Handbook of Polymer Synthesis Second Edition Episode 17 pot

Another option would be to use the term ‘living’ polymerization with quotation marks or apparently livingwhich could indicate a process of preparing well-defined polymers under conditions

Controlled/Living Radical Polymerization

Krzysztof Matyjaszewski and James Spanswick

Center for Macromolecular Engineering, Carnegie Mellon University,

of copolymers with properties dependent on the proportion of incorporated mers The major limitation of RP is poor control over some of the key structuralelements that allow the preparation of well defined macromolecular architectures such

comono-as molecular weight (MW), polydispersity, end functionality, chain architecture andcomposition

Living polymerization was first defined by Szwarc [2] as a chain growth processwithout chain breaking reactions (transfer and termination) Such a polymerizationprovides end-group control and enables the synthesis of block copolymers by sequentialmonomer addition However, it does not necessarily provide polymers with MW controland narrow molecular weight distribution (MWD) Additional prerequisites to achievethese goals include that the initiator should be consumed at the early stages ofpolymerization and that the rate of initiation and the rate of exchange between species

of various reactivity should be at least as fast as propagation [3–5] It has been suggested

to use the term controlled polymerization if these additional criteria are met [6] This termwas proposed for systems, which provide control of MW and MWD but in which chainbreaking reactions continue to occur, as in RP However, the term controlled does notspecify which features are controlled and which are not controlled Another option would

be to use the term ‘living’ polymerization (with quotation marks) or apparently livingwhich could indicate a process of preparing well-defined polymers under conditions

in which chain breaking reactions undoubtedly occur, as in radical or carbocationicpolymerization [7] The term controlled/living could also describe the essence of these

systems [6] and will be used in this chapter as we discuss in detail the polymerizationprocedures that have been developed for control over radical copolymerization of vinylmonomers.

Well-defined polymers with precisely controlled structural parameters areaccessible through living ionic polymerization processes, however, ionic livingpolymerization requires stringent process conditions and the procedures are limited

to a relatively small number of monomers [8–10] Therefore, it remained desirable toprepare, by free radical means which are more practical for industrial manufacturingprocedures, new well-defined block and graft copolymers, materials with star, comband network topology, end-functional polymers and many other materials preparedunder mild conditions, from a larger range of monomers, than available for ionic livingpolymerizations [11]

The concept of living radical polymerization was first discussed by Otsu [12] butdid not come to the forefront of scientific scrutiny until after the publishing of theinfluential work of Georges [13] in 1993 who had built upon the earlier work ofRizzardo [14] Georges pointed out to the scientific community that controlled radicalpolymerization was feasible This is one reason why since 1995 we have witnessed areal explosion of academic and industrial research on controlled/living radicalpolymerizations (CRP) with over five thousand papers and hundreds of patentsdevoted to disclosing, and improving the various types of CRP discussed in thischapter, and to developing an understanding of the implications of molecular structure

on material properties In all of the CRP processes developed to date there is a lowoccurrence of side reactions (e.g., termination or chain transfer) due to creation of adynamic equilibrium between a dormant species present in large excess and a lowconcentration of active radical sites By reducing the instantaneous concentration ofactive radicals, and hence the number of side reactions, polymerization is able toproceed in a controlled manner This results in the formation of (co)polymers havingpredictable MW and controllable MWD with MW increasing as a function of time in

a batch polymerization process, all the while maintaining a narrow MWD In almostall of the references included in this chapter initiation efficiencies are high, and theexperimental molecular weight is close to the theoretic molecular weight and MWD isless than 1.3 CRP is also able to produce materials with well-defined block lengths,complex architecture, and functionalized chain ends

There are several requirements that have to be met for any process that claims tocontrol radical polymerizations, including assuring quantitative initiation and suppressingthe contribution of chain breaking reactions All of the controlled/living radical basedprocesses developed to meet these requirements, along with many other new livingpolymerization systems, such as carbocationic, ring-opening, group transfer, ligatedanionic polymerization of acrylates, etc., depend upon the existence of a dynamicequilibration between an active and a dormant species In CRP the equilibrium is betweengrowing free radicals and some kind of dormant species [15] The equilibrium isestablished via activation (ka) and deactivation (kd) steps

Currently three approaches generally appear to be successful at controlling radicalpolymerization and the major processes will be discussed in historical order

1 Thermal homolytic cleavage of a weak bond in a covalent species whichreversibly provides a growing radical and a less reactive radical (a persistent orstable free radical) (Scheme 1) There are several examples of persistent radicalsbut it seems that the most successful are nitroxides [13,14,16], triazolinyl radicals

[17,18], bulky organic radicals, e.g., trityl [19–21] or compounds with photolabileC–S bonds [22] and some organometallic species [23–26].

Scheme 1

A subset of this process is the transition metal catalyzed, reversiblecleavage of the covalent bond in the dormant species via a redox process(Scheme 2) Since the key step in controlling the polymerization is transfer of anatom (or group) between a dormant chain and a transition metal catalyst in alower oxidation state forming an active chain end and a transition metaldeactivator in a higher oxidation state, this process was named atom transferradical polymerization (ATRP) [27–32]

Scheme 2

2 The second approach to CRP is based on a thermodynamically neutral exchangeprocess between a growing radical, present at very low concentrations, anddormant species, present at much higher concentrations (generally three tofour orders of magnitude) (Scheme 3) This degenerative transfer processcan employ alkyl iodides [33,34], unsaturated methacrylate esters [35,36], orthioesters [37,38] The latter two processes operate via addition-fragmentationchemistry

Scheme 3

3 Finally, there is a third approach that has not yet been as extensively examined

as the above systems This process is the reversible formation of persistentradicals, by reaction of the growing radicals with a species containing aneven number of electrons, which do not react with each other or with monomer(Scheme 4) Here, the role of a reversible radical trap may be played by

phosphites [39] or some reactive, but non-polymerizable alkene, such astetrathiofulvalenes, stilbene or diphenylethylene [40,41].

Scheme 4

In the remaining pages of this chapter we will discuss the chemistry of thesesuccessful approaches to controlled/living radical polymerization and some examples ofnew materials prepared by these techniques will be discussed

Several reviews devoted to CRP have been already been published, and readers mayrefer to proceedings from ACS Meetings on CRP [42,43], general reviews on CRP [44–48],reviews on ATRP [30,49–54], on macromolecular engineering and materials prepared

by ATRP [55], on nitroxide mediated polymerization (NMP) [56–58], on catalytic chaintransfer [59,60], and on reversible addition fragmentation transfer polymerization,RAFT [61]

REVERSIBLE THERMAL CLEAVAGE OF WEAK COVALENT BONDSThe homolytic cleavage of weak covalent bonds results in the formation of an activeradical capable of propagating the polymerization and a counter radical which, inprinciple, should only be involved in the reversible capping of the growing chains Thestable counter radicals should not react with themselves, with monomer to initiate thegrowth of new chains, or participate in other side reactions such as the abstraction ofb-H atoms These persistent radicals should be relatively stable, although some recent dataindicate that their slow decomposition may help in maintaining appropriate polymeriza-tion rates [17]

There are several examples of persistent radicals used in controlled radicalpolymerization but perhaps the most extensively studied are nitroxides, specificallyTEMPO [62,63] (Scheme 5) Hawker showed that the two radicals on the right-hand side

of Scheme 5 were not closely associated with each other during the polymerization [64]allowing for a statistical replacement of the nitroxide with functional end groups [65].Interesting results were also obtained with organometallic species, especially withparamagnetic high spin cobalt (II) compounds [23] However, often a particular trapacts efficiently only for one class of monomers For example, Co(II) porphyrine derivativesare excellent for controlling the polymerization of acrylates [66] but poor for styrene, whilefor methacrylates they act as very efficient transfer reagents (catalytic chain transfer) Thenitroxide TEMPO is efficient only for the CRP of styrene and its copolymers, however,some newly developed nitroxides have also been successful for acrylates [67].Consequently, the range of monomers controllably polymerizable by this procedure is

slowly expanding [58].

Scheme 5Nitroxides were originally described in the patent literature as agents in thepolymerization of (meth)acrylates [14], but the resulting products were essentially eitherstable oligo-polymeric alkoxyamines or unsaturated species It was only after the seminalpaper by Georges using TEMPO in styrene polymerizations at elevated temperatures(>120
C), that real advances in controlled radical polymerization were made [13] Initialresults were most encouraging, since they employed very simple reaction conditions(bulk styrene, [BPO]o: [TEMPO]o¼1.3 : 1 and simple heating) and obtained the desiredoutcome (DPn¼
[Sty]/[TEMPO]o in the range of Mn¼1000 to 50,000 and with lowpolydispersities, Mw/Mn<1.3) The reactions were slow with rates similar to the thermalpolymerization of styrene Under typical conditions, the majority of the chains are present

in the form of alkoxyamines, which are the covalent bonded dormant species, while a verysmall fraction of radicals are continuously generated by thermal initiation and by thethermal cleavage of the alkoxyamines ([P*]  108M) [68] Chains continuously terminate

by coupling/disproportionation and lead to an excess of TEMPO via the persistent radicaleffect ([TEMPO]  105M) [69–71] The alkoxyamine functional group on the chain endscan also slowly decompose and generate unsaturated structures and a hydroxylamine(Scheme 6) [72] that can be reoxidized to TEMPO in the presence of traces of oxygen

Scheme 6

In the system described by Georges control was initially relatively good but decreased

as the reaction progressed and molecular weights exceed Mn¼20,000, however, more recentwork indicates that molecular weights over 150,000 can be obtained [58,67] Typically,above 80% of chains are in the form of dormant, potentially active species but this numberdrops as chain length increases, the remaining 20% of chains are terminated and notcapable of growth Under appropriate conditions it is possible to conduct chain extensionsand therefore prepare block copolymers Several improvements to the original systemhave been made; these include the use of different initiators such as AIBN instead of BPO[73], using a simple pure thermal process [74,75], or preformed alkoxyamines, so-calledunimolecular initiators [76] Also di- and multi-functional initiators have been successfullyused to make novel materials with chains growing in several directions, or from multiplesites on a backbone polymer [57,77] The rate of polymerization can be increased over that

of TEMPO mediated systems by using new nitroxides, which are sterically bulkier anddissociate easier, thereby providing a larger equilibrium constant Examples include

phosphoric and phosphonic acid cyclic and acyclic nitroxide derivatives [78,79] ing N,N-(2-methylpropyl-1)-(1-diethylphosphono-2,2-dimethyl-propyl-1-)-N-oxyl, (SG1)expanding the range of monomers polymerizable by (NMP) (see Scheme 7) [67].

includ-Scheme 7 Phosphorous containing nitroxides

Rates of propagation for nitroxide mediated systems follow a simple law (Eq 1) anddepend on the concentration of radicals, which are defined by the equilibrium constant(Keq), and the concentration of dormant species [P-SFR] and SFR (Eq 2), where [SFR] isthe concentration of the persistent radical

However, when the equilibrium constants are very small the polymerizations are slow,

as in the classic case of the TEMPO mediated polymerization of styrene, Keq1011M

at 130
C In that case, the rate can be increased to an acceptable level by increasing thenumber of radicals either from thermal initiation by the monomer or by adding a secondconventional radical initiator, which has an appropriate lifetime at the polymerizationtemperature, such as dicumyl peroxide [68,80,81] In that case, the concentration of radicals

is defined by the balance between rates of initiation and termination:

A stationary concentration of SFR must therefore self adjust and be reduced tofulfill the equilibrium requirement and obey both equations (2) and (3)

Another approach to increase rates is to reduce the concentration of the SFR, such

as TEMPO, by other reactions The lower thermal stability of 4-oxoTEMPO results in itscontinuous decomposition, thereby reducing its concentration and resulting in a shift of theequilibrium towards more growing radicals, and finally faster rates The decomposition/dissociation may also be catalyzed intra- or inter-molecularly by addition of acidderivatives and acetyl compounds (potentially acid generators) [82,83] The principle oflow thermal stability of persistent radicals was also employed in the use of triazolinylradicals, which decompose at elevated temperatures and spontaneously reduce theirconcentration [17] Research is presently being focused on the high throughput synthesisfor the design of new alkoxyamine initiators for nitroxide mediated living free radicalprocedure [84] and Hawker has shown that the rates of polymerization can be significantlyenhanced, even when compared to the second generation a-hydrido-based alkoxyaminesrecently developed He has demonstrated that intramolecular H-bonding is a powerfultool for increasing the performance of alkoxyamine initiators for nitroxide mediated

living free radical polymerizations Increases in the rate of polymerization (ca 1000%)were observed for polar monomers such as acrylamides and especially acrylates [67], whileonly moderate improvements were obtained for non-polar monomers, such as styreneand isoprene In each case, the degree of control during the polymerization was improved,leading to lower polydispersities and a better correlation between experimental andtheoretical molecular weights Nitroxide mediated polymerization has also been conducted

in heterogeneous systems including emulsion [85,86], miniemulsion [87], and suspension[88,89], however, as fully discussed below for biphasic ATRP reactions, an understanding

of partition coefficients for all components of the system between all phases is critical for acontrolled polymerization [90,91]

Probably the most important factor for the future of NMP will be the development

of new compounds that allow polymerization and copolymerization of a broader range

of monomers under milder reaction conditions; we should however note that nitroxidemediated polymerization has already been applied to styrene [92], acrylates [93],acrylamides [94], acrylonitrile [67], dienes [95], and recently polymerization of ethylenehas been claimed to be controlled [96,97] NMP has also been extended to functionalmonomers such as sodium styrene sulfonate [98], 2-vinylpyridine [99,100], 3-vinyl pyridine[101,102], and 4-vinylpyridine [103] However, since a nitroxide residue ends up at the end

of each chain, these new compounds should be inexpensive, and introduce no adverseproperties (color, poor thermal stability, etc.) to the final material

RADICAL POLYMERIZATION

Atom transfer radical polymerization (ATRP) is based on the reversible transfer ofhalogen atoms, or pseudo-halogens, between a dormant species (Pn–X) and a transitionmetal catalyst (Mnt/L) by redox chemistry The alkyl (pseudo)halides are reduced to activeradicals and transition metals are oxidized via an inner sphere electron transfer process[28,50] In the most studied system, the role of the activator is played by a copper(I) speciescomplexed by two bipyridine ligands and the role of deactivator by the correspondingcopper(II) species Scheme 8, shows such a system with the values of the rate constant foractivation (ka), deactivation (kd), propagation (kp) and termination (kt) for a bulk styrenepolymerization at 110
C [32] The rate coefficients of termination decrease significantlywith the progress of the polymerization reaction due to the increase in the chain length andincreased viscosity of the system In fact, the progressive reduction of ktis one of the mostimportant features of many controlled radical polymerizations [104]

Scheme 8

The main difference between nitroxide mediated systems and ATRP is that the lattercan be used for a much larger range of monomers, including methacrylates, is practicalfor a full range of copolymerizations, and it is generally much faster [105] The rate

of propagation for an ATRP (Eq 4) can be adjusted conveniently, not only by theconcentration of deactivator but also by the concentration of activator, since catalysis is

at the very nature of ATRP [51] The activity of the catalyst can be adjusted by selection

of the ligand [106,107] and optionally addition of a solvent [108] The ligand can also

be selected for the reaction medium and can encompass hydrophilic or hydrophobicsubstituents, or in the case of polymerization conducted in supercritical carbon dioxide,fluroalkyl groups [109]

Chain breaking reactions do occur in these controlled radical systems [110],fortunately, at typical reaction temperatures, the contribution of transfer is relativelysmall For example, in the polymerization of styrene, less than 10% of chains participate

in transfer to monomer before reaching Mn¼100,000 However, since the tion of transfer progressively increases with chain length molecular weights should belimited by the appropriate ratio of monomer to initiator concentrations (for styrene

contribu-
[M]/[I]o<1000)

Termination does occur in radical systems and currently cannot be completelyavoided On the other hand, since termination is second order with respect to radicalconcentration and propagation is first order, the contribution of termination increaseswith radical concentration, and therefore also with the polymerization rate, consequently,most controlled radical polymerizations are designed to be slower than conventionalsystems It is possible to generate relatively fast controlled radical polymerizations, butonly for the most reactive monomers, such as acrylates, and/or for relatively short chains.For short chains, the absolute concentration of terminated chains is still high buttheir percentile in the total number of chains is small enough so as not to affect endfunctionalities and blocking efficiency A typical proportion of terminated chains liesbetween 1 and 10%, with a large fraction of those being very short chains that may notmarkedly affect the properties of the synthesized polymers and copolymers It is possible

to measure the evolution of concentration of terminated chains by following the copper(II)species by EPR in a system starting from pure copper(I) catalyst Commercially in asystem using a higher cost low molecular weight initiator the addition of copper(II) to the

system will increase initiator efficiency by reducing termination reactions between lowmolecular weight radicals.

