SYNTHESIS OF CYCLIC POLY(ε-CAPROLACTONE) USING ALUMINUM(III) COMPLEXES Pisanu Pisitsopon a, Phonpimon Wongmahasirikun b, Khamphee Phomphrai *,b a Department of Chemical Engineering, School of Energy Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong, Thailand b Department of Materials Science and Engineering, School of Molecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong, Thailand Keywords: Cyclic polyesters, Biodegradable polymers, ε-caprolactone ABSTRACT Poly(ε-caprolactone) is one of the most promising biodegradable polymers because it can solve the problem of excess plastic waste issues. To develop more advanced materials, changing the polymer topology is one common way to deal with. Cyclic polymers have received significant attention because they have different physical properties compared to their linear counterparts. Cyclic polymers can be efficiently made from ring-opening polymerization (ROP) using metal alkoxide complexes as a catalyst. Herein, two aluminum complexes containing salicylaldiminate ligands were synthesized and polymerized with ε- caprolactone via solution polymerization giving cyclic poly(ε-caprolactone). *khamphee.p@vistec.ac.th INTRODUCTION Living green has been paid attention over the last few decades. The ultimate goal for such sustainably life is to reduce the consumption of petroleum-based product to be zero. While, the petroleum-based plastics, which is one of the largest manufacturing industry, still has an important role in daily life due to their notable properties, broad applications, and low cost. They have known to be environmental unfriendly. Furthermore, current level of their usage and disposal is still high leading to an environmental problem. The ecological drawbacks of petroleum-based plastics have pushed researchers to investigate and develop biodegradable plastics as environmentally-friendly alternatives. 1, 2 Polyesters such as polylactide and poly(ε-caprolactone) were used extensively in various applications including biomaterials, drug carrier, and packagings because of biodegradable and biocompatible properties. 1 So far, poly(ε-caprolactone) (PCL), which was one of the earliest polyesters from cyclic esters 3, can be prepared by ring-opening polymerization (ROP). Due to its good solubility, low melting temperature, and exceptional blendcompatibility, the advanced research on the synthesis of PCL has been stimulated into its potential applications. 4 Petrochemical and Materials Technology Tuesday May 23, 2017, Pathumwan Princess Hotel, Bangkok, Thailand Page 1
Special and tailored polymer properties can be obtained by changing the polymer architecture and microstructure. Cyclic polymers have gained significant attentions lately due to the different properties compared to their linear counterparts. For instance, cyclic polymers expose the longer elution time due to small hydrodynamic volume, have a higher T g than linear polymers, and have lower intrinsic viscosity and self-diffusion coefficient. As mentioned above, cyclic polymers can broaden the range of applications such as biomedical field especially in drug delivery. 5, 6 Cyclic polymers can be synthesized using two main strategies: ring-closure technique and ring-expansion technique (Figure 1). The ring-closure method deals with the coupling of end-capped functionalized linear polymers. The limitation of this method is the highly dilute condition requirement and poor purity with linear contaminants which are difficult to purify. Another method, ring-expansion method, mainly involves with catalysts and initiators having labile bond in order that can break bond of cyclic monomers and subsequently reform and grow macrocycle. This technique can overcome the drawback from ring-closure method giving high molecular weight cyclic polymers with high purity. 7 (a) (b) Figure 1 Simple schematic of (a) ring-closure technique (b) ring-expansion technique. Some effective catalysts for cyclic polymers have been reported recently. The pioneer work using ring-expansion technique reported by Kricheldorf and Lee in 1995. They successfully developed cyclic tin initiator to polymerize β-butytolactone and ε-caprolactone. 