition metal of the catalyst.
The present invention is also directed to polymers comprising high molecular weight. Embodiments include polystyrene comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000 and polyacrylonitrile comprising end groups typical of an ATRP process and a molecular weight of greater thatn 50,000. In ATRP processes, the initiator is of the formula R-X, where X is the radically transferable atom or group. After polymerization, a typical polymer formed by ATRP will have the R group on one end and the X group on the other end. The definitions of R and X are defined in United States patents that are incorporated by reference.
In certain embodiments of an ICAR ATRP or ARGET ATRP process, the free radical initiator or the reducing agent controls the rate of polymerization by regenerating the activator catalyst complex while allowing sufficient amounts of the catalyst complex efficiently deactivates the growing chains to remain. In such embodiments, controlled synthesis (Mw/Mπ < 1.2) of polystyrene and poly(alkyl (meth)acrylates) can be performed with catalyst concentrations between 1 and 50 ppm. At such concentrations, catalyst removal or recycling may be unnecessary for many industrial applications, since the color of products are not significantly affected by the such low concentrations of catalysts.
Furthermore, because some of the components of the ATRP equilibrium are not oxidatively stable, special handling procedures are often required to remove all oxidants from the system. Embodiments of the ICAR ATRP and ARGET ATRP process comprise initial use of the oxidatively stable catalyst precursors that can be prepared, stored, and shipped for use in ATRP. The transition metal complex in the activator state may be generated in situ from free radical initiators, a reducing agent, an in situ formed peroxide in the case of acrylate polymerization, or a combination thereof [Acar, A. E.; Yagci, M. B.; Mathias, L. J. Macromolecules 2000, 33, 7700- 7706] and the oxidatively stable transition metal catalyst, for example Cu11 or Fe11. In certain embodiments, the free radical initiator slowly and continuously decomposes to prevent the build up of the persistent .radical, or higher oxidation state transition "metaTcbmpTex, formed by termination reactions. This decomposition of the free radical initiator may be used to maintain a substantially constant rate of polymerization; i.e. keep the ratio of transition metal in the low oxidation state (activator state) to transition metal in the higher oxidation state (deactivator state) relatively constant. In other embodiments, the free radical initiator or reducing agent may be used to increase or decrease the polymerization rate.
In other embodiments, the ATRP polymerization process comprises two different free radical initiators. For example, one free radical initiator may quickly activate the catalyst complex to ensure rapid initiation of the polymerization and the other may slowly act throughout the reaction to reactivate the complex, for example. The self-formed free radical initiator such as present in nitroxide mediated polymerizations with styrene and TEMPO may also be used. [Georges, M. K., Veregin, R. P. N., Kazmaier, P. M., Hamer, G. K.; Macromolecules 26: 2987-2988, 1993.] Free radical initiators may be used in coordination with reducing agents, also. The following examples exemplify the broad applicability of this novel CRP. In order to obtain consistent kinetics the reagents used in most of the examples were purified however as detailed in some examples this is not a requirement and the reaction can be conducted directly with industrial grade monomers and in the presence of low concentrations of oxygen.
EXAMPLES
Chemicals. Styrene (St) (Aldrich, 99%) and n-butyl acrylate (raBA) (Acros 99+%) were passed through a column filled with neutral alumina, dried over calcium hydride, and distilled under reduced pressure. Tris(2-(dimethylamino)ethyl)amine (Me6TREN) was synthesized following previously reported procedure. Ethyl 2-bromoisobutyrate (EtBrIB) (Acros, 98%), copper(II) chloride (Acros, 99%), tin(II) 2-ethylhexanoate (Sn(EH)f) (Aldrich), anisole (Aldrich, 99%) were used as received.
In order to obtain consistent kinetics, the reagents used in most of the examples were purified, however as detailed in some examples this is not a requirement and the reaction can be conducted directly with industrial grade monomers. Analysis. Molecular weight and polydispersity were determined by gel permeation chromatography (GPC). The GPC was conducted with a Waters 515 pump and Waters 2414 differential refractometer using PSS columns (Styrogel 105, 103, 102 A) in THF as an eluent at 35 0C and at a flow rate of 1 mL/min. Linear polystyrene standards were used for calibration. Conversion of styrene were determined using a Shimadzu GC 14-A gas chromatograph equipped with a FID detector using a J&W Scientific 30 m DB WAX Megabore column and anisole as an internal standard. Injector and detector temperatures were kept constant at 250 0C. Analysis was carried out isόthermally "at 600C for 2 min followed by an increase of temperature to 140 0C at a heating rate of 40 °C/min and holding at 1400C for 2 min. Conversion was calculated by detecting the decrease of the monomer peak area relative to the peak areas of the standards.
Comparative Examples
Table 2 is shows typical ratio's of reagents used various ATRP processes and in a RAFT polymerization process. Table 2. Typical molar ratios of reagents used in various ATRP processes and a RAFT process
Polymerization R-X Reducing
M Cu1X Cu11X Ligand AIBN method X = Br1 Cl agent
Normal ATRP 200 1 1 - 1 - -
Reverse ATRP 200 - 1 1 - 0.5
SR&NI ATRP 200 1 0.2 0.2 - 0.1
AGET ATRP 200 1 0.2 0.2 0.18 -
ARGET ATRP 200 1 < 0.01 0.1 0.1 -
ICARATRP 200 1 < 0.01 0.01 - < 0.1
RAFT 200 1 dithioester - - - 0.1
As shown in Table 2 significantly less transition metal complex is typically comprised in ARGET ATRP and ICAR ATRP processes than the other listed ATRP process. While similar reagents are used in simultaneous reverse and normal initiation ("SR&NI") ATRP as in ICAR ATRP, ICAR ATRP allows the advantage of the use of much lower concentrations of transition metal catalysts. For more description of SR&NI ATRP, see United States Patent No. 6,759,491.
The following examples show that a controlled radical polymerization is possible with low levels of transition metal catalysts, or catalytic halogen transfer agents, providing polymers with known chain end functionality. PREDICI simulations were conducted on embodiments of ICAR ATRP and ARGET ATRP process and the simulations confirmed applicability of the process parameters and provided further understanding of the parameters of the process.
In the following examples, the polymerization of styrene with 5 ppm of CuCl2Me6TREN and 500 ppm of Sn(EH)2 resulted in the formation of essentially colorless high Ψ> molecular weight polystyrene with
Figure imgf000021_0001
When the •polymerization was carried out with 1 ppm of CuCl2/Me6TREN, the molecular weight of the resulting polymer was still well controlled
Figure imgf000021_0002
but polydispersifies were higher, Mw/Mn=1.64. The polymerization of n-butyl acrylate was conducted with 50 ppm of 5 CuCl2/Me6TREN and 500 ppm of Sn(EH)2 forming ρoly(butyl acrylate) with Mn=I 9,400 (Mnilh=18,100) and Mw/Mn=1.26.
These examples show that a controlled radical polymerization is possible with low levels of transition metal catalysts, or catalytic halogen transfer agents, providing polymers with known chain end functionality.
10 Example 1: General procedure for Activators ReGenerated by Electron Transfer ("ARGET") ATRP of styrene (with number average degree of polymerization (DPn) of 200 and at 50 ppm of Cu).
Degassed styrene (5.0 ml, 44 mmol) and anisole (1.5 ml) were transferred via degassed syringes to dry, thoroughly purged by flushing with nitrogen Schlenk flask. Next, CuCl2
15 (0.29 mg, 0.22χl0"2 mmol)/Me6TREN (0.57 μl, 0.22xl0'2 mmol) complex in degassed anisole (0.5 ml) was added. Mixture was stirred for 10 minutes and then purged solution of Sn(EH)2 (7.0 μl, 2.2x10"2 mmol) and Me6TREN (5.7 μl, 2.2x10"2 mmol) in anisole (0.5 ml) was added. At the end EtBrIB (32.1 μl, 21.9x 10'2 mmol) initiator was added. An initial sample was taken and the sealed flask was placed in thermostated oil bath at 110 0C. The samples were taken at timed intervals and
20 analyzed by gas chromatography and gel permeation chromatography. The polymerization was stopped after 7.6 h by opening the flask and exposing the catalyst to air. Mn, GPC=12700, Mw/Mn=l .11, conversion=59%.
Example 2: General procedure for ARGET ATRP of styrene under air (DPn=200, 50 ppm of
25 Cu).
Styrene (5.0 ml, 44 mmol) and anisole (1.5 ml) were added to open Schlenk flask. Next, CuCl2 (0.29 mg, 0.22x10'2 mmol)/Me6TREN (0.57 μl, 0.22x10'2 mmol) complex in anisole (0.5 ml) was added. Mixture was stirred for 10 minutes and then solution Of Sn(EH)2 (7.0 μl, 2.2x10"2 mmol) and Me6TREN (1.7 μl, 0.7x10"2 mmol) in anisole (0.5 ml) was added. At the end
30 EtBrIB (29.7 μl, 20.3x 10"2 mmol) initiator was added. Next, Schlenk flask was closed sealed and, after taking initial sample, placed in thermostated oil bath at 1100C. The samples were taken at timed intervals and analyzed by gas chromatography and gel permeation chromatography. The polymerization was stopped after 20 h (Mn,
Figure imgf000022_0001
by opening the flask and exposing the catalyst to air.
Example 3: Preparation of block copolymers: PS-PnBA and PnBA-PS An embodiment of ARGET ATRP was used for preparation of block copolymers.
Copolymers PS-PnBA styrene and PwBA-PS were synthesized using previously specified conditions for polymerization of styrene (WJ-03-27) and n-butyl acrylate (WJ-03-53) in the presence of reducing agent Sn(EH)2. The conditions and results for all the reactions are presented in Table 3. The polystyrene macroinitiator was prepared (WJ-03-55) by polymerization of styrene in the presence of 15 ppm of Cu. As in experiment WJ-03-27, a well controlled polymerization was observed demonstrating that results are reproducible.
Polystyrene with Mw=IoOOO and PDI=I.18 was precipitated and then used as macroinitiator in an ARGET ATRP of nBA (WJ-03-56). Chain extension of PS with nBA was performed in the presence of 50 ppm of Cu species. As expected from the results on homopolymerization of nBA (WJ-03-53) the reaction was less controlled than with styrene, although molecular weights were close to theoretical values the PDI increased through reaction from 1.18 to 1.33.
A similar synthetic strategy was used for preparation of PnBA-PS block copolymer. First PwBA macroinitiator was obtained (WJ-03-57) and then chain extended by formation of a PS block (WJ-03-59). In this case polymerization of nBA resulted in macroinitiator PnBA with Mw=I 7600 and PDI=I.32 (WJ-03-57) and since the polymerization of styrene is much better controlled this resulted in a decrease in the PDI of the final block copolymer to 1.18 (WJ-03-59). In all reactions monomodal distribution of MW was observed, molecular weights were close to theoretical values. Polymerization of nBA at 10 ppm in the presence of reducing agent Sn(EH)2 was carried out. From the tables it can be seen that molecular weights were close to theoretical values and a PDI >1.50 was observed. Il ^
Table 3. Conditions and results for ARGET ATRP of Styrene and n-butylacrylate.
Figure imgf000023_0001
8
WJ-O3-530 1 50 0.0078 0.1 0.1 370 0.91 18100 19400 1.26
WJ-03-55a EtBrBB 15 0.003 0.1 0.1 1180 0.77 15500 16000 •; 1.18
WJ-03-56c PS 50 0.0078 0.1 0.1 1260 0.59 27800 26300 1.33
WJ-03-55
WJ-O3-570 EtBrIB 50 0.0078 0.1 0.1 240 0.76 15200 17600 . '[ 1.32
1.54
1.18
il
I
Figure imgf000023_0002
Ti c ι- m ro σ>
Table 4. Experimental conditions and properties of PS prepared by ARGET ATRP - effect of amount of copper.a
Cu Time Conv.
Entry - Molar ratios
Mn> theo Mn1 QPC '■ ;|MW/Mn w
St EtBrIB CuCl2 Me6TREN Sn(EH)2 [ppm] (min) (%)
WJ-03-05 200 1 0.1 0.1 0.1 500 1020 67 14000 17000 , 1.12j : i i
WJ-03-08 200 1 0.01 0.1 0.1 50 460 59 12300 12700 ; l.π;
WJ-03-27 200 1 0.003 0.1 0.1 15 1230 76 15300 17100 1.18:
WJ-03-24 200 1 0.001 0.03 0.1 5 1440 45 9000 7200 1.28] 64, 18! 17: \
Figure imgf000024_0001
73
C ι- m ro σ>
DISCUSSION OF RESULTS
Several examples of an ATRP process comprising a reducing agent were
^rfόϊmfdrMd^ϊe sύϊhMarizea in Table 4. TKe~cWcen1ϊatiOfi oϊ^^ " varied in the first four experiments. At 1 ppm transition metal catalyst complex, CuCl2/ Me6TREN, in the polymerization medium, polystyrene was prepared with the characteristics of a polymer prepared by a CRP process. The polymerization processes formed substantially colorless polystyrene.
Figure 1 is a kinetic plot of data obtained during the ATRP polymerization process comprising polymerizing styrene in the presence of 15 ppm of a copper/Me6 TREN catalyst and a reducing agent Sn(EH)2, and an ATRP initiator, EtBrIB, wherein the SN(EH)2 corresponds to 10% of the ATRP initiator (Table 3, entry WJ-03-27). Figure 1 shows that the rate of polymerization was constant with only a slight decrease after 500 minutes. The molecular weight and PDl curves in Figure 2 indicates excellent control over the polymerization process. Figure 3 shows smooth shift of entire molecular weight distribution towards higher molecular weights. However when the concentration of transition metal catalyst, or catalytic transfer agent, is reduced below 5 ppm of copper under these conditions (or without Cu) uncontrolled polymerization is observed (Table 3, entry WJ-03-28). Note however that the reaction with 5 ppm transition metal halogen transfer catalyst (Table 3, entry WJ-03-24) does produce a polymer with low PDI.
