Living Anionic

Communication pubs.acs.org/OPRD

Feasibility Study on Continuous Flow Controlled/Living Anionic Polymerization Processes Aiichiro Nagaki,*,†,‡ Yuichi Nakahara,‡,§ Mai Furusawa,‡,∥ Tomoya Sawaki,‡,⊥ Tetsuya Yamamoto,‡,⊥ Hideaki Toukairin,‡,⊥ Shinsuke Tadokoro,‡,# Toshiya Shimazaki,‡,¶ Toshihide Ito,‡,¶ Masakazu Otake,‡,¶ Hidenori Arai,‡,¶ Naoya Toda,‡,¶ Keita Ohtsuka,‡,& Yusuke Takahashi,† Yuya Moriwaki,† Yuta Tsuchihashi,† Katsuyuki Hirose,† and Jun-ichi Yoshida*,†,‡ †

Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan ‡ Micro Chemical Production Study Consortium in Kyoto University, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan § Process Engineering Group, Fundamental Technology Laboratories, Institute of Innovation, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kanagawa 210-8681, Japan ∥ Oppama Research Laboratory, Toho Chemical Industry Co., Ltd., 5-2931, Urago-cho, Yokosuka-shi, Kanagawa 237-0062, Japan ⊥ Iwata Factory, Takasago International Corporation, Ebitsuka, Iwata City, Shizuoka 438-0812, Japan # Chemical Research Laboratory, Nissan Chemical Industries, Ltd., 2-10-1, Tsuboi-nishi, Funabashi, Chiba 274-8507, Japan ¶ Tacmina Co. 2-2-14 Awajimachi, Chuo-ku, Osaka 541-0047, Japan & Sankoh Seiki Kougyou Co., Ltd., 2-7-2, Keihinjima, Ota-ku, Tokyo 143-0003, Japan S Supporting Information *

the flow microreactor technology is expected to serve as a key technology for chemical and pharmaceutical industries. To accelerate the progress of this field the Micro Chemical Production Study Consortium in Kyoto University (MCPSCKU)4 was founded in 2009. The consortium has promoted research and development relevant to the flow microreactor technology and has disseminated industry−academia collaboration facilitating the development of next-generation chemical plants based on the technology. The members of MCPSC-KU identified that keeping process flow at defined conditions during the operation is one of the key issues of the microchemical production in industry. We chose to study controlled/living anionic polymerization as a test reaction because the molecular weight and molecular weight distribution of polymer products are quite sensitive to the relative flow rate of an initiator solution and that of a monomer solution. Also, controlled/living anionic polymerization5,6 using flow microreactors has received significant interest from industry because it enables the production of structurely well-defined polymers such as end-functionalized polymers, block polymers, gradient polymers, graft polymers, and star polymers under easily accessible conditions because of livingness and high reactivity of the anionic polymer chain ends.7 In contrast, the batch controlled/living anionic polymerization in polar solvents should be carried out at cryogenic conditions.8 Such prerequisite conditions severely limit its use in industry. Using nonpolar solvents, the polymerization can be conducted at higher temperatures, but a much longer reaction time is needed for reaction completion.9

ABSTRACT: A practical microchemical reaction system for keeping process flow at defined conditions, which is one of the key issues of industrial production, was developed. Controlled/living anionic polymerization was chosen as a test reaction because the molecular weight and molecular weight distribution of polymer products are quite sensitive to the relative flow rate of an initiator solution and that of a monomer solution. The polymerization of styrene in THF/hexane was carried out using a flow microreactor system consisting of two T-shaped micromixers and two microtube reactors using Smoothflow pumps at 0 °C. Poly(styrene) with higher molecular weight such as Mn > 10000 could be synthesized using sBuLi (Mn = 14 000, Mw/Mn = 1.11). n-BuLi could also be used as an initiator. The continuous operation was performed for 3 h without any problems to obtain ca. 1 kg of the polymer, indicating the feasibility of continuous flow processes for controlled/living anionic polymerization on a relatively large scale.

