One-pot synthesis for gradient copolymers via concurrent tandem living radical polymerization: mild and selective transesterification of methyl acrylate through Al(acac)3 with common alcohols

A series of gradient copolymers were synthesized by the ruthenium-catalyzed living radical polymerization (LRP) of methyl acrylate (MA) and aliphatic alcohols using aluminum acetylacetonate Al(acac)3. In this polymerization system, Al(acac)3 was successfully used not only as an additive for the Ru-catalyzed LRP but also as a catalyst for the selective transesterification of an unsaturated ester monomer in mild conditions in a process known as concurrent tandem living radical polymerization. The resulting MA-based gradient copolymers showed well-controlled molecular weight and distribution in a one-pot reaction and exhibited a well-controlled gradient sequence in their polymer chain. Control of transesterification and the metal-catalyzed living radical polymerization (Mt-LRP) rate varied depending on the concentration of the Al(acac)3 and the structure of varying alcohols, which were confirmed by 1H NMR, SEC, and DSC analysis. In particular, this research opens a new synthetic methodology for preparing acrylate-based gradient copolymers via concurrent tandem LRP not limited to the synthesis of methyl methacrylate types of gradient copolymers.


Introduction
Aer the rst proposal for the concept of a "gradient copolymer" in 1977, 1 the studies of their synthesis and properties have attracted signicant interest in related elds. Gradient copolymers possess highly interesting molecular structures, in which a progressive transition of repeating components continues along the development of a polymer chain. Owing to the continuously changing structural nature along the chains, the gradient copolymers have unique properties which lead to less intra-and interchain repulsion, unlike block copolymers. These characteristics make them usable in a number of applications such as in thermoplastic elastomers, 2 nanostructured carbons, 3 multishape memory materials, 4 dispersants, functionalized surfaces, bio-medical materials, 5,6 and vibration damping materials. 7 In the past decades, the living radical polymerization (LRP) method has been developed as a powerful tool which has signicantly impacted the eld of polymer materials synthesis. Specically, nitroxide-mediated radical polymerization (NMP), 8,9 reversible addition-fragmentation chain transfer radical polymerization (RAFT), [10][11][12] and metal-catalyzed living radical polymerization (Mt-LRP) [13][14][15][16] have been used to synthesize gradient copolymers. Among these, Mt-LRP is known as a prominent method to synthesis various polymers with tailoring polydispersity and molecular weight distribution such as homopolymers, block copolymers, random copolymers, and star polymers. [17][18][19] In addition, Mt-LRP systems have attracted much attention based on high controllability in the addition of metal alkoxides, which not only control the molecular weights but also increase the polymerization rate.
Over the past few years, Sawamoto and Terashima have reported a new synthetic strategy for the preparation of gradient copolymers in one-pot synthesis using a concurrent catalysis system. [20][21][22] This polymerization system, known as concurrent tandem LRP, is a combination of the transesterication of an unsaturated ester monomer with alcohols using a metal alkoxide such as Al(Oi-Pr) 3 or Ti(Oi-Pr) 4 and ruthenium (Ru)catalyzed LRP in conjunction with a metal alkoxide as a cocatalyst, and has led to well-dened polymer structures via resulting smooth redox reactions. 13 Thereby, it induces selective transesterication for only the methyl methacrylate monomer (MMA) type monomer with various alcohols (not polymer chain in propagation), which allows for well-controlled gradient sequences in the polymer chain. However, this strategy is not perfectly applicable to the acrylate type monomer owing to the high reactivity of metal alkoxide, which led to partial trans-esterication of the polymer chains.
Thus, in this work, we report the concurrent tandem LRP used to prepare an acrylate-based gradient copolymer using aluminum (Al) acetylacetonate (Al(acac) 3 ). The Al(acac) 3 is also an effective catalyst for transesterication and has relatively lower Lewis acidity than other metal alkoxides. 21 In addition, it can be used as an additive to Ru-catalyzed LRP. 13 These two roles of Al(acac) 3 for each reaction are successfully synchronized in the concurrent tandem LRP to create an acrylate-based gradient copolymer carrying a well-controlled gradient sequence in the polymer chain in a one-pot synthesis through the gradual transesterication of the acrylate monomer (Scheme 1). Note that our focus is to expand the monomer scope in concurrent tandem LRP as well as synthesis of well-dened gradient copolymers.

