Synthesis, characterization of aluminum complexes and the application in ring-opening polymerization of l -lactide

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EUROPEAN POLYMER JOURNAL

European Polymer Journal 43 (2007) 5040–5046

www.elsevier.com/locate/europolj

Synthesis, characterization of aluminum complexes and the application in ring-opening polymerization of L-lactide Jincai Wu a

a,*

, Xiaobo Pan a, Ning Tang a, Chu-Chieh Lin

b

Chemistry and Chemical Engineer College, Lanzhou University, Lanzhou 730000, People’s Republic of China b Department of Chemistry, National Chung-Hsing University, Taichung 402, Taiwan, ROC Received 4 May 2007; received in revised form 18 June 2007; accepted 27 June 2007 Available online 18 July 2007

Abstract Aluminum complexes supported by a sulfonamide/Shiff base ligand are described. Reaction of AlMe3 with 1 equiv of ligand 1, gives methyl aluminum complex 2, and aluminum complex 3 is prepared by the reaction of complex 2 with 1 equiv of benzyl alcohol. Experimental results show that complex 3 is an efficient initiator for the ring-opening polymerization of lactide in controlled fashion, yielding polymers with expectative molecular weight and low polydispersity indexes. Furthermore, the complex 3 has isotactic selectivity for the ring-opening polymerization of rac-lactide. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Aluminum; Sulfonamide/Shiff base; Lactide; Polymerization

1. Introduction Polylactide (PLA) is one of the most important synthetic biodegradable and bicompatible polymer investigated for a wide range of biomedical and pharmaceutical applications such as controlled drug delivery, resorbable sutures, medical implants, and scaffolds for tissue engineering [1–5]. A particularly convenient method for the synthesis of polylactides is the ring-opening polymerization (ROP) of lactides. Due to the advantages of well controlled molecular weight and low polydispersity (PDI), many metal complexes have been used to ring-opening polymerize lactides [6–12]. In this aspect, alumi* Corresponding author. Tel.: +86 (0) 931 8912552; fax: +86 (0) 931 8912582. E-mail address: [email protected] (J. Wu).

num alkoxides supported by Salen ligands show good controlled manner, especially isotactic selectivity in the stereo controlled ROP of rac-lactides [13–27]. While these aluminum Salen complexes have low activity, reasonable conversions are generally attained only at high temperatures (>70 °C) over a long period of time (h). This prompts us to explore a new system for improving activity and excellent isotactic selectivity as Salen aluminum complexes for ROP of rac-lactides. Here, we report a new aluminum alkoxide for ring-opening polymerization of lactide supported by a sulfonamide/Shiff base ligand (Scheme 1). The aluminum alkoxide 3 is similar to Salen aluminum alkoxide, because the oxygen atom of sulfonyl group can coordinate to aluminum instead of the phenol oxygen atom in Salen complexes. As we expected, this aluminum is a potential initiator for

0014-3057/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.eurpolymj.2007.06.041

J. Wu et al. / European Polymer Journal 43 (2007) 5040–5046

N OH

HN

N

Ts

Al

AlMe3 Toluene, 100 οC

1

O

N S O O Me

5041

N Al

BnOH Toluene, 90 οC

O

N S O O OBn

3

2

Scheme 1. Synthesis of aluminum compounds 2 and 3.

ring-opening polymerization of lactides, which was confirmed by the experiment results. 2. Results and discussion 2.1. Synthesis and structure determination The ligand was synthesized by condensation of 4,6-ditertbutyl-2-aldehydephenol and N-(2-aminocyclohexyl)-toluylsulfonamide derived from trans1, 2-diaminocyclohexane [28–31]. The methyl aluminum complex 2 can be obtained by the reaction of ligand 1 and AlMe3 in toluene at 100 oC for 36 h in 89% yield, the temperature should be high enough for this reaction, if the temperature was kept under 50 °C, only one methyl group was replaced to give dimethyl aluminum complex as the main product. The complex 3 was prepared by the reaction of complex 2 and benzyl alcohol in toluene at 90 oC for one day in 81% yield. Single crystals suitable for X-ray determination of complex 2 were obtained by slow cooling of a toluene solution. An ORTEP [32] drawing of this molecular structure is given in Fig. 1. The geometry around aluminum is a distorted square pyramid with methyl group at the axial positions and the nitrogen and oxygen atoms occupy the basal positions. This is verified by the N(1)–O(1)–O(2)–N(2) torsion angle of 4.23o and the 88.24o angle between C(29)–Al bond and N(1)–O(1)–O(2)–N(2) plane. The bond distances between sulfur atom and bridg˚ and S(1)– ing oxygen atoms are S(1)–O(2) 1.483 A ˚ O(3) 1.430 A, respectively, which is in agreement with the coordination of O(2) to aluminum. Compared to sulfonamide aluminum complex, the ˚ , suggests that O(2)–Al long bond distance, 2.193 A O(2) is weakly coordinated to Aluminum [33–35]. Therefore, the O(2) atom can be replaced possibly by oxygen atom of lactide in ring-opening polymerization when complex 3 was used as initiator. Trying to grow single crystals of 3 failed, however, it is

Fig. 1. ORTEP drawing of compound 2 (non-hydrogen atoms) with thermal ellipsoids drawn at 20% probability level. Selected ˚ ) and bond angles (o) : S(1)–O(3) 1.430(2), S(1)– bond lengths (A O(2) 1.483(2), S(1)–N(2) 1.566(2), S(1)–C(22) 1.757(3), S(1)–Al 2.6952(10), O(1)–C1 1.337(3), O(1)–Al 1.759(2), Al–N(2) 1.917(2), Al–C29 1.952(3), Al–N(1) 1.996(2), Al–O(2) 2.193(2), O(2)–S(1)–N(2) 97.83(12), O(1)–Al–N(2) 132.01(11), O(1)–Al– C(29) 113.28(14), N(2)–Al–C(29) 113.51(14), O(1)–Al–N1 91.82(9), N(2)–Al–N(1) 79.85(9), C(29)–Al–N(1) 112.62(14), O(1)–Al–O2 91.68(9), N(2)–Al–O(2) 67.64(9), C(29)–Al–O(2) 103.51(13), N(1)–Al–O(2) 138.74(9).

verified that the methyl group was substituted by benzyl oxide based on the 1H NMR studies. 2.2. Ring-opening polymerization of L-lactide ROP of L-Lactide (LLA) employing 3 as an initiator was systematically examined in toluene as shown in Table 1. Experimental results indicate that complex 3 is an efficient initiator for ring-opening polymerization of L-lactide. The conversion can reach to 98% using 3 as an initiator in 24 h in refluxed toluene, when [M]0/[I]0 ratio is 50 (Table 1, entry 2). The good polymerization control is demonstrated by the linear relationship between Mn and [M]0/[I]0 (Fig. 2) and the polymers with very low PDIs, ranging from 1.05 to 1.10 (Fig. 3). So the living character of the polymerization has been proved, which was further confirmed by a secondfeed experiment (entry 6) in which another portion of L-LA monomer ([M]0/[I]0 = 50) was added after

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J. Wu et al. / European Polymer Journal 43 (2007) 5040–5046

Table 1 Ring-opening polymerization of L-Lactide initiated by complex 3 O O O

3

H

n

O OR

O

O

n

O O

Entry

[M]0/[I]0

t (h)

PDI

Mn (GPC)a

Mn (NMR)b

Mn (calcd)c

Conv (%)

1 2 3 4 5 6

25:1 50:1 75:1 100:1 50(50):1 25:1

24 24 24 30 24(24) 24

1.03 1.07 1.05 1.08 1.10 1.04

6300 (3700) 11,300 (6600) 21,000 (12,100) 27,300 (15,800) 25,900 (15,000) 7100 (4100)

3700 6600 11,000 15,500 13,100 4100

3600 7200 10,300 13,900 13,800 3400

98 98 94 96 95 93

a

Obtained from GPC analysis and calibrated by polystyrene standard. Values in parentheses are the values obtained from GPC times 0.58 [45–47]. b Obtained from 1H NMR analysis. c Calculated from the molecular weight of L-lactide times [M]0/[I]0 times conversion yield plus the molecular weight of BnOH.

2.0 15000

Mn PDI

1.8

1.6

PDI

Mn(GPC)