One of the limitations of ATRP is that unlike RAFT the reactions have not been able to prepare very high molecular weight copolymers. One possible explanation is that the radicals could interact with the catalyst complex. E.g. the polystyryl radical can be oxidized to a cation by the Cu(II) species and this maybe the main side reaction limiting formation of well- defined high molecular weight polystyrenes by ATRP. However, since the continuous activation process can now be run with very small amounts of Cu(II) species the synthesis of high molecular weight polystyrenes are now much more feasible. Figures 4 and 5 demonstrate application of ARGET to formation of higher molecular weight polystyrenes. The amount of Cu was reduced down to 10 ppm with preservation of an appropriate level of control (Table 3, entry WJ-03-15). Figure 5 illustrates some tailing towards lower molecular weight due to termination reactions, but overall control is still excellent. When a stoichiometric amount OfMe6TREN to Cu was used, less control was observed. Only low molecular weight oligomers were formed (Table 5, entry WJ-03-06). This suggests changing of polymerization mechanisms from radical to cationic. It is possible that formed stronger Lewis acids SnCl2(EH)2 can catalyze a cationic process, it is also possible that they can undergo metathesis and generate even stronger Lewis acids; SnCl4 or SnCl3EH. These Table 5. Experimental conditions and properties of PS prepared by ARGET ATRP - effect of ligand.a
Figure imgf000026_0001
WJ-03-07 200 1 0.01 0.03 0.1 50 460 34 7100 6900 ιU0 ϊ '"
WJ-03-06 200 1 0.01 0.01 0.1 50 1000 44 9200 oligomers
H1
[St]o=5.82 M; T=IlO 0C, in anisole (0.5 volume equivalent vs. monomer); b Mn, theo =([M]o/[EtBrIB]o) x conversion.
under air;
Figure imgf000026_0002
I m m
Ti c ι— m ro σ>
Lewis acids may also destroy the active Cu/MeβTREN species by direct complexation with the ligand. In certain embodiments, a small excess of ligand, or ligand surrogate, should be used.
TheTcinefic plot frδrrf trreψδlyrnerizatibn of styrene with 15 ppm t>f Εόppef "= " " targeting DP=200 at two different temperatures 60 and 1100G (Table 6, entry WJ-03-27 and WJ- 03-46) indicates that the rate of polymerization is faster at 110 0C, although both reactions are well controlled.
A successful polymerization of n-butyl acrylate was also performed in the presence of 50 ppm of copper. As expected, polymerization of the acrylate was much faster than for styrene at similar conditions (Table 6, entry WJ-03-08 and WJ-03-53). Cu(IyMe6TREN complexes are easily oxidized by air. However, the resulting
Cu(II) species can be still regenerated to Cu(I) state by the action of a reducing agent, such as Sn(EH)2. Thus, in one experiment (Table 6, entry WJ-03-09 and WJ-03-13) no nitrogen purging was conducted but an excess OfSn(EH)2 was added to the reaction medium. A short induction period was observed but then polymerization started and good control over molecular weight and polydispersities was observed.
Table 6. Experimental conditions and properties of PS and PnBA prepared by ARGET ATRP — effect of monomer, temperature and' air.
Molar ratios Cu Time Conv.
Entry — Mn,theoe Mn, GPC Mw/Mn
M EtBrIB CuCl2 Me6TREN Sn(EH)2 [ppm] (min) (%)
WJ-03-27a 200 1 0.003 0.1 0.1 15 1230 76 15300 17100 1.18
WJ-03-46b 200 1 0.003 0.1 0.1 15 3150 0.24 4800 4500 1.18
WJ-03-08a 200 1 0.01 0.1 0.1 50 460 59 12300 12700 i;.ii
WJ-O3-530 160 1 0.0078 0.1 0.1 50 370 91 18100 19400 1.26
WJ-03-07a 200 1 0.01 0.03 0.1 50 460 34 7100 6900 ψo
CΛ
C WJ-03-13d 200 1 0.01 0.03 0.1 50 1415 76 15200 15900 t!.28 OO CΛ WJ-03-09d 200 1 0.01 0.1 0.1 50 1380 75 15000 16200 ll45
ON m
CΛ
I m m
73
C ι- m ro σ>
The amount of transition metal catalyst complex species in ATRP can be reduced down to a few ppm without losing control of polymerization, if an appropriate amount of reducing
Figure imgf000029_0001
There are several requirements for an efficient reaction in the presence of a reducing agent: • The redox process should occur without generation of initiating radicals.
• Reducing agent may also be involved in atom transfer process (this would generate dual catalytic system, e.g. bimetallic catalysis), however, the sufficient amount of quickly deactivation species (i.e., X-Cu(II) ) is needed for control. Molecular weight distribution and initial molecular weight, both depend on the ratio of propagation to deactivation rates, according to equations: 2 and 3.
• The position of equilibrium between reducing species and ATRP true catalyst should allow for a sufficient amount of Cu(II) species and sets the overall rate of ATRP.
• The concentration of reducing agent should account for [Cu(II)] sufficient amount of transition metal species to be activated, amount of air or some other radical traps present in the system, and the amount of terminated chains. When Sn(EH)2 species are used as the reducing agent this concentration is ~ 50 ppm but depends on the particular reaction conditions.
The minimal amount of active ATRP catalyst also depends on the particular system, for styrene polymerization the transition metal catalyst may be to a few ppm, significantly lower than in any other reported ATRP process. The examples of ARGET ATRP detailed herein demonstrate a significant improvement over traditional ATRP, since it can be carried out with drastically reduced amount of Cu species and FDA approved Sn(EH)2 or other environmentally sound reducing agents (sugars, ascorbic acid).
Example 4: Development of Initiators for Continuous Activator Regeneration (ICAR) ATRP.
In the set of examples described above the catalyst complex was reactivated by addition of a reducing agent however other approaches, closer to present industrial practice for RP, for reactivation of the lower oxidation state transition metal complex have now been shown to also work. The polymerization medium comprises a significantly lower catalyst concentration, for example many times less than the total number of polymer chains formed in the polymerization, in order that the reaction can continue the radical initiator has to continuously generate radicals at a rate comparable to radicals consumed by termination reactions. The radicals can be formed by any reaction mechanisms. Indeed, as shown below, in the case of styrene polymerization this is the mechanism that actually operates, but it was analysis of the above results that led to this unexpected recognition.
" - "■ ~
Figure imgf000030_0001
the overall rate of polymerization did not change with varying amounts of Cu5 ligand or Sn(EH)2. Due to the high temperature (110 0C), which was used in all previous experiments, this indicated that the rate of polymerization was controlled by thermal production of radicals from the monomer. [Odian, "Principles of Polymerization" 4th edition, page 226] The rate of polymerization is controlled by thermal initiation of styrene. Styrene based radicals can form independently to reduce Cu(II) to Cu(I) and regenerate the active catalyst. Therefore polymerizations were conducted with a low concentration of catalyst without the presence of a reducing agent. The regeneration of Cu(I) activator species, which can be lost due to termination reactions (e.g. radical coupling), was performed by two different methods:
- generation of radicals by thermal initiation from styrene monomer (polymerization at 1100C)
- generation of radicals by thermal decomposition of AIBN (polymerization at 60 °C)\ In both cases, radicals are produced slowly throughout the reaction and are able to continuously reduce Cu(II) to Cu(I), so that the activator complex was continuously regenerated. The conditions employed for these initial reactions and the results are presented in Tables 5-6. In first experiments (WJ-03-30, 31, 32), styrene was polymerized with 3 ppm of added Cu species and radicals were produced by thermal initiation of styrene. The results show that the reactions were not controlled and a high molecular weight product with high PDI was obtained. The relatively uncontrolled character of the polymerization could be due to too low a concentration of ligand, which allows the copper to be complexed by monomer leading to loss of active metal catalyst complex (Cu(I)/ligand), as the ligand was involved in side reactions. Consequently, in next two reactions (WJ-03-36, 37) amount of ligand was increased. Styrene was polymerized in the presence of 50 and 5 ppm of Cu species respectively. CuCl2ZMe6TREN was used as catalyst complex and ratio of In/Cu/ligand was 1/0.01/0.1 and 1/0.001/0.1. The results showed that the polymerization in the presence of 50 ppm Cu species was well controlled, molecular weights were close to theoretical values and low PDI (1.17) was observed, hi reaction WJ-03-37 with only 5 ppm of Cu species much higher PDI (1.63) was observed and molecular weights were higher than the theoretical values. This suggests that the concentration of radicals was initially too high and all of Cu(II) species were reduced to Cu(I). This leads to higher molecular weights since the amount of deactivator Cu(II) is too small to efficiently deactivate the growing polymer chains. In order too obtain controlled ATRP one should increase the effective amount of Cu(II) species in IE the system. This can be accomplished either by increasing the initial amount of Cu(II) species in the system or by decreasing the temperature. At lower temperature less Cu(II) species will be reduced to Cu(Ij ilirice corfceήtrMlnicff radicals" produced in
Figure imgf000031_0001
In the next series of experiments (See Table 8) styrene was polymerized with 15 5 ppm of Cu species present in the reaction and radicals were produced by thermal decomposition of AEBN. In the first reactions (WJ-03-33, 34, 35) styrene was polymerized at 600C in the presence of AIBN and/or reducing agent Sn(EH)2. hi experiment WJ-03-33 AEBN and Sn(EH)2 were used together. The polymerization was slow but low PDI (<1.4) was observed and MW were close to calculated values. The next reaction, WJ-03-34, was performed only in the presence
10 of Sn(EH)2. The results shows that polymerization was relatively well controlled, molecular weigh is were close to theoretical values and low PDI (1.30) was observed but the rate of the reaction was slightly slower than the previous one when AIBN and Sn(EHh were used together. In reaction WJ-03-35 styrene was polymerized in the presence of AD3N without any added reducing agent. The polymerization was initially controlled but after 20 h a bimodal distribution
15 of MW could be observed. This could be due to loss of active complex from the system due to complexation of the ligand with the monomer, which is present in large excess compared to the transition metal.
In the following set of experiments a higher amount of ligand was used and the amount of AIBN added to the reaction was varied to increase the rate of polymerization. 0 CuCl2/Me6TREN was used as catalyst complex and the ratio of In/Cu/ligand was 1/0.003/0.1 while the concentration of AIBN was varied from 0.01 to 0.1 equivalents vs. initiator. In all reactions a monomodal distribution of MW was observed. Molecular weights were close to theoretical values, but slightly higher PDIs (>1.4) were observed. Increasing the concentration of added AIBN from 0.01 to 0.1 equivalents vs. ATRP initiator resulted in an increased rate of 5 polymerization but reactions were still very slow.
Example 5: Polymerization of styrene in the presence of AIBN
ATRP with low catalyst concentration was performed without the presence of added reducing agent. The regeneration of Cu(I) species, which can be lost due to termination 0 reactions (e.g. radical coupling), was performed by generation of radicals by thermal decomposition of AEBN (polymerization at 600C). In this case, radicals are produced slowly through whole reaction time and are able to reduce Cu(II) to Cu(I), so that active complex can be regenerated. The conditions and results for all the reactions are presented in Table 9. 1P
Table 8. Conditions and results for ATRP of St initiated by AIBN at low catalyst : concentration
Time Conv. a [St]0/[EtBrIB]o=200;
Label EtBrIB Cu [ppm] CuCl2 Me6TREN AIBN Sn(EH)2 [St]0=5.82 M; T=600C5 in (min) Mn, theo Mn, GPC My1Mn (%) anisole (0.5 volume equivalent
WJ-03-27 1 15 0.003 0.1 0.1 1230 0.76 15250 17100 1.18 vs. monomer); b Mnj
WJ-03-33 1 15 0.003 0.02 0.01 0.02 4635 0.19 3720 4100 1.3.6
Figure imgf000032_0001
x conversion
WJ-03-34 1 15 0.003 0.02 0.02 4600 0.12 2360 2590 1.30
WJ-03-35 1 15 0.003 0.003 0.01 - 4570 0.19 3560 37200 1.40
WJ-03-38 15 0.003 0.1 0.01 - 7200 0.26 5200 3800 1.51 WJ-03-39 15 0.003 0.1 0.05 - 7200 0.28 5500 5100 1.44
CΛ
C OO WJ-03-40 15 0.003 0.1 0.1 - 7200 0.56 11200 9800 1.38 CΛ
O m M; volume Mn_
Figure imgf000032_0002
WJ-03-62 1 50 0.01 0.01 0.1 2760 0.44 8700 7900 1.12
Mj
I
1
In the last two experiments in Table 9 (Runs WJ-03-61 and 62) the amount of
- - ■'- " tϊgaϊid, Me6TREN, was varied "with a cOfrsfahrcαrieMtatiόn of 50 ppm of Cu present in the : r'-- ~ polymerization of styrene. The ratio of In:Cu:ligand in the first and second reactions were 5 1 :0.01 :0.01 and 1 :0.01 :0.1 respectively. In reaction WJ-03-62 no excess of ligand was used while in experiment WJ-03-61 the polymerization of styrene was performed in the presence of 10 fold excess of ligand. The molecular weights were close to theoretical values and low PDI was observed for both runs. This suggests that no excess of ligand is needed since the excess ligand could participate in side reactions and influence the final PDI. This is the contrary to the
10 experience with ARGET ATRP where an excess of ligand may be needed, due to possible complexation with the reducing agent Sn(EH)2 or its products Sn(EH)2Ck » SnCl4.
In reactions WJ-03-60 polymerization of styrene was performed starting with 50 ppm of the Cu(I) complex formed in the presence of excess ligand. It can be seen that the results from this reaction are slightly improved compared to reaction where Cu(II) was used (WJ-03-61).
15 Molecular weights were close to theoretical values and a lower PDI (<1.20) was observed. There are two possible reasons for this result:
(i) The equilibrium between Cu(I) and Cu(II) species in the system may form faster when Cu(I) species are used, and thus better control of polymerization can be obtained. When starting from Cu(II) species and using AEBN to activate the polymerization (according to Predici) a lot of
20 Cu(I) is generated at the beginning stage of the reaction and high molecular weight polymers are obtained, since there is not enough Cu(II) in the system to deactivate growing chains, (ii) Cu(I) is more soluble than Cu(II) with Me6TREN ligand, thus during the transfer of active complex froni preparation flask to the Schenk flask some of Cu(II) species which are not fully soluble in the transfer medium are lost. Therefore the real value of Cu species in the reaction
25 medium can be different, higher when Cu(I) is used.