Measurements
The M n and M w /M n of polymers were measured by SEC at 40 C using tetrahydrofuran (THF) as an eluent. For the THF-SEC, three polystyrene-gel columns [GP LF-404 (from Shodex); pore size, 3000Å; 4.6 mm i. d. Â 250 mm]; were connected to a PU-4180 pump, a RI-4030 refractive-index detector, and a UV-4075 ultraviolet detector (JASCO) and the ow rate was set to 0.3 mL min À1 . The columns were calibrated against 13 standard poly(methyl methacrylate) samples (Agilent Technologies; Mp ¼ 2380-1120 000). Proton nuclear magnetic resonance ( 1 H NMR) was recorded on a Bruker Ultrashield spectrometer operating at 300 MHz. The thermal properties of the gradient copolymer were determined using differential scanning calorimetry (DSC, TA 3000).

Al(acac) 3 -catalyzed transesterication of MA with varying alcohols
Transesterication was conducted using the syringe technique under dry Ar in baked glass tubes equipped with a three-way stopcock. A typical procedure for the MA with varying alcohols is given. For example, MS 4Å (0.33 g mL À1 ) was added into a tube and dried in vacuo. In another 30 mL tube, toluene (1.46 mL), ethanol (1.96 mL), tetralin (0.14 mL), a 0.2 M toluene solution of Al(acac) 3 (0.5 mL, 0.1 mmol), and MA (10 mmol, 0.95 mL) were added in the same order at room temperature. The solution was added into to the glass tube containing MS 4Å. The total volume of the reaction mixture was controlled to 5 mL. Then, the mixture was immediately moved in an oil bath that was at 80 C. Aliquots from the reaction solution were withdrawn in predetermined intervals using a syringe and the subsequent reaction was terminated by cooling to À78 C. The conversion of transesterication was determined using 1 H NMR spectroscopy.
Metal-catalyzed living radical polymerization of MA using Al(acac) 3

as an additive
The Mt-LRP was conducted using a similar procedure described above and a typical procedure for MA with varying alcohols is given. Ru(Cp*)Cl(PPh 3 ) 2 (0.0398 g, 0.05 mmol), toluene 3.66 mL, tetralin (0.14 mL), MA (0.95 mL, 10 mmol), and EBP (0.25 mL of 0.4 M in toluene, 0.1 mol) were sequentially added into a 30 mL glass tube. The total volume of the reaction mixture was controlled to 5 mL and immediately heated to 80 C. Aliquots from the reaction solution were withdrawn in predetermined intervals using a syringe, and the subsequent reaction was terminated by cooling to À78 C. Total monomer conversion was determined using 1 H NMR spectroscopy using an internal standard.

Gradient copolymer synthesis via tandem catalyst
The gradient copolymerization with tandem catalyst was carried out by a similar procedure described above and a typical procedure for MA with varying alcohols is given. For example, MS 4Å (0.33 g mL À1 ) was added into a tube and dried in vacuo. In another tube, Ru(Cp*)Cl(PPh 3 ) 2 (0.0398 g, 0.05 mmol), toluene (1.33 mL), tetralin (0.14 mL), Al(acac) 3 (0.5 mL of 0.2 M in toluene, 0.1 mmol), MA (0.95 mL, 10 mmol), EtOH (1.83 mL), and EBP (0.25 mL of 0.4 M in toluene, 0.1 mmol) were sequentially added. The solution was added into to the glass tube containing MS 4Å and the total volume was controlled to 5 mL. The mixture was immediately heated to 80 C and aliquots from the reaction solution were withdrawn in predetermined intervals using a syringe. The polymerization was terminated by Scheme 1 Concurrent tandem living radical polymerization for acrylate-based gradient copolymer synthesis.
cooling to À78 C. Total monomer conversion and monomer compositions in polymer solution were determined using 1 H NMR spectroscopy using an internal standard. The products in each aliquot were obtained upon solvent removal using rotary evaporation and further dried under reduced pressure. The cumulative (F cum ) contents and instantaneous (F inst ) contents were calculated from the repeat-unit composition of resulting polymers, which was determined using 1 H NMR spectroscopy.
Al(acac) 3 -catalyzed transesterication of poly(methyl acrylate) (PMA) with ethanol The transesterication of PMA 100 was conducted using a similar procedure as described above. MS 4Å (0.33 g mL À1 ) was added into a tube and dried in vacuo. In another tube, 0.88 g of PMA 100 (M n,SEC ¼ 10 200, M w /M n ¼ 1.16, DP n,NMR ¼ 100), toluene (1.93 mL), EtOH (2.43 mL), tetralin (0.14 mL), and a 0.2 M toluene solution of Al(acac) 3 (0.5 mL, 0.1 mmol) were sequentially added. The solution was added into to the glass tube containing MS 4Å and the total volume was controlled to 5 mL. The mixture was immediately heated to 80 C and aliquots from the reaction solution were withdrawn in predetermined intervals using a syringe. The reaction was terminated by cooling to À78 C and the products in each aliquot were obtained upon solvent removal using rotary evaporation. The product was further dried under reduced pressure and the structural change was tracked using 1 H NMR spectroscopy.

