Stereospecific radical polymerization of optically active (S)-N-(2-hydroxy-1-phenylethyl) methacrylamide catalyzed by Lewis acids

European Polymer Journal 49 (2013) 3673–3680

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Stereospecific radical polymerization of optically active (S)-N-(2-hydroxy-1-phenylethyl) methacrylamide catalyzed by Lewis acids Xiaodong Xu ⇑, Siwei Feng, Yuanqi Zhu, Han Li, Xiande Shen, Chunhong Zhang, Jianwei Bai, Lili Zhang Polymer Materials Research Center and Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China

a r t i c l e

i n f o

Article history: Received 29 March 2013 Received in revised form 20 July 2013 Accepted 29 July 2013 Available online 20 August 2013 Keywords: Stereospecific polymerization Optically active polymer Polymethacrylamide Lewis acid Tacticity

a b s t r a c t The effects of Lewis acids, namely, rare earth metal trifluoromethanesulfonates, on the radical polymerization of (S)-N-(2-hydroxy-1-phenylethyl) methacrylamide were examined under various conditions. In the absence of Lewis acids, syndiotactic-rich polymers (r = 84%) were obtained, whereas in the presence of a catalytic amount of Lewis acids, the polymerization proceeded in an isotactic-specific manner (m up to 64%). Polymerization solvents strongly influenced the effect of the Lewis acids. The polymerization in nbutyl alcohol showed the highest isotactic selectivity, whereas the polymerization in DMSO showed no isotacticity-enhancing effect. Further increases in the Lewis acid concentration and the polymerization temperature did not produce clear effects on the tacticity of the polymers. The interaction between the monomer and Lewis acids was investigated, and the plausible mechanism of stereocontrol in the radical polymerization of (S)-HPEMA was analyzed based on the Lewis acid-monomer interaction. Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction Optically active poly[(meth)acrylamide]s have been proved to be good chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) to separate polar racemates, particularly chiral drugs [1,2]. Blaschke et al. reported that the chiral recognition ability of optically active polymethacrylamides is greatly influenced by their higher-order structure. For instance, polymethacrylamides directly synthesized via the radical polymerization of methacrylamide monomers exhibited a higher chiral recognition ability than that of polymethacrylamides derived from poly(methacryloyl chloride) [1]. Morioka et al. also demonstrated that the chiral recognition ability of polymethacrylamide is affected by stereoregularity

⇑ Corresponding author. Tel.: +86 451 82568191. E-mail address: [email protected] (X. Xu). 0014-3057/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.eurpolymj.2013.07.035

[3,4]. Therefore, the stereocontrol of an optically active poly(meth)acrylamide is very important from the viewpoint of the development of a novel CSP with excellent chiral recognition ability. N-monosubstituted (meth)acrylamides can be polymerized only by a radical process because of the active amide proton. However, stereocontrol during radical polymerization is not easy to realize, although radical polymerization has been widely used in industry, because a growing free radical is often very active and electrically neutral, which prevents it from interacting with other reagents and makes control during the propagation difficult. Therefore, stereoregular polymers have been mainly produced by ionic polymerization and coordinate polymerization [5–7]. Nevertheless, over the past two decades, remarkable progress has been made in radical polymerization, such as for the synthesis of block, end-functionalized, graft, and star polymers as well as polymers exhibiting more-complex

