Tổng hợp polycaprolacton bằng xúc tác cơ magie theo phương pháp trùng hợp mở vòng

NGUYEN THI NHAN MINISTRY OF EDUCATION AND TRAINING HANOI UNIVERSITY OF SCIENCE AND TECHNOLOGY - Nguyen Thi Nhan CHEMICAL SCIENCE SYNTHESIS OF POLYCAPROLACTONE USING MAGNESIUM COMPOUNDS AS CATALYSTS BY RINGOPENING POLYMERIZATION MASTER THESIS OF CHEMICAL SCIENCE MAJOR: CHEMICAL ENGINEERING CH2016B Hanoi - 2018 MINISTRY OF EDUCATION AND TRAINING HANOI UNIVERSITY OF SCIENCE AND TECHNOLOGY Nguyen Thi Nhan SYNTHESIS OF POLYCAPROLACTONE USING MAGNESIUM COMPOUNDS AS CATALYSTS BY RING-OPENING POLYMERIZATION Major: Chemical engineering MASTER THESIS OF CHEMICAL SCIENCE MAJOR: CHEMICAL ENGINEERING SCIENCE ADVISORS: Prof Dr Tran Thi Thuy Dr Esteban Mejia Hanoi-2018 Acknowledgment I would first like to thank my thesis advisors: Prof Dr Tran Thi Thuy of the School of Chemical Engineering at Hanoi University of Science and Technology and Dr Esterban Mejia of the Polymer Department at Leibniz Institute for Catalysis They consistently allowed this paper to be my own work, but steered me in the right the direction whenever they thought I needed it I really respect those useful advices, which help me to have more motivation in my research I would also like to thank Dr Swarup Ghosh, who taught me enthusiastically and help me broaden my knowledge I would also like to acknowledge RoHan Project and DAAD, having brought me a great opportunity to experience the studying in Germany That was meaningful time, and left me many valuable lessons This research would not have been possible without the project Finally, I must express my very profound gratitude to my parents and my sister, brother and all best friends for providing me with unfailing support and continuous encouragement throughout my years of study and through the process of researching and writing this thesis Thank you Hanoi, May 2018 Nguyen Thi Nhan ASSURANCE I pledge that this is my own independent scientific research The data used in the dissertation analysis has a clear, published source in accordance with the regulations The research results in the thesis are self-study, analyzing honestly, and objectively These results have not been published in any other study Author Nguyen Thi Nhan LIST OF SYMBOLS AND ABBREVIATIONS Abbreviation Explanation AM Activated monomer AROP Anionic ring-opening polymerization BnOH Benzyl alcohol Catalyst Dibutyl magnesium, nBu2Mg Catalyst Etyl n-butyl magnesium, (Et)Mg(nBu) Catalyst CDCl3 n-Butyl n-octyl magnesium, (nBu)Mg(nOct) Chloroform D CROP Cationic ring-opening polymerization DCM Dichloromethane DEPT DPE Distortionless Enhancement by Polarization Transfer 1,1-diphenylethylene DSC Differential scanning calorimetry FT-IR Fourrier Transformation InfraRed GPC Gel permeation chromatography Mn Molar mass averages of the number Mw Molar mass averages of the weight NMR Nuclear magnetic resonance PCL Polycaprolactone PDI Polydispersity index (weight distribution) PET Polyethylene terephthalate PGA Poly(glycolic acid) PHB Polyhydroxybutyrate PLA Poly(lactide acid) ROP Ring-opening polymerization SEC Size exclusion chromatography Tg Glass transition temperature THF Tetrahydrofuran Tm Melting point XRD X-Ray Diffraction ε-CL Caprolactone monomer LIST OF TABLES Table Number of publications in the past 110-year period Table Properties of PCL Table Examining kinetic of reactions 23 Table ROP of ɛ-caprolactone catalyzed by catalyst 1, 2, in dichloromethane 23 Table Oligomer of ɛ-caprolactone 24 Table Oligomer of ɛ-caprolactone with presence of BnOH 24 Table Effect of the molar ratio of monomer and catalyst on the ROP 25 Table Effect of the mole ratio of monomer and catalyst on the ROP 25 Table