Results and discussion
Al(acac) 3

-catalyzed transesterication of MA and PMA with alcohols
To obtain the well-controlled gradual composition of the monomer used in the gradient copolymer chain by in situ trans-esterication, the following factors had to be satised: (i) transesterication should have selectively occurred to the monomer only (not the polymer); (ii) the cooperative catalytic system was required for the Ru-catalyzed LRP and trans-esterication; (iii) the propagation must have been living without termination and chain transfer. 20,22 Thus, Al(acac) 3 was used to the transesterication of MA and PMA in alcohol/toluene (1/1, v/ v) at 80 C (Fig. 1). The transesterication of MA was observed for different alcohols, but PMA (M n,SEC ¼ 10 200, M w /M n ¼ 1.16, DP n,NMR ¼ 100) did not participate in the transesterication reaction, indicating that the selective transesterication occurred ( Fig. S1 and S2 †). Particularly, primary alcohols showed higher transesterication efficiency than secondary alcohol due to its higher reactivity. In addition, in molecular sieve (MS, 4Å), the transesterication efficiency was enhanced by removing of the methanol molecule that formed during the reaction. 23 Effect of Al(acac) 3
To optimize the catalyst amount in the polymerization conditions, varying concentrations of RuCp* from 2 to 10 mM were examined using 10 mM Al(acac) 3 and MA was smoothly consumed up to a higher conversion. The higher concentration of RuCp* showed a fast polymerization rate with linearly increased molecular weight (M n,SEC ) and controlled dispersity, suggesting a controlled nature of the LRP ( Fig. 2A, C, S3, and S4 †). Further, the effect of Al(acac) 3 as an additive was evaluated compared with the absence of the Al cocatalyst ([Al(acac) 3 ] 0 ¼ 0 mM) and the (n-Bu) 3 N cocatalyzed polymerization system ( Fig. 2B and C). In Al cocatalyst, a fast reaction was afforded by keeping controlled MWDs similar to other polymerization conditions, indicating that Al(acac) 3 can be considered not only a transesterication catalyst but also an additive for Rucatalyzed LRP.