All three experiments (WJ-03-60, 61 and 62) bimodal distribution of molecular weight was observed at the earliest stage of the reaction. At low conversion, 3%, a small fraction of high molecular weight polymer was observed. This is probably a product of terminated chains which were initiated by radicals produced from the direct thermal decomposition of AIBN which
30 would indicate that the concentration of radicals at the beginning stage of reaction can be high enough not only to quickly reduce Cu(II) to Cu(I) but also initiate new polymer chains. The fraction of terminated chains is small and disappears into the baseline of later GPC traces over time, due to overlapping with the intense signal from main polymer product; Figure 6. The polymerization rates for all three reactions are the same and independent of the amount of copper, Cu(I) or Cu(II) species, used at the beginning of the reaction or the amount of
' - ~ ligafld aflaeϋ." This proves "that the reaction is theriSMly cdnttollέd fe>theHήal:ϊiecornposition of AIBN. In embodiments of the polymerization process a sequential or gradual addition of the
5 initiator will overcome the initial excess of radicals leading to lower level of uncontrolled polymerization.
Example 6: Synthesis of a PSt-ft-PnBA block Copolymer by ICAR and ARGET ATRP.
A PSt-Br macroinitiator (Mw=l 1000, Mw/Mn =1.12) (0.5 g, 4.5x 10"2 mmol), which was 0 prepared by an embodiment of ICAR ATRP, was dissolved in BA monomer (2.80 ml, 19.6 mmol) in a 10 mL Schlenk flask and bubbled with nitrogen for 15 minutes. Next, a solution OfCuCl2 (0.13 mg, LOOxIO"3 mmol)/Me6TREN (1.32 μl, 5.0OxIO"3 mmol) complex in deoxygenated DMF (0.7 ml) was added. The resulting mixture was stirred for 10 minutes before a purged solution OfPhNHNH2 (0.49 μl, 5.0OxIO"3 mmol) in anisole (0.5 ml) was added. An initial sample was taken and the sealed flask 5 was placed in a thermostated oil bath at 60 0C. Samples were taken at timed intervals over 48.5 hours and analyzed by GC and GPC (Mn, Gpc= 65300, Mw/Mn= 1.19, conversion = 82%).
A clean shift in molecular weight indicates successful chain extension of the PS- macroinitiator prepared by ICAR and formation of a block copolymer and thereby confirms the "livingness" of the macroinitiator prepared by an embodiment of ICAR ATRP. 0
Example 7: Selection of Ligand.
Several factors should be considered when attempting to optimize the reaction and select the appropriate conditions ICAR ATRP and AGET ATRP processes which are conducted with low concentrations of transition metal catalysts. 5 First, control over molecular weight distributions in ATRP is at least in part dependent upon absolute deactivator concentration. The rate constant of deactivation of a given catalyst can be calculated from equation 4. hi preferred embodiments of ICAR ATRP and AGET ATRP, the polymerization process may comprise complexes with high values of KATRP (resulting in sufficiently high concentrations of Cu11 in solution) and relatively fast deactivation rates, (i.e. above 10"8 or even 0 preferably above 10"7; [Tang, W., Tsarevsky, N. V. & Matyjaszewski, K.; J. Am. Chem. Soc. 128, 1598-1604.])
Second, in preferred embodiments of ICAR ATRP and AGET ATRP, the polymerization process may comprise the catalyst that does not dissociate appreciably under the polymerization conditions. The dissociation problem may be compounded by competitive complexation between the s ErSfc- l πl monomer and the ligand to the metal, as the monomer is present in very large excess compared to the catalyst in these reactions.
""Tfiird^i€ verylϋw eMeenWtio'ris'of transition it was not immediately clear whether radical concentration, and consequently rate of polymerization, 5 would be governed by KATRP (as in normal ATRP) or by the rate of new radical generation (as in
RAFT).
In the initial runs listed in Table 10, four ATRP catalysts with a broad range of KATRP values were selected to exemplify the scope of embodiments of the ICAR ATRP process. These included the
CuCl2 complexes of tris[2-(dimethylamino)ethyl] amine (MeβTREN), tris[(2-pyridyl)methyl]amine 0 (TPMA), N,N,N',N"5N"-ρentamethyldiethylenetriamine (PMDETA), and 4,4'-di-(5-nonyl)-2,2'- dipyridyl (dNbpy). ICAR ATRP of St was first conducted at low temperature (600C) where organic radicals were produced solely by the slow decomposition of azobisisobutyronitrile (AIBN) (0.1 eq vs. ethyl 2-bromoisobutyrate (EtBrIB) initiator) in the presence of 50 ppm of CuCl2/L complexes (entries
1-4, Table 10). Interestingly, rates of polymerization differ by less than a factor of two among 5 reactions catalyzed by CuCl2/L complexes of Me6TREN, TPMA, PMDETA, and dNbpy. This was initially surprising given that values of KATRP, which govern radical concentration and the rate of polymerization under normal and SR&NI ATRP conditions, for these four complexes differ by more than four orders of magnitude in a "standard" ATRP.
Table 10. ICARATRP of Styrene
Temp. Monomer/ [Cu] Ligand / AIBN / Time Conv.
Entry Mn, GPC Mw/Mπ (°C) Initiator/Cu ppm Ratio to Cu Initiator (min) (%)
1 60 200 St/1/0.01 50 Me6TREN / 1 0.1 2760 44 8700 7900 1.12
2 60 200 St/1/0.01 50 TPMA / 1 0.1 2880 39 7800 6800 1.09
3 60 200 St/1/0.01 50 PMDETA / 1 0.1 2880 29 5600 4500 1.62
4 60 200 St/1/0.01 50 dNbpy / 2 0.1 2940 36 7200 5600 1,68
5 70 200 St/1/0.01 50 Me6TREN / 1 0.1 2400 47 9500 7600 1.11
6 70 200 St/1/0.01 50 Me6TREN / 1 0.2 2500 60 11,900 10,000 1.15
C 7 70 200 St/1/0.01 50 Me6TREN / 1 0.4 1140 66 13,200 10,100 1.22 00
8 110 200 St/1/0.01 50 Me6TREN / 10 - 1775 65 12,900 11,000 1.25
9 110 200 St/1/0.01 50 TPMA / 10 - 1930 49 9800 9600 1.13
10 110 200 St/1/0.002 10 TPMA / 50 - 1720 42 8400 7600 1.38 m
11 110 200 St/1/0.0002 1 TPMA / 500 - 1700 55 11,000 8400 1.72
I m [St]o/[EtBrIB]o = 2OO; [St]0= 5.82 M; 50% anisole by volume. m
Ti
C |— m ro σ>
: . - ■ ■ ■ "While polymerizations mediatedby CuCIfMe6TREN anα"CuCl2/TPMA were" very well controlled in terms of molecular weight and Mw/Mn (entries 1 & 2, Table 10), control over Mw/Mn 5 was significantly poorer in the polymerization mediated by CuCVPMDETA and CuCl2/dNbpy (entries 3 & 4). This behavior is consistent with the fact that these two complexes have the lowest of the four values of KATRP-
An experiment conducted later with an even less active ATRP catalyst complex, N-(n- octyl)-2-pyridylmethanimine, frequently used for the bulk polymerization of more active
10 methacrylate monomers, [Hovestad, N. J.; etal.: Macromolecules 2000, 33, 4048-4052.] with a molar ratio of reagents: St:I:Cu:L:AIBN = 200:1:0.01:0.02:0.1 was even less controlled, especially at the beginning stage of reaction, resulting in even higher PDI (1.9) even though, as with PMDETA and dNbpy, absolute molecular weight control quite was good, (Mn,theo 8,000; Mn, ope 6900.)
15 This would indicate that values for KATRP directly influence molecular weight distribution and all reactions are controlled, since initiation efficiency is high, and consequently terminal functionality is present in the majority of polymer chains. The broader PDI is a consequence of slower rate of deactivation. The polymers can be further chain extended and/or functionalized. The materials are not "dead" nor were they prepared in a totally uncontrolled reaction but remain 0 "living" and will display different rheology and perhaps even different physical properties, particularly for block copolymers with segment(s) displaying broader PDI.
Such observations concerning attainable control can also be rationalized based on the stability of these complexes towards dissociation at high dilution and high temperature. The stability of Cu11 complexes of PMDETA, Me6TREN, and TPMA in aqueous media over a range of
25 temperatures are illustrated in Figure 2 and can be used as a general guide for ligand selection in these systems. [Paoletti, P. & Ciampolini, M. (1967) Inorg. Chem. 6, 64; Anderegg, G., Hubmann, E., Podder, N. G. & Wenk, F. (1977) HeIv. Chim. Acta 60, 123.] These stability constants suggest that such a significant degree of dissociation of the CuCl and CUCI2/PMDETA complexes would ultimately result in a lower absolute value of deactivator concentration, helping
30 to explain the observed poor control over Mw/Mn in this system (entry 3, Table 10). Conversely polymerizations mediated by CuCl2/Me6TREN and CuCk/TPMA were very well controlled in terms of molecular weight distribution (Mw/Mn = 1.1). The observed molecular weights were only slightly lower than theoretical values. This lower than theoretical molecular weight is a likely result of the constant generation of new chains throughout the polymerization inherent in this ICAR ATRP process. Representative examples of the evolution of molecular weight with conversion and the linear first order kinetics obtained in ICAR under these conditions are shown "in Figure 8.~ ~ ~ ~ " ""*- ' "~~- ■■ —÷ " ~ -■=-_ --
The rates of polymerization differ by less than a factor of two among reactions catalyzed by CuCl2 complexes OfMe6TREN5 TPMA, and PMDETA (entries 1-3, Table 10), suggesting KATRP may not play a significant role in determining polymerization rate. However, control over molecular weight distribution was significantly lower in the polymerization mediated by CuC^/PMDETA. This behavior can be rationalized based on the stability of these complexes towards dissociation at high dilution. The fraction of non-dissociated Cu complex can be calculated from equation (5) knowing the stability constant (βJ) and total concentration of the complex ([CuVL]o, where j is the Cu oxidation state and L is the ligand).
Figure imgf000038_0001
According to the above dependence, for 90% of the catalyst to remain in solution at a total concentration of 10"δ M (the present lower limit for ICAR or ARGET), the catalyst should have a stability constant larger than 108. This should be true for both the Cu1 and Cu11 states of the catalyst. From this perspective, ligands such as PMDETA displaying a value of β^ < 108 at room temperature [Navon, N.; et al; Inorg. Chem. 1999, 38, 3484] are not suitable for ICAR or ARGET ATRP if narrow molecular weight distribution is desired. However this can be relaxed if broader molecular weight distribution is acceptable or even desired for certain applications.
The stability constants for a large number of Cu complexes with various N-based ligands are available in the literature. [Paoletti, P.; Ciampolini, M. Inorg. Chem. 1967, 6, 64: Anderegg, G.; Hubmann, E.; Podder, N. G.; Wenk, F. HeIv. CUm. Acta 1977, 60, 123.] These values have been determined primarily in aqueous solutions at 25°C but can still be used as a general guide for ligand selection and all suitable transition metal complexes formed with ligands displaying a β-* > 108 at room temperature are herein incorporated as potentially suitable complexes for ICAR ATRP targeting narrow Mw/Mn.
Furthermore, polymerizations in this study carried out at high temperatures (60 - 11O0C) indicate destabilization of the ATRP catalysts at these temperatures and this should also be accounted for. The thermochemistry of polyamine complexes of metal ions, including Cu11, has been extensively studied. [Paoletti, P.; Fabbrizzi, L.; Barbucci, R. Inorg. Chim. Acta Rev. 1973, 7, uts
43] The enthalpies of formation of Cu11 polyamine complexes are in the range of -10 to -20 kcal/mol, and a temperature increase from 25 to HO0C should lead to a decrease in the stability " consiarϊf&y 2-3 orders of magnitude. As discussed in these references the temperature dependence of the stability of the Cu11 complexes of PMDETA, Me6TREN, and TPMA is illustrated in Figure 5 14 which shows that the stability constant of Cuπ/PMDETA complexes is considerably lower than that of copper complexes formed with Me6TREN or TPMA, which is consistent with the polymerization results in Table 10. Significant dissociation of the CuCl and CUCI2ZPMDETA complexes would ultimately result in a lower absolute value of deactivator concentration in the polymerization medium and consequently poorer control over Mw/Mn.
10 Additionally, the coordination of various polar monomers such as St and (meth)acrylates to the Cu1ZPMDETA complex with non-coordinating anions has recently been reported. [Braunecker, W. A.; etal; J. Organometal. Chem. 2005, 690, 916; and Macromolecules 2005, 38, 4081.] While this complexation is comparatively weak the high concentration of monomer present in bulk, and even solution polymerization processes especially at low ppm catalyst concentration, result in
15 competitive complexation which could lead to a further destabilization of the catalyst.
Additional experiments and kinetic simulations (vide infra) explore the possibility that:
1) the rate of polymerization and radical concentration under ICAR ATRP conditions are actually controlled by the rate of free radical initiator decomposition and,
2) that the relative concentration of Cu1 and Cu11 present in the reaction medium conform 20 accordingly, as dictated by the value for KATRP-
Example 8. Varying Concentration of Free Radical Initiator and Transition Metal
Among the controlled polymerizations conducted at 6O0C, that mediated by CuCl2/Me6TREN was (marginally) the fastest; however, it was still rather slow, ~ 50 % conversion in 2 days. In
25 experiments 5, 6 and 7 in Table 10 the temperature was increased to 7O0C and several reactions were performed varying the amount of AIBN versus alkyl halide initiator. All three of these reactions mediated by CuCl2ZMe6TREN were well controlled. Increasing the amount of AIBN from 0.1 to 0.4 equivalents resulted in just a slight increase in MwZMn (from 1.1 to 1.2), likely due to the higher number of terminated chains resulting from a higher radical concentration produced in the
30 early stages of the reaction. However, the rate of polymerization clearly increased with increasing concentration of free radical initiator.
