The Copolymerization of ?-Caprolactone With Tetrahydrofyran Using a Proton Exchanged Montmorillonite Clay As Initiator

Polycaprolactone (PCL) is one of the most important biodegradable polymers due to its biodegradability, biocompatibility, non-toxicity and good permeability to drug [1–3]. Many copolymers of CL with other monomers such as lactide (LA) [4, 5], 5-methyl-5 benzyloxycarbonyl-1,3-dioxane-2-one (MBC) [6, 7], 1,3- dioxane-2-one (TMC) [8–10], glycolide (GA) [11, 12],tetrahydrofuran(THF)[13] and poly (ethylene glycol) (PEG) [14, 15] have been extensively investigated in order to expand applications of PCL, but most of the cationic initiators used in the synthesis of these copolymers are expensive. They may be poisoned by products of the reaction or impurities present in the monomer feed, and contain heavy metals, such as chromium, mercury, antimony, etc., that presents environmental disposal problems for the user. Frequently, these initiators require the use of very high or very low temperature and high pressures during the polymerization reaction. The separation of the initiators from the polymer is not always possible. Therefore, the presence of toxic initiators presents problems in the manufacture of polymers used especially in medical and veterinary procedures. There is still a great demand for heterogeneous catalysis under mild conditions and in environmentally friendly processes. Montmorillonite, a class of inexpensive and noncorrosive solid acids, have been used as efficient catalysts for a variety of organic reactions. The reactions catalyzed by montmorillonite are usually carried out under mild conditions with high yields and high selectivity, and the workup of these reactions is very simple; only filtration to remove the catalyst and evaporation of the solvent are required. Montmorillonite catalysts are easily recovered and reused [16, 17]. The purpose of this paper is to study the copolymerization of ε- caprolactone with tetrahydrofyran, catalyzed by Maghnite-H+ [18], a proton exchanged Montmorillonite clay. This new non-toxic cationic catalyst has exhibited higher efficiency via the polymerization of vinylic and heterocyclic monomers [19, 20]. The effects of the amounts of the Maghnite-H+ and the temperature on the synthesis of poly (ε-caprolactone-co-tetrahydrofuran) are also discussed.

2. METHODS

2.1. General The 1H-NMR spectra were recorded on Bruker Avance-300 spectrometer in deuterochloroform. Chemical shifts are shown in δ values. 2.2. Materials ε-Caprolactone (grade 99%) was used as purchased from Aldrich. Tetrahydrofuran (THF) was distilled over the blue benzophenone–Na complex. Acetic anhydride was distilled with the anhydrous sodium acetate under a

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pressure reduced to eliminate the halogenous compounds and metals. Chloroform was dried on CaH2 anhydrous and distilled before use. Raw-Maghnite: Algerian Montmorillonite clay was procured from BENTAL (Algerian Society of Bentonite). 2.3. Preparation of “Maghnite-H+ 0.25M” Maghnite-H+ was prepared according to the process similar to that described by Belbachir et al. [20]. Raw- Maghnite (20 g) was crushed for 20 mn using a prolabo ceramic balls grinder. It was then dried for 2 hours at 105◦C the Maghnite was placed in an Erlenmeyer flask together with 500 ml of distilled water. The Maghnite/water mixture was stirred using a magnetic stirrer and combined with 0.25 M sulfuric acid solution, until saturation was achieved over 2 days at room temperature, the mineral was then washed with distilled water to became sulfate free and then dried at 105◦C. 2.4. Copolymerization and products characterization The bulk copolymerization’s were carried out in stirred flasks at 25°C for 24 hours. The catalyst was dried in a muffle furnace at 120°C overnight and then transferred to a vacuum desiccator containing P2O5. After cooling to room temperature under vacuum, the mineral was added to the ε-caprolactone (0.03mol), THF (0.03mol) mixtures previously kept in the stirred flask at 25°C. After the required time was reached, an aliquot of the reaction mixture was then removed in such a manner as to exclude any clay mineral, and then dried by evaporation to remove solvent and remaining monomer.