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architecture [8–14]. In addition, stereocontrol during radical polymerization has greatly advanced, especially the wide application of Lewis acids to control stereoregularity during the radical polymerization of polar monomers. The conventional radical polymerization of methacrylates and methacrylamides, except for those having bulky side chains, generally produces a syndiotactic-rich polymer due to the steric repulsion between the side chains [15–17]. After the addition of Lewis acids, they might interact with the monomers and the propagating chainend to change the stereochemistry of the polymerization in an isotactic-selective manner. Among the many Lewis acids, rare earth metal trifluoromethanesulfonates (triflates), such as Y(OTf)3, Sc(OTf)3, Yb(OTf)3, La(OTf)3, Pr(OTf)3 and Lu(OTf)3, are particularly effective in the stereospecific radical polymerization of various methacrylates [18–21] and (meth)acrylamides [22–33]. Although these Lewis acids have been successfully applied to control the stereoregularity of polymethacrylates and poly(meth) acrylamides, the detailed mechanism has not yet been clarified. For a hydroxyl-functionalized monomer, specific interactions toward hydroxyl group are introduced, thus, different effect of Lewis acid on the tacticity of the corresponding polymer is expected. In this study, the stereospecific radical polymerization of a hydroxyl-functionalized methacrylamide, (S)-(2-hydroxy-1-phenylethyl) methacrylamide ((S)-HPEMA), in the presence of various Lewis acids was systematically investigated and the plausible mechanism of stereocontrol in the radical polymerization of (S)-HPEMA was analyzed based on the Lewis acid-monomer interaction.

drofuran, dichloromethane, chloroform and diethyl sulfoxide (Tianjin Kermel Chemical Reagent Co., Ltd. China) were dried over calcium dihydride and distilled before use. Methacryloyl chloride (Shanghai Hatch Chemical Co., Ltd., China), rare earth metal trifluoromethanesulfonates (Ln(OTf)3, Ln = Y, Yb) (Aldrich chemical Co. Inc., USA), Ln(OTf)3 (Ln = Ce, Eu, La, Nd, Pr), metal chlorides (LaCl3, NdCl3, ZnCl2), and (S)-2-amino-2-phenylethanol (Shanghai Jingchun Scientific Co., Ltd., China) were used as received. Other chemicals were analytical reagents and used without further purification.

2.2. Synthesis of monomer (S)-HPEMA was synthesized by the reaction of (S)-2amino-2-phenylethanol and methacryloyl chloride in the presence of triethylamine in dichloromethane according to a slightly modified version of a previously reported procedure (Scheme 1) [34]. (S)-2-Amino-2-phenylethanol (6.86 g, 50 mmol) and triethylamine (14.6 mL, 105 mmol) were dissolved in dichloromethane (100 mL); then, methacryloyl chloride (5.1 mL, 53 mmol) was added dropwise at 0 °C. After the addition, the mixture was stirred overnight, with the temperature rising to room temperature. The reaction mixture was washed with 1 M HCl (100 mL  2), dilute NaHCO3 aqueous solution (100 mL  1) and deionized water (100 mL  2). The organic layer was dried over anhydrous MgSO4, filtered and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel (eluent, nhexane/ethyl acetate = 1:3, v/v) to afford (S)-HPEMA as a  white solid (5.83 g, yield 57%); m.p.: 104 °C, ½a25 D ¼ þ55 (c = 1.0 g/L, l = 10 cm, THF). 1H NMR (500 MHz, CDCl3): 7.26–7.40 (m, 5H, C6H5), 6.47 (s, 1H, NH), 5.77–5.40 (d, 2H, CH2 = C(CH3)), 5.12 (q, 1H, CHNH), 3.94 (m, 2H, CH2OH), 2.39 (s, 1H, OH), 2.00 (s, 1H, CH3) ppm. 13C NMR (500 MHz, CDCl3): 168.9 (C = O), 139.7 (CH2 = C(CH3)), 139.1, 128.9, 127.9, 126.7 (C6H5), 120.2 (CH2 = C(CH3)), 66.4 (CH2OH), 55.9 (CHNH), 18.6 (CH3) ppm. IR (KBr, pellet): 3419 (NH), 3332 (OH), 3088, 930 (CH2 = C<), 3039, 1614, 1495, 705 (phenyl), 2965, 2933, 2884, 1454 (saturated CH), 1650, 1525 (CONH), 1033 (CH2OH) cm1. Elem.