At higher temperatures (1100C), where the complexes are more prone to dissociate, a 10 fold excess of ligand compared to Cu was employed to help suppress dissociation. AIBN was not needed at this temperature for the polymerization of styrene as the radical reducing agents, or catalyst activators, were regenerated by thermal initiation of St. In accordance with the relative stabilities of the two complexes the polymerization mediated by CuCl2/TPMA was better controlled than that mediated by CuGliMeβTREN (in terms of polydispersity) IJMerthese^cσlSϊfions.tHierefore, CuCh/TPMA was employed in an additional series of reactions to investigate the lower limits of catalyst concentration necessary for a controlled reaction. The Cu concentration was decreased from 50 ppm to 10 and then to just 1 ppm (entries 10 and 11, Table 10). While a slight curvature was observed in the first order kinetics of these polymerizations (indicating the radical concentration is not constant throughout the reactions) as expected from equation 3, the decreased amount of Cu resulted in broader molecular weight distributions (Mw/Mn ~ 1.4 and 1.7 for 10 and 1 ppm of Cu, respectively). Figure 8 illustrates the control attainable with 1 ppm of Cu catalyst and compares the result to that obtained with 50 ppm catalyst. When 1 ppm Cu was present molecular weights are slightly higher than theoretical values at very low conversion. However, quite impressively, just 1 ppm of Cu in the presence of excess TPMA was ultimately sufficient to control molecular weight and the terminal functionality in the ICAR ATRP of St although the molecular weight distribution was broader.
Example 9. Polymerization of BA and MMA
ICAR ATRP of MMA was then attempted in the presence of AIBN and 50 ppm Cu. The reaction was initiated by EtBPA in the presence of 0.01 equivalents of CuCl2Me6TREN at 600C. The results are reported as in Table 11. Polymerization was not as well controlled as in analogous reactions of St (entry 1, Table 10). However, CUCI2/TPMA proved very efficient in mediating the controlled polymerization of MMA. Observed molecular weights agreed well with theoretical values, linear first order kinetics are observed, and narrow molecular weight distributions were attained (Mw/Mn ~ 1.2). Both CuCl2/Me6TREN and CuCl2/TPMA were employed in the polymerization of BA initiated by EtBrIB. Acceptable polydispersities (Mw/Mn ~ 1.4) and good control over molecular weights were attained in both polymerizations (entries 3 & 4, Table 11).
These experiments provided sufficient information to allow the system to be modeled. Table 11: PBA prepared by ARGET ATRP under various conditions.
Monomer / CuCl2 Ligand / RA / Time Conv
Entry Initiator [ppm] Ratio to Cu Ratio to Cu (min) Mπ, theo Mn> GPC Mw/Mn
1 200/1/0.01 50 Me6TREN/10 PhNHNH2 /10 1098 78 19,994 26,100 1.23
2 200/1/0.01 50 Me6TREN/ 3 PhNHNH2/10 1098 33a 8500 20,200 2.3
3 200/1/0.01 50 TPMA/10 PhNHNH2 /10 3780 59 15,124 16,700 1.27
4 200/1/0.01 50 TPMA/3 PhNHNH2AO 1300 32a 8202 8100 1.57
5 200/1/0.01 50 PMDETA/10 PhNHNH2AO No Rxn
64 16,405 25,481 1.70
86 17,100 21,600 1.83
90 17,800 20,520 1.20
95 19,000 21,220 1.22
96 19,100 19,970 1.26
41 8270 8690 1.32
60 11,840 12,490 1.25
28a 5650 5540 1.37
21a 4320 4730 1.40
No Rxn
16a 3200 4300 1.33 Polymerization did not occur past this limited conversion
Figure imgf000041_0001
Example 10: Kinetic Modeling.
The Predici program (version 6.3.1) was used for all kinetic modeling. It employs an adaptive Rothe methoU as a ήuήϊeΗcal sjχafegy"foτ"tinϊe:3iscrifizatiori. The
Figure imgf000042_0001
be followed with time. Each actual calculation took 3-5 min to complete on a personal computer. The modeling was conducted in order to obtain a clear picture of the kinetics of ICAR ATRP and determine whether the rate of polymerization in ICAR is governed by KATRP or by the rate of AIBN decomposition. (AIBN is being used herein as an exemplary free radical initiator and it is believed that any free radical initiator can be used. One would just insert the appropriate rate of decomposition into the formulae.) The multitude of parameters necessary for these simulations and typical rate constants for three CuBr2ZL complexes (with bipyridine (bpy), PMDETA, and TPMA) are shown in Table 12. These three catalysts were chosen for the modeling studies since they represent a broad range of KATRP values. Figures 9-11 illustrate the results of these simulations for the ICAR polymerization of styrene. According to these simulations, the polymerization rates for all three complexes are essentially the same (Figure 9), and the first order kinetic plots are (nearly) linear. This suggests that the concentration of radicals remain almost constant during the polymerization. The polymerization rate and radical concentration in ICAR ATRP does not appear to depend on the choice of catalyst or value of KATRP-
However, while the polymerization rate does not depend on the choice of catalyst, control over molecular weight and molecular weight distribution are catalyst dependent. As shown in Figure 10, when TPMA is used as the ligand (meaning a catalyst complex displaying appropriate values of activation and deactivation rate constants were employed in the simulations), polydispersity is low throughout the reaction (< 1.5) and approaches 1 at high conversion. Molecular weights increase linearly with conversion and are approximately equal to theoretical values. Similar results are observed with PMDETA, although polydispersity is slightly higher than in the reaction with TPMA. However, polydisperisty and molecular weights are less controlled when CuBr2/(bpy)2 is employed as the ligand to form the catalyst complex.
Table 12. Parameters and reaction conditions employed in Predici simulations of ICAR
Figure imgf000043_0001
DP=200, 50 ppm of Cu, [St] = 5.82 M, 600C; I2 = AIBN; RX = EtBrIB; M = St. St/EtBrIB/X-Cu"/AIBN = 200/1/0.01/0.1; t50o/o = 1.8E5 s
Source of the values of rate constants (60 0C): ftdc: the decomposition rate constant for ADBN at 60 0C [Bamford, C. H. & Tipper, C. F. H. (1976) Comprehensive
Chemical Kinetics, Vol. 14A: Free Radical Polymerization (American Elsevier, New York).] k&: the deactivation rate constant for free radical with X-Cu" species, estimated from kάcacl for ATRP (10"5 ~ 10'8 M"1 0 s"1) [Matyjaszewski, K., Paik, H.-j., Zhou, P. & Diamanti, S. J. (2001) Macromolecules 34, 5125.]
*ac«b *act: the activation rate constant for ATRP, measured at 35 0C and extrapolated to 60 0C. [Tang, W., Tsarevsky,
N. V. & Matyjaszewski, K. (2006) J. Am. Chem. Soc. 128, 1598-1604.]
*deactθϊ ^deπct: the deactivation rate constant for ATRP, calculated from KJKATKP at 35 0C and extrapolated to 60 0C.
[Tang, W., Tsarevsky, N. V. & Matyjaszewski, K. (2006) /. Am. Chem. Soc. 128, 1598-1604.] 5 Ato^ the termination rate constant for small molecular radicals. [Fischer, H, et.al. Ace. Chem. Res. (1987) 20, 200-206: and
Angew. Chem., Int. Ed. (2001) 40, 1340-1371.
Auand ka: the rate constant for addition of radicals from EBIB (Aii) and AIBN (k^) to styrene. Values are calculated at 60
0C from the frequency factor and activation energy taken from the literature [Fischer, H. & Radom, L. Angew. Chem., Int.
Ed. (2001)40, 1340-1371.]
Ap: the addition and propagation rate constant, kpis taken from the literature [Buback, M., et. al.: (1995) Macromol.
Chem. Phys. 196, 3267-80.]
AtC)A:ω: the termination rate constant for polymeric radicals, the combination rate constant (&,c) and disproportion rate constant (Jc^). Values estimated from the literature [Buback, M., et al.: (2002) Macromol. Chem. Phys. 203, 2570-
2582.] To better illustrate all intricacies of the ICAR ATRP system, kinetic plots were constructed, Figure 11, where the rates of evolution and concentrations of all species are ~ iϊlusiraied bn a"d6ύT5le-lόgarithmic scale iri the same
Figure imgf000044_0001
It can be seen " that the dormant species (the initial ATRP initiator, R-X, and the formed polymeric dormant species) remain constant throughout the reaction, which gives rise to a linear increase in molecular weight with monomer conversion, and further indicates that most of the chain end functionality survives throughout the reaction. The ATRP quasi-equilibrium (Ra ~ i?da throughout entire time span) was reached almost immediately (far before polymerization starts) due to the initial presence of the Cu11 species. Once this state is reached, the concentration of radicals, Cu1, and Cu11 remain essentially constant, and the termination rate (Rt) approaches the decomposition rate of AEBN (Ri). The radical concentration can be estimated by setting Ri = Ru i.e., Ik^[I2] = 2k,[R]) .
Figure imgf000044_0002
Equation (7) shows how the radical concentration (and hence, the polymerization rate) under steady state conditions is primarily dependent on the AIBN decomposition rate constant, its , concentration, and the radical termination rate constant. Radical concentration should therefore not be governed by the choice of ATRP catalyst, KATRP, or the initial concentration of Cu11 species. This further suggests that polymerization rates can be adjusted with the choice of an appropriate free radical initiator. These predictions are in relatively good agreement with experimental observations, where apparent rates of polymerization in CuCVMe6TREN, TPMA and PMDETA mediated polymerizations (entries 1, 2, & 3, Table 10) are very similar.
While polymerization rates are controlled by the decomposition rate of the free radical initiator in ICAR ATRP (as they are in RAFT and free radical polymerizations), control over polymer molecular weights and molecular weight distribution are still governed by the ATRP equilibrium reactions. The ratio of polymerization rate to the deactivation rate, i.e., (Ap[M])/(£da[Cuπ]), represents the number of monomer units that will add to an actively propagating radical chain before it is deactivated to the dormant state. This provides a qualitative method to estimate how well a given catalyst can control the molecular weight distribution in a polymerization (as will be illustrated below). Since such a small amount of Cu catalyst is employed in ICAR ATRP, catalysts with large values of KATRP (higher concentration of Cu11) and fast deactivation rate constants will minimize this ratio, allowing for more uniform polymer chain growth, i.e. less monomer units added at each activation step, hence ultimately better cbhfrH.iGu compTexes" with:TPMA have a large
Figure imgf000045_0001
. While the KATRP of CU/PMDETA complex is much lower (~ 5.9><10"8 at 600C)5 the deactivation rate constant (&da) for Cu/PMDETA is approximately six times larger than that of TPMA, which compensates for the product ofkάz[Cuu]. The Cu catalyst formed with bpy is the least active among the three complexes in this discussion, with .KATRP (<~3.6X10'9) and a relatively small k^ (8.3x106 M"1 s"1). The concentration of Cu11 species present at quasi-steady state can be estimated from the ATRP equilibrium.
Anp [Cu1 ][RX] ~ ([Cu1^0 -[Cu1 J)[RX]0
and where [R]8 is estimated from equation (7),
Figure imgf000045_0002
As calculated from equation (9), and illustrated in Figure 11, with their respective values of KATRP, 90% of the total concentration of Cu in the quasi-steady state exists in the Cu11 oxidation state for complexes with TPMA. This can be compared with just 7% for PMDETA and 0.3% for bpy. The ratios of (Ap[M])/(^da[Cuu]) at the quasi-steady state can be calculated from equation (7) and (9) and indicate that approximately 4.0, 9.3, and 230 monomer units will add to a propagating chain every time it is activated by Cu/L complexes formed with TPMA, PMDETA, and bpy, ligands respectively. These values are qualitatively consistent with the attainable control illustrated in Figure 6 for each system. The experimental value of Mw/Mn for the ICAR polymerization of St mediated by Cu complexed with TPMA is also in good agreement with Mw/Mn shown in Figure 6. However, in ICAR systems employing PMDETA as the ligand, control is overestimated in Figure 6 as complex stability is not taken into account in these simulations.
Within this application the concept of Initiators for Continuous Activator Regeneration in ATRP was introduced. ICAR ATRP allows use of 50 ppm or less of Cu catalyst to mediate well-controlled polymerizations of several radically (co)polymerizable monomers providing polymers with Mw/Mn < 1.2 with this technique. Other monomers disclosed in incorporated references wόuTdf also wbrlc " ^- - ^- -~ ~- - - ^ " : '~ — ~
The rational for selection of suitable Cu complexing ligands has been discussed in detail, primarily in regards to the value of KATRP for a given catalyst but also with respect to complex stability at high dilution and at elevated temperatures. For these reasons, it was determined that ' Me6TREN and TPMA were more suitable ligands than PMDETA and dNbpy in ICAR ATRP at low Cu catalyst concentrations; however, other ligands meeting the criteria discussed herein would also be expected to work. Indeed this provides a model for examination of potential ligands to predetermine whether they would be suitable for use in New ERA ATRP preparation of materials meeting targeted applications.
Experimental data as well as simulations confirmed that the rate of polymerization in ICAR is governed by the rate of free radical initiator decomposition (as in RAFT) while control is ultimately determined by KATRP and the rate of deactivation (as in ATRP).
Halogen Exchange
In further embodiments, ICAR ATRP and ARGET processes comprise a halogen exchange process. Halogen exchange processes comprise switching the radically transferable atom or group in a polymerization process to another radically transferable atom or group. In an example of halogen exchange process, the catalyst employed for the second step of a block polymerization is chlorine based while that employed for the first polymerization step was bromine based. The halogen on the growing chain end was converted to a chlorine soon after the macroinitiator was activated thereby, in the case of bromine to chlorine, slowing down the rate of propagation of the second polymerization to more closely to match the rate of initiation, for example. This cannot be accomplished when the ratio of catalyst to end group on the macroinitiator is significantly less than 1 : 1 and certainly not when less than 10%.
Two approaches were taken to resolve this issue.