8 The second generation which used the lone-pair electron as an initiator reported by Waymouth and coworkers in 2007. They presented cyclic polylactide and polycaprolactone using N- heterocyclic carbenes (NHCs) by solution polymerization at room temperature. Unexpectedly, NHCs together with alcohol initiators give the linear polymers. 9 In 2015, Phomphrai and coworkers developed the new concept using salicylaldiminato tin(ii) complexes (Figure 2) with an alkoxy side chain as an initiator. Complexes with a short length side chain can produce cyclic polylactide and polycaprolactone via intramolecular transesterification. 10 Figure 2 Catalyst structures of tin(ii) complexes Herein, we further explore the efficiency of this ligand system containing a sidearm with aluminium metal for the synthesis of cyclic polymers. Petrochemical and Materials Technology Tuesday May 23, 2017, Pathumwan Princess Hotel, Bangkok, Thailand Page 2
EXPERIMENTAL All operations for air- or moisture-sensitive compounds are carried out under a nitrogen atmosphere using standard Schlenk techniques. Chemicals were purchased from commercial suppliers and used as received. n-hexane was dried using a solvent purification system MB SPS5 system from M. BRAUN, Inc. ε-caprolactone was purified by distillation over calcium hydride under nitrogen and stored in a freezer in a glove box. 3,5-Di-tertbutyl-2-hydroxybenzaldehyde and ligand 1a-1b 10 were synthesized according to the literature procedure. Characterization of compound can be conducted by NMR spectra using a Bruker AVANCE III HD 600 MHz spectrometer and referenced to protio impurities of commercial chloroform-d (CDCl 3, δ 7.26 ppm, 77.16 ppm) as internal standard for 1 H and 13 C{ 1 H}, respectively. Mass spectra were obtained from a Bruker compact-qtof mass spectrometer, APCI Direct Probe mode. A. Synthesis of complexes Synthesis of complexes 2a Dry hexane (50 ml) was added to a ligand 1a (1.331 g, 4.798 mmol). The mixture was stirred and submerged in a coolant mixed between isopropanol and liquid nitrogen. Al(CH 3 ) 3 was injected (2.9 ml, 5.758 mmol) dropwise in to the solution and stirred for 12 h. The volatile components were subsequently removed under vacuum. The solid was washed with dry hexane giving a pale yellow powder (0.891 g, 59 %) 1 H NMR (600 MHz, CDCl 3, 30ºC): δ 8.24 (s, 1H, N=CHAr), 7.49 (d, J HH = 2.6 Hz, 1H, ArH), 7.06 (d, J HH = 2.6 Hz, 1H, ArH), 4.30 (m, 1H, CH 2 ), 4.12 (m, 1H, CH 2 ), 4.09 (m, 1H, CH 2 ), 3.80 (m, 1H, CH 2 ), 1.48 (s, 9H, (CH 3 ) 3 ), 1.31 (s, 9H, (CH 3 ) 3 ), -1.12 (s, 3H, CH 3 ), 13 C{ 1 H} NMR (150 MHz, CDCl 3, 30ºC): δ 166.49 (N=CAr), 161.90, 140.30, 138.00, 129.92, 127.67, 118.89 (ArC), 59.42, 55.81 (CH 2 ), 35.56, 34.16 (CMe 3 ), 31.60, 29.42 (CH 3 ) Synthesis of complexes 2b Complex 2b was synthesized similarly to the complex 2a by adjusting the amount of ligands 1b. A white powder product was obtained (0.413 g, 26 %) 1 H NMR (600 MHz, CDCl 3, 30ºC): δ 8.05 (s, 1H, N=CHAr), 7.49 (d, J HH = 2.6 Hz, 1H, ArH), 7.02 (d, J HH = 2.6 Hz, 1H, ArH), 4.31 (m, 1H, CH 2 ), 4.10 (m, 1H, CH 2 ), 3.78 (m, 1H, CH 2 ), 3.45 (m, 1H, CH 2 ), 2.23 (m, 1H, CH 2 ),1.82 (m, 1H, CH 2 ), 1.48 (s, 9H, (CH 3 ) 3 ), 1.31 (s, 9H, (CH 3 ) 3 ), - 1.04 (s, 3H, CH 3 ), 13 C{ 1 H} NMR (150 MHz, CDCl 3, 30ºC): δ 167.62 (N=CAr), 161.52, 139.85, 138.12, 129.86, 127.73, 118.89 (ArC), 60.59, 56.80 (CH 2 ), 35.38, 34.11 (CMe 3 ), 31.59 (CH 3 ), 30.20 (CH 2 ), 29.64 (CH 3 ) B. Polymerization of ε-caprolactone (CL) The following representative polymerization is for a CL:2a mole ratio of 10:1. The amount of catalysts can be adjusted accordingly for complex 2b. Complex 2a (33.3 mg, 0.105 mmol, 1 equiv.), CL (0.120 g, 1.05 mmol, 10 equiv.) and dry toluene (1.5 ml) were added to a Schlenk flask. The flask was submerged with continuous stirring into a pre-heated oil bath at 70 º C. After specific time, the polymer was sampled and quenched with a small amount of 10% acetic acid in CH 2 Cl 2 solution for NMR analysis and mass spectroscopy. Petrochemical and Materials Technology Tuesday May 23, 2017, Pathumwan Princess Hotel, Bangkok, Thailand Page 3