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low microreactors1−3 have received significant research interests both from academia and industry, because they are expected to make revolutionary changes in chemical synthesis and production. The flow microreactor technology improves not only selectivity, safety, and sustainability of reactions, but also speed and efficiency of discovery and optimization of new drugs and functional materials. Moreover, another attractive feature of flow microreactor technology is that the scale-up of a reaction from laboratory synthesis to industrial production can be performed with minimun reoptimiziation of the process. Because of these advantages, © XXXX American Chemical Society

Received: April 30, 2016

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DOI: 10.1021/acs.oprd.6b00158 Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Organic Process Research & Development

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Flow microreactors serve as effective methods for accomplishing controlled/living anionic polymerization.10−13 Poly(styrenes), poly(alkyl methacrylates), poly(tert-butyl acrylate), and poly(perfluoroalkyl methacrylates) can be obtained with very narrow molecular weight distribution under easily accessible conditions. However, the feasibility studies on continuous flow controlled/living anionic polymerizations have not been reported from a viewpoint of industrial production. Thus, we initiated our studies on the controlled/ living anionic polymerization of styrene focusing on the following points. (a) narrow molecular weight distribution; (b) molecular weight higher than 10 000; (c) production on kilogram scales. We used alkyllithiums as initiators of the polymerization, because they are commonly used for anionic polymerization of styrenes. For stable continuious operation, the selection of appropriate pumps is crucial. Syringe pumps are often used for flow reactions in laboratories, but they are not appropriate for production in industry. Plunger pumps and diaphragm pumps can be suitable choices for such purposes. In general, diaphragm pumps have advantages over other pump designs because they offer accurate metering and less possibility of leakage. We chose to use a Smoothflow pump manufactured by Tacmina Corporation (Figure 1). This diaphragm pump has excellent performance in several different aspects, including metering function, linearity, and repeatability, as well as the nonpulsation property which has been considered difficult to be achieved by conventional diaphragm pumps. More importantly, the completely sealed structure allows the operation without air contact. This feature makes the Smoothflow pump particularly suitable for the present purpose because organolithiums are airand moisture-sensitive. A flow microreactor system composed of three precooling units (P1 (ϕ = 1000 μm, length =200 cm), P2 (ϕ = 1000 μm, length = 200 cm), P3 (ϕ = 1000 μm, length = 200 cm)), two T-shaped micromixers (M1 (ϕ = 250 μm) and M2 (ϕ = 500 μm)), and two microtube reactors (R1 (ϕ = 1000 μm, length = 200 cm) and R2 (ϕ = 1000 μm, length = 50 cm)) was used (Figure 2). A solution of styrene (2.00 M in THF, 10 mL/min) and a solution of s-BuLi (0.050 or 0.025 M in hexane/cyclohexane, 5−10 mL/min) were introduced to M1 (ϕ = 250 μm) by the Smoothflow pumps. The resulting solution was passed through R1 (ϕ = 1000 μm, length = 200 cm). The resulting solution was mixed with a solution of methanol (0.15 M in THF) in M2 (ϕ = 500 μm), and the resulting solution was passed through R2 (ϕ = 1000 μm, length = 50 cm) to stop the polymerization. A Shimadzu LC-6AD (plunger pump) was used to pump the methanol solution. After a steady state was reached, the product solution was collected for 1 min for the analysis. After the solvent was removed under reduced pressure, the resulting polymer product was analyzed by size exclusion chromatography with the calibration using poly(styrene) standard. The polymer products of various molecular weights (Mn = 5000 to Mn = 10 000) with narrow molecular weight distribution (Mw/Mn = 1.08−1.16) were successfully synthesized simply by changing the relative flow rate of the solution of styrene and that of s-BuLi (Figure 3; see the Supporting Information for details). Moreover, poly(styrene) with higher molecular weight such as Mn > 10 000 could also be synthesized by decreasing the concentration of s-BuLi from 0.050 to 0.025

Figure 1. Structure of the Smoothflow pump manufactured by Tacmina Corporation and the mechanism of its operation; a liquid (marked in blue) is pumped in and out by the motion of two diaphragms (marked in black) moved by unique drive mechanism, which realize precise continuous flow without pulsation.

Figure 2. Schematic diagram of a flow microreactor system for anionic polymerization of styrene. microtube precooling units: P1, P2, P3, Tshaped micromixers: M1, M2, microtube reactors: R1, R2.