ROP of ɛ-caprolactone with the presence of benzyl alcohol as a co-initiator 26 Table 10 The effect of co-initiator, BnOH .38 LIST OF SCHEMES Scheme Synthesis of CL by condensation method Scheme ROP of CL Scheme Ring-opening polymerization 11 Scheme General mechanism of AROP 12 Scheme ROP of lactones .13 Scheme AROP mechanism 13 Scheme Propose mechanism of ROP initiated by dibutylmagnesium 14 Scheme CROP of CL 15 Scheme Coordination-insertion ring-opening polymerization 16 Scheme 10 ROP with the presence of alcohols as co-initiators .17 Scheme 11 Polymer from the reaction with catalyst 27 Scheme 12 Polymer from the reaction with catalyst and the presence of BnOH 27 Scheme 13 ROP of CL without BnOH 28 Scheme 14 ROP of CL with the presence of BnOH 28 Scheme 15 Proposed mechanism of polymerization without BnOH .41 Scheme 16 Proposed mechanism of polymerization with the presence of BnOH 42 LIST OF FIGURES Figure Applications of PCL Figure Bruker Avance 400 21 Figure GPC equipment 21 Figure DSC curves of PCLs 28 Figure The GPC spectrum of Oligomer of ε-CL 29 Figure The GPC spectrum of PCL at ratio 200:1 29 Figure The GPC spectrum of PCL at ratio 200:1 with the presence of BnOH 30 Figure Semi-logarithmic plots of ε-CL and conversion in time: [M]o/[Cat 1]o = 200 at 40 °C 32 Figure The plot of the initial rate vs the concentration of catalyst for the ROP of ε-CL 33 Figure 10 The effect of catalysts on Mn of PCL 34 Figure 11 The effect of catalyst on PDI of PCL 35 Figure 12 The effect of molar ratio on ROP when using catalyst 36 Figure 13 The effect of molar ratio on ROP when using catalyst 36 Figure 14 : 1H NMR spectrum of PCL at ratio 20/1 39 Figure 15 13C NMR spectrum of PCL at ratio 20/1 40 TABLE OF CONTENTS Acknowledgment ASSURANCE LIST OF SYMBOLS AND ABBREVIATIONS LIST OF TABLES LIST OF SCHEMES LIST OF FIGURES INTRODUCTION .1 CHAPTER REVIEW OF LITERATURES .3 1.1 Biodegradable polyester, poly (ɛ-caprolactone) 1.1.1 Biodegradable polyester 1.1.2 Poly(ε-caprolactone) 1.2 Main-organometallic catalysts, magnesium complexes 1.3 Ring-opening polymerization (ROP) .10 1.3.1 Anionic ring-opening polymerization (AROP) of cyclic esters 12 1.3.3 Coordination-insertion Ring-opening polymerization .15 1.3.4 ROP with the presence of alcohols as co-initiators 16 1.3.5 Kinetics and mechanism 18 CHAPTER EXPERIMENT .20 2.1 Chemicals .20 2.2 Equipment .20 2.3 Polymerization of ɛ-caprolactone 21 2.4 Examining kinetic of reactions with catalysts 22 2.5 Attachments 23 CHAPTER RESULTS AND DISCUSSION .27 3.1 General ROP 27 3.2 The kinetic of ROP of PCL 31 3.3 Effect of catalysts on the polymer properties .33 3.4 Effect of mole ratio to ROP 35 of catalysts on polymerization of CL, the effect of ligands in other words, processes with two ratioes 100:1 and 200:1 were performed cover three catalysts The results form GPC method is showed in Figure 10 and 11 It is found that Catalyst & bring to PCLs with much higher Mn compared to catalyst 1, and PDI values repectively have less difference among three catalysts As also can be seen that while PDI values are nearly the same between catalyst and 2, the Mn of obtained PCL using catalyst is higher than of catalyst 2, 86 kg/mol and 110 kg/mol in ratio 200:1 respectively That means, catalyst allows the polymerization to achieve the highest effection in general 110 100:1 200:1 100 Mn (Kg/mol) 90 80 70 60 50 40 30 Catalyst Figure 10 The effect of catalysts on Mn of PCL 34 2,0 100:1 200:1 1,8 PDI 1,6 1,4 1,2 1,0 Catalyst Figure 11 The effect of catalyst on PDI of PCL 3.4 Effect of mole ratio to ROP The influence of mole ratio on the number-average molecular weight (Mn ) and molecular weight distribution (PDI) was determined by GPