Effect of Radical Copolymerization of the (Oxa)norbornene End-group of RAFT-prepared Macromonomers on Bottlebrush Copolymer Synthesis via ROMP †

a Bottlebrush polymers are attractive for use in a variety of different applications. Here we report synthesis of two novel trithiocarbonate RAFT agents bearing either a oxanorbornenyl or norbornenyl moiety for bottlebrush synthesis via ROMP grafting-through polymerization. RAFT polymerization kinetics were evaluated as a function of monomer type, degree of polymerization (DP) and RAFT agent structure. The correlation between oxa/norbornenyl moiety and the type of RAFT monomer (methyl acrylate, n -butyl acrylate, and styrene) has been investigated. The reactivity of the oxa/norbornenyl group of the RAFT agent towards the radical propagating species during RAFT polymerization influences the molar mass, molar mass distribution and the residual olefinic end-group functionality of the resulting polymeric macromonomers. The RAFT synthesized macromonomers (MMs) are subjected to “grafting - through” ROMP using Grubbs 3rd generation catalyst, resulting in bottlebrush polymers. The ‘defects’ in MMs structure have been found responsible for high er MMs residue after the ROMP process and hence affect the microstructure of synthesized bottlebrush polymers.


Introduction
2][3] Molecular bottlebrushes consist of long linear polymeric backbone densely grafted with short side-chains.][6] There are three main approaches for the preparation of bottlebrush polymers: 1) 'grafting-to' -attachment of side chains to the polymeric backbone; 2) 'grafting-from'polymerization of monomers from the backbone; and 3) 'grafting-through' -polymerization of macromonomers. 7Each method has its own advantages and limitations.Generally, these well-defined bottlebrushes are synthesised via combination of two or more polymerization techniques. 8,9 e grafting-through strategy is the polymerization of macromonomers (MMs) that contain polymerizable endgroups.The grafting density and dispersity play a crucial role in the performance of these bottlebrush polymers.Unlike the two other strategies, the grafting-through technique ensures high grafting density as well as low brush dispersity and hence extraordinary properties and high efficacy toward application.Often, ring-opening metathesis polymerization (ROMP), using Grubbs-type Ru catalysts, has been utilized for the graftingthrough technique due to its rapid polymerization rates.In addition, the molar mass of MMs and the reactivity of polymerizable moiety are key factors in the grafting-through strategy. 1,10 r the preparation of functional MMs with tailored molecular properties (i.e.targeted molar mass, low dispersity) reversible deactivation radical polymerization (RDRP) techniques are highly attractive.Reversible additionfragmentation chain transfer (RAFT) polymerization is arguably the most versatile RDRP method as it has a superior tolerance for wide range of functional groups; 11 the RAFT technique is compatible with non-ionic, cationic, and anionic monomers.Through careful selection of the RAFT agent and reaction conditions, MMs amenable to polymerization by "graftingthrough" ROMP polymerization can be prepared. 1,10,12 Ithe broader scientific literature exo-norbornenes are the cyclic olefin (monomer) of choice for ROMP; their rapid ring opening metathesis kinetics and low incidence of chain transfer renders their polymerization 'living'. 13An added advantage of norbornenes is their thermal stability.While less commonly used, exo-oxanorbornenes (i.e.oxygen-bridged analogues of norbornenes) are also widely reported in ROMP. 7n the context of functional RAFT agent synthesis, exooxanorbornene derivatives are quite attractive starting materials as they are relatively inexpensive.In contrast, exonorbornenes tend to be quite expensive and are often prepared 'in-house' by laborious isomerization methods from the cheaper endo-isomers.Whilst this suggests oxanorbornenes as an attractive alternative to norbornenes, for the synthesis of 'ROMP-able' RAFT agents, their main drawback is their thermal lability; they can readily undergo retro-Diels-Alder reactions extruding furan. 14erein, we directly compare the utility of oxanorborneneand norbornene-based trithiocarbonate RAFT agents for the preparation of bottlebrush polymers via sequential RAFT/ROMP.The influence of the identities of the RAFT polymerizable monomer (i.e.methyl acrylate (MA), n-butyl acrylate (BA), and styrene (St)) and the strained olefin endgroup (i.e.oxanorbornenyl, norbornenyl) on macromonomer (MM) synthesis is investigated in detail.While both norbornene 1,12,[15][16][17] and oxanorbornene 5,18 end-groups have been used for the synthesis of polymers via a sequential RAFT/ROMP strategy (or other RDRP/ROMP methods) in the past, the incidence and effect of radical propagation to the endgroup has largely been ignored and a direct comparison is lacking; here we seek to remedy these points.Additionally, the effect of the resultant MM structure on the subsequent ROMP grafting-through polymerization is also investigated.

Experimental
Materials.

Characterization.
Nuclear magnetic resonance (NMR) spectra were recorded on a Joel 400 MHz spectrometer at room temperature. 1H and 13 C NMR spectra were internally referenced to residual solvent. 19ize exclusion chromatography (SEC) was conducted on an EcoSEC-HLC 8320GPC system with Dual Flow RI Detector and TSKgel super HZM-N 3µm (4.6 ×150mm) column.THF was used as the eluent at a flow rate of 0.35 mL/min at 40 °C and low dispersity polystyrene standards were used for the calibration.

RAFT polymerization of methyl acrylate and butyl acrylate
Methyl acrylate (MA) or n-butyl acrylate (BA) (60 wt % in toluene), oxanorbornene RAFT agent 7-ONb or norbornene RAFT agent 8-Nb, and AIBN in ratio (200:1:0.1)or (50:1:0.1)were mixed in a 25 mL round bottomed flask (RBF), and the resulting solution was degassed by sparging with nitrogen for 30 min.The solution polymerization was initiated by raising the temperature to 60 °C.For kinetic studies, an aliquot of the reaction mixture (0.3 mL) was taken at predetermined times and quenched by rapid cooling in liquid nitrogen.The polymer was recovered by precipitation three times in methanol/water solution.

RAFT polymerization of Styrene
RAFT polymerization of styrene was performed in bulk.Styrene (St), oxanorbornene RAFT agent 7-ONb or norbornene RAFT agent 8-Nb, and AIBN in ratio (250:1:0.1)or (50:1:0.1)were mixed in a 25 mL RBF, and the resulting solution was degassed by sparging with nitrogen for 30 min.The polymerization was initiated by raising the temperature to 65 °C.For kinetic studies, an aliquot of the reaction mixture (0.3 mL) was taken at predetermined times and quenched by rapid cooling in liquid nitrogen.The polymer was recovered by precipitation three times in methanol.This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins Please do not adjust margins i) Scheme 1: Synthesis of (i) alkylating agents 5 and 6 and (ii) RAFT agents 7-ONb and 8-Nb

Preparation of Macromonomers
Defined macromonomers with low molar mass (~2000-4000 g mol -1 ) derived from both RAFT agents (7-ONb or 8-Nb) are prepared as described above (M:RAFT:I = 50:1:0.1)and the polymerization was quenched after certain time to obtain the desirable molar mass.

ROMP of Macromonomers via 'Grafting through' ROMP
defined macromonomer was added to a dry, 5 mL RBF charged with a stir bar.The flask was then degassed by applying vacuum for 30 min, and the desired amount of degassed, anhydrous THF was added (total macromonomer concentration was ~0.03 M).The required amount of degassed Grubbs catalyst G3 solution was transferred to the reaction flask containing the macromonomer to initiate the polymerization and stirred at room temperature for at least 3 h.The reaction was quenched by addition of few drops of ethyl vinyl ether.The product was collected by precipitation in methanol and dried under vacuum.

RAFT Agent Design and Synthesis
To probe the differences in performance between oxanorbornene and norbornene strained olefinic groups in both (a) RAFT-based macromonomer (MM) synthesis and (b) ROMPbased bottlebrush polymer synthesis via grafting-through polymerization, two RAFT agents were prepared; these were the oxanorbornenyl RAFT agent 7-ONb and the norbornenyl RAFT agent 8-Nb (see Scheme 1).Briefly, the alcohol functional imides 3 and 4 were obtained in moderate to high yield from the relevant exo-anhydrides 1 and 2 by treatment with ethanolamine as per published literature procedures. 20,23 bsequent reaction of the alcohols 3 and 4 with 2bromopropionyl bromide adapted from the procedure of Keddie et al. 24 delivered the alkylating agents 5 and 6.The RAFT agents 7-ONb and 8-Nb were isolated in moderate yield following standard RAFT agent syntheses; 25 i.e. alkylation of the carbodithioate salt derived from dodecanethiol and CS2. 26

Kinetic Analysis of RAFT Polymerization
Three monosubstituted monomers of interest were selected for preparation of macromonomers via RAFT polymerization; methyl acrylate (MA), n-butyl acrylate (BA), and styrene (St) (see Scheme 2).Importantly, these monomers allow us to probe the effect of electronics and/or sterics in the preparation of (oxa)norbornenyl-functional macromonomers.
MA was the first monomer investigated.Initially, we targeted a number average degree of polymerization (Xn) of 50 (i.e.[MA]:[RAFT] = 50:1), using the RAFT agents 7-ONb (see Table 1, Entry 1, and Figure 1 (a, b)) or 8-Nb (see Table 1, Entry 2, and Figure 1 (c, d)).From the SEC data, it can be clearly observed that the oxanorbornene RAFT agent 7-ONb delivered polymers of higher molar mass and higher dispersity (see Table 1, Entry 1, and Figure 1 (b)) than that of the analogous norbornene RAFT agent 8-Nb (see Table 1, Entry 2, and Figure 1  (d)).Note, the high percentage "livingness" (L%) 27,28 calculated from kinetic factors indicates the high molar mass shoulder(s) observed in the SEC traces are due to 'branching', formed via reaction of the olefinic RAFT end-groups, rather than chaincoupling via termination by combination (see Table 1).The degree of branching (DB%), a quantification of the presence of branched polymers (i.e.polymer dimers, trimers etc.) calculated by either NMR analysis of olefinic RAFT end-group consumption # or SEC deconvolution, was significantly higher for 7-ONb than for 8-Nb (see Table 1 Entries 1 and 2).This is also clearly evidenced by kinetic analysis of the rate of olefinic endgroup consumption during polymerization; the oxanorbornene end-group is consumed to a greater extent than that of the norbornene (see Table 1, Entries 1 and 2, and Figure 1 (a) and (c)).Clearly the propensity for cross-propagation of poly(methyl acrylate) propagating radical (PMA•) to the olefinic polymer end-group is higher for the 7-ONb based systems than those that use 8-Nb.We postulate this is likely due to a retro Diels-Alder extrusion of furan from 7-ONb derived chain-ends during the reaction to produce a more reactive maleimido end-group, ‡  27,28 where f is the initiator efficiency (= 0.7), 29 d is number of chains formed by radical-radical termination (= 1), 30 and kd = 9.67 × 10 -6 s -1 at 60°C 31 or kd = 1.95 × 10 -5 s -1 at 65°C (calculated from Arrhenius parameters) 31 ; f DB% = percentage degree of branching; g calculated following deconvolution of SEC chromatograms.which can then undergo rapid copolymerization with PMA• (see Scheme 3 (a) and (b)).Indeed estimations of indicative copolymerization reactivity ratios, using the Alfrey-Price Q-e system, 32,33 indicate a significantly larger preference for PMA• to cross-propagate to a maleimide than to a norbornene.§, ¶ When targeting higher chain lengths of Xn = 200 (i.e. [MA]:[RAFT] = 200:1) much the same trends were observed as were for the Xn = 50 examples, with the oxanobornene-based materials displaying higher number-average molar mass (Mn), molar mass dispersity (Ɖ) and degree of branching (DB%) (see Table S1, Entries 1 and 2, and Figure S1 (a) and (b)).