2. Experimental 2.1. Materials

a,a0 -Azobisisobutyronitrile (AIBN, Tianjin Kermel Chemical Reagent Co., Ltd. China) was purified by recrystallization from ethanol. n-Butyl alcohol and methanol (Tianjin Kermel Chemical Reagent Co., Ltd. China) were dried over calcium oxide and distilled before use. Tetrahy-

H2N

H N

Cl OH O TEA

0 oC

OH

O in DCM

s) N acid h AIB wis 24 (Le oC 60

n O HN OH

Scheme 1. Synthetic route of monomer (S)-HPEMA and the corresponding polymer PHPEMA.

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Anal. Calc. for C12H15NO2: C, 70.22; N, 6.83; H, 7.37%. Found: C, 70.00; N, 6.73; H, 7.32%. 2.3. Polymerization procedure Radical polymerization was carried out according to the following procedure (Scheme 1). (S)-HPEMA and Lewis acid were placed in a glass reaction tube equipped with a three-way stopcock under dry nitrogen atmosphere. AIBN solution and solvent were introduced with a syringe under a dry nitrogen atmosphere, and the reaction tube was sealed and placed in an oil bath at 60 °C for 24 h. The polymerization at 0 °C was initiated by UV irradiation in the presence of AIBN. The reaction mixture was then poured into a large excess of acetone for the polymerization systems without Lewis acid or hot water for the polymerization systems with Lewis acid. The obtained polymers were isolated by centrifugation, washed with a precipitator and dried under vacuum at 60 °C for 12 h. 2.4. Measurements 1 H and 13C NMR spectra was recorded on a Bruker Avance III-500 NMR instrument in CDCl3, methanol-d4 and DMSO-d6 at room temperature for monomers and in DMSO-d6 at 80 °C for polymers. The tacticity of PHPEMA was determined from the peaks of the a-methyl carbon (d = 16–24 ppm) [3,4,26,30]. Elemental analysis was performed on a Vario EL CHNOS elemental analyzer. FT-IR

Table 1 Effect of Lewis acids on the radical polymerization of (S)-HPEMA in methanol.a m/rd

Yield (%)b

½a25 D (°)c

Mn (103)

PDI

1.30 16/ 84 1.59 47/ 53 2.43 47/ 53 2.36 54/ 46 2.38 49/ 51 2.73 56/ 44 2.47 52/ 48 2.32 54/ 46 2.16 35/ 65 2.14 34/ 66 1.84 17/ 83

1

None

72

+68

61.0

2

Y(OTf)3

96

+88

3.6

3

Yb(OTf)3 88

+80

11.0

4

Ce(OTf)3 90

+83

7.9

5

Eu(OTf)3 93

+83

8.0

6

La(OTf)3

90

+61

9.6

7

Nd(OTf)3 90

+83

7.7

8

Pr(OTf)3

92

+72

7.7

9

LaCl3

89

+79

9.4

10

NdCl3

89

+78

8.1

11

ZnCl2

85

+68

5.2

mm/mr/ rr 3/25/72e 29/36/35 30/34/ 36e 35/38/27

3. Results and discussion 3.1. Effect of Lewis acids on the radical polymerization of (S)HPEMA in methanol The results of the radical polymerization of (S)-HPEMA in the absence and presence of various Lewis acids in methanol at 60 °C in dry nitrogen are summarized in Table 1. The polymerization proceeded homogeneously, and the reaction solution was precipitated in acetone or hot water for the removal of residual Lewis acids and other impurities. The polymerization of (S)-HPEMA in the presence of various Lewis acids in methanol exhibited 13– 24% higher yield compared with that in the absence of Lewis acid. This is probably because the Lewis acids applied in this study might coordinate with the monomer and increase the reactivity of the monomer [7,19]. To confirm this activation effect, the radical polymerization in the absence and presence of Lewis acid Pr(OTf)3 in methanol at 60 °C was monitored by 1H NMR and the time–conversion plots were shown in Fig. 1. A clear acceleration effect was observed in the presence of Lewis acid and the conversion of the polymerization in the presence of Lewis acid is about 20% higher than that in the absence of Lewis acid after 5.5 h of polymerization.

100

30/37/33 36/39/25 33/38/29 34/39/27 18/33/49 18/31/51 6/22/72

a [(S)-HPEMA]0 = 0.50 mol/L; [AIBN]0 = 0.02 mol/L; [Lewis acid]0 = 0.10 mol/L; time = 24 h. b Acetone-insoluble part (without Lewis acid); Hot-water-insoluble part (with Lewis acid). c Determined by spectropolarimetry in THF. c = 1 mg/mL, l = 10 cm. d Determined by 13C NMR in DMSO-d6 at 80 °C. e Data from Ref. [33].

80

conversion (%)

Entry LA

spectra were recorded on a PerkinElmer Spectrum 100 FT-IR spectrometer. Specific optical rotations (½a25 D ) were measured in THF at 25 °C using a PerkinElmer polarimeter (model 341). The number-average molecular weight (Mn) and polydispersity [weight-average molecular weight/ number-average molecular weight (Mw/Mn)] of the polymers were determined by a gel permeation chromatography (GPC) instrument calibrated with standard polystyrenes with a Waters Delta-600 pump equipped with a Waters 2414 detector and a set of Styragel HR-5, HR-4 and HR-0.5 columns (with THF as an eluent) in series at 35 °C or a set of Styragel HR-4, HR-2 and HR-1 columns (with N,N-dimethylformamide containing 0.1 mol/L of LiBr as an eluent) in series at 60 °C.

60

Pr(OTf)3 None

40

20

0

0

50

100

150

200

250

300

350

Time (min) Fig. 1. Time–conversion plots of the polymerization of (S)-HPEMA in the absence and presence of Pr(OTf)3 in methanol at 60 °C ([(S)HPEMA]0 = 0.5 M, [AIBN]0 = 0.02 M, [Pr(OTf)3]0 = 0.1 mol/L, if added).

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X. Xu et al. / European Polymer Journal 49 (2013) 3673–3680

DMSO 2

DMSO

1 3

n

8 9 O

4

HN 5

a1

mm

b

8 9

CH3

6

mm

mr

b1

CH mr

rr

OH

7 8 10

rr

a

10

24

22

20

18

24

16

22

20

18

16

δ / ppm

δ / ppm

9

10

6

7

3

5

6

7

1

5

4

3

4

200

180

160

140

120

100 80 δ / ppm

60

1

2

2

40

20

0 200

180

160

140

120

100

80

60

40

0

20

δ / ppm

Fig. 2. 13C NMR spectra of PHPEMA prepared by the free radical polymerization in the absence (a) and presence (b) of Pr(OTf)3 in methanol at 60 °C [500 MHz, DMSO-d6, 80 °C].

The tacticity of PHPEMA was estimated by 13C NMR spectroscopy based on the splitting of the methyl signals, as shown in Fig. 2. In the absence of Lewis acids, syndiotactic-rich polymers (r = 84%) were obtained, whereas in the presence of a catalytic amount of Lewis acids, the polymerization proceeded in an isotactic-specific manner. All of the rare earth metal trifluoromethanesulfonates (triflates) applied in methanol exhibited a similar isotacticity-enhancing effect and produced PHPEMA with a meso (m) value of 47–56%. Among the Lewis acids applied, Ce(OTf)3, La(OTf)3 and Pr(OTf)3 have been found to be most effective in exerting stereocontrol during radical polymerization. Conversely, rare earth metal chlorides, such as NdCl3 and LaCl3, are less effective in exerting stereocontrol than the corresponding triflates, and transition metal chlorides, such as ZnCl2, are not effective in exerting stereocontrol at all. Rare earth metal triflates are known as unique Lewis acids characterized by strong Lewis acidity, large ionic radii of the central metal, high coordination numbers, and tolerance toward protic solvents and water [7]. These Lewis acids can coordinate with the pendant groups of the polar monomers and the propagating chain ends, which may restrict the free rotation of the propagating radical species to induce stereospecific propagation [35]. To investigate the interaction between the Lewis acids and the monomer, 1H NMR spectra of (S)-HPEMA in the absence and presence of various Lewis acids were obtained in methanol-d4. As shown in Fig. 3, the 1H NMR spectrum of (S)-HPEMA in the presence of the Lewis acid Pr(OTf)3 shows the greatest changes, including the changes in chemical shift and peak width. However, only slight changes in chemical shift and peak width are observed in the 1H NMR spectrum of (S)-HPEMA in the presence of Lewis acid LaCl3 (Fig. 3c), and no obvious changes are observed in the case of ZnCl2 (Fig. 3b). The peak shift values for the 1H NMR spectrum of (S)-HPEMA in the presence of various Lewis acids are summarized in Table 2. In the 1H NMR spectra of (S)-HPEMA, clear downfield or highfield shifts of up to 0.271 ppm are observed in the presence of Pr(OTf)3, whereas the shifts are much smaller (up to 0.046 ppm) in the case of LaCl3, and almost no shifts were