12000

9000 1.4 6000 1.2 3000 20

30

40

50

60

70

80

90

100

1.0 110

[M]0 / [I]0

Fig. 2. Polymerization of L-LA catalyzed by 3 in toluene at 100 °C. The relationship between Mn(h)(PDI(s)) of polymer and the initial mole ration [M]0/[I]0 is shown

should be capped with one benzyl ester and one hydroxyl end with a ratio of 5:1 (Fig. 4). Furthermore, epimerization of the chiral centers in PLLA does not occur as observed by the homonuclear decoupled 1H NMR studies in the methine region (Fig. 5) [36]. Comparing to aluminum sulfonamide complexes reported by Cui et al., complex 3 initiates ROP of polymerization in excellent controlled manner [33], and the activity of complex 3 appears as moderate as Salen Aluminum complexes. 2.3. Ring-opening polymerization of rac-lactide Polymerization of rac-lactide by complex 3 is also performed. The homonuclear decoupled 1H NMR spectrum at the methine region of the PLA derived from 3 is isotactic predominance with Pm = 0.60 (Fig. 6) [37–42]. So this complex has a similar, but slightly lower selectivity for polymerization of raclactide to Salen aluminum alkoxide complex. For improving the selectivity, we think the sulfonamide/Shiff base ligand should be more bulky, and the related research is in progress. 3. Conclusions

Fig. 3. GPC profile for PLLA 100:1 from entry 4 with Mn = 27300 (PDI = 1.08).

the polymerization of the first addition ([M]0/ [I]0 = 50) had gone to completion. The 1H NMR spectrum of PLLA indicates that the polymer chain

In conclusion, a new sulfonamide/Shiff base aluminum alkoxide has been synthesized and characterized. The aluminum complex 3 was an efficient initiator for ring-opening polymerization of lactide under controlled manner with isotactic selectivity.

J. Wu et al. / European Polymer Journal 43 (2007) 5040–5046

d H

O e

c O O O

d

c O O

O c d

O

b

5043

a

O n-1 d

Fig. 4. 1H NMR PLLA 25:1 from entry 1 in CDCl3.

Fig. 5. Homonuclear decoupled 1H NMR spectrum reveals only one resonance at d 5.16 ppm in the methane region in the polymer of PLLA-100 (left one is original 1H NMR spectrum, right one is homodecoupled spectrum).

4. Experimental section 4.1. General procedures All manipulations were carried out under a dry nitrogen atmosphere. Toluene and n-hexane were freshly distilled from sodium before use. CDCl3 ˚ molecular sieves. Benzyl alcohol was dried with 4 A was dried with CaH2 and distilled prior to use. L-lac-

tide and rac-lactide were recrystalized three times with toluene and dried in vacuum. The compound 1 was prepared as reference [28]. Trimethylaluminum (2.0 M in hexane) were purchased from Aldrich and used as received. 1H NMR and 13C NMR spectra were recorded on a Varian Mercury-400 (400 MHz) or a Unity Inova-600 (600 MHz) spectrometer with chemical shifts given in parts per million from the peak of internal

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J. Wu et al. / European Polymer Journal 43 (2007) 5040–5046

Fig. 6. Homonuclear decoupled 1H NMR spectra (600 MHz, CDCl3) of the methine region of PLA prepared using complex 3.

TMS. Microanalyses were performed using a Heraeus CHN-O-RAPID instrument. The GPC measurements were performed on a Hitachi L-700 system equipped with a differential Bischoff 8120 RI detector using THF (HPLC grade) as an eluent running at 1 mL/min. Molecular weight and molecular weight distributions were calculated using polystyrene as standard. 4.2. Preparation of complexes 4.2.1. Synthesis of complex 2 AlMe3 (1.2 ml, 2 M in hexane solution, 2.4 mmol) was added slowly to a solution of compound 1 (0.96 g, 2 mmol) in 40 ml toluene and the mixture was kept at 100 oC for 36 h. Then volatile materials were removed under vacuum. The residue was recrystallized in toluene to give yellow crystalline solid. Yield: 0.92 g (89%). 1H NMR (CDCl3, ppm): d 8.09(s, 1H, CH@N), 7.85d, 2H, J = 8.0 Hz, ArH, 7.54 d, 1H, J = 2.4 Hz, ArH, 7.27 d, 2H , J = 8.0 Hz, ArH, 7.11 d, 1H, J = 2.4 Hz, ArH, 3.50 m, 1H, CH, 2.98 m, 1H, CH, 2.41 (s, 3H, CH3), 2.22–2.35 (m, 1H, HCH), 1.74–1.97 (m, 2H, CH2), 1.68 (m, 1H, HCH), 1.45 (s, 9H, C(CH3)3), 1.32 (s, 9H, C(CH3)3), 1.21–1.51 (m, 4H, CH2), 0.65 (s, 3H, AlCH3) ppm; 13C NMR (CDCl3, ppm) 163.71, 160.06, 142.77, 141.11, 139.11, 138.85, 130.53, 129.43, 129.01, 128.19, 127.36, 126.92, 125.26, 118.79, 65.66, 60.61, 35.41, 34.06, 32.23, 31.36, 29.64, 29.39, 26.25, 24.09, 23.74, 21.46 ppm; Anal. Calcd.