One was a polymerization process comprising adding of a halogen containing salt to interact with the transition metal catalyst complex and converting the radically transferable atom or group, such as the bromine counterion/ligand to a chlorine counterion/ligand, for example. Organic and inorganic salts with the desired halide counterion were examined and a preferred salt is lithium chloride. Another approach was a copolymerization process for either ICAR ATRP or ARGET ATRP comprising forming the second block with a different monomer, such as, for example, styrene which
Figure imgf000047_0001
= and in the end group on the dormant growing polymer chain predominately comprised a styrene unit then the macromolecule could be controllably reactivated. This system was modeled by Predici and the results can be summarized as follows:
• The Λϋeact (2E6) for MMA in the simulation is 10 times smaller than before. This gives uncontrolled ICAR ATRP of MMA. Also, the
Figure imgf000047_0002
for MMA is 2 times smaller. (Figure 12) • Addition of styrene to the copolymerization process significantly increase the level of control over polymerization as seen in both DP and PDI. The addition of more styrene leads to better results, which is reasonable since polymerization of styrene is more controllable than MMA.
• Kinetically, to have a better control, one would expect the chain end to be preferentially capped with styrene as much as possible. That is to say, more chains that are terminated P2X ("2" refers to St) is preferable. While 5% of St is not enough to provide control when 20% of styrene is added to the copolymerization most of the chain ends (~90%) becomes styrene units. This is good enough for the control on DP but PDI is fairly broad at 1.25. More St is needed if one wants to have lower PDI. (Figure 8)
• The conclusion is that more styrene gives better control, and a minimum 10% of St is needed to have a better control in such an embodiment.
An embodiment of ARGET ATRP process comprised adding acrylonitrile to the polymerization of acrylate. The following polymerization conditions were performed: PBA-Br: Sty: AN: CuCl2: Me6TREN: Sn(EH)2 = 1 : 2000: 1300: 0.1 : 1 : 1 in anisole (1 vol equiv of monomers) at 8O0C. MnMMR 250,000; PDI 1.22..
Example 11: Expanding Range of Exemplified Reducing Agents.
Several variables were examined in the ARGET ATRP processes comprising butyl acrylate (Table 11). hi the first six experiments, the relative concentration of ligand to Cu is varied to trap evolving acid throughout the BA polymerization. The effect of the concentration of reducing agent on attainable control is investigated in the next eight experiments. The final two experiments employ another reducing agent, 4-methoxyphenol (MPO), which is much less reducing than the hydrazine derivatives, to mediate ARGET reactions. Optimized conditions were then extended to the excess reducing agent ATRP processes of MMA and St.
Mechanism of the Reduction Process and Relevance for Selected Reducing Agents. Desmarquest studied the mechanism and kinetics of reduction of CuCk by hydrazine. [Desmarquest, J. P.; Bloch, O. Electrochim. Acta 1968, 13, 1109-1113]. The final product of oxidation of hydrazine is molecular nitrogen and each step of this multi-step process is accompanied by liberation of acid. The rate-determining step is the reversible transfer of the first electron from N2H4 to the metal center leading to formation of the radical intermediate N2H3; it is characterized by rate constants ki = δxlO"4 M"1 s'1 and k_i = 3xlO3 M"1 s"1. The oxidation OfPhNHNH2 leads to the formation OfPhN=NH, again with the release of acid. [Kosower, E. M. Ace. Chem. Res. 1971, 4, 193-198.] However the studies of those redox processes are complicated by the fact that both N2H4 and PhNHNH2 form complexes with the Cu11 ions. [Srivastava, A. K.; Varshney, A. L.; Jain, P. C. J. Inorg. Nucl. Chem. 1980, 42, 47.] Competitive complexation with ligand will also have implications on the stability of the catalyst towards dissociation, and excess ligand maybe required in ARGET ATRP at concentrations where it is not required in ICAR ATRP. Retrospectively the role of trialkylamines in activating a catalyst complex disclosed in incorporated patents based on application 09/369,157 may be due to the reducing properties of the amine and would therefore account for the faster reaction producing broader MWD.
The oxidation of MPO and its derivatives by CuCl2 has also been studied. [Matsumoto, M.; Kobayashi, H. Synth. Commun. 1985, 15, 515.] The major product is/?- benzoquinone, but a small amount of o-chlorinated phenol is also formed. Although the kinetics of the reduction process have not been studied in detail, it was demonstrated that reduction of CuCl2 by MPO is relatively slow at ambient temperature.
Selection of the Ligand/Ligand Concentration.
The first six entries in Table 11 illustrate the dramatic difference in the level of attainable control over molecular weight distribution of poly(butyl acrylate) depending on the ligand employed (PMDETA, Me6TREN, or TPMA) and the concentration of the ligand relative to Cu. PDI, (Mw/Mn), for example, was much lower at similar conversions in a reaction employing a 3 fold excess of TPMA to 50 ppm OfCuCl2 compared to the analogous reaction with Me6TREN (Mw/Mn = 1.57 vs. 2.3, entries 2 & 4, Table 11). However, in both of these reactions, monomer conversion was limited to just 35%. No polymerization was observed after the first 24 hours in these reactions activated by a single addition of phenylhydrazine. Similar results (in terms of conversion limited to < 35%) were observed
Figure imgf000049_0001
with" hydrazine and a 3" fdld'excess 6f TPTvIΑ~fό~ Gu ("entries 12 & 13, Table 11). When a larger excess, such aslO fold, of free ligand was used, polymerization reached much higher conversions. In reactions mediated by 1 : 10 CuCl2/Me6TREN and CuCl2/TPMA, molecular weight distributions were very well controlled (Mw/Mn = 1.2-1.3, entries 1 & 3, Table 11). Observed molecular weights were also in good agreement with theoretical values, particularly in the case of TPMA.
However, no reaction was observed when a 10 fold excess of PMDETA to 50 ppm Cu was employed. Even when 500 ppm Cu was used with PMDETA, control over molecular weights and molecular weight distribution was worse (entries 5 & 6, Table 11). The behavior of the three complexes can in part be rationalized based on their stability towards dissociation which may be further compounded by the fact that these reducing agents can complex with the catalyst. The observation that, 50 ppm of CuCl2/PMDETA can mediate an ICAR ATRP while it cannot mediate an ARGET ATRP can be attributed to the stability of the ligand towards protonation in the presence of acid. Addition of a base should overcome this. Therefore, further embodiments of the polymerization process comprise adding a base to the polymerization medium.
Stability was quantitatively determined by both the value of βJ and the basicity of the ligand L. In the presence of an acid, the stability of the complex decreases by a factor of OCL (taking into account the amount of protonation or other side reactions of L) to a new value, termed the conditional stability constant β^'*. If any of the reaction components (monomer, solvent, polymer, reducing agent or the product of its oxidation, designated by A) reacts with the copper ions, the stability of CuVL decreases additionally by a factor of αcu taking into account these side reactions with A (characterized by stability constants βJcuJAm), according to eq (5). [Schwarzenbach, G. Die Komplexometrische Titration, 2nd ed.; Enke: Stuttgart, 1956. and Ringbom, A. Complexation in Analytical Chemistry; Interscience: New York, 1963.]
Figure imgf000050_0001
«« = 1 + βou-Λ [A] + βU2 [A]2 + ... + βUm MT
In the presence of side reaction, the amount of catalyst actually present in the system can be calculated using equation (6) but with the new conditional stability constant βJ'* instead of βJ.
Figure imgf000050_0002
Figure 11 illustrates the pH dependence of the stability of the Cu11 complexes of PMDETA, Me6TREN, and TPMA, calculated from equation 5 (knowing the protonation constants which are available in literature) and shows that the complexes of basic ligands are very much destabilized in acidic media, especially when their stability constants in the absence of protonation (Figure 12) are relatively low (e.g., the Cu11 complex of PMDETA). Figure 12 also illustrates why PMDETA is less applicable for ARGET ATRP than the other ligands. Further the complex of the basic Me6TREN is markedly more destabilized in acidic media than that of the less basic ligand TPMA. From the point of view of temperature and pH stability, TPMA appears a preferred ligand for ARGET reactions where one of the byproducts of the reducing reaction is an acid.
Varying Concentrations of Reducing Agent and Cu. The reducing agent will be quickly be consumed if too little is used, and too much might lead to fast and uncontrolled polymerizations or unwanted side reactions with the catalyst Amine based ligands can also act as reducing agents. [Wang, F.; Sayre, L. M. J. Am. Chem. Soc. 1992, 114, 248-255.] The results of BA ARGET ATRP in the presence of varied amounts of N2H4 reducing agent are also presented Table 11. In a control experiment, a 10 fold excess OfMe6TREN (with four tertiary amine groups capable of reducing On11) was used in the absence of any other reducing agent (entry 7, Table 11). Polymerization was initiated under these conditions in the presence of alkyl halide, suggesting that Me6TREN can reduce Cu11 (Mw/Mn > 1.8 at 86% conversion). Control over Mw/Mn is much better in the presence of an added reducing agent, N2H4. First order linear kinetics are also observed when a 10 fold excess of TPMA to Cu is used in the presence of a 5 fold excess OfNIH4 irfa hwΕKA" ATRP OΪBA~ The rate of polymerization Increase's"" - with increasing concentration OfN2H4, and first order kinetics remain linear (Figure 8). 5 Rates of polymerization similarly increase with increasing concentration of reducing agent when a 10 fold excess OfMe6TREN to Cu is employed. However, while good control is achieved over molecular weights and poldispersity, linear first order kinetics are not observed in the presence of a 5, 10, or 100 fold excess OfNjH4 (entries 7, 8, & 9, Table 11, Figure 9). While all five of these polymerizations are well controlled in terms of 0 narrow molecular weight distribution, steadily increasing molecular weights, and initiation efficiencies near 100%, the kinetics of the CuCIaZMe6TREN mediated system are not easily . explained. These observations may be a function of the lower relative stability of Cu complexes with Me6TREN vs. TPMA.
5 Examination of Other Reducing Agents.
In addition to hydrazines, another class of organic reducing agent was investigated with MPO. When 10 equivalents of this reducing agent were employed with CuCl2/TPMA in the ARGET ATRP of BA at 9O0C, no polymerization was observed. With -_. the use of 200 equivalents of MPO, 16% conversion was reached in 32 hours (although PDI 0 was relatively low, entries 15 & 16, Table 11). The inefficiency of MPO as a reducing agent (in terms of polymerization rate) compared to hydrazine and phenylhydrazine is fully consistent with the voltammetric data for these organic complexes; literature values for the oxidation waves of phenols are typically one full volt more positive than the oxidation waves of hydrazine derivatives in acetonitrile. [Sawyer, D. T.; Sobkowiak, A.; Roberts, J. J. 5 L.; Eds. Electrochemistry for Chemists: Second Edition; Wiley: New York, 1995.]
Reducing agents such as glucose were also examined. The polymerization process with glucose as the reducing agent stopped after 500 minutes or so. The kinetic plots and the molecular weight curves showed that each time ATRP stopped at 8-9 hours and then thermal initiated conventional radical polymerization of styrene took place, see 0 Figure 10. Addition of a base can potentially extend the conversion of a polymerization with glucose as a reducing agent by diminishing the protonation of ligand and in fact triethylamine was effective, hi addition, increasing the concentration of ligand also resulted in higher conversion. Another base, 1,4-di-tert-butyl-pyridine was probably to weak to affect protonation and the polymerization but the polymerization process still stopped prior to high conversion.
In these polyϊnerizaiiohsϊnl ^laeMtϊatiδή of Cu11 was not at an extfeπiely ~ - - - low level. In fact the stability constant OfMe6TREN and Cu is not very high which makes the concentration of ligand very important when [Cu] is low. When the concentration of ligand remained constant, the polymerization rate did not change too much with the change of [Cuπ], An ARGET ATRP with styrene as monomer and glucose as reducing agent the concentration of Cu(II) can be reduced to 10 ppm or below and the polymerization was observed to be under control; Figure 16.
ARGET ATRP processes comprising methyl methacrylate (MMA) and styrene.
ARGET ATRP processes comprising MMA initiated by EtBrIB at 600C resulted in observed molecular weights higher than theoretical values with Mw/Mn ~ 1.6 (entries 1 & 2, Table 12a). Better control was observed in the ARGET ATRP of MMA employing Sn(EH)2 as a reducing agent. Polymerization of St was initiated by EtBnB at 9O0C (where thermal initiation should not be significant) in the presence of a 10 fold excess OfPhNHNH2 and ligand to 50 ppm of Cu. These reactions were fairly well controlled (Mw/Mn ~1.3, entries 3 & 4, Figure 12a). However, polymerization reached limited conversions when phenylhydrazine was employed as the reducing agent. This could be due to the instability of phenylhydrazine in the presence of air or UV light making it incompatible with strong oxidizing agents. rhttp://www.phvschem.ox.ac.uk/MSDS/PH/phenylhvdrazine.html'|
No styrene polymerization was observed in the presence of hydrazine. To confirm suspicions that the alkyl halide chain end was reacting with hydrazine and consuming the reducing agent in polymerizations of styrene, a model kinetic study was conducted with a low molecular weight analogue of bromine-terminated polystyrene, namely 1 -phenylethyl bromide (1-PhEtBr), with both N2H4 and PhNHNH2. The nucleophilic substitution was followed by 1H NMR in DMSOd6, where it was determined that the reaction with N2H4 was markedly faster than with the less basic PhNHNH2. While nucleophilic substitution reactions will be slower in less polar solvents (DMF/monomer) than in DMSO, these results provide a satisfactory explanation for the aforementioned observations. In the presence OfN2H4, the alkyl bromide oligomeric initiator reacts very rapidly with the reducing agent and consumes it at an early stage of the reaction. As a result, essentially no polymerization is observed. When PhNHNH2 is employed, the model reaction indicates the substitution reaction is much slower, which is consistent with the observations that polymerization does occur but gradually slows down and stops before monomer conversion has been completed. While derivatives of hydrazine are obviously not well suited for polymerization of styrene earlier results indicate that -Sfi(EH)2 όr-glucose would be a ^ more apγrόpπ"ate"rVducing agenViή St ARGET ATR^ that one has to consider all side reactions when selecting the reducing agent. A series of MMA polymerizations were conducted with different initiators in order to determine whether there would be a big difference in degree of control over the polymerization. ARGET ATRP of MMA was controlled when very active initiators like BrPN was employed leading to polymers with low PDI and molecular weights close to theoretical values. (Table 12b)
SUBl
Cl
Table 12a. PMMA and PS prepared by ARGET ATRP.