2

3

8

7

6

5

4

3

2

δ / ppm Fig. 3. 1H NMR spectra of (S)-HPEMA in the absence (a) and presence of Lewis acids ZnCl2 (b), LaCl3 (c) and Pr(OTf)3 (d) in methanol-d4.

observed in the case of ZnCl2. These results indicate the strong interaction between Pr(OTf)3 and monomer (S)-HPEMA, which probably include the coordination of the amide group and hydroxyl group of (S)-HPEMA to the rare earth metal ion of the Lewis acid. These strong interactions are associated with stereocontrol during the radical polymerization of (S)-HPEMA. The stronger these interactions are, the more effective the stereocontrol effect is. This behavior suggests that the interactions between the Lewis acids and the monomer or growing species are responsible for stereocontrol during the radical polymerization of (S)-HPEMA. 3.2. Effect of solvents on the radical polymerization of (S)HPEMA in the absence and presence of Lewis acids The effect of solvents on the radical polymerization of (S)-HPEMA was studied in the absence and presence of Pr(OTf)3 in various solvents; the results are summarized

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X. Xu et al. / European Polymer Journal 49 (2013) 3673–3680 Table 2 Changes in the 1H NMR chemical shifts of (S)-HPEMA in the presence of various Lewis acids.a Proton No.b

1 2 3 5 6 a b

Chemical shift d without Lewis acids (ppm)

5.749 5.407 1.965 5.038 3.792 3.781

ZnCl2

LaCl3

Yb(OTf)3

d (ppm)

Dd (ppm)

d (ppm)

Dd (ppm)

d (ppm)

Dd (ppm)

5.751 5.409 1.965 5.039 3.793 3.778

+0.002 +0.002 0 +0.001 +0.001 0.003

5.770 5.421 1.974 5.084 3.802 3.790

+0.021 +0.014 +0.009 +0.046 +0.010 +0.009

6.020 5.591 2.161 5.143 3.942 3.688

+0.271 +0.184 +0.196 +0.105 +0.150 0.093

[(S)-HPEMA] = 0.10 mol/L; [LA] = 0.02 mol/L; solvent = methanol-d4. The number of protons in Fig. 3.

Table 3 Effect of solvents on the radical polymerization of (S)-HPEMA in the absence and presence of Pr(OTf)3.a

a b c d e f

Entry

Solvent

LA

Yield (%)b

½a25 D (°)

1 2 3 4 5 6 7 8 9 10

n-BuOH n-BuOH THF THF CHCl3 CHCl3 CH3OH CH3OH DMSO DMSO

None Pr(OTf)3 None Pr(OTf)3 None Pr(OTf)3 None Pr(OTf)3 None Pr(OTf)3

82 93 83 94 89 96 72 92 85 97

+69 +95 +78 +92 +80 +75 +68 +72 +72 +55

c

Mn (104)