Gradient copolymerization of MA with alcohols via concurrent tandem LRP
Based on the discussed above, to control the gradient sequence in a polymer chain by concurrent tandem LRP, Al(acac) 3 was used for acrylate-based gradient copolymer synthesis with ethanol. As demonstrated in Fig. 3 (le), for example, the polymerization smoothly proceeded up to higher conversion and ethyl acrylate content (EA) was gradually increased via transesterication in polymerization solution, whereas the MA content slowly decreased by participating in polymerization and transesterication.
Particularly, the rate of polymerization and trans-esterication depended on the amount of Al and the reaction temperature (Table 2 and Fig. S5 †). However, in the case of [Al] 0 ¼ 40 mM, although the polymerization rate was much faster than the other cases, the initial transesterication rate remained slow, indicating unfavorable to poor control of gradient sequence in the polymer chain.
However, the function of cumulative (F cum ) contents and instantaneous (F inst ) contents were good tools for the explaining the composition of gradient sequences in polymer chains. 22,27 To evaluate the well-controlled gradient sequence in the polymer chain, the F cum in isolated polymer chains was calculated using 1 H NMR (Fig. 3 (right) and Fig. S6-S8 †). While the F cum,MA (solid line) gradually decreased, F cum,EA gradually increased from 0 to 11% in the obtained polymer chains. These results indicated that EA generated by transesterication gradually participated in the polymerization; thus, the content of EA in the polymer chain increased. In addition, F inst,EA (dash line), which represents the differential increasing of F cum,EA , also  gradually increased, with the increasing of the total conversion of monomers from 0 to 67% indicating that the gradient copolymer was successfully obtained via concurrent tandem LRP. The fairly controlled molecular weight and the narrow MWDs of obtained polymers were observed by SEC analyses ( Table 2 and Fig. S9 †). Encouraged by the successful gradient copolymerization of MA with EtOH, the copolymerizations of MA with varying alcohols such as octanol (long alkyl chain), iso-propanol (secondary), and benzyl alcohol were further explored (Fig. 4, Table 3, and Fig. S10-S12 †). The MA and the RA newly generated by transesterication in concurrent tandem catalysis participated in polymerization and gave a similar monomer composition pattern in obtained polymer chains. In particular, the well-controlled gradient sequence of BzA in the obtained polymer chain was observed for the polymerization with benzyl alcohol while the polymerization with octanol showed a less controlled gradient sequence of OcA in the product. This likely occurred owing to a long alkyl chain, which might have affected the transesterication efficiency. However, unfortunately, the total monomer conversions of those polymerizations did not reach a high conversion and especially, the polymerization with iso-propanol showed low transesterication efficiency, which lead to a low content of i-PrA in the gradient sequence. It can be owing to the lower reactivity of transesterication for the secondary alcohol than that of primary alcohol. Regardless, concurrent tandem polymerization system using Al(acac) 3 as an additive for the LRP and as a catalyst for transesterication of the acrylate monomer with varying alcohols provides acrylate-based gradient copolymers, despite the remaining challenges regarding well-controlled gradient sequences in the polymer chain as well as molecular weight control.
We then evaluated the effects of the gradient sequence in the polymer chain on the glass transition behaviors with differential scanning calorimetry (DSC). In general, gradient copolymers have broader phase transition ranges than the corresponding each homopolymers. 7,28 Here, the obtained gradient copolymers indicated broad glass transition temperatures (T g ) ranges (Fig. 5) compared with PMA homopolymers (DT g ¼ 14.2 C for PMA 43 and DT g ¼ 14.5 C for PMA 100 in Fig. S13 †). For example, MA-grad-OcA, where the PMA and POcA homopolymers have different T g s, showed a broad transition in differentiated DSC proles, supporting that the control of the gradient sequence in the polymer chain successfully occurred (DT g ¼ 33.6 C). In addition, other series of gradient copolymers exhibited a similarly broader glass transition region, with DT g ¼ 22-25 C, than PMA homopolymers, which would be attributed to their gradient sequence controlled polymer chains. These results indicate that Al(acac) 3 cocatalyzed concurrent tandem polymerization of MA can successfully provide the acrylatebased gradient copolymers.

Conclusions
Al(acac) 3 was an effective catalyst for the transesterication of MA with various alcohols in the presence of MS 4Å and separately, it provided good catalysis as a cocatalyst for Ru-catalyzed  Extended DSC thermograms (2 nd heating process at 10 C min À1 after heating up to 120 C) of (A) the obtained gradient copolymers and (B) their differentiated DSC thermograms. LRP. These two roles of Al(acac) 3 for each reaction were successfully synchronized in concurrent tandem LRP, which led the gradient copolymers carrying well-controlled gradient sequences in the polymer chain in one-pot synthesis. Particularly, the monomer library, which was almost limited to the methyl methacrylate type monomers using metal alkoxide catalyzed concurrent tandem LRP, is expanded to the synthesis of acrylate-based gradient copolymers.

Author contributions
The manuscript was written through the contributions of all authors. All authors have given approval to the nal version of the manuscript.

Conflicts of interest
There are no conicts to declare.