M in hexane/cyclohexane (Mn = 14 000, Mw/Mn = 1.11). These results indicate that the flow microreactor polymerization using Smoothflow pumps serves as a practical method for synthesizing poly(styrene) of molecular weights higher than 10 000 with the narrow melecular weight distribution (Mw/Mn = ca. 1.1). Polymers of higher molecular weight can hopefully be synthesized by further tuning of the flow system.10d With the above information in hand, the reaction conditions were further optimized aiming at practical processes for poly(styrene) production. In general, productivity of flow B



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Figure 3. Plots of the molecular weight against the monomer/initiator ratio in anionic polymerization of styrene in THF at 0 °C using the flow microreactor. Figure 5. Picture of the flow microreactor system.

reactions can be easily increased by increasing the flow rate. This feature is a great advantage of flow processes over batch processes. Thus, we next examined the polymerization at higher flow rates. As shown in Table 1, the total flow rate could be

solution of styrene and that of n-BuLi from glass tanks. A Shimadzu LC-6AD plunger pump was used to introduce a solution of methanol from a glass tank. The reaction temperature was maintained at 0 °C using an ice/water bath. Mass flow meters MF (Keyence, FD-S) and pressure gauges PI (Nagano Keiki, KH15) were placed between the Smoothflow pumps and the precooling units to monitor the flow conditions. Switching valves SV were placed between PI and precooling units to introduce a cleaning solution (THF) into the flow system. The flow rate and the pressure did not change appreciably throughout the 3 h operation as shown in Figure 6 and Figure

Table 1. Effect of the Flow Rates and the Initiator for Anionic Polymerization of Styrene at 0 °C Using the Flow Microreactor flow rate (mL/min) initiator

styrene

initiator

[M]/[I]

Mn

Mw/Mn

s-BuLi s-BuLi n-BuLi

10 30 30

5 15 15

80 80 80

10000 9200 7400

1.14 1.08 1.06

increased from 15 mL/min to 45 mL/min without any problem. Moreover, the molecular weight distribution became slightly narrower with an increase in the flow rate10b,d,e presumably because of the faster mixing.14 In spite of significant shortening of the residence time with the higher flow rate, the molecular weight decreased only slightly, indicating that the polymerization was complete in very short time. Another point to be considered is an initiator. In general, sBuLi has been used as an initiator for anionic polymerization of styrene. In practical processes, however, a high reactivity of sBuLi should be problematic from a viewpoint of handling and safety. If more stable n-BuLi can be used as an initiator, it would be more useful for practical production. This is indeed the case. n-BuLi served as an excellent initiator and gave the polymer with narrow molecular weight distribution (Table 1). Next we examined a continuous operation of the polymerization under the optimized conditions (n-BuLi 0.05 M in hexane, flow rate: 15 mL/min; styrene 2.0 M in THF, 30 mL/ min) for a longer time. A schematic diagram and a picture of the flow microreactor system are shown in Figure 4 and Figure 5, respectively. Smoothflow pumps were used for introducing a

Figure 6. Plots of the flow rate for 3 h continuous operation.

Figure 7. Plots of the pressure for 3 h continuous operation.

7, respectively. The yield decreased slightly with an increase in the operation time as shown in Figure 8. The molecular weight slightly decreased, and molecular weight distribution became slightly broader as shown in Figure 9. However, these changes are acceptable. Therefore, the process was successfully operated continuously for 3 h without any problem to obtain the corresponding polymer with the narrow molecular weight distribution in kilogram scale (1.03 kg/3h).