To probe the effect of the acrylate ester chain length on the RAFT system, BA was the next monomer investigated, targeting Xn = 50.Unsurprisingly, the additional sterics from the n-butyl ester of the monomer made little difference to the reactivity of the poly(n-butyl acrylate) propagating species (PBA•) towards the different end-groups of 7-ONb and 8-Nb when compared to the PMA• systems.PBA prepared in the presence of the oxanorbornene 7-ONb displayed significantly higher Mn, Ɖ and  DB% than the norbornene 8-Nb prepared PBA examples (see Table 1, Entries 3 and 4, and Figure 2).Again, analogous outcomes were observed when targeting PBA of Xn =200 (see Table S1, Entries 3 and 4, and Figure S1 (c) and (d)).The final monomer investigated was St, again initially targeting Xn = 50 (i.e.[St]:[RAFT] = 50:1).As with the previous examples discussed above, for St polymerization the oxanorbornene RAFT 7-ONb agent led to significantly higher Mn, Ɖ and DB% than the norbornene RAFT agent 8-Nb (see Table 1, Entries 5 and 6, and Figure 3).Interestingly, for polymerization of St controlled with the norbornene RAFT agent 8-Nb minimal branching (DB% = 1.2%) was observed, particularly when compared to the acrylate systems (cf.DB% ~20% for MA and BA at ~90% monomer conversion).We attribute this to electronic differences between the electronrich polystyryl radical (PSt•) and the electron-poor acrylatebased radicals (i.e.PMA• and PBA•).PSt• cross-propagates to the electron-rich norbornene end-group more slowly than do either of the acrylate-based radicals; this observation is in agreement with indicative copolymerization reactivity ratios. 32,33 §t appears electronics play a less significant role in the DB% for the oxanorbornene case, which provides further indirect evidence for the contribution of retro Diels-Alder to branching.Indicative copolymerization reactivity ratios, between St and maleimide, suggest a tendency towards alternation which would lead to consumption of a maleimide the chain end.On the other hand an unreacted, electron-rich oxanorbornene would be expected to behave in much the same way as norbornene in St polymerization (i.e.display conversion via cross-propagation to the chain end).Similar polymerization outcomes were obtained when targeting PSt of Xn = 250 (i.e. [St]:[RAFT] = 250:1) with 7-ONb delivering materials with higher Mn, Ɖ and significantly higher DB% than 8-Nb (see Table S1, Entries 5 and 6, and Figure S1 (e) and (f)).In summary, cross propagation of the propagating species (PMA•, PBA• and PSt•) to the olefinic RAFT chain-end was found to occur in all cases discussed, albeit to varying degrees.This results in a proportion of branched structures, a generally undesired topological 'impurity' in the final polymer sample.This is also is expected to adversely impact the preparation of the targeted bottlebrush copolymers due to the (partial) consumption of the ROMP polymerizable end-group.It is clear from the results discussed above that 8-Nb is the preferred RAFT agent for preparing macromonomers from monosubstituted monomers via RAFT.Significantly more 'defects' in the macromonomer structure is the trade-off of using the more easily prepared 7-ONb instead of 8-Nb.It should be noted, even when using the norbornene-based RAFT agent 8-Nb in the polymerization of the acrylates MA and BA significant end-group consumption was observed (up to 20%, see Table 1, Entries 2 and 4).To decrease the incidence of these 'defects' in the synthesis of MMs we recommend targeting higher molar masses and quenching the reaction at lower conversion; from a copolymerization standpoint this effectively decreases the monomer feed ratio of the norbornene chain-end reducing the rate of cross-propagation.