3. RESULTS AND DISCUSSION

3.1. Copolymerization and products characterization The result of bulk copolymerization experiment of ε-caprolactone (0.03mol), with THF (0.03mol) induced by “Maghnite-H+ 0.25M” is reported in Table 1. For all these experiments, the temperature was kept constant at 25°C for 24 hours. 3.2. Effect of temperature on copolymerization The effect of temperature on the copolymerization of ε-caprolactone (0.03mol) with THF (0.03mol) initiated by Maghnite-H+(5% by weight) for 5 hours, is shown in Figure 1. The copolymerization yield reaches maximum value around 60–70◦C. On the other hand, with the increase in the reaction temperature above 60◦C the molecular weight of the obtained copolymer decreases progressively, suggesting the possible occurrence of thermal degradation. On the basis of these results, subsequent copolymerizations were carried out at 60◦C.

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3.3. Effect of the amount of Maghnite-H+ on the copolymerization Figure 2 shows the effect of the amount of Maghnite-H+ on the copolymerization yield of ε-caprolactone with THF. Indeed, using various amounts of Maghnite-H+, 1, 2, 3, 5, 7.5, and 10% by weight, this copolymerization was carried in bulk at 60°C, for 5 hours. The copolymerization yield increased with the amount of Maghnite-H+, thus clearly showing the effect of Maghnite-H+ as a catalyst. This phenomenon is probably the result of an increase in the number of "initiating active sites" responsible of inducing polymerization, a number that is pro rata to the amount of catalyst used in reaction. Figure 2: Effect of the amount of the catalyst on copolymerization of ε-caprolactone (0.03 mol), with THF (0.03 mol).

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3.4. Characterization of products The formation of the copolymer was confirmed by 1H NMR spectroscopy at 300 MHz (Figure 4). The reaction taking place is shown in the following scheme: The signals corresponding to the three methylene in position 3, 4 and 5 of ε-caprolactone (-O-CH2-CH2-CH2- CH2-CH2-CO-) and in position 3 and 4 of THF (-O-CH2-CH2-CH2-CH2-). Lie between δ = 1.74 ppm and δ = 1.76 ppm. The peak appears to δ = 2.61 ppm corresponds to the proton carried by the carbon in position 2 of ε- caprolactone (-O-CH2-CH2-CH2-CH2-CH2- CO-). The methylene in position 2 and 5 of THF (-O-CH2-CH2-CH2-CH2-) and 6-position of the ε-caprolactone (- O-CH2-CH2-CH2-CH2-CH2-CO-) give One refers to δ = 4.21 ppm. Figure 3: 1H NMR spectrum of poly(ε-caprolactone-co-THF) in CDCl3.

4. CONCLUSION

Maghnite-H+, proton exchanged montmorillonite clay, is effective as an acidic catalyst for the copolymerization of ε-caprolactone with THF. The balance of copolymerization moves towards the formation of copolymer with the rise in the temperature and the increase in the quantity of catalyst. The copolymerization proceeds smoothly, and a simple filtration is sufficient to recover the catalyst.