The list of monomers polymerized successfully by ATRP is extensive andpolymerizations have been investigated with a wide range of transition metals includingcopper [27], ruthenium [111], iron [112–116], rhodium [117], rhenium [118] The mainrequirement for a transition metal catalyst to be suitable for an ATRP is an ability toundergo a one electron redox reaction with an appropriate redox potential selected forthe (co)monomers being polymerized The initial range of monomers, which started withpolymerization and copolymerization of styrene, acrylates, and methacrylates [28,119],have been extended to substituted styrenes [120], including 4-acetoxy styrene [121], benzylethers [122], and 4-trimethylsilyl derivatives [123]; substituted acrylates include methyland n-butyl [28,124–127], ethyl [128], t-butyl [129–132], and isobornyl [133,134];substituted methyl methacrylates [29,112,135–138], and various other alkyl methacrylates[131,134,139–144], including hydroxyethyl methacrylate [145,146], 2-(N-morpholino)ethylmethacrylate [147], 2-(dimethylamino)ethyl methacrylate [148,149], acrylamides[150,151], including methacrylamides [152–154], and substituted acrylamides, N-t-butylacrylamide homopolymer and N-(2-hydroxypropyl)methacrylamide [153], alsovinylpyridine [100,155] and dimethylitaconate [156] In addition, several other monomershave been successfully copolymerized using ATRP and include, for example, isobutyleneand vinyl acetate [157]

A big advantage of any radical process, ATRP included, is its tolerance to manyfunctional groups such as amido, amino, ester, ether, hydroxy, siloxy and others All

of them have been incorporated as substituents into (meth)acrylate monomers andsuccessfully polymerized One current exception is a ‘free’ carboxylic acid group whichpotentially complexes with the catalyst and disables ATRP, and therefore, presently, it has

to be protected Recent work has shown that monomers bearing ionic substituents such

as sodium 4-vinylbenzoate, sodium 4-vinylbenzylsulfonate and 2-trimethylammonioethylmethacrylate methanesulfonate and triflate, and dimethylaminoethyl methacryate can bepolymerized directly [148]

Another advantage of ATRP is a multitude of commercially available initiators.Nearly all compounds with halogen atoms activated by the presence of b-carbonyl,phenyl, vinyl or cyano groups have been used as efficient initiators Also compounds with aweak halogen–heteroatom bond can be used, such as sulfonyl halides [31] Small moleculeinitiators can carry additional functionalities, a few examples are shown in Scheme 9, thefunctionality is incorporated at the residual chain end

Scheme 9 Some low MW functional ATRP initiators

Many compounds with multiple active halogen atoms have been used to initiatebi- or multi-directional growth to form ABA block copolymers and star-like polymersand copolymers [158] Active halogens can be incorporated at the chain ends of polymers

prepared by other techniques such as cationic, anionic, ring-opening metathesis andconventional radical processes to form macroinitiators Such macroinitiators have beensuccessfully chain extended via ATRP to form novel diblock, and triblock copolymers[159–162] A useful tool that is available for the preparation of block copolymers when thesecond monomer to be polymerized is a methacrylate is the halogen switch technique [163],which allows one to match the rate of initiation with the rate of propagation.

When the active halogen is incorporated along the backbone of a (co)polymer,graft copolymers are formed Many commercial polymers including modified poly-butene, polyisobutylene, polyethylene, and polyvinyl chloride have been used asmacroinitiators for the preparation of graft copolymers by the ‘grafting from’ procedure[164–166]

The halogen atoms, at the active chain ends, can be removed either by a reductionprocess or transformed to other useful functionalities [167], as shown for styrene andacrylate systems (Scheme 10) [168]

Copolymerization is facile and many statistical, gradient and block copolymershave been prepared [143,174,175] The reactivity ratios are nearly identical to conventionalradical processes [50,176] The key feature of ATRP is a transition metal compound, that

is made available to participate in a redox cycle with the initiator or growing polymerchain, most often this is accomplished by complexation of the transition metal with asuitable ligand This ligand should assure solubility of both oxidation states of the catalyst,adjust its electronic and steric properties, and should enhance the versatility of atomtransfer chemistry when compared to other reactions The catalyst complex shouldallow for a dynamic atom transfer by the reversible expansion of the coordinationsphere Successful ATRP polymerizations have been conducted with transition metalcomplexes based on Cu, Ru, Fe, Ni, Pd, Rh [105,126,135,138,139,116,157] Ligands areusually mono or polydentate species such as ethers, amines, pyridines, phosphines and thecorresponding polyethers, polyamines and polypyridines The transition metal complex

is very often a metal halide but pseudohalides, carboxylates and compounds with coordinating triflate [177] and haxafluorophosphate anions [128] have been also usedsuccessfully Transition metal salts comprising an onium counterion [178,179],and solutions of transition metals salts in ionic liquids, have also been used for ATRP[172,173]

Control by degenerative transfer (DT) involves perhaps the smallest change from

a conventional free radical process of all the controlled/living polymerizationprocesses developed to date A recent review of various methods of telomer synthesis[180] discusses the different types of transfer agents and monomers and the contribution

of the techniques of telomerization to CRP (includes discussion of iodine transferpolymerization, RAFT, and macromolecular design through interchange of xanthates(MADIX)) [181,182]

DT relies on a thermodynamically neutral (degenerative) transfer reaction Thekey for control is a minimal energy barrier for that reaction Conventional free radicalinitiators are used, i.e., peroxides and diazenes, at temperatures typical for radicalpolymerization and the polymerization is carried out in the presence of a compound with alabile group or atom which can be either reversibly abstracted or added-fragmented bythe growing radical The simplest examples are reactions in the presence of alkyl iodides[33,183–184]; Scheme 11:

Scheme 11

unsaturated methacrylate esters [36]:

Scheme 12and dithioesters [37]:

Scheme 13Polymerization rates in degenerative transfer are typically the same as in aconventional radical polymerization process, however, molecular weights and polydisper-sities are much lower [183] The degree of polymerization is roughly defined by the ratio

of the concentration of converted monomer to the added transfer agent (more precisely asum of concentrations of transfer agent and consumed initiator):

overall relative rate of degenerative transfer One is the structure of the alkyl group in theinitial transfer agent, the second is that of transferable atom or group and the third can

be the substituent stabilizing the radical It appears that for degenerative transfer, the onlyacceptable atom is iodine with the transfer coefficient in polymerization of styreneand acrylates being in the range of ktr/kp2 to 3 Degenerative transfer with bromine orchlorine was much too slow; the polymerizations behaved the same as without addedtransfer agent Transfer coefficients for aryl halcogenides are also relatively slow; rates foraryl sulfides correspond to that for chlorides, aryl selenides to bromides and potentiallyonly tellurides could have sufficient transfer rates, similar to those for iodides (see Curran,

D P [185])

The other class of compounds useful for degenerative transfer reactions are thosewith either C ¼ C or C ¼ S double bonds Methacrylate derivatives have transfer ratessimilar to that of the propagation of methacrylates, and are successful only for thepolymerization of methacrylates [35,36] Due to steric effects the intermediate radicalshown in Scheme 12 cannot react directly with monomer but only fragment.Unfortunately, mono substituted alkenes such as styrenes and acrylates react with theintermediate radicals and give branched structures, i.e., there is inefficient fragmentation.Among compounds with C ¼ S double bonds, dithiocarbamates were initially used.This system was used by Otsu in the first studies of controlled radical polymerizations,and he termed them iniferters [12,46] The main mode of action for these compoundswas, however, a photochemical cleavage rather than bimolecular degenerative transfer(ktr=kp<0:1)) Subsequently replacement of the electron donating group in dithiocarba-mates (–NR2) or xanthates, (–OR) by an electron neutral (–Me, –Ph) group, or electronwithdrawing (–CN) group increased enormously the relative rates of degenerative transfer

to values of ktr/kp>100 [37] This new process, called reversible addition fragmentationtransfer (RAFT) [186] can be applied to the polymerization of many monomers includingstyrene, (meth)acrylates and vinyl benzoate [187,188] has been conducted in emulsionsystems [189], with functional monomers such as 4-acetoxy styrene [190], and enablesthe synthesis of new block copolymers However, the efficiency of the block copolymersynthesis, as well as the consumption of the initial transfer agent depends strongly onthe structure of the alkyl precursor For example, cumyl derivatives have been excellenttransfer agents in RAFT but, isobutyrate derivatives were unsuccessful in polymerization

of MMA As described by Moad [61], the choice of CTA is critical in producing monodisperse polymers via the RAFT process It was noted that fragmentation efficiency

near-is governed largely by the steric hindrance of the leaving group However, the stability ofthe leaving radical cannot be ignored Another consideration for choosing an appropriateCTA is the ability of the leaving radical to initiate polymerization Ideally, the leavinggroup of the CTA would preferentially fragment, yielding a radical that would quicklyadd to monomer, Scheme 13 Indeed the role of the structure of the chain transfer agent

in the polymerization of N,N-dimethyl-s-thiobenzoylthiopropionamide was examined byDonovan and coworkers [191], and they attributed the success of N,N-dimethyl-s-thiobenzoylthiopropionamide as the CTA to faster initiation rates of acrylamido radicaland the increased steric bulk of the leaving group The reaction can also be conducted inemulsion systems [188,192]

This would indicate that RAFT is in many ways similar to NMP and ATRP in thatthe components that contribute to the dynamic fast and reversible equilibrium betweendormant and growing species have to be selected for each monomer, if the full benefits of acontrolled polymerization are to be optimized, a set of universal reagents, or conditions,

do not yet exist for any of these systems

Work on design and use of molecules suitable as iniferters continues and recentlyseveral block copolymers such as poly(vinyl acetate-b-styrene-b-vinyl acetate), have beenprepared utilizing di-Et 2,3-dicyano-2,3-di( p-N,N-diethyldithiocarbamymethyl)phenylsuc-cinate (DDDCS) as a multi-functional iniferter Under heating without ultra-violet (UV)light, DDDCS acts as a thermal iniferter by the reversible cleavage of the hexa-substitutedC–C bond, while under UV light irradiation at ambient temperature, it serves as aphotoiniferter by the reversible cleavage of the two diethyldithiocarbamyl (DC) functionalgroups [193] The polymerization proceeds by a CRP mechanism realized by a macro-iniferter technique The macro-iniferters were designed and synthesized by CRP of vinylmonomers The polymers bearing alpha- and omega-DC end groups are macro-inifertersand can be used for the preparation of ABA triblock copolymers with different blockcomponents [193] Thioether-thiones have been used for the preparation of severaldifferent block copolymers [194].

Another approach that has provided some level of control over radical tion has been the use of cobalt complexes as transfer agents and has been employed forpolymerization of styrene, acrylates and methacrylates [195]

RADICAL POLYMERIZATIONCurrently, the three most efficient methods of controlling radical polymerization areNMP, ATRP and degenerative transfer Each of these methods has advantages over theother processes and also some drawbacks that may direct the choice of process employedfor preparation of a particular material The relative advantages and limitations ofeach method can be grouped into four categories They include range of monomers,reaction conditions, active end groups and other required components such as catalysts,accelerators, etc