RESULTS AND DISCUSSION A. Synthesis of complexes Complexes 2a and 2b were successfully synthesized by the reaction in Scheme 1. Scheme 1 Synthesis of complexes 2a-2b Complex 2a is a pale yellow solid with 59 % yield. According to 1 H NMR spectrum, all peaks of the complex shifted from ligand 1a s peak and hydroxyl proton (-OH) disappeared. The signal at δ -1.12 was the characteristic peak of methyl protons attached to the aluminum. Furthermore, the signals of methylene protons of sidearm at about δ 3.8 to 4.3 became inequivalent protons due to asymmetric environment. Complex 2b is a white solid with 21 % yield. According to 1 H NMR spectrum, all peaks of the complex shifted from ligand 1b s peak and hydroxyl proton (-OH) disappeared. The signal at δ -1.04 was the characteristic peak of methyl protons attached to the aluminum. Furthermore, the signals of methylene protons of sidearm at about δ 1.8 to 4.3 became inequivalent protons due to asymmetric environment. B. Polymerization of ε-caprolactone (CL) Solution polymerizations of CL:2a and CL:2b were conducted at 70 ºC as shown in Scheme 2. Scheme 2 ROP of ε-caprolactone with aluminium complexes Conversions of both polymerizations were shown in Figure 3. The conversion from complex 2a and 2b were at similar speed. This result was in agreement that the sidearms should involve in initiation step only. Subsequent ROP of CL should not affect the rates of polymerization. Petrochemical and Materials Technology Tuesday May 23, 2017, Pathumwan Princess Hotel, Bangkok, Thailand Page 4
Figure 3 Polymerization of CL using CL:2a and CL:2b = 10:1 in toluene solution at 70 ºC Results from APCI mass spectrometry were shown in Figure 4. At 2 h, both complexes gave the same series of 72.02n + 1 assigned to be a cyclic PCL ( ) where the mass of end group e.g., hydroxyl group and ligand was not detected. The attraction of the propagation chain closed to metal center from the sidearm which facilitated the cyclization process led to the cyclic PCL. 2 h, 91 % conv. 2 h, 82 % conv. Figure 4 APCI mass spectra of PCL synthesized from (a) CL:2a = 10:1 at 70 ๐ C terminated at 2 h and (b) CL:2b = 10:1 at 70 ºC terminated at 2 h: = [CL] n + H + From the results, cyclic PCL were obtained even at low conversion. The linear polymer having methyl as an end group was not observed. Alkoxide side chain which is nucleophilic species can act as an initiator of ROP occurred via coordination and insertion mechanism. First, alkoxide side chain which is a good nucleophile attacks the carbonyl carbon of CL leading to the insertion of the ester bond and a new alkoxide species. After the propagation step the cyclization of polymers take places via intramolecular transesterification as shown in Scheme 4. Petrochemical and Materials Technology Tuesday May 23, 2017, Pathumwan Princess Hotel, Bangkok, Thailand Page 5
Scheme 4 Proposed cyclization mechanism of PCL CONCLUSIONS Novel aluminum(iii) complexes containing alkoxide side chain which were active to the solution polymerization of ε-caprolactone were successfully synthesized. These complexes polymerize CL effectively giving cyclic PCL in quantitative yield. ACKNOWLEDGEMENTS This work was financially supported by a student scholarship from Vidyasirimedhi Institute of Science and Technology (VISTEC). Support of scientific instrument by the Frontier Research Center (FRC) is gratefully acknowledged. REFERENCES 1. J. Rydz, W. Sikorska, M. Kyulavska and D. Christova, Int J Mol Sci, 2015, 16, 564-596. 2. Y. Tokiwa, B. P. Calabia, C. U. Ugwu and S. Aiba, Int J Mol Sci, 2009, 10, 3722-3742. 3. F. J. V. H. Natta, J. W.; Carothe, W. H., Journal of the American Chemical Society, 1934, 56, 455-457 4. M. Labet and W. Thielemans, Chem Soc Rev, 2009, 38, 3484-3504. 5. B. A. Laurent and S. M. Grayson, Chem Soc Rev, 2009, 38, 2202-2213. 6. X. Y. Tu, M. Z. Liu and H. Wei, Journal of Polymer Science Part A: Polymer Chemistry, 2016, 54, 1447-1458. 7. J. N. Hoskins and S. M. Grayson, Polym. Chem., 2011, 2, 289-299. 8. H. R. Kricheldorf and S. R. Lee., Macromolecules, 1995, 28, 6718-6725. 9. D. A. Culkin, W. Jeong, S. Csihony, E. D. Gomez, N. P. Balsara, J. L. Hedrick and R. M. Waymouth, Angew Chem Int Ed Engl, 2007, 46, 2627-2630. 10. P. Wongmahasirikun, P. Prom-on, P. Sangtrirutnugul, P. Kongsaeree and K. Phomphrai, Dalton Trans, 2015, 44, 12357-12364. Petrochemical and Materials Technology Tuesday May 23, 2017, Pathumwan Princess Hotel, Bangkok, Thailand Page 6