The Rationale Behind Sequence-Controlled Maleimide Copolymers

Chapter 14

The Rationale Behind Sequence-Controlled Maleimide Copolymers Downloaded by UNIV OF ALBERTA on November 9, 2014 | http://pubs.acs.org Publication Date (Web): September 22, 2014 | doi: 10.1021/bk-2014-1170.ch014

Bert Klumperman* Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa *E-mail: [email protected]

The rationale behind sequence-controlled maleimide copolymers is discussed. To that end, two specific features of styrene – maleic anhydride copolymerizations are highlighted. Maleic anhydride (MAnh) is chosen as a mimic of N-substituted maleimide monomers since they both represent electron-poor species. The alternating tendency of styrene (STY) with MAnh is discussed in light of the penultimate unit model. On the basis of reactivity ratios it can be assessed that the probability for MAnh addition to a STY-centered growing polymer radical is two to four times larger in the case of a STY penultimate unit compared to a MAnh penultimate unit. The expected initialization behavior of a polySTY macro-RAFT agent with maleic anhydride (or maleimide) is highly beneficial for the precise introduction of a single unit in a PSTY chain at a predetermined location. The kinetic/mechanistic features discussed in this contribution provide a rationale for the successful sequence control in styrene – maleimide copolymerizations.

Introduction Recent years have witnessed various attempts to induce sequence control during chain growth processes such as living radical polymerization (1, 2). A traditional method to achieve sequence control is by templated copolymerization, © 2014 American Chemical Society In Sequence-Controlled Polymers: Synthesis, Self-Assembly, and Properties; Lutz, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.

Downloaded by UNIV OF ALBERTA on November 9, 2014 | http://pubs.acs.org Publication Date (Web): September 22, 2014 | doi: 10.1021/bk-2014-1170.ch014

which somewhat mimics the sequence control in protein synthesis (3). Older versions of templated copolymerization largely suffer from the difficulty of separating the newly formed chain from the template. In order to overcome this complication, one would need to mimic the role of tRNA as a vehicle to introduce the next monomer without the monomer itself being bound to the template. This would be very elegant, but the synthetic efforts to make the tRNA mimics are quite significant. A much simpler and currently quite successful method turns out to be the precise incorporation of maleic anhydride or maleimide moieties in a polystyrene chain (4, 5). Two major characteristics of the RAFT-mediated copolymerization of styrene and maleimides are expected to play an important role. The first characteristic is the strong alternating tendency of electron rich and electron poor monomers such as styrene and maleic anhydride or maleimides, respectively, which has received significant attention throughout the history of radical copolymerization (6). This tendency towards alternation is equally observed for living radical polymerization techniques (7) as it is for conventional radical copolymerization (8). The other characteristic that may play an important role is the process of initialization in Reversible Addition–Fragmentation Chain Transfer (RAFT) mediated polymerization that was investigated and described in literature a number of years ago (9, 10). Initialization has only been investigated for low molar mass RAFT agents. In the present contribution, the potential application of initialization towards macro-RAFT agents will be discussed.

The Mechanism Behind Alternating Copolymerization It has been known for a long time that electron-rich monomers such as styrene and electron-poor monomers like maleimides and maleic anhydride have a strong tendency towards alternating copolymerization (6). The underlying mechanism has long been a point of debate, where some studies would conclude that the alternating tendency was due to normal terminal or penultimate unit model with a high rate of cross-propagation (8), and others would conclude that the addition of charge-transfer complexes was responsible for the alternating tendency (11). It turns out that on the basis of copolymer composition and/or monomer sequence distribution measurements, it is impossible to distinguish between the two models. However, when accurate measurements of the propagation rate coefficient are combined with the composition measurements, model discrimination strongly favors the conclusion that the penultimate unit model is the only model that can adequately describe the copolymerization (8). Just as an example for the case of the copolymerization of styrene (STY) and maleic anhydride (MAnh), all rate parameters according to the penultimate unit model (PUM) could be determined with reasonable accuracy, except for the addition rate of styrene to a maleic anhydride chain end radical. The fit of the model to the experimental data was good as long as that addition rate constant was larger than 105 L·mol-1·s-1 (8). Figure 1 shows the average propagation rate coefficient as a function of the fraction of MAnh in the STY/MAnh copolymerization. The curves are based on a combined fit to the propagation rate constant and composition data (latter not 214 In Sequence-Controlled Polymers: Synthesis, Self-Assembly, and Properties; Lutz, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


shown). The copolymerization model is a restricted PUM in which all MAnh homopropagation events have been set to zero. The high value of the average propagation rate coefficient at high fraction MAnh (fMAnh ≈ 0.9) is due to the previously indicated rate constant kSMS > 105 L·mol-1·s-1 (8).

Figure 1. Average propagation rate coefficient () as a function of fraction MAnh in STY-MAnh copolymerization (fMAnh) at 25 °C (○), 35 °C (×) and 50 °C (+). Curves are calculated on the basis of the PUM. Reprinted with permission from reference (8). Copyright (2010) Royal Society of Chemistry.

On the basis of the rate constants, conditional probabilities for propagation events can be defined. A STY-centered propagating chain-end radical can either add a STY monomer or a MAnh monomer. The conditional probability is dependent on the penultimate unit, and can be written as in Equations 1 and 2.

215 In Sequence-Controlled Polymers: Synthesis, Self-Assembly, and Properties; Lutz, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


The probabilities for MAnh addition increase with a decrease in the product of reactivity ratio (rSS or rMS) and ratio of [STY]/[MAnh]. The reactivity ratios have been determined experimentally from intermediate conversion continuous copolymerizations at 60 °C (12). The values are rSS = 0.023 and rMS = 0.148, respectively. Effectively this means that the probability for MAnh addition to a STY-centered growing polymer radical is two to four times larger in the case of a STY penultimate unit compared to a MAnh penultimate unit if the fraction MAnh in the monomer mixture is in the range of 0.02 < fMAnh < 0.10. In other words, in a living polymerization system, where all polymer chains have equal probability of chain growth, there is as much chance that all chains will add one MAnh unit as compared to a few chains adding a larger number of MAnh units. Obviously, this discussion neglects the effect of activation and deactivation reactions in living radical polymerization. However, for the reactivity of the propagating radical and for the conditional probabilities in copolymerization reactions this is a legitimate approach. Nevertheless, it is known from previous work that living radical copolymerization kinetics may show deviations from conventional copolymerization reactions. Especially in those cases where the stability of the radical is strongly dependent on the nature of the terminal monomer unit in a propagating chain, these deviations may occur. Our group previously reported a modest example of this phenomenon (13).

Initialization in RAFT-Mediated Polymerization In 2004, kinetic studies on the initial stages of RAFT-mediated polymerization led to understanding of what is now known as initialization (9). During the initialization process, the original RAFT-agent is converted into its single monomer adduct. Several examples of efficient initialization have been reported. The polymerization of styrene mediated by cyanoisopropyl dithiobenzoate (CiPDB) shows a very clean initialization in a reasonably short reaction time (Figure 2A) (9). In Figure 2A, AD represents the CiPDB RAFT agent, ASD is the single monomer (STY) adduct and AS2D is the two-monomer adduct. If CiPDB is replaced by cumyl dithiobenzoate (CDB), the initialization is equally selective, but it takes much longer (Figure 2B) (14). In Figure 2B, CD represents the CDB RAFT agent and CSD, CS2D, ASD and AS2D are the monomer adducts similar to previously explained for Figure 2A, where C represents the cumyl leaving group of CDB. The much longer initialization time is assigned to the slower re-initiation rate of the cumyl radical compared to the cyanoisopropyl radical in the case of styrene polymerization. When maleic anhydride is added to this polymerization, a very interesting phenomenon is observed (10). In the case of the AIBN initiated CiPDB-mediated polymerization, it is almost as if the maleic anhydride is not present. The duration of the initialization period is identical to the styrene homopolymerization, and the styrene adduct is virtually exclusively formed in the early stages of 216 In Sequence-Controlled Polymers: Synthesis, Self-Assembly, and Properties; Lutz, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


the reaction (Figure 3A). Conversely, in the AIBN initiated CDB-mediated polymerization, the addition of the cumyl radical to maleic anhydride is extremely fast. Under specific conditions where the initialization in CDB-mediated styrene polymerization would take 240 minutes, initialization in the CDB-mediated copolymerization of styrene and maleic anhydride is over in less than five minutes for the polymerization at 70 °C (results not shown). Only upon lowering the reaction temperature to 60 °C, initialization can be properly observed (Figure 3B). The underlying feature in these polymerizations is the nature of initiating radical and added monomer. In the case of the cyanoisopropyl radical, even though it has been reported as being weakly nucleophilic (15), the radical is fairly electron poor as compared to the cumyl radical, which is electron rich. Styrene as a monomer is electron rich, whereas maleic anhydride is electron poor. It is known from the early days of copolymerization that the combination of an electron rich and an electron poor monomer leads to a strong tendency towards alternation. The same effect leads to fast or slow initialization when electron poor and electron rich radicals, respectively, add to styrene. If then the case of a macromolecular radical is considered, it is quite likely that the same rules apply. A styrene-centered chain-end radical (of a growing polystyrene chain) is electron rich due to the nature of the constituting monomers. Although to the author’s knowledge the experiment has never been performed, it is highly likely that an initialization experiment with a polystyrene macro-RAFT agent would lead to a very short initialization time when the monomer to add is electron poor such as maleic anhydride or most of the maleimide derivatives. In the initialization experiments for styrene – maleic anhydride, it almost seemed as if two initialization steps were taking place. The first one, highly selective, would only add maleic anhydride in the case of the cumyl radical or styrene in the case of the cyanoisopropyl radical. After that selective first monomer addition, a second monomer addition would take place with slightly less specificity. If the radical chain end is maleic anhydride, exclusively styrene would add, whereas if styrene is the chain-end radical, the majority of chains would subsequently add maleic anhydride. Some further monomer addition would be witnessed before the “second initialization” was complete. However, if the concept of initialization with macro-RAFT agents is extrapolated to the site-specific insertion of maleimide monomers in a polystyrene chain, the similarities are obvious. The addition of an equimolar amount of maleimide relative to the number of polystyrene chains will start a process that very much resembles initialization. As soon as a chain is reactivated, the styrene-centered chain-end radical will have a great preference for the addition of a maleimide over a styrene. After subsequent chain transfer, it is likely that the maleimide-centered leaving group is a worse leaving group than a styrene-centered one. In other words, if an asymmetrical intermediate radical is formed with a styrene-centered radical on one side and a maleimide-centered one on the other side, the styrene-centered radical is the one that will have the highest probability of being released. Hence, there is an effective process by which all the chains add exactly one maleimide unit as opposed to some chains adding an alternating sequence of styrene and maleimide units and other chains adding no maleimide at all. Obviously, after all the maleimide has been consumed, further styrene homopolymerization will continue. 217 In Sequence-Controlled Polymers: Synthesis, Self-Assembly, and Properties; Lutz, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


Figure 2. A: Relative concentrations of methyl protons of dithiobenzoate species versus time in the AIBN initiated, cyanoisopropyl dithiobenzoate (AD)-mediated polymerization of styrene at 70 °C. Reproduced with permission from reference (9). Copyright (2004) American Chemical Society. B: Relative concentrations of methyl protons of dithiobenzoate species versus time in the AIBN initiated, cumyl dithiobenzoate (CD)-mediated polymerization of styrene at 70 °C. Reproduced with permission from reference (14). Copyright (2005) American Chemical Society.



Figure 3. A: Conversion of the initial RAFT agent and the formation of the first, second and third monomer adducts for a AIBN initiated, cyanoisopropyl dithiobenzoate-mediated STY-MAnh copolymerization at 70 °C. B: Conversion of the initial RAFT agent and the formation of the first and second monomer adducts for a AIBN initiated, cumyl dithiobenzoate-mediated STY-MAnh copolymerization at 60 °C. Reproduced with permission from reference (10). Copyright (2006) CSIRO.



Conclusions The precise incorporation of maleimides in a polystyrene chain is currently one of the most promising techniques for sequence controlled chain growth polymerization. Two specific phenomena for the copolymerization of electron rich and electron poor comonomers are discussed in this contribution. The penultimate unit effect in the copolymerization of styrene (STY) and maleic anhydride (MAnh) leads to a preference single MAnh insertion over alternating sequences. Specifically for RAFT-mediated living radical polymerization, the initialization behavior of STY/MAnh copolymerization is also likely to favor the selective addition of one MAnh unit to a growing polystyrene chain. Confirmation of this behavior for a polySTY macro-RAFT agent should still be carried out. However, based on initialization studies with low molar mass RAFT agents, the expectation is that initialization is playing a large role in the single monomer insertion. Based on the large similarity between MAnh and maleimides, it is expected that the phenomena investigated for MAnh will also apply for maleimides. It must be taken into account that the nature of the N-subtitution may influence the electron-poor character of the maleimide. This will also have a consequence on the initialization behavior, and therefore on the precision of sequence control.

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The Rationale Behind Sequence-Controlled Maleimide Copolymers

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