PDI

m/rd

mm/mr/rr

11.6 1.53 7.58 1.25 8.70 –e 6.10 0.77 7.03 6.32

2.07 3.11 1.73 2.78 1.34 – 1.30 2.32 1.22 1.41

14/86 62/38 16/84 59/41 17/83 55/45 16/84 54/46 11/89 11/89

4/19/77f 42/40/18 5/21/74 40/38/22 5/24/71 33/43/24 3/25/72 34/39/27 4/14/82 1/19/80

[(S)-HPEMA]0 = 0.50 mol/L; [AIBN]0 = 0.02 mol/L; [Lewis acid]0 = 0.10 mol/L; time = 24 h. Acetone-insoluble part (without Lewis acid); Hot-water-insoluble part (with Lewis acid). Determined by spectropolarimeter in THF. c = 1 mg/mL, l = 10 cm. Determined by 13C NMR in DMSO-d6 at 80 °C. The sample was not dissolved in THF and DMF. Data from Ref. [33].

70

meso diad (%)

60 50 40 30 20 10 0 DMSO

CH3OH

Lewis acid:

CHCl3

solvent none

THF

n-BuOH

Pr (OTf)3

Fig. 4. Comparison of tacticity of PHPEMA in the absence and presence of Lewis acid in various solvents.

in Table 3. Similar to the results for the polymerization in methanol, the polymerization of (S)-HPEMA in the presence of Pr(OTf)3 in various solvents exhibited 7–20% higher yield compared with that in the absence of the Lewis acid. In the absence of Pr(OTf)3, the influence of the solvents on the tacticity was very small and syndiotactic-rich polymers (r = 83–89%) were produced. In the presence of Pr(OTf)3, however, the effect of the Lewis acids significantly depended on the polymerization solvent. In n-butyl alcohol, THF, CHCl3 and methanol, radical polymerization proceeded in an isotactic-specific manner, and the highest isotacticity-enhancing effect was observed in n-butyl alco-

hol (m = 62%). The effect of Lewis acids in different solvents decreases in magnitude in the order of n-butyl alcohol > THF > CHCl3 > methanol, which seems to be associated with the polarity of the solvents. The effect of solvent polarity on the tacticity of PHPEMA is illustrated in Fig. 4. The lower the polarity of the solvent is, the stronger the isotacticity-enhancing effect is. Clearly, this result is because the polarity of the solvents may influence the interaction between the Lewis acid and the monomer or the propagating chain end. Conversely, the isotacticityenhancing effect disappeared in DMSO, which could be attributed to the fact that DMSO interacts strongly with the Lewis acid, preventing the Lewis acid from interacting with the monomer and the propagating chain end [22,24]. To prove this assumption, 1H NMR spectra of (S)-HPEMA in the absence and presence of Lewis acid Pr(OTf)3 were obtained in methanol-d4 and DMSO-d6 and are shown in Fig. 5. The great changes in chemical shift and peak width in the 1H NMR spectra of (S)-HPEMA in methanol-d4 in the presence of Pr(OTf)3 have been discussed in Section 3.1. Compared with these great changes, no obvious changes are observed in the 1H NMR spectrum of (S)-HPEMA in DMSO-d6 in the presence of Pr(OTf)3, which suggests that the strong interaction between the monomer and the Lewis acid disappears in DMSO. As a result, the isotacticityenhancing effect of Pr(OTf)3 disappears in DMSO. Because the highest isotacticity-enhancing effect of Pr(OTf)3 on the radical polymerization of (S)-HPEMA was obtained in n-butyl alcohol, the effect of other rare earth

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70 2

60

meso diad (%)

3

50 40 30 20

2

10 0.0

0.4

0.8

1.2

1.6

2.0

2.4

[Pr(OTf)3] 0 /[Monomer]0 9

8

7

6

5

4

3

2

δ /ppm Fig. 5. 1H NMR spectra of (S)-HPEMA in DMSO-d6 in the absence (a) and presence (b) of Pr(OTf)3 and in methanol-d4 in the absence (c) and presence (d) of Pr(OTf)3 ([(S)-HPEMA]/[Pr(OTf)3] = 5/1).

