Reversible addition-fragmentation chain transfer polymerization

RAFT polymerization was firstly reported and named in 1998 by Moad, Rizzardo, and Thang et al. inAustralia.13 A few months prior, a similar process called MADIX

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was reported in France,35 but MADIX is limited to the use of xanthates as chain transfer agents (CTA) and thus RAFT is still the most widely used term. The mechanism of RAFT polymerization differs from ATRP and NMP, where in RAFT polymerization control is not attained by equilibrium between a dormant species and its corresponding active radical chain end, but achieved by an equilibrium between polymer chains led by a reversible transfer reaction using a thiocarbonyl-thio as the CTA, which gives all polymer chains equal opportunities to grow and thus achieve a controlled system. A general mechanism of RAFT polymerization is shown in Scheme 1.6, which consists of the steps of free radical polymerization (initiation, propagation, and termination steps) and extra steps (chain transfer and equilibration steps).14 More specifically, radical initiators decompose and then react with monomers to form radical polymer species (Pn•). This growing chain adds to the

reactive C=S bond of the CTA (1) to generate a radical intermediate (2). This intermediate can undergo a reversible fragmentation reaction either toward starting species (Pn• and 1) or to release the R group from the CTA (R•) and a macro-CTA

(3). The R group then re-initiates and reacts with monomers to form a new growing chain (Pm•). Once all the initial CTA has been consumed, macro-CTA is only present

in the reaction medium which enters the main equilibrium. This equilibrium is very important in the RAFT polymerization process and by a process of rapid exchange between active radical chain ends and dormant ends (thiocarbonyl-thio capped) all polymer chains have equal probability to grow which ensures the production of polymers with narrow molecular weight distributions. It should be noted that the intermediates (2 and 4) may be involved in a variety of side reactions during polymerization such as termination with growing polymer chains. The final step is termination by either combination or disproportionation which is minimized in

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RAFT polymerization due to the presence of a CTA with high transfer efficiency, high ratio of CTA to initiator and the low concentration of radical initiator used.

Scheme 1.6 Proposed general mechanism of RAFT/MADIX polymerization.14

In addition, there are some remarks drawn from the mechanism of RAFT polymerization:

(1) The amount of initiator should be low; otherwise it will increase the probability of chain termination (dead chains) and lead to broad molecular weight distributions. (2) As termination is minimized, the majority of polymers consist of the re-initiating R group at one end and a thiocarbonyl-thio group at the other end.

(3) The molecular weight increases linearly with conversion and the theoretical molecular weight can be estimated by using Equation 1.1, where Mn,th is the

theoretical number-average molecular weight; [monomer]/[CTA] is the mole ratio between monomer and CTA; FW(M) is the molecular weight of monomer; c is the conversion; FW(CTA) is the molecular weight of CTA.

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( ) ( ) Equation 1.1 36

The choice of CTA is very important in RAFT as it has a significant effect on the polymerization kinetics and control. The common structure of a CTA is shown in Scheme 1.6 (1), where the identity of Z and R groups both affect the efficiency of the CTA.14,36

The Z group affects the activity of the C=S bond and stability of the radical intermediates. In other words, the Z group should be able to aid radical formation and stabilize the intermediate, however, the stability should be modest to favor its fragmentation which can free the reinitiating group R. Rankings for the Z group for a CTA are listed in Figure 1.1, where from left to right the addition rate decreases and fragmentation rate increases.

Figure 1.1 Guidelines for selection of RAFT agents for various polymerizations. For Z, addition rate decreases and fragmentation rates increases from left to right. For R,

fragmentation rates decrease from left to right.37

The R group should be a good leaving group and also governs the re-initiation steps. It also contributes to stabilize the intermediates although is less important compared to the Z group. Rankings for R groups for a CTA are shown in Figure 1.1, where from left to right the fragmentation rates decrease.

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Figure 1.2 Types of RAFT chain transfer agent (CTA).36

By varying and combining different R and Z groups, a variety of CTAs can be synthesized. There are four types of CTA based on the identity of the Z group which are commonly used: dithioesters, trithiocarbonates, dithiocarbamates, and xanthates (Figure 1.2).36 These CTAs can all be readily synthesized and more importantly have different properties, such as different transfer constants and tolerance towards functionalities, which make them suitable to mediate the polymerizations of different types of monomers. For monomers that form comparatively stable propagating radicals or possess high propagation rate constant, such as methacrylate, styrene, methacrylamide, acrylate, and acrylamide, dithioesters or trithiocarbonates are favored to prevent termination and broad distributions, as they possess high transfer constants.37 In comparison, xanthates and dithiocarbamates are suitable for polymerization of monomers, such as N-vinyl pyrrolidone (NVP), vinyl acetate (VAc), and related vinyl monomers, where propagating radicals are poor homolytic leaving groups.37 The lone pair of nitrogen or oxygen in the structure of dithiocarbamate and xanthate respectively is delocalized with the C=S bond, which results in their low reactivity and low transfer constants. Moreover, electron- withdrawing substituents on Z group can enhance the activity of dithiocarbamate and xanthate as delocalization between lone pair and C=S bond would be weakened.36,37 Among the controlled radical polymerization techniques, RAFT polymerization appears to be one of the most versatile processes in terms of the mild reaction conditions, the variety of monomers that can be polymerized and the feasibility for

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the incorporation of various functionalities. The main disadvantages of RAFT polymerization are the use of toxic and odorous starting materials such as carbon disulfide and thiol-containing alkyls to make CTAs and the presence of RAFT polymerization end groups in the polymers that lead to colored polymers. The first drawback is hard to avoid although synthetic improvements have been achieved.38 The second disadvantage can be solved as the CTA end groups are easy to remove or transform into other functionalities.39,40 Given the advantages of RAFT polymerization and few reports on preparation of nucleobase-containing polymers by RAFT technique, in our work, RAFT polymerization was therefore investigated and used for the preparation of nucleobase-containing polymers.