Figure 4. Schematic diagram of the flow microreactor system. C



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EXPERIMENTAL DETAILS

General. Tetrahydrofuran (THF) was purchased from Kanto as a dry solvent and used as obtained. Hexane was purchased from Wako and were used without further purification. Styrene was purchased from TCI, and were used without further purification. Stainless steel (SUS304) T-shaped micromixers having inner diameter of 250 and 500 μm were manufactured by Sanko Seiki Co., Inc. Stainless steel (SUS316) microtube reactors having inner diameter of 1000 μm were purchased from GL Sciences. Micromixers and microtube reactors were connected with stainless type fittings (GL Sciences, 1/16 OUW). The flow microreactor system was dipped in a cooling bath to control the temperature. Solutions were introduced to a flow microreactor system using a Smoothflow pump manufactured by TACMINA corporation and a shimadzu LC-6AD. Mass flow meters (KEYENCE, FD-S) and pressure gauges (NAGANO KEIKI, KH15) were placed at the flow setup to monitor continuous operations. Molecular Weight and Molecular Weight Distribution. The molecular weight (Mn) and molecular weight distribution (Mw/Mn) were determined in THF at 40 °C with a Shodex GPC-101 equipped with two LF-804L columns (Shodex) and an RI detector using a polystyrene (polySt) standard sample for calibration. Anionic Polymerization of Styrene Using a Flow Microreactor System. A flow microreactor system composed of two T-shaped micromixers (M1 and M2) and two microtube reactors (R1 and R2) was used. Three precooling units (P1: ϕ = 1000 μm, length = 200 cm, P2: ϕ = 1000 μm, length = 200 cm, P3: ϕ = 1000 μm, length = 200 cm) were connected to each inlet of the micromixers M1 and M2. The whole flow microreactor system was dipped in a cooling bath of 0 °C. A solution of styrene (2.00 M in THF) and a solution of s-BuLi (0.050 or 0.025 M in hexane/cyclohexane) or n-BuLi (0.050 M in hexane) were introduced to M1 (ϕ = 250 μm) by Smoothflow pumps. The resulting solution was passed through R1 (ϕ = 1000 μm, length =200 cm). The resulting solution was mixed with a solution of methanol (0.15 M in THF) in M2 (ϕ = 500 μm) by a Shimadzu LC-6AD (plunger pump). The resulting solution was passed through R2 (ϕ = 1000 μm, length = 50 cm). After a steady state was reached, the product solution was taken (1 min). The solvent was removed under reduced pressure to obtain the polymer product, and the polymer sample was analyzed with size exclusion chromatography with the calibration using standard polystyrene samples (Figure S1−S-8); the results are summarized in Table 2. A somewhat lower initiation efficiency than the theoretical one might be the decomposition of a part of s-BuLi by some

Figure 8. Plots of the yield of polymer for 3 h continuous operation.

Figure 9. Plots of the molecular weight and the molecular weight distribution of polymer for 3 h continuous operation.

One of the important points of the continuous operation from a viewpoint of industrial production is a easy stop and restart of the process. The Smoothflow pump has a structure which allows a solution to be contained in its pump head during a resting time. This feature offers significant superiority for a reaction operation with a reactant solution which is unstable to air and/or water. Thus, we examined the polymerization with successive stop and restart. A three hour continuous operation was carried out and then stopped. The flow system was washed by introducing the cleaning solution (THF) from switching valves SV for 10 min, and the operation was stopped. The system was suspended for 12 h. The polymerization was then restarted and operated for 0.5 h. In this case the polymer with narrow molecular weight distribution (Mn = 10000, Mw/Mn = 1.08) was obtained as in the former operation. In conclusion, the process of controlled/living anionic polymerization of styrene initiated by n-BuLi using the flow microreactor system was successfully operated for 3 h to obtain ca. 1 kg of the polymer with narrow molecular weight distribution. We hope that the present study paves the way to microflow production processes in industry, in particular those sensitive to relative flow rates of reaction components.

Table 2. Control of the Molecular Weights of Polymers by Modulating the Flow Rates flow rate (mL/min) initiator

concentration of initiator (M)

styrene

initiator

methanol

[M]/[I]