Specific nitroxides have to be selected for specific monomers [58] TEMPO can besuccessfully applied only to styrene and copolymers due to its relatively small equilibriumconstant Polymerization of acrylics requires the use of either nitroxides with a higherequilibrium constant (phosphate derivatives) or those with a lower thermal stability (4-oxyTEMPO) Homopolymerization of methacrylates still await the development of a suitablenitroxide [196], although methacrylate containing copolymers can be prepared [67].Together these limitations indicate that nitroxides still have to be developed that willallow for greater freedom in cross-propagation reactions to afford increased capability toprepare copolymers and block copolymers Typical reactions are carried out in bulk and

at high temperatures (>120
C for TEMPO) because the reactions are inherently slow.Polymerizations in solution, dispersion and emulsion have been reported [85,91,171] Theinitiator can be either a combination of conventional initiator and free nitroxide (1.3 : 1ratio is apparently the best) [13] or a preformed alkoxyamine can be used [76] End groups

in the dormant species are alkoxyamines although some unsaturated species formed

by abstraction of b-H atoms or other inactive groups formed by side reactions, e.g.,termination can also be present Alkoxyamines are relatively expensive since they arejust beginning to become commercially available on an industrial scale Nitroxides aregenerally difficult to remove from the chain end, although chain end functionalizationchemistry is being developed [198] On the more positive side the process typically does notrequire a catalyst and is carried out at elevated temperatures, optionally in commerciallyavailable standard free radical polymerization equipment The polymerizations are usually

slow, although some acceleration was reported in the presence of additional radicalinitiators [81,199], sugars, acyl compounds [83], and acids [82] and anhydrides [200] thatact to control the concentration of the deactivator.

ATRP has been used successfully for the largest range of monomers, although thedirect polymerization of vinyl acetate and acrylic acids has not yet been successful ATRPhas been carried out in bulk, solution, dispersion and emulsion at temperatures rangingfrom  20
C to 130
C Some tolerance to oxygen has been reported in the presence ofzero-valent metals [201] The catalyst complex is based on a transition metal that regulatesboth polymerization rate and polydispersity furthermore since the catalyst must beavailable for the reaction to occur both oxidation states should be sufficiently accessible

in the reaction medium The catalyst can be selected to facilitate cross-propagation for thesynthesis of difficult block copolymers, and can scavenge some oxygen through in situformation of the deactivator, but in homogeneous systems it should be removed orrecycled from the final polymerization product since the concentration of the transitionmetal complex is generally higher than desired in most products In some supported orhybrid catalyst systems the concentration of transition metal in the final product may beacceptably low [202–205] Perhaps the biggest advantage of ATRP is the readily accessibleinexpensive initiators whose active end group, normally consists of simple halogens This

is especially important for lower molecular weight polymers due to the high proportion

of the end groups Additionally, there is a multitude of commercially available initiators for ATRP Moreover, the halogen end groups can be easily displaced with otheruseful functionalities using SN2, SN1, radical or other chemistries [206,207]

macro-Most of the work reported in the open literature has used Schlenk techniques for thepolymerizations but this reflects a desire to obtain reproducible kinetics and the use ofmonomers stored long term under normal laboratory conditions, rather than indicating

a need for excessive purification of commercially available materials It is expected that incommercial scale operations use of standard industrially available radically polymerizablemonomers would not require any pretreatment of the reaction medium prior to initiation

of the controlled polymerization

Degenerative transfer can potentially be used for any radically polymerizablemonomer However, reactions of vinyl esters are apparently more difficult and RAFTpolymerization of vinyl benzoate requires very high temperatures (T  150
C) It may bedifficult to assure an efficient cross-propagation for some systems [208] In principle,all classic radical systems can be converted to RAFT, or to another degenerative transferprocess, in the presence of efficient transfer reagents With the current systems theend groups are alkyl iodides, methacrylates or thioesters The latter are colored and canprovide some odor for low molar mass species and require radical chemistry for removaland displacement Methacrylate oligomers are efficient only for the polymerization ofmethacrylates No transition metal catalyst is needed for activation in degenerativetransfer since that role is fulfilled by addition of a standard radical initiator however thisresults in the incorporation of some undesired end groups The amount of termination

is governed by the amount of decomposed initiator A potential disadvantage ofdegenerative transfer is that there is always a low molecular weight reactive radicalavailable for termination reactions, in contrast to the ATRP and TEMPO systems where

as conversions increase only reactive radicals associated with longer chains exist, andtermination reactions occur more slowly

Thus, the prime advantage of the nitroxide mediated system is the absence of anymetal ATRP may be especially well suited for low molar mass functional polymers due tothe low cost of end groups and easier catalyst removal from low viscosity systems It may

be also very suitable for the synthesis of ‘difficult’ block copolymers and some specialhybrids with end functionalities However, it requires catalyst removal or the use of asupported catalyst Degenerative transfer, and especially RAFT, should be successfulfor the polymerization of many less reactive monomers and for the preparation of highmolecular weight polymers It is likely that the search for new efficient transferable groupswill continue due to some color and odor limitations of the sulfur containing compoundscurrently employed.

RADICAL POLYMERIZATIONAfter all this discussion about radical polymerization and new methods to developprocesses to obtain better control of the polymerization, the question remains: Why? Whyshould one use these novel methods to polymerize vinyl monomers? The answer that firstcomes to mind is supplementation of anionic and cationic polymerization as the primarymeans of obtaining well-defined (co)polymers, in these cases by radical polymerizationprocesses which are more tolerant of impurities, functional groups and are applicable to awider range of monomers This increased level of control over radical polymerizationwill allow industry to tailor a material to the requirements of a specific application usingthe most robust polymerization process available, ensuring the polymers have the optimalbalance of physical and chemical properties for a given application

Well-defined (co)polymers are generally recognized as polymers with molecularweights defined by DPn¼
[M]/[I]o, and with low polydispersities, say, Mw/Mn<1.3 (anarbitrary figure) However, such homopolymers are of little interest commercially; insome instances, materials with broad molecular weight distributions are desired forvarious rheological reasons What controlled/living polymerizations offer is the ability

to prepare entirely new polymers with a myriad of compositions, architectures, andfunctionalities (Figure 1) with each polymer chain in the bulk material having the samemicrostructure (composition, architecture and functionality) (Table 1), and not adistribution of composition and properties from chain to chain