REFERENCES

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[1] Chen JH, Huang CX, Chen ZL, 2000. Study on the biocompatibility and toxicology of biomaterials - poly(ε- caprolactone). Journal of Biomedical Engineering, 17:380–382. [2] Le Ray AM, Chiffoleau S, Iooss P, et al., 2003. Vancomycin encapsulation in biodegradable poly(epsilon- caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility. Biomaterials, 24:443–449. [3] Pitt CG, Jeffcoat AR, Zweidinger RA, et al., 1979. Sustained drug delivery systems I. The permeability of poly(epsilon-caprolactone), poly(DL-lactic acid), and their copolymers. Journal of Biomedical Materials Research, 13:497–507. [4] Ye WP, Du FS, Jin WH, et al., 1997. In vitro degradation of poly(caprolactone), poly(lactide) and their block copolymers: Influence of composition, temperature and morphology. Reactive and Functional Polymers, 32:161–168. [5] Yavuz H, Babac C, Tuzlakoglu K, et al., 2002. Preparation and degradation of l-lactide and unknowing caprolactone homo and copolymer films. Polymer Degradation and Stability, 75:431–437. [6] Storey RF, Mullen BD, Melchert KM, 2001. Synthesis of novel hydrophilic poly(ester-carbonates) containing pendent carboxylic acid groups. Journal of Macromolecular Science: Pure and Applied Chemistry, 38:897–917. [7] Guan HL, Xie ZG, Tang ZH, et al., 2005. Preparation of block copolymer of epsilon-caprolactone and 2- methyl-2-carboxyl-propylene carbonate. Polymer, 46:2817–2824. [8] Pêgo AP, Luyn MJAV, Brouwer LA, et al., 2003. In vivo behavior of poly(1,3-trimethylene carbonate) and copolymers of 1,3-trimethylene carbonate with D,L-lactide or e-caprolactone: Degradation and tissue response. Journal of Biomedical Materials Research, 67A:1044–1054. [9] Albertsson AC, Eklund M, 1995. Influence of molecular structure on the degradation mechanism of degradable polymers: In vitro degradation of poly(trimethylene carbonate), poly (trimethylene carbonate- co-caprolactone), and poly(adipic anhydride). Journal of Applied Polymer Science, 57:87–103. [10] Albertsson AC, Eklund M, 1994. Synthesis of copolymers of 1,3-dioxan-2-one and oxepan-2-one using coordination catalysts. Journal of Polymer Science, Part A: Polymer Chemistry, 32:265–279. [11] Barakat I, Dubois PH, Grandfils CH, et al., 2001. Poly(e-caprolactone-b-glycolide) and poly(D,L-lactide-b- glycolide) diblock copolyesters: Controlled synthesis, characterization, and colloidal dispersions. Journal of Polymer Science, Part A: Polymer Chemistry, 39:294–306. [12] Bero M, Czapla B, Dobrzynski P, et al., 1999. Copolymerization of glycolide and ε-caprolactone, 2. Random copolymerization in the presence of tin octoate. Macromolecular Chemistry and Physics, 200:911–916. [13] Dzhavadyan EA, Rozenberg BA, Yenikolopyan NS, 1973. Kinetics of the copolymerization of tetrahydrofuran with ε-caprolactone. Polymer Science USSR, 15:2235-2242. [14] Ge H, Hu Y, Jiang X, et al., 2002. Preparation, characterization, and drug release behaviors of drug nimodipine-loaded poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) amphiphilic triblock copolymer micelles. Journal of Pharmaceutical Sciences, 91:1463–1473. [15] He F, Li S, Vert M, et al., 2003. Enzyme-catalyzed polymerization and degradation of copolymers prepared from ε-caprolactone and poly(ethylene glycol). Polymer, 44:5145–5151. [16] Brown DR, Carpathica G, 1994. Clays as catalyst and reagent supports. Ser Clays, 45:45. [17] Laszlo P, 1987. Preparative Chemistry Using Supported Reagents. Academic Press, San Diego. [18] Belbachir M, Bensaoula A, 2006. Composition and method for catalysis using bentonites. US Patent No. 6,274,527 B1. [19] Harrane A, Meghabar R, Belbachir M, 2002. A proton exchanged Montmorillonite Clay as an efficient catalyst for the reaction of isobutylene polymerization. International Journal of Molecular Sciences, 790- 800. [20] Meghabar R, Megherbi A, Belbachir M, 2003. Maghnite-H+, an ecocatalyst for cationic polymerization of N-vinyl-2-pyrrolidone. Polymer, 2397.