Mn

Mw/Mn

s-BuLi

0.05

s-BuLi n-BuLi

0.025 0.05

10 10 10 10 10 30 10 30

10 9 8 7 5 15 7 15

10 9 8 7 5 15 7 15

40 44 50 57 80 80 114 80

5000 5400 6400 7600 10000 9200 14000 7400

1.16 1.14 1.12 1.11 1.14 1.08 1.11 1.06

D



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impurities in the monomer, which was used without purification. Continuous Operation. A flow microreactor system composed of two T-shaped micromixers (M1 and M2) and two microtube reactors (R1 and R2) was used. Three precooling units (P1: ϕ = 1000 μm, length = 200 cm, P2: ϕ = 1000 μm, length = 200 cm, P3: ϕ = 1000 μm, length = 200 cm) were connected to each inlet of the micromixers M1 and M2. The whole flow microreactor system was dipped in a cooling bath of 0 °C. A solution of styrene (2.00 M in THF, 30 mL/min) and a solution of n-BuLi (0.050 in hexane, 15 mL/ min) were introduced to M1 (ϕ = 250 μm) by Smoothflow pumps. Mass flow meters (MF1 and MF2), pressure gauges (PI-1 and PI-2), and two switching valves (SV) were placed to monitor continuous operations. The resulting solution was passed through R1 (ϕ = 1000 μm, length = 200 cm). The resulting solution was mixed with a solution of methanol (0.15 M in THF, 15 mL/min) in M2 (ϕ = 500 μm) by a shimadzu LC-6AD (plunger pump). The resulting solution was passed through R2 (ϕ = 1000 μm, length = 50 cm). After a steady state was reached, the product solution was taken (30 min). The solvent was removed under reduced pressure. After the reprecipitation with MeOH, the polymer samples were analyzed with size exclusion chromatography with the calibration using standard polystyrene samples (Figure S-10− S-15). The results are summarized in Table 3. The data obtained by the analysis with mass flow meters and pressure gauges are summarized in Table 4 (Figure S-16−S-19).

1 2 3 4 5 6

(0:00−0:30) (0:30−1:00) (1:00−1:30) (1:30−2:00) (2:00−2:30) (2:30−3:00)

Mn

Mw/Mn

yield (%)

7900 7600 7300 7100 7000 7000

1.08 1.11 1.11 1.11 1.17 1.14

99 quant. 84 87 89 89

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.oprd.6b00158. Size exclusion chromatography data for all polymers with the calibration using standard polystyrene samples, flow rate data for a 3 h continuous operation, and pressure data for a 3 h continuous operation (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was partially supported by the Grant-in-Aid for Scientific Research (S) (no. 26220804), Scientific Research (S) (no. 25220913), Scientific Research (B) (no. 26288049), and Scientific Research on Innovative Areas 2707 Middle molecular strategy from MEXT (no. 15H05849).

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REFERENCES

(1) Books on flow microreactor synthesis: (a) Ehrfeld, W.; Hessel, V.; Löwe, H. Microreactors; Wiley-VCH: Weinheim, 2000. (b) Hessel, V.; Hardt, S.; Löwe, H. Chemical Micro Process Engineering; Wiely-VCH Verlag: Weinheim, 2004. (c) Yoshida, J. Flash Chemistry. Fast Organic Synthesis in Microsystems; Wiley-Blackwell, 2008. (d) Hessel, V.; Renken, A.; Schouten, J. C.; Yoshida, J., Eds. Micro Precess Engineering; Wiley-VCH Verlag: Weinheim, 2009. (e) Wirth, T., Ed. Microreactors in Organic Chemistry and Catalysis, 2nd ed.; Wiley-VCH Verlag: Weinheim, 2013. (2) Reviews on flow microreactor synthesis: (a) Jähnisch, K.; Hessel, V.; Löwe, H.; Baerns, M. Angew. Chem., Int. Ed. 2004, 43, 406. (b) Doku, G. N.; Verboom, W.; Reinhoudt, D. N.; van den Berg, A. Tetrahedron 2005, 61, 2733. (c) Watts, P.; Haswell, S. J. Chem. Soc. Rev. 2005, 34, 235. (d) Geyer, K.; Codée, J. D. C.; Seeberger, P. H. Chem. - Eur. J. 2006, 12, 8434. (e) deMello, A. J. Nature 2006, 442, 394. (f) Song, H.; Chen, D. L.; Ismagilov, R. F. Angew. Chem., Int. Ed. 2006, 45, 7336. (g) Kobayashi, J.; Mori, Y.; Kobayashi, S. Chem. Asian J. 2006, 1, 22. (h) Brivio, M.; Verboom, W.; Reinhoudt, D. N. Lab Chip 2006, 6, 329. (i) Mason, B. P.; Price, K. E.; Steinbacher, J. L.; Bogdan, A. R.; McQuade, D. T. Chem. Rev. 2007, 107, 2300. (j) Ahmed-Omer, B.; Brandt, J. C.; Wirth, T. Org. Biomol. Chem. 2007, 5, 733. (k) Watts, P.; Wiles, C. Chem. Commun. 2007, 443. (l) Fukuyama, T.; Rahman, M. T.; Sato, M.; Ryu, I. Synlett 2008, 2008, 151. (m) Hartman, R. L.; Jensen, K. F. Lab Chip 2009, 9, 2495. (n) McMullen, J. P.; Jensen, K. F. Annu. Rev. Anal. Chem. 2010, 3, 19. (o) Yoshida, J.; Kim, H.; Nagaki, A. ChemSusChem 2011, 4, 331. (p) Wiles, C.; Watts, P. Green Chem. 2012, 14, 38. (q) Kirschning, A.; Kupracz, L.; Hartwig, J. Chem. Lett. 2012, 41, 562. (r) McQuade, D. T.; Seeberger, P. H. J. Org. Chem. 2013, 78, 6384. (s) Elvira, K. S.; i Solvas, X. C.; Wootton, R. C. R.; deMello, A. J. Nat. Chem. 2013, 5,