_ Temp. CuCl2 Ligand / RA / Time Conv. Λ , Λ , , , ύΛ Entry O(/ Monomer/Initiator/Cu
[ppm] Ratio to Cu Ratio to Cu (min) (%). ^*60 M"'GPC MwTή
1 60 200 MMA/1 EtBrIB/0.01 50 Me6TREN/10 NH2NH2/10 1200 20 4030 13,160 1.6'I
Figure imgf000054_0001
[St]0 = 5.82 M, 50% DMF by volume; [MMA]0 = 6.23 M; 50% DMF by volume; Mn^e0= ([M]o/[In]o) x conversion
Figure imgf000054_0002
ttwn=(π> /TWrinln) x conversion
^l
ARGET ATRP process comprising MAO as a reducing reagent
In order to determine if the Cu^1V bpy complex could be reduced by methyl aluminoxane (MAO) all three reagelSs wereϊdled=seqύentially to a sealed'flask, thf reactiόri colof l&anged from green to dark brown indicating MAO reduced Cu(I1) (green) to Curo (dark brown). Two ARGET ATRP 5 processes were conducted comprising MAO as reducing agent. The results are shown below. Reaction conditions a)
BA/EtBriB/ Cu(1I)/TPMA/MA0 Cuppm Time (h) Conv. (%) Mn1H Mn0Pc Mw/Mn
A) 200/1/1/2/1 5000 3 79 20,200 21,000 1.32
B) 200/1/0.1/0.2/1 500 5 85 . 21,700 22,700 1.1 10 a) BA ; butyl acrylate, EtBrIB ; ethyl 2-bromoisobutyrate, temperature ; 60 0C,
Anisole was used as an internal standard (10 vol.% of BA)
With the lower level of copper the reaction was better controlled and followed linear increase in conversion with time with final molecular weight close to theoretical values and showed quite 15 narrow (PDI = 1.10 in 85% conversion). These results indicate that MAO is a good reducing reagent for ARGET ATRP and should work with reduced amounts of Cu and MAO.
Example 12. Synthesis of PSt-6-PBA Prepared by ICAR and ARGET ATRP.
20 A polymerization process comprising a ratio of reagents
[St]o:[EtBrIB]o:[CuCl2]o:[TPMA]o= 200 : 1 : 0.01 : 0.01; [St]0= 5.82 M; was conducted at 60 0C in 50% anisole by volume providing a macroinitiator of 11100 molecular weight and Mw/Mn 1.12. This macroinitiator was then extended with BA using ARGET ATRP, to minimize the production of new chains, employing |ΕA]0:|TSt]o:[CuCl2]o:[Me6TREN]o:[PhNHNH2]o= 400 : 1 : 0.02 : 0.1 :
25 0.1; [BA]0= 5.88 M; and a reaction temperature of 600C5 in the presence of 20% DMF by volume. Both polymerizations were carried out with 50 ppm of copper catalyst. Chain extension of the polystyrene macroinitiator with BA using ARGET ATRP with 50 ppm of copper proved very efficient and the final block copolymer had Mn,GPC = 65300, Mn)th= 52900, Mw/Mn=1.19. GPC traces of the polymers were monomodal after each synthetic step and illustrates the utility of
30 these techniques in the production of block copolymers. Example 13. (Co)polymerization of Different Monomers and Exemplification of Ability to Prepare High MW Polymers.
ATRP processes WithTdw concentration of copper catalysft," as 'low Is oFlϋwerthah 10 ppm, in the polymerization medium may suppress some of the side reactions associated with 5 one or both oxidations states of the transition metal complex and allow higher molecular weight copolymers to be prepared. This example demonstrates this advantage of low catalyst concentrations.
Control Run: Copolymerization of styrene and acrylonitrile by ATRP (amounts entry 2 in Figure 13a).
10 A Schlenk flask was charged with Me6TREN ligand (7.2 μl, 0.031 mmol) and copper (II) bromide (0.64 mg, 2.87 μmol), then anisole (5.52 ml) was added and the contents stirred. When the system became homogeneous styrene (4.0 ml, 0.0349 mmol), acrylonitrile (1.52 ml, 0.0231 mmol) and ethyl 2-bromoisobutyrate (8.12 μl, 0.0553 mmol) were added to the flask. After three freeze-pump-thaw cycles the flask was filled with nitrogen, then while the mixture
15 was immersed in liquid nitrogen, 4.11 mg (0.0287 mmol) of CuBr was added. The flask was sealed with a glass stopper, evacuated, and back-filled with nitrogen four times. After melting the reaction mixture and warming the contents of the flask to room temperature, the initial sample was taken and the sealed flask was placed in a thermostated oil bath at 800C. Samples were taken at timed intervals and analyzed by gas chromatography (GC) and gel permeation chromatography
20 (GPC) to follow the progress of the reaction. The polymerization was stopped by opening the flask and exposing the catalyst to air. The overall polydispersity of the polymer for both catalytic systems was low, especially at the moderate stages of the copolymerization, indicating good control over the reaction.
25 Considerations of ARGET ATRP of SAN: Copolymerization of styrene and acrylonitrile by ARGET ATRP (amounts appropriate for entry 4 in Figure 13b)
Styrene (4.0 ml, 0.0349 mmol), acrylonitrile (1.52 ml, 0.0231 mmol) and anisole (4.22 ml) were added to a dry Schlenk flask. Then a solution OfCuCl2 complex (0.223 mg, 1.66 μmol)/Me6TREN (0.38 μl, 1.66 μmol) in anisole (0.8 ml) and the EBiB (8.12 μl, 0.0533 mmol)
30 initiator were added. The resulting mixture was degassed by four freeze-pump-thaw cycles. After melting the mixture, a purged solution OfSn(EH)2 (8.95 μl, 0.0278 mmol) and Me6TREN (6.36 μl, 0.0278 mmol) in anisole (0.5 ml) was added. An initial sample was taken and the sealed flask was placed in thermostated oil bath at 80 0C. Samples were taken at timed intervals and analyzed by gas chromatography (GC) and gel permeation chromatography (GPC) to follow the progress of K s the reaction. The polymerization was stopped by opening the flask and exposing the catalyst to air. -" " ■-' " "
Figure imgf000057_0001
was used for
Figure imgf000057_0002
In order to examine some of the effects of catalyst complexes on the reaction two catalytic 5 systems were used for the synthesis of SAN by ATRP; copper (I) bromide complexes with dNbpy and Me6TREN respectively. Since Cu1 complexes with dNbpy are approximately 10,000 times less active than Me6TREN based copper complexes a significantly greater amount of dNbpy/Cu1 catalyst was used in Figure 13a entry 2 than the concentration OfMe6TREN based complex used in entry 1 in order to provide a sufficiently fast polymerization rate. Furthermore in the case of 0 the reaction using Me6TREN as complexing agent 10% of deactivator was added to increase initiator efficiency due to the persistent radical effect.
A preferred ATRP catalyst possesses a low affinity for alkyl radicals and hydrogen atoms on alkyl groups in order to suppress the contribution of side reactions in the transition metal mediated polymerization. In the case of copper-mediated ATRP of styrene loss of terminal 5 halogen functionality by elimination of HX results in loss of chain functionality and consequently loss of control over the reaction. [Matyjaszewski, K.; Davis, K.; Patten, T. E.; Wei, M. Tetrahedron 1997, 53, 15321-15329.] Studies with model compounds demonstrated that the elimination reaction was induced by the presence of the copper11 complex. This process was even more pronounced in bromine mediated ATRP than in chlorine transfer systems and was more 0 noticeable in the presence of polar compounds. In the case of a SAN copolymerization the highly polar nature of arylonitrile monomer exacerbates this specific side reaction. Another side reaction is due to a one electron oxidation of the polymeric radical by the copper11 catalyst to form a carbocation, which then eliminates a proton creating an unsaturated end group. This reaction can occur in hydrocarbon solvents. On the other hand, Lazzari [Lazzari, M.; Chiantore, O.; Mendichi, 5 R.; Lopez-Quintela, M. A. Macromolecular Chemistry and Physics 2005, 206, 1382-1388] proposed the reduction of the styryl radical by reaction with a proton source forms anionic intermediates that can result in dead polymer chains. Furthermore, there are also side reactions associated with the acrylonitrile radical that have to be considered. According to previous studies an acrylonitrile radical can easily react with copper1 complex to form a carboanion and copper11. 0 The carboanion is a very unstable and undergoes chain transfer termination. Additionally the copper center can coordinated with either the monomer or polymer chain through the cyano group resulting in its deactivation or lowering its effective concentration. Nevertheless on the base of copolymerization parameters calculated by Baumann et al [Baumann, M.; Roland, A.-L; Schmidt- Naake, G.; Fischer, H. Macromolecular Materials and Engineering 2000, 280/281, 1-6] it is the styryl radical which is predominately present in the active state (rs = 0.47±0.05, ΓAN = 0.03±0.03) and side reactions typical for that radical are thought to be the main reason for chain deactivation. -Probably all' aforementioned reactions:όaii"bccur"to various-degrees leading to less then ideal ~ * ' living behavior.
The experimental data for the copolymerizations are presented in Tables 13a and 17b and Figure 17 presents the semilogarithmic kinetic plot for polymerization of SAN with dNbpy and MeβTREN/Cu1 catalysts. It appears that neither dNbpy nor Me6TREN provide a constant number of growing radicals during the ATRP polymerization as severe deviations from the straight line can be observed, (Figure 17). Monomer conversion stopped at around 50% and 60% respectively, showing the deactivation of the active species. However the overall polydispersity of the polymer for both catalytic systems was low, especially at the moderate stages of the copolymerization, indicating good control over certain aspects of the reaction. The deactivation of active species for both catalytic systems is clearly seen from the shape of SEC traces (Figure 18). The initial narrow symmetrical peaks lose their regularity and a significant low molecular weight shoulder becomes visible. The tail and irregular shape of the curves were sustained as the molecular weight increases. However it has to be pointed out, the overall level of control remained satisfactory.
Table 13a. Experimental conditions and properties of SAN copolymers prepared by ATRP0
Figure imgf000058_0001
a The reactions were conducted in anisole at 80 0C. [Sty] = 3.17 M.
TbJ repieronas t
Figure imgf000059_0001
It appeared that it was not possible to suppress the side reactions by accelerating the reaction rate through addition of an increased amount of Me6TRENZCu1. Indeed, the reaction rate was initially signfficantiyϊaster, but at the same time the rate of irreversible termination of growing radicals was also enhanced. The reaction stopped at low conversion with very low initiation efficiency.
Synthesis of SAN by ATRP:
The main advantage of ARGET ATRP is that the system comprises continuous reactivation of a small amount of catalyst to maintain control. In most systems this means that catalyst solubility problems and purification issues are easily overcome. ARGET ATRP of styrene and acrylonitrile was conducted with ethyl 2-bromoisobutyrate (EBiB) as an initiator and MeβTREN/Cu as the catalyst. Experimental conditions and properties of the SAN copolymers prepared by ARGET ATRP are shown in Figure 13b. In order to optimize the amount of copper three different concentrations of catalyst were evaluated: 10, 30 and 50 ppm versus monomer (Figure 13b, entries 3-5). The amount of the reducing agent, Sn(EH)2 was kept constant at 50 mol% of the initiator. Kinetic plots for all aforementioned reactions with different copper concentrations are presented in Figure 19. As expected the rate of polymerization increased significantly as the copper concentration increased. A slight deviance from the straight line kinetic plots is visible which means that the number of radicals present in the system changed, to some extent, during the reaction but control was maintained. The theoretical molecular weight of the copolymer samples did not vary significantly from values obtained from GPC analysis. These results are significantly different than the results from the normal ATRP when the same monomer to initiator molar ratio was used. Figure 21 shows a smooth shift of the entire molecular weight distribution toward higher molecular weight for the system containing 30 ppm of catalyst: c.f. Figure 19.
When a higher DP was targeted, (DPn = 1650), polymerization was slower. Figure 17 presents the kinetic plots for the copolymerization of styrene and acrylonitrile with 30 ppm of copper versus monomer, as well as the molecular weight and polydispersities of the polymers formed in this system. Although the kinetic plot showed a very small deviation from linear characteristics and the molecular weight was only slightly different from theoretical, a constant increase of molecular weight distribution with conversion was observed. The increase in polydispersity was visible on the SEC traces with tailing to the low molecular weight species which means formation of dead chains from various termination reactions cannot be completely neglected and high monomer conversion cannot be attained with good control over polymerization under these conditions.
Sirnilarbehaviϋf was-'dbserved for the reaction where
Figure imgf000061_0001
- higher, DPn = 3300. In this reaction a higher concentrations of copper catalyst (50ppm versus monomer) and reducing agent were used due to the very high dilution of initiator in the reaction media but an even more significant deviation from the straight line on the kinetic plots was observed even though differences between theoretical molecular weight and that obtained from GPC measurements were negligible but again an increase in molecular weight distribution was observed when monomer conversion was still relatively low. The amount of solvent was reduced in order to increase the rate of monomer conversion and retain control over the reaction, (Figure 13b, entries 8-9). The actual concentration of monomers equaled 3.17 M and 5.07 M respectively and 30 ppm catalyst was used in these examples. Significant differences in the reactions rate were observed when the kinetic plots of the reactions were compared. At higher monomer concentration, 5.07 M, monomer conversion reached 70%, and while high molecular weight polymer was obtained Mn = 211 ,800 the molecular weight distribution was broader than desired, Mw/Mn > 1 A, but still within the range expected from a controlled reaction. Some deviance from theoretical molecular weight was also detected indicating some deactivation of radicals through side reactions with catalyst.