Macromonomer synthesis via RAFT Polymerization
Following on from the kinetic investigations described above, we successfully prepared three macromonomers based on MA, BA, and St with low molar masses (~2000-4000 g mol -1 ) by RAFT polymerization using the RAFT agents (7-ONb or 8-Nb).The reactions used to prepare the MMs were quenched after the desired time and purified by precipitation three times in methanol to completely remove any unreacted monomer present. 1 H-NMR spectroscopy and size exclusion chromatography (SEC) were used to characterize the resulting MMs.The properties of prepared MMs are summarized in Table 2 and SEC chromatograms are shown in Figure 4 (black traces).Akin to the data described above, the norbornenyl RAFT agent 8-Nb delivered MMs with the lowest Ɖ and DB% in the case of each monomer (see Table 2 entries 2, 4 and 6.).The oxanorbornenyl RAFT agent 7-ONb resulted in higher dispersities (and biomodality in the molar mass distribution) (see Entries 1, 3 and 5, Table 2).Compared to styrene MMs, the acrylates MMs exhibit slightly higher dispersities and DB% (see Table 2 and Figure 4-black traces).

ROMP of Macromonomers
Grafting-through polymerization via ROMP of the (oxa)norbornene macromonomers (see Table 2) was carried out using MM to catalyst ratio 25:1 with Grubbs' third generation catalyst G3 (see Scheme 4 and Table 3).Exhibiting rapid initiation kinetics and high functional-group tolerance, G3 is well known to successfully polymerize sterically hindered substrates, allowing for synthesis of polymers with narrow molar mass distributions.
Due to the difference in thermal stability between the RAFT agents 7-ONb and 8-Nb and their behaviour in RAFT polymerization (i.e. higher DB%) as described above, it was found that the bottlebrush polymers based on the 7-ONb have higher levels of residual MM than those prepared using 8-Nb; ROMP of MMs based on 8-Nb gives bottlebrush polymer with low amount of MMs residue (≤5%).
Bottlebrush polymers with [MM]/[I] ratio of 50:1 were prepared and full characterization attempted, however the polymers contained fractions that were larger than the exclusion limit of our SEC columns, limiting the ability to assess their molar masses and dispersity accurately (see Table S2 and Figure S2 in the supplementary information).With this drawback aside these materials displayed similar MM incorporation for the [MM]/[I] 25:1 samples.
From these experiments it is clear that using the less effective 7-ONb in the RAFT synthesis of MMs also leads to a less desirable outcomes (e.g. higher residual MM%) in the sequential RAFT/ROMP process for preparation of bottlebrush polymers than the use of 8-Nb.here f is the initiator efficiency (= 0.7), 29 d is number of chains formed by radical-radical termination (= 1), 30 and kd = 9.67 × 10 -6 s -1 at 60°C 31 or = 1.95 × 10 -5 s -1 at 65°C (calculated from Arrhenius parameters) 31 ; d DB % = percentage degree of branching; e calculated following deconvolution of SEC chromatograms.

Notes and references
# The conversion of the (oxa)norbornene end-group is calculated in the same standard manner that conversion of the vinyl monomer is achieved; the resonances from vinylic end-groups are well resolved in all cases.A representative example can be found in the supplementary information (Figure S1).‡No categorical evidence of in situ maleimide end-group formation could be observed in NMR analysis of the kinetic samples or of the final product polymers.We believe this is due to its rapid consumption upon its formation and coupled the low feed ratio rendering analysis of the molecular microstructure difficult.Additionally, the furan by-product was also not observed, presumably due to its volatility; all kinetic samples were taken directly from the polymerization reaction mixtures which were higher in temperature than the boiling point of furan (31 °C)

a.
School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY, United Kingdom b.Polymer and Pigments Department, National Research Centre, Cairo, 12622, Egypt.c. School of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, United Kingdom *Author to which correspondence should be addressed.Email d.keddie@wlv.ac.uk †Electronic Supplementary Information (ESI) available: details of additional polymers prepared by RAFT and ROMP targeting higher degrees of polymerization, including additional pseudo-first order kinetic plots and SEC data.See DOI: 10.1039/x0xx00000x

Figure 1 :
Figure 1: Pseudo-first order kinetics plots (a, c) for conversion of MA (red circles) and (oxa)norbornene end-group (black squares), and SEC chromatograms illustrating the evolution of the molar mass distribution with reaction time (b, d) for polymerizations of MA with the RAFT agents 7-ONb (a, b) or 8-Nb (c,d).All polymerizations performed with [MA]:[RAFT] = 50:1.

Scheme 3 :
Scheme 3: (a) Proposed formation of a maleimide chain-end via retro Diels-Alder reaction, and (b) cross-propagation of propagating polymer species to the maleimide chain-end leading to branching, during RAFT polymerization reactions using the oxanorbornene RAFT agent 7-ONb.Pn, Pm = polymer chains, M = monomer.

Figure 2 :
Figure 2: Pseudo-first order kinetics plots (a, c) for conversion of BA (red circles) and (oxa)norbornene end-group (black squares), and SEC chromatograms illustrating the evolution of the molar mass distribution with reaction time (b, d) for polymerizations of BA with the RAFT agents 7-ONb (a, b) or 8-Nb (c, d).All polymerizations performed with [BA]:[RAFT] = 50:1.

Figure 3 :
Figure 3: Pseudo-first order kinetics plots (a, c) for conversion of St (red circles) and (oxa)norbornene end-group (black squares), and SEC chromatograms illustrating the evolution of the molar mass distribution with reaction time (b, d) for polymerizations of St with the RAFT agents 7-ONb (a, b) or 8-Nb (c, d).All polymerizations performed with [St]:[RAFT] = 50:1.