When two or more monomers are combined and polymerized, statistical copolymersare formed where the relative compositions of the monomers in the polymer chain is afunction of the reactivity ratios and the monomer feed ratios at the instant ofpolymerization In conventional radical polymerization, high molecular weight polymer

is formed early in the reaction and then is irreversibly terminated As one monomer isgenerally consumed faster than the other(s), there is a faster depletion of that monomercompared to the other monomers fed to the reactor At higher conversions, the morereactive monomer will likely be present only in low amounts, while the other(s) will bepresent in higher amounts, which leads to polymers that contain lower (or zero) amounts

of the first monomer when compared to the chains prepared early in the polymerization.This gradient of compositions from chain to chain can be overcome by continuouslyadding monomer(s) so that the monomer feed remains relatively stable throughout thepolymerization In contrast, for controlled polymerizations, all chains grow at nearly thesame rate, with little irreversible termination The relative rate of monomer consumption

(based on the reactivity ratios) is nearly the same as in a conventional process [50,209].What is different is that the relative amount of monomer A vs B in the polymer chainsdoes not vary from chain to chain, but along the chains themselves This results in thepreparation of novel gradient copolymers [210], where composition of the copolymergradually changes from a higher concentration of one monomer to the other alongthe length of the chain Such polymers have been prepared by nitroxide based systems[63,211], by ATRP [157,212], and by RAFT [38,213] (Table 1).

Instead of a gradual change in the composition, an abrupt transition from onemonomer to another may be desired as in segmented copolymers, i.e., block and graftcopolymers Block copolymers can be prepared in one of two manners: through the use ofmacroinitiators or by sequential addition of monomer Macroinitiators can be prepared by

a number of polymerization techniques, including controlled/living radical tion In this case, a monomer is polymerized and the polymer is isolated then dissolved in

polymeriza-a second monomer polymeriza-and used to initipolymeriza-ate polymerizpolymeriza-ation, in this mpolymeriza-anner, there is polymeriza-a very clepolymeriza-anbreak between monomer units (blocks) Such a methodology has been used to prepareblock copolymers that act as thermoplastic elastomers [175,238] and as amphiphiliccopolymers [149,239,240] The isolated macroinitiator approach has been extended toprepare ABC and ABCBA block copolymers by sequential polymerization of threedifferent monomers [241] In another approach to block copolymers a second monomercan be added at the end of the polymerization of the first monomer This sequentialaddition of monomer may result in a slight taper or gradient of the transition from block AFigure 1 Molecular structures possible with controlled/living polymerizations

to block B if monomer A is not completely consumed Novel materials may be developed

by adjusting the length and degree of this taper and this affects the properties of theresulting block copolymer [54,210]

Nitroxide-mediated polymerization has been used to prepare many blockcopolymers: p(4-CMSt)/St [242–244]; p(BrSt)/St and St/p(BrSt) [219]; St/tBuSt [92];p(tBOSt)/St [245]; St/PIMS [246]; St/MPCS [247]; p(AcOSt)/MPVB [248]; p(St-r-CMI)/St[217]; p(St-r-NVC)/St [217]; St/StAN [216]; p(SSt)/DMAM and p(SSt)/SSC [249]; p(SSt)/

VN [250]; p(nBA)/St and p(nBA)/St [251]; p(St)/MA [252]; p(4VP)/St and p(CMSt)/St[253]; p(St)/DMA [94]; p(EBPBB)/St [254]; p(St)/BD and p(St)/IP [95,255]; p(St)/nBAand nBA/St [67]; various isoprene block copolymers [256]; p(St-alt-Mah)St [257]; olefins/acrylates [258]; poly(2,5-dioctyloxy-1,4-phenylenevinylene)/St-co-p(CMSt) [259] Table 2lists the block copolymers prepared by ATRP and includes the catalyst complex employed

In reference [241] Davis provides a good review of block copolymers prepared by ATRP

A benefit of the relatively stable end groups of polymers prepared by controlled/

‘living’ polymerizations, is that they can be isolated and stored as macroinitiators withrelative ease Such is not the case for polymers prepared by ionic polymerizations; theactive anion or cation will be quenched by advantageous moisture This also allows one tomodify polymers prepared by other methods so that they can become macroinitiatorsfor controlled/‘living’ radical polymerization Such ‘mechanism transformation’ can beused to prepare a wide array of novel polymers; block copolymers of combinations ofradically prepared polymers with those synthesized by step-growth polymerizations[160,276], ROMP [159,277], cationic [161,278] and anionic polymerizations [255,279]have been prepared (Table 3)

Some examples of materials prepared from the presently extended range ofcontrollably polymerizable monomers are seen in Table 4 where block copolymers withtwo disparate ionic blocks have been prepared

Table 1 Summary of CRP copolymerizations

TEMPO derivatives

St/nBMA; St/ClMS; St/MMA [214]; St/AN [215,216]; St/NVC [215,217]; St/VP [218]; St/AcOSt[214]; St/BrSt, St/MSt, St/BuSt, with MOTEMPO [219]; St/CMI [220]; St/BMI [221]; and CMSt/MVB-TMS [222]

ATRP systems

St/MA [210]; St/MMA; St/nBA [174,223]; St/BuMA [224]; MMA/BA [176,225]; MMA/nBMA [209];St/MMA [226]; MMA/MA [227,126]; St/AN [212]; MMA/HEMA [138,134]; MMA/MAA [134];St/EPSt z[228]; MMA/NCMI [229]; St/Mah and St/AEMI or St/PMI [230]

Table 2 Summary of block copolymers prepared using ATRP.

p(MMA)-Cl MA and BA NiBr2(Pn-Bu3)2/Al(OiPr)3Sawamoto [126]

a

Sequential monomer addition without isolation of macroinitiator;bN,N,N 0 ,N 0 0 ,N 0 0 0 ,N 0 0 0 tetraamine;c4,4 0 -dimethyl-2,2 0 -bipyridine;dconducted in supercritical CO 2 ;econducted in a fluorous biphasic system;fethyl 2-bromoisobutyrate,24,4 0 -di(5-alkyl)-2,2 0 -bipyridine.