When the amount of copper was decreased to 10 ppm, keeping monomer concentration at the same level 5.07 M, the kinetic plot was linear, indicating a constant number of growing radicals, (Figure 13b, entry 10). Deviation from theoretical molecular weight was also smaller and molecular weight distribution was as low as 1.26 for SAN with molecular weight equals 166,200.
The high molecular weight SAN copolymer was obtained in a controlled radical polymerization, which leads to the conclusion that the very low concentration of catalyst used in this example significantly suppresses the side reactions of growing radicals with copper species leading to the preparation of well defined high molecular weight linear copolymers.
Copolymerization of SAN from a Macroinitiator: A macroinitiator was also used for the copolymerization of styrene and acrylonitrile. The macroinitiator used was a poly(ethylene oxide) based macroinitiator containing a terminal 2-bromoisobutyrate group. The reaction conditions are shown in Figure 13b, entry 13. The linear character of the kinetic plot indicates a constant number of growing species in the reaction medium, up to 20% of monomer conversion after which the rate of monomer consumption was reduced. Slight discrepancies between theoretical molecular weight and that determined by GPC was observed only the early stage of the polymerization, due to the presence
- - " of the macroinitiatof, and 1he%δlec1ilar"weig¥t "distribution remained low'at each stage of the polymerization pointing to the high degree of control over the process. 5
Synthesis of SAN from Di- and Trifunctional Initiators:
The reaction conditions developed using a monomfunctional initiator (EtBriBu) and PEO-macroinitiator were employed in a series of reactions with multifunctional initiators. Identical concentrations of catalyst and initiator were used in each system which should provide
10 the same number of growing radicals. The rate of polymerization was the same with all the initiators, indicating that each initiating site was independently participating in the polymerizations. However when the concentration of active species was kept constant for initiators with different functionality, the monomer-to-initiator ratio changes for each system which results in different rates of change of absolute molecular weight during polymerizations.
15 Noticeable deviations from theoretical values were observed only at higher molecular weight in case of SAN synthesized from di- and trifunctional initiating species. However the polydispersity of the polymer remained low Mw/Mn < 1.3, throughout the reactions indicating good control during each stage of the reaction. Using triple detector SEC, the absolute molecular weights of (branched) PSAN and PEO block polymers were measured. The value dn/dc of the polymer was
20 determined using a known concentration of linear PSAN solution in THF. The value of dn/dc for a copolymer of SAN with certain composition (styrene = 60%) is known and is equal to 0.157. The block polymer of PEOsooo-b-PSAN contains less than 5 wt% of PEO moiety so that the results obtained from 3D-SEC were still reliable. In addition, the number-average intrinsic viscosity was also given by the instrument. Table 12 compares the data measured by normal GPC
25 and 3D-SEC.
Table 12. Relative and absolute molecular weight data for SAN copolymers prepared from mono-, di-, and trifunctional initiators as well as PEO based macroinitiator
— Mn initiator SEC" 3D-SEC* [η]a c (dL/g)
EBiB 100 100 116 900 0.633
EBiB 211 000 216 600 1.013 di-BriBu 98 100 92 100 0.569 di-BriBu 157 000 160 400 0.846 tri-BriBu 98 400 126000 0.602 tri-BriBu 188 800 203 700 0.790
PEO50Oo-BnBu 100 800 98 900 0.641 a Measured by SEC with linear polystyrene standard. Measured by triple detection SEC and the dn/dc value of SAN copolymer (60% styrene) is determined as 0.157 mL/g. c Number-average intrinsic viscosity determined by 3D-SEC.
There was no significant difference between standard GPC and 3D-SEC for any of the copolymers, meaning the results obtained from standard GPC are reliable. Changes of the number-average intrinsic viscosity measured using the on-line viscometer corresponds to the expected trend for linear and star polymers: a star polymer has a lower viscosity than linear one with a similar molecular weight.
ARGET ATRP allows a significant reduction in the amount of catalyst complex employed in the reaction and it was possible to synthesize high molecular weight polymer due to significant suppression of side reactions through reduction of the absolute concentration of the copper species in the system. Side reactions between the growing radicals and the catalyst were avoided to a significant extent. The amount of copper species present in the system can be as low as 10 ppm without loss of control making this process very useful for industrial scale production. Polymerization with mono-, di- and trifunctional initiators low molecular weight initiators and a macroinitiator resulted in the formation of well-defined polymers with controlled architecture. Synthesis Of SiO2-PSAN:
SiO2-Br (20 nm): Sty/AN/SiOz-Br/CuOa^MesTREN/SnCEH^ = 2000: 1300: 1 : " =-ΘΓ10:T.O: LtπϊFamsolW"(l vol equiv of monomer) at 8O0C. Cu^Oppmf /The SEC trace of the sample taken at 42.4 h was symmetric with low polydispersity, indicating that there was no coupling reaction during the polymerization. From our previous experience, the initiator efficiency for polymerization of SAN on small silica particles is around 30%. The conversion at 42.4 h was estimated about 14% providing tethered chains with a molecular weight of 127,000 and PDI of 1.3 (measured from cleaved polymer). However as is common with multifunctional initiators in solution polymerization when the reaction was driven to higher conversion the polydispersity increased and some insoluble gel was observed, indicating some crosslinking had occurred. Composite structures can be prepared by ARGET ATRP processes.
As disclosed in other patent applications the use of mini emulsion ATRP allows for compartmentalization of multifunctional initiators in the well dispersed droplets and reduces crosslinking as a consequence of low instantaneous concentration of radicals in a given droplet. •
HEMA-TMS by ARGET ATRP:
Several polymerizations of HEMA-TMS were conducted targeting a high molecular weight polymer suitable as a backbone for a grafting from polymerization, m the past when targeting very high molecular weight p(HEMA-TMS) RAFT was selected as the appropriate CRP. In this series of runs the ratio of monomer to initiator was 10,000 to 1 and the amount of catalyst, tin and solvent were varied to find the best conditions. The best conditions were HEMA- TMS:EBiB:CuCl2:Me6TREN:Sn(EH)2 =10,000:1:2:25:25. in 50% anisole at 50 0C. The final polymer had Mn = 2.45 x 106 and Mw = 5.27 x 106 with a PDI of 1.63.
It is probable that early in the reaction there was some initial initiator/initiator termination reactions resulting a higher actual molecular weight than targeted for the selected level of conversion. As disclosed below, this phenomenon can be avoided by a sequential addition of the reducing agent which allows a slower activation/initiation procedure followed by an increased rate of polymerization.
High Molecular Weight Polyacrylonitrile (PAN) by ATRP
PAN is not soluble in monomer and most organic solvents such as THF, anisole, methanol, acetone. Generally when targeting high Mn one also attains high PDI and there is a non-linear first order kinetic plot of monomer consumption (ln(M0/M) vs. t) and inadequate characterization of Mn by GPC (DMF). The broader PDI can be attributed to side reactions. • Side reaction 2: too fast activation (~10 times faster than standard ATRP Initiator EBiB) —* too much termination.
• Side reactibn~2Vre3ucfϊόn of the radical to an anion by copper1: R* + Q? —^Rr resulting in loss of chain end. • Side reaction 3 : Cu center coordinating to cyano groups on monomers or polymers resulting in loss of catalyst: P-Br + R-CN → P-CN-R The following variables were examined and the best reagents are highlighted in bold font.
• Solvent: DMF5 EC, DMSO
• Initiator: BPN, CPN, BAN, CAN • Reducing agent: Sn(EH)2, ascorbic acid, glucose, phenylhydrazine
• Temperature: 65, 55, 40, 25 0C
• Amount of Cu11Cl2: 100, 75, 50, 25, 10 ppm
Initially the ARGET polymerization of acrylonitrile was slow therefore the reaction was examined with the addition of ascorbic acid and at higher temperature. Addition of ascorbic acid led to a fast reaction while higher temperature had no significant advantage. The use of Sn(EH)2 at 55 0C resulted in the production of a polymer with an acceptable PDI. The broader PDI was caused by the presence of a long tail in the GPC curve which was attributed to fast increase of initial molecular weight. The initiation was slowed down by using ClPN with Sn(EH)2 and later ClPN/BrAN with glucose at 25 ppm Cu but this resulted in a slower reaction with worse control !
A series of experiments were run with glucose as reducing agent.
The best results were obtained at 40-65 0C in DMSO as solvent. The mole ratio reagents used in such a reaction were:
AN: BrPN: CuC12: TPMA: glucose = 4000: 1: 0.2: 2.2: 2 in DMSO (2.5 vol equiv of monomer) at 40 0C.
This is the equivalent of 50 ppm Cu in the reaction. It is noteworthy that both the reaction medium and product were colorless. Conversion was estimated by NMR to be ~69% after 166 hours reaction. GPC indicates that measured Mn/3 is close to theoretical molecular weight based on conversion data. The clean shift of the GPC traces for this run can be seen in Figure 18. This example indicates that the reducing agent should be matched with the ligand and monomer(s). The Mn/3 of the sample was 135,000 and the polymer had a PDI of 1.18 indicating that there was almost no termination during the polymerization because when the reaction temperature is decreased, the chain transfer reaction rate is also decreased to a significant degree. PBA-b-PSAN by ARGET ATRP
PBA-Br: Sty: AN: CuCl2: Me6IjREN: Sn(EH)2 = 1: 2000: 1300: 0.1: 1: 1 in anisole (1 vol equiv ofmonomefs) at 80oe: TVIff250,000TDri.22. " ~τ-.- ' - " -----
Example 14. Polymerization of Monomers Bearing Additional Functional Groups. Preparation OfAMPSA27BA46SAMPSA27 by AGET ATRP:
AMPSA based block copolymers are desired as templating agents for the preparation of flexible conductive polymers however their preparation by standard ATRP techniques have met with a limitation on the MW of the AMPSA block. The following example was run under conditions developed for the preparation OfAMPSA27BA46SAMPSA27 in a standard ATRP reaction. The conditions for this AGET ATRP are similar to those used in the 'regular' ATRP polymerization of AMPSA, with the addition of a proportion of ascorbic acid in addition to the other components. In this type of reaction the role of the added reducing agent is to reactivate any excess Cu11 formed by termination reactions.
Figure imgf000066_0001
Scheme 2. Chain extension of a difunctional macroinitiator by AMPSA
General procedure:
AMPSA (16.6 g) was added to a Schlenk flask, along with 8.2 g of PBA macroinitiator (MW 60,000g/mol) and degassed for 30 minutes. Degassed tributylamine (19.2 mL) and degassed DMF (48 mL) were then added, followed by stirring until the AMPSA and PBA dissolved, then another 20 minutes of degassing. Copper chloride (79.2 mg), ascorbic acid (47 mg) and bpy (87.6 mg) were added to a separate Schlenk flask, and oxygen was removed by 3 cycles of vacuum pumping and nitrogen purging. Degassed DMF (3 mL) was then added to this mixture, and it was stirred for 10 minutes to allow the copper complex to form. A portion of the copper complex solution (1 mL) was then added to the reaction flask, followed by degassing for several minutes. The flask was lowered into a 600C oil bath, and the reaction was allowed to run overnight. The reaction was quenched by addition of DMF and exposure to air. The DMF/polymer solution was poured slowly into water, and the resultant micellar solution was
= = ^ • " puπSed^by dialysis for two days. iϊc^Bf dingTp ©Iy^GE€"analysis of ffie resultant product, the" difunctional macroinitiator was chain extended with polyAMPSA. After passing the polymer 5 through a Dowex ion exchange column, the molecular weight decreased (elution volume increased) due to loss of the tributylammonium counter-ion. The molecular weight of the macroinitiator was 60,000 g/mol by DMF GPC, while the final acid-containing block copolymer had a molecular weight of 82,000 g/mol, with a PDI of 1.13. According to elemental analysis this polymer is 27 wt% AMPSA, with a DP OfAMPSA53BA468AMPSA53 i.e. slightly less than twice
10 the amount of AMPSA present in polymers prepared by conventional ATRP.
Again this novel activation procedure reduces side reactions and provides materials with higher AMPSA content suitable for use in preparing templated conducting polymers with good mechanical properties. AGET ATRP of NIPAAm:
15 TPMA has been found to be an effective ligand for AGET ATRP of NIPAAm in water when using a solvent such as 2-propanol. The polymerization can be driven to >90% conversion and low polydispersity polymers can be obtained. When a ratio of NIPAAm (200), methylchloropropionate (1), TPMA (1), CuC12 (1), ascorbic acid (0.5) in 2-propoanol, 91% conversion was reached with Mn = 20,000 and PDI = 1.16. In an attempt to obtain higher
20 molecular weight polymer the molar ratio of NIPAAm to the other reagents was increased to 500. 1.0 grams of NIPAAm was used with 1.7 mL of 2-propoanol and 0.3 mL of water to help dissolve the ascorbic acid. The NPAAm, CuCl2, and TPMA were vacuum dried for 20 minutes. 1.2 mL of 2-propanol and MCP were added. This was bubbled with nitrogen for 40 minutes. In a separate flask, ascorbic acid was dried under vacuum and mixed with 0.5 mL 2-propanol and 0.3
25 mL of water and bubbled with nitrogen for 40 minutes. The flasks were combined to start the reaction. A molecular weight of 42,000 was obtained after 5 hours and the polymer displayed a PDI of 1.10. AGET ATRP of OEOMA 475 in Water, Targeting DP = 1000:
The AGET ATRP of OEOMA 475 using a bromine functionalized PEO5000 initiator was
30 investigated targeting high molecular weight polymer, i.e. DP = 1000. In the first set of experiments, the amount of reducing agent (ascorbic acid) was varied from 10 to 30 mol % of CuBr2. The results are summarized in the following table entries 1-3. Increasing the amount of ascorbic acid led to higher conversion. When ascorbic acid was added at only 10 mol % or 15 mol % of Cu11 the reaction reached limited conversion as evidenced by the plateau on the first order kinetic plots. Molecular weight linearly increased with conversion, and narrow polydispersity and monomodal distribution were observed. However, with 30% of ascorbic acid, although higher (xmversion"was"acKieved,"polydispersity was broader and a shoύrdet^as-observed onGPC traces.
Table 13a AGET ATRP of OEOMA 475 in water at 300C.