metal triflates, including Y(OTf)3, Yb(OTf)3, La(OTf)3, and Ce(OTf)3, on the radical polymerization of (S)-HPEMA in n-butyl alcohol were investigated, and the results are summarized in Table 4. All of the rare earth metal triflates exhibited a similar isotacticity-enhancing effect in n-butyl alcohol and produced a polymer with a meso (m) value of 58–64%. Among these Lewis acids, La(OTf)3 showed the highest isotactic selectivity in n-butyl alcohol (m = 64%). 3.3. Effect of Lewis acid concentration on the radical polymerization of (S)-HPEMA The effect of the Lewis acid concentration on the radical polymerization of (S)-HPEMA was studied in n-butyl alcohol. Fig. 6 illustrates the relationship between the Pr(OTf)3 concentration and the m value of the obtained PHPEMA at 60 °C. As shown in Fig. 6, the isotacticity of PHPEMA increased drastically when small amount of Pr(OTf)3 was introduced to the reaction system and the highest isotacticity was obtained in the presence of 20 mol% of Pr(OTf)3 to the monomer, but the further addition of Pr(OTf)3 did Table 4 Effect of Lewis acids on the radical polymerization of (S)-HPEMA in n-butyl alcohola.

a

Entry

LA

Yield (%)b

½a25 D (°)

1 2 3 4 5 6

None Y(OTf)3 Yb(OTf)3 La(OTf)3 Ce(OTf)3 Pr(OTf)3

82 61 76 94 92 93

+69 +92 +90 +63 +87 +95

c

m/r

d

14/86 59/41 58/42 64/36 61/39 62/38

mm/mr/rr 4/19/77e 39/39/22 38/39/23e 43/42/15 40/41/19 42/40/18

[(S)-HPEMA]0 = 0.50 mol/L; [AIBN]0 = 0.02 mol/L; [Lewis acid]0 = 0.10 mol/L; time = 24 h. b Acetone-insoluble part (without Lewis acid); Hot-water-insoluble part (with Lewis acid). c Determined by spectropolarimeter in THF. c = 1 mg/mL, l = 10 cm. d Determined by 13C NMR in DMSO-d6 at 80 °C. e Data from Ref. [33].

Fig. 6. Relationship between the mole ratio of Pr(OTf)3 to (S)-HPEMA and the diad tacticity (m) of the obtained polymer (solvent: n-BuOH, initiator: AIBN, temperature: 60 °C, [(S)-HPEMA]0 = 0.5 M, [AIBN]0 = 0.02 M).

not enhance the isotactic selectivity. These results suggest that a catalytic amount of the Lewis acid is enough to control the stereoregularity. 3.4. Effect of temperature on the radical polymerization of (S)HPEMA To investigate the effect of temperature on the stereoregularity of the polymer, (S)-HPEMA was polymerized in the absence and presence of Pr(OTf)3 at 0 °C instead of 60 °C in n-butyl alcohol, and the results are summarized in Table 5. In the absence of the Lewis acid, the radical polymerization of (S)-HPEMA at lower temperature produced PHPEMA with a slightly higher syndiotacticity (r = 91%), although the polymerizations resulted in a rather poor yield (only 41%). In the presence of the Lewis acid, however, the polymerization of (S)-HPEMA produced much higher yields, although they were still slightly lower than the yield obtained at the higher temperature. For the polymerization of (S)-HPEMA at 0 °C with a lower Pr(OTf)3 concentration, the isotacticity of the polymer is slight lower than that of the polymer formed at 60 °C. Decreasing the reaction temperature may have two effects that result in tacticity changes in the opposite directions. The monomer and the Lewis acid may have a stronger interaction at low temperatures, but lower solubility of the Lewis acid in the solvent would be the disadvantage of reducing the temperature. Thus, the influence of changing the temperature might reflect a balance between the two conflicting effects [20,36]. In the case of (S)-HPEMA, the stereocontrol achieved during radical polymerization was not strongly affected by the temperature. 3.5. Plausible mechanism of stereocontrol during the radical polymerization of (S)-HPEMA Based on the results and discussion in the previous sections of this paper, we propose the following stereocontrol mechanism in the radical polymerization of (S)-HPEMA, which is mainly based on the Lewis acid-monomer