(Found) for C29H41N2O3SAl: C 66.38 (66.45), H 7.88 (8.23), N 5.34 (5.71)%. 4.2.2. Synthesis of complex 3 BnOH (0.11 ml, 1 mmol) was added to a solution of complex 2 (0.53 g, 1 mmol) in 20 ml toluene, and the mixture was kept at 90 oC for 24 h. Then volatile materials were removed under vacuum. The residue was dissolved in toluene, and precipitates formed by addition of hexane. The yellow powder product was obtained after filtration. Yield. 0.50 g (81%). 1H NMR (CDCl3, ppm): d 7.52d, 2H, J = 8.0 Hz, ArH), 7.38 d, 2H, J = 2.8 Hz, ArH), 7.16 7.29 m, 3H, ArH, 6.74d, 2H, J = 8.0 Hz, ArH), 6.56– 6.72(m, 2H, ArH), 6.39 (d, 2H, J = 2.8 Hz, ArH), 5.78 (d, 1H, J = 16.0 Hz, PhCHHO), 4.92 (d, 1H, J = 16.0 Hz, PhCHHO), 4.24 m, 1H, CH, 2.69 m, 1H, CH, 2.50 2.61 (m, 1H, HCH ), 2.17 (s, 3H, CH3), 1.82–2.02 (m, 3H, CH2), 1.28 (s, 9H, C(CH3)3), 1.26 (s, 9H, C(CH3)3), 1.02–1.60 (m, 4H, CH2)13C NMR (CDCl3, ppm) 160.87, 158.88, 140.96, 140.75, 139.44, 138.89, 138.81, 129.28, 129.00, 128.62, 127.93, 127.56, 127.05, 125.77, 119.44, 67.79, 64.75, 62.76, 34.92, 33.80, 31.41, 31.07, 29.51, 26.61, 25.10, 24.23, 21.18 ppm; Anal. Calcd. (Found) for C35H45N2O4SAl: C 68.16 (67.90), H 7.35(7.61), N 4.54 (4.71)%. 4.3. Typical polymerization procedures A typical polymerization procedure was exemplified by the synthesis of PLLA-25 (the number 25

J. Wu et al. / European Polymer Journal 43 (2007) 5040–5046

indicates the designed [M]0/[I]0) (Table 1, entry 1). The conversion (98%) of PLLA-25 was analyzed by 1H NMR spectroscopic studies. A mixture of complex 3 (0.031 g, 0.05 mmol) and L-lactide (0.18 g, 1.25 mmol) was dissolved in 10 ml toluene at room temperature, then the solution was refluxed for 24 hours, the reaction was cooled to room temperature and quenched by the addition of an aqueous acetic solution (0.35 N, 10 ml), and the polymer was precipitated on pouring the mixture into n-hexane (40 ml) to give white crystalline solids. The solid was filtered and washed with cold ethanol (10 ml) twice and was then dried under vacuum. 4.4. X-ray crystallographic studies Single crystal suitable for X-ray structural determination of 2 was sealed in a thin-walled glass capillary under nitrogen atmosphere and was mounted on a Brucker AXS SMART 1000 diffractometer. Intensity data were collected in 1350 frames with increasing x (width of 0.3° per frame). The absorption correction was based on the symmetry-equivalent reflections using SADABS program [43]. The space group determination was based on a check of the Laue symmetry and systematic absence, and was confirmed using the structure solution. The structure was solved by direct methods using the SHELXTL package [44]. All non-H atoms were located from successive Fourier maps, and hydrogen atoms were refined using a riding model. Anisotropic thermal parameters were used for all non-H atoms, and fixed isotropic parameters were used for H-atoms. Acknowledgement Financial support from the National Natural Science Foundation of China (20601011) is gratefully appreciated. References [1] Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Chem Rev 1999;99:3181. [2] Dechy-Cabaret O, Martin-Vaca B, Bourissou D. Chem Rev 2004;104:6147. [3] Nakano K, Kosaka N, Hiyama T, Nozaki K. J Chem Soc Dalton Trans 2003:4039. [4] Wu J, Yu T-L, Chen C-T, Lin C-C. Coord Chem Rev 2006;250:602. [5] Lanza RP, Langer R, Vacanti J. Principles of tissue engineering. 2nd ed. San Diego, CA: Academic Press; 2000.

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