Figure imgf000068_0001
Reaction conditions: [OEOMA 475]/[PEO5000-Br]/[CuBr2]/[TPMA] = 1000/1/0.5/0.5. Water/monomer ratio (v/v) = 2.5 for all experiments.
hi a second set of experiments, the water to monomer ratio (v/v) was decreased thereby increasing the concentration of catalyst in the medium. The molar ratio of ascorbic acid to CuBr2 was chosen as 15%, since this condition seemed to provide a good balance between rate of polymerization and control among the previous experiments. Results are summarized as entries 4- 6 in the table below. Decreasing the water to monomer ratio (v/v) led to higher conversion. First order kinetic plots were linear but a plateau was still observed. Molecular weight linearly increased with conversion, monomodal distributions were observed and polydispersities remained quite low even at high conversion.
Table 15b AGET ATRP of OEOMA 475 in water at 3O0C.
Figure imgf000068_0002
Reaction conditions: [OEOMA 475]/[PEO5000-Br]/[CuBr2]/[TPMA] = 1000/1/0.5/0.5. [Asc Ac]o/[CuBr2]o = 15% for all experiments. In a third set of experiments, sequential addition of the reducing agent was performed. Ascorbic acid was added at zero time and at regular time intervals during the polymerization. Resulfi-ale sϋnimsfϊzid ϊfi th"e"Table 15c, entries 7-9. Since tEe reaction reacKed limited conversion after 30 minutes when ascorbic acid was added at 15 mol % of CuBr2 to start the polymerization, the same quantity was added every 30 minutes. As expected, the first order kinetic plot was linear and 76% conversion was achieved within 2 hours. Molecular weight increased linearly with conversion, and monomodal molecular weight distribution was observed and while polydispersity increased to 1.49 the GPC curve was still quite narrow and symmetrical.
When the water to monomer ratio was decreased from 2.5 to 2.0 by volume, keeping the same conditions, the first order kinetic plot was still linear but bimodality was observed in the GPC traces.
Table 15c AGET ATRP of OEOMA 475 in water at 300C.
Figure imgf000069_0001
Reaction conditions: [OEOMA 475]/[PEO5000-Br]/[CuBr2]/[TPMA] /[Asc Ac]0= 1000/1/O.5/O.5/0.075.
Sequential or gradual addition of the reducing agent therefore does allow one to control the rate of reduction and hence the ratio of Cu1 to Cu11 throughout the reaction and attain higher molecular weight materials.
Example 15. Development of a Simple Procedure for "Grafting from" Flat Surfaces.
The main goal of this example is to define and demonstrate a very simple procedure for grafting from flat surfaces with different monomers. The initial target was to perform AGET or ARGET ATRP at room temperature in the presence of a limited amount of air in a dish (e.g. Petri dish) which can be just simply covered and insulated with parafilm. In the first experiment a Petri dish was used, covered and insulated with parafilm. The polymerization did not occur even after degassing all the reagents with N2 and adding a higher amount of reducing agent Sn(EH)2. The next set of experiments were performed in a weighing dish, which is equipped with ground cover and is deeper than a Petri dish. This type of flask allows ready access to the contents but canT5effllled"clbs"eT:oτthe top wϊffi liquids then sealed in a similar "manner ϊo sT ~ ~ - -'- - ' commercial reactor. The conditions for the reaction, run WJ-04-71, and results are shown below. Conditions for the reaction
Figure imgf000070_0001
Solvent: anisole/acetone 0.05/0.05 volume equivalents vs. M. 1.5 equivalents Of Sn(EH)2 was added after 49.5 h.
All the reagents were mixed together in a weighing dish and bubbled with N2 for 20 min. Next, the initial sample was taken and then the reducing agent was added and reactor was sealed. After 49.5 h reactor was opened and a test sample was taken. (Time zero sample in Table 16) To check if polymerization can be continued the reaction mixture was bubbled with N2 again and an extra amount OfSn(EH)2 was added. Reaction was stopped after 95 h and the molecular weight of the tethered polymer had increased while PDI remained low thereby showing that two sequential controlled ARGET ATRP polymerizations had been conducted.
Table 16: Results
Figure imgf000070_0002
+ Sn(EH)2
Each opening of the reactor in Example 15 resulted in addition of air, which can consume catalyst and reducing agent, however, the molecular weight of the polymer moved to higher molecular weight without any sign of tailing. The polymerizations were well controlled, molecular weights were close to theoretical values and low PDI (1.28) was observed. This example does show that an ATRP can be conducted from a solid flat surface and that the initial presence of a small amount of air can be compensated for by addition of excess reducing agent.
- : - ■ '■-'- ' Further the successiverreactivation of the tethered chains shows thaftetKerea blδβE '^ copolymers can be prepared by this procedure and/or the terminal functionality can be modified to 5 attache additional responsive functionality.
Example 16. Non-Acid Forming Reduction Reactions.
A consequence of the examination of a broader spectrum of reducing agents suggests that it would be advantageous in certain circumstances to conduct the reduction with an agent that
10 does not release an acid upon oxidation. Examples of such reducing agents are viologens and sulfites. The reducing properties of viologens, which undergo electron transfer rather than hydrogen transfer seen with of ascorbic acid, 2,3-dimethoxy-5-methyl-l,4-hydroquinone, and the vitamin E analog Trolox, are easily adjusted by changing the substituents on the molecule. This would modify Scheme 1 in that the X atom or group no longer results in the formation of an acid which should
15 reduce the side reactions associated with acid forming reducing agents and allow the reaction to be conducted in the absence of excess ligand as demonstrated in ICAR ATRP.

Claims

1. A polymerization process, comprising:
~ polymerizing free radically Xcδ)pόlyMerfz~able monomers in a polymerization" medium comprising: one or more radically (co)polymerizable monomers, a transition metal catalyst complex capable of participating in a one electron redox reaction with an ATRP initiator; a free radical initiator; and an ATRP initiator; (wherein the concentration of transition metal catalyst complex in the polymerization medium is less than 100 ppm).
2. The polymerization process of claim 1 , wherein the concentration of transition metal in the polymerization medium is less man 50 ppm.
3. The polymerization process of claim 1, wherein the concentration of transition metal in the polymerization medium is less than 10 ppm.
4. The polymerization process of claim 1 , wherein the transition metal catalyst complex is a (pseudo)halogen transfer agent.
5. The polymerization process of claim 1 , wherein the radically polymerizable monomers are selected from the group consisting of monomer(s) of the formula:
Figure imgf000072_0001
wherein Rl and R2 are indepen ently selected from the group consisting of H, halogen, CN, CF3 straight or branched alkyl of from 1 to 20 carbon atoms, unsaturated straight or branched alkenyl or alkynyl of 2 to 10 carbon atoms, unsaturated straight or branched alkenyl of 2 to 6 carbon atoms substituted with halogen, C3-C8 cycloalkyl, phenyl which may optionally have from 1 to 5 sύbstituents on the phenyl ring selected from the group consisting of Cj-C6 alkyl, C1-C6 alkenyl, Q-Cό-alkoxy, halogen, nitro, carboxy, C1-C6 alkoxycarbonyl, hydroxy protected with a CpCe-acyl, cyano and phenyl, heterocyclyl, C(=Y) R5, C(=Y)NR6R7, YCR6R7R8 and YC(=Y)R8; where Y may be NR8 or O; R5 is alkyl of from 1 to 20 carbon atoms, alkoxy of from 1 to 20 carbon atoms, aryloxy or heterocyclyloxy; R6 and R7 are independently H or alkyl of from 1 to 20 carbon atoms, or R6 and R7 may be joined together to form an alkylene group of from 2 to 5 carbon atoms, thus forming a 3- to 6-membered ring; and R8 is H, straight or branched C1-C6 alkyl or aryl; and *a
R3 and R4 are independently selected from the group consisting of H, halogen, Ci-C6 alkyl and COOR9, where R9 is H, an alkali metal, or a Q-C6 alkyl group; or
" " Tt1 and"R3~may~be joined to ϊδrm a groujfdf theTόrmϋla (GES)nr of a group of the formula C(=O)— Y— C(=O). where n' is from 2 to 6, the group (CH2)n' may be substituted with from 1 to 2 n' halogen atoms or Ci-C4 alkyl groups, and Y is as defined above; and at least two of R1, R2, R3, and R4 are H or halogen.
6. The polymerization process of claim 1 , wherein the radically polymerizable monomers are selected from the group consisting of (meth)acrylate esters of Ci -C20, alcohols, acrylonitrile, cyanoacylate esters of Ci -C2o alcohols, didehydromalonate diesters of Ci -C6 alcohols, vinyl pyridines, vinyl N-Ci-C6 -alkylpyrroles, vinyl oxazoles, vinyl thiazoles, vinyl pyrimidines and vinyl imidazoles, vinyl ketones in which the α-carbon atom of the alkyl group does not bear a hydrogen atom, and styrenes which may bear a Ci -C6 -alkyl group on the vinyl moiety and from 1 to 5 substituents on the phenyl ring selected from the group consisting of Ci -C6 alkyl, Ci -C6 alkenyl, Ci -C6 -alkynyl, Ci -C6 -alkoxy, halogen, nitro, carboxy, Ci -C6 -alkoxycarbonyl, hydroxy protected with a Ci -C6 acyl, cyano and phenyl, methyl acrylate, methyl methacrylate, butyl acrylate, 2-ethylhexyl acrylate, and styrene.
7. The polymerization process of claim 1 , wherein the polymerization medium further comprises a solvent. *,
8. The polymerization process of claim 1 , wherein the polymerization medium further comprises water and the polymerization process is one of a suspension polymerization process, emulsion polymerization process, a miniemulsion polymerization process, or a microemulsion polymerization process.
9. The polymerization process of claim 1 , wherein the transition metal catalyst complex comprises a ligand.
10. The polymerization process of claim 9, wherein the stability constant of the transition metal catalyst complex is greater than 108.
11. The polymerization process of claim 10, further comprising forming a polymer comprising a molecular weight distribution of less than 2.0.
12. The polymerization process of claim 10, wherein the stability constant of the transition metal ligand is less than 108.
13. The polymerization process of claim 12, further comprising forming a polymer comprising a molecular weight distribution of less than 1.5. I
14. The polymerization process of claim 1 , wherein the free radical initiator is added to the polymerization process initially, slowly, sequentially, or continuously during the ": polymeSzmg." - " : i : " ">- ÷~ -;j - : :Ϊ~ ~ H_ I " :
15. The polymerization process of claim 1 , wherein the rate of the polymerization reaction is determined at least in part by the free radical initiator.
16. The process of claim 1 , where the value of Katrp for the transition metal catalyst complex is above 10"8.
17. A polymerization process, comprising: polymerizing one or more radically (co)polymerizable monomers in the presence of: at least one transition metal catalyst complex; and an ATRP initiator;; and a reducing agent; wherein the transition metal catalyst complex is present at less than 10"3 mole compared to the moles of radically transferable atoms or groups present on the ATRP initiator.
18. The polymerization process of claim 17, wherein the reducing agent comprises compounds capable of reducing the transition metal catalyst by one oxidation state.
19. The polymerization process of claim 18, wherein the polymerization process is one of a suspension polymerization process, emulsion polymerization process, a miniemulsion polymerization process, or a microemulsion polymerization process.
20. The polymerization process of claim 18, wherein the reducing agent is selected from the group consisting of includes SO2, sulfites, bisulfites, thiosulfites, mercaptans, hydroxylamines, amines, hydrazine (N2H4), phenylhydrazine (PhNHNH2), hydrazones, hydroquinone, food preservatives, flavonoids, beta carotene, vitamin A, α-tocopherols, vitamin E, propyl gallate, octyl gallate, BHA, BHT, propionic acids, ascorbic acid, sorbates, reducing sugars, sugars comprising an aldehyde group, glucose, lactose, fructose, dextrose, potassium tartrate, nitrites, nitrites, dextrin, aldehydes, glycine, and transition metal salts.
W . The polymerization process of claim 17, wherein the polymerizing is conducted in a polymerization medium and the concentration of transition metal in the reaction is less than 100 ppm.
12. The polymerization process of claim 21, wherein the concentration of transition metal in the reaction is less than 50 ppm.
3. The polymerization process of claim 21 , wherein the concentration of transition metal in the reaction is less than 10 ppm.
4. The polymeπzMόnprόceYsijβclaihi 17, wherein" the transition metal tϊatMysTc"όMpTe1ris "a- ~ ' (pseudo)halogen transfer agent.
,5. The polymerization process of claim 17, wherein the transition metal catalyst complex in an activator state is generated in situ from the reduction of the transition metal catalyst complex in the deactivator state by the reducing agent. :6. The polymerization process of claim 17, wherein the transition metal catalyst complex comprises a transition metal and a ligand. 7. The polymerization process of claim 17, wherein the ligand and transition metal form a transition metal catalyst complex wherein the higher oxidation state is an efficient deactivator. '8. The polymerization process of claim 26, wherein conditional stability constant of the transition metal catalyst complex is greater than 106. \9. The polymerization process of claim 17, wherein the ligand on the transition metal complex and the reducing agent are selected to control the PDI of the formed polymer. i Q. The polymerization process of claim 17, wherein the reducing agent is added continuously or periodically to the polymerization.
11. The polymerization process of claim 17, wherein the ligand is selected to provide a stable complex in the presence of an acid.
12. The polymerization process of claim 17, wherein the reduction of the transition metal catalyst complex in an deactivator state is to the transition metal catalyst complex in the activator state by the reducing agent does not result in formation of an acid.
13. The polymerization process of claim 17, wherein the reducing agent and catalyst complex act to remove oxygen from the reaction medium or reaction environment.
(4. The polymerization process of claim 33, wherein the ligand is present from greater than a stoichiometric amount relative to the transition metal to 10 times a stoichiometric amount relative to the transition metal. S 5. The polymerization process of claim 33, wherein the ligand is present from greater than a stoichiometric amount relative to the transition metal to 3 times a stoichiometric amount relative to the transition metal. 16. The polymerization process of claim 17, wherein the reducing agent and catalyst complex act to remove oxygen from the reaction medium or reaction environment.
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