-hexamethyltriethylene-Graft copolymers are a special class of segmented copolymer which can be prepared

by use of a macroinitiator which contains multiple initiating sites along the polymer chain;initiation at these sites allows for the growth of polymer chains from the backbone[307–309] The degree of branching can vary from a few grafts per chain to a graft sitefrom every monomer unit along the backbone polymer (Table 5)[309]

Table 3 Block copolymers prepared from a combination of ionic and CRP polymerizationtechniques

Table 4 Ionic block copolymers

2-Acrylamido-2-methylpropanesulfonate-N,N-dimethylacrylamide-styrene block copolymer [305]

PAA-poly(benzyl ether) anionic linear-dendritic

block amphiphiles [306]

a

(4VPC16Br): N-hexadecyl-4-vinylpyridinium bromide, (DMAA): N,N-dimethylacrylamide.

Backbone macroinitiators can be prepared by any polymerization process andseveral commercially available polymers (Table 6) have been used as macroinitiatorsincluding polyethylene [156,318], polyisobutylene [312,319], and PVC [164,166] forpreparation of both block and graft copolymers.

Block, graft, star and surface tethered hybrid copolymers have been prepared by use

of inorganic macroinitiators [326,343,344]

Graft copolymers have also been prepared by grafting through techniques Nitroxidemediated copolymerization has been successful using styrene as comonomer andp(CL), p(LA), or p(EG) [345] as macromonomers, also p(EO) [346] NVP and NBAhave been copolymerized with p(St) [347] and p(MMA) macromonomers [348] and

Table 5 Examples of ‘grafting from’ using CRP methods

Table 6 Commercially available macroinitiators transformed into CRP initiators

homopolymerized p(IBVE) using ATRP [349] Polydimethylsiloxane macromonomershave been copolymerized with MMA using ATRP [350] and RAFT [351] In both systems

it was found that the use of a compatible macroinitiator assisted in incorporation of themacromonomer [352]

Another area where controlled/living radical polymerizations can make a significantcontribution is in the development of polymers with unique architectures When aninitiator site is incorporated into a monomer, branching of the polymer chain can beinduced When such functionalized monomers are homopolymerized, hyperbranchedpolymers are obtained [307,353,354] When they are copolymerized with conventionalmonomers, polymers with a random distribution, or a gradient of branching alongthe chain can be obtained [307,353] Homopolymerization of these monomers usingtechniques that do not consume the initiating sites for the controlled/living radicalpolymerization results in a polymer with initiating sites at every repeat unit [309] By usingsuch a polymer as a macroinitiator, graft copolymers with very densely graftedpolymer chains have been obtained, including preparation of cylindrical core/shell

or amphiphilic bottle brush copolymers [355] The macromolecules are very large(Mn¼5,000,000, Mw/Mn¼1.2) and have been called by the trivial name ‘bottle brush’copolymers due to their shape Such macromolecules with styrene and acrylate grafts havebeen prepared by ATRP from poly(2-(2-bromoisobutyryloxy)ethyl methacrylate [240,309],with attached block copolymers [264,355,356] The individual macromolecules have beenresolved by atomic force microscopy with length in the range of 100 nm and width 10 nm(Figure 2) The AMF image of an unusual non-symmetrical bottle brush copolymerprepared from a backbone gradient copolymer is shown in Figure 3

An extension of this concept of ‘grafting from’ is the formation of surface tetheredcopolymers TEMPO moieties containing reactive groups that could be used to tether theinitiator to silicon surfaces (wafers or gel particles) have been prepared [344,357,358]and this has been extended to ATRP [359–361] The tethered initiators have been used toinitiate CRP forming attached copolymers trivially named ‘brush’ (co)polymers One ofthe major difficulties associated with growing the polymers off the surfaces, which Wirth[150] had not addressed but that Fukuda [343] had considered, is the extremely low

Figure 2 AFM image of poly(butyl acrylate) brushes on mica [263]

concentration of initiating sites This leads to a low concentration of radical mediators(i.e., free nitroxide for NMP or Mt n þ 1 for ATRP) in the contacting solution and leads

to an uncontrolled polymerization Hawker added a small amount of unattached1-phenylethyl-TEMPO to the system and was able to control the polymer growth from thesurface [344], the free polymer chains were separated from those attached to the surface bywashing the surface with an appropriate solvent Later, addition of the persistent radicalalone was also shown to be effective at providing controlled polymerization from surfaces[359] Two groups of workers initially examined functionalization of silica surfacesfollowed by polymerization of a range of vinyl monomers forming homopolymersand block copolymers [344,359] Monomers included styrene [360], MMA [140], andacrylamide Amphiphilic block copolymers were prepared by ATRP [151,362,363], and byRAFT [364] Tethered PS-b-PMMA was prepared by sequential carbocationic polymer-ization of styrene followed by ATRP of MMA [365,366]

Controlled polymerization from organic, silicon based and carbon particles, andgold surfaces has also been demonstrated [360,367–369] Bio-active particles wereprepared using nitroxide based CRP [370], functional carbon particles were also preparedwith nitroxides [369], and ATRP has been used for CRP from silica particles [371–374],and from luminescent particles [375]

Another approach to core shell polymers, or multiarmed star polymers is thearm first approach, where a growing polymer formed by a CRP is copolymerized with adifunctional monomer to form a crosslinked core with the attached first formed arms[131,376,377] Other surfaces include organic resins and latexes [315]

Controlled/‘living’ radical polymerizations have great potential for the production ofpolymers of lower molecular weight, but with high degrees of functionality [44] Precisecontrol of the end groups is readily attained in controlled radical polymerizations, thismethodology is ideally suited to preparing telechelic materials [63,168,207,208,378–380].Figure 3 AFM image of poly(butyl acrylate) brushes on mica [356]