Table 3. Yield, the Molecular Weight, and the Molecualr Weight Distribution of the Polymer for a 3 h Continuous Operation run run run run run run

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Three hours of continuous operation was carried out and then stopped. The microreactor was washed by introducing the cleaning solution (THF) from switching valves SV for 10 min, and the operation was stopped. The reaction was suspended for 12 h. The reaction was then restarted, and the product solution was taken (10 min). The solvent was removed under reduced pressure to obtain the polymer product, and the polymer sample was analyzed with size exclusion chromatography with the calibration using standard polystyrene samples (Mn = 10000, Mw/Mn = 1.08) (Figure S-20).

Table 4. Flow Rate and Pressure for a 3 h Continuous Operation

run run run run run run

1 2 3 4 5 6

MF-1 (MPa)

standard deviation

MF-2 (MPa)

standard deviation

PI-1 (mL/min)

standard deviation

PI-2 (mL/min)

standard deviation

2.36 3.01 2.78 2.71 3.73 3.45

0.68 1.09 0.98 0.79 1.18 1.06

1.46 2.10 1.88 1.80 2.83 2.56

0.68 1.10 0.99 0.79 1.20 1.07

29.68 29.54 29.65 29.70 29.22 29.35

2.13 1.49 1.19 0.96 1.99 1.69

15.44 15.19 15.27 15.32 14.93 15.02

1.37 1.79 1.26 1.07 2.13 1.81

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Communication

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(12) Radical polymerization using microreactors: (a) Wu, T.; Mei, Y.; Cabral, J. T.; Xu, C.; Beers, K. L. J. Am. Chem. Soc. 2004, 126, 9880. (b) Serra, C.; Sary, N.; Schlatter, G.; Hadziioannou, G.; Hessel, V. Lab Chip 2005, 5, 966. (c) Enright, T. E.; Cunningham, M. F.; Keoshkerian, B. Macromol. Rapid Commun. 2005, 26, 221. (d) Russum, J. P.; Jones, C. W.; Schork, F. J. Ind. Eng. Chem. Res. 2005, 44, 2484. (e) Xu, C.; Wu, T.; Drain, C. M.; Batteas, J. D.; Beers, K. L. Macromolecules 2005, 38, 6. (f) Rosenfeld, C.; Serra, C.; Brochon, C.; Hadziioannou, G. Chem. Eng. Sci. 2007, 62, 5245. (g) Rosenfeld, C.; Serra, C.; Brochon, C.; Hadziioannou, G. Lab Chip 2008, 8, 1682. (h) Enright, T. M.; Cunningham, M. F.; Keoshkerian, B. Macromol. React. Eng. 2010, 4, 186. (13) Reviews on polymerizations using microreactors: (a) Hessel, V.; Serra, C.; Lowe, H.; Hadziioannou, G. Chem. Ing. Tech. 2005, 77, 1693. (b) Steinbacher, J. L.; Mcquade, D. T. J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 6505. (c) Tonhauser, C.; Natalello, A.; Löwe, H.; Frey, H. Macromolecules 2012, 45, 9551. (d) Nagaki, A.; Yoshida, J. Adv. Polym. Sci. 2013, 259, 1 and references therein.. (14) Ehrfeld, W.; Golbig, K.; Hessel, V.; Lowe, H.; Richter, T. Ind. Eng. Chem. Res. 1999, 38, 1075.

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Living Anionic

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