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X. Xu et al. / European Polymer Journal 49 (2013) 3673–3680 Table 5 Effect of reaction temperature on the radical polymerization of (S)-HPEMA in n-BuOHa.

a b c d e f

Entry

LA

[LA]0

Initiator

Temp. (°C)

Yield (%)c

o ½a25 D ( )

1 2 3 4 5 6

None Pr(OTf)3 Pr(OTf)3 None Pr(OTf)3 Pr(OTf)3

0 0.1 0.5 0 0.1 0.5

AIBN AIBN AIBN AIBN/UVb AIBN/UVb AIBN/UVb

60 60 60 0 0 0

82 93 90 41 85 86

+69 +95 +88 +59 +77 +89

d

m/re

mm/mr/rr

14/86 62/38 61/39 9/91 57/43 61/39

4/19/77f 42/40/18 42/37/21 3/12/85 38/38/24 42/38/20

[(S)-HPEMA]0 = 0.50 mol/L; [AIBN]0 = 0.02 mol/L; time = 24 h. Initiator: AIBN with UV irradiation. Acetone-insoluble part (without Lewis acid); Hot water-insoluble part (with Lewis acid). Determined by spectropolarimeter in THF. c = 1 mg/mL, l = 10 cm. Determined by 13C NMR in DMSO-d6 at 80 °C. Data from Ref. [33]

Scheme 2. Plausible stereocontrol mechanism in the radical polymerization of (S)-HPEMA in the presence of Lewis acids.

interaction (Scheme 2). A monomer is activated by the interaction between a Lewis acid and the monomer, and the activated monomer is preferentially polymerized. Therefore, the Lewis acid is incorporated into the propagating chain end [6]. The interactions between monomer (S)HPEMA and the Lewis acid probably include the coordination of the amide group and hydroxyl group of (S)-HPEMA to the rare earth metal ion of the Lewis acid. The Lewis acid could interact with two or more structural units because of its high coordination number and more than one triflate ions and thereby control the stereochemistry of the polymerization in an isotactic-selective manner. The Lewis acid might weakly interact with the polymer chain to be readily transferred to another monomer and activate it. As a result, a catalytic amount of the Lewis acid is enough to control the stereoregularity [6,19,35,37,38]. 4. Conclusions The stereospecific radical polymerization of optically active (S)-N-(2-hydroxy-1-phenylethyl) methacrylamide was realized in the presence of Lewis acids, namely, rare earth metal trifluoromethanesulfonates. In the absence of the Lewis acids, syndiotactic-rich polymers (r = 84%) were obtained, whereas in the presence of a catalytic amount

of the Lewis acids, the polymerization proceeded in an isotactic-specific manner. Polymerization solvents strongly influenced the effect of the Lewis acids. The polymerization in n-butyl alcohol showed the highest isotactic selectivity, whereas the polymerization in DMSO showed no isotacticity-enhancing effect. Further increases in the Lewis acid concentration and the polymerization temperature did not induce a clear effect on the tacticity of the polymers. The interaction between the monomer and Lewis acids was investigated, and the plausible mechanism of stereocontrol in the radical polymerization of (S)-HPEMA was analyzed based on the Lewis acid-monomer interaction. Acknowledgements This work was financially supported by the National Natural Science Foundation of China (Nos. 51103030 and 51310105019), the Fundamental Research Funds for the Central Universities (Nos. HEUCFT1009, HEUCF201310003, and HEUCF201310009), the Harbin City Scientific and Technological Innovation Fund of China (No. 2013RFLXJ027), Daicel Corporation (Tokyo, Japan) and Foreign Affairs Office of Harbin Engineering University. Dr. Xiaodong Xu is grateful to Professor Yoshio Okamoto for his valuable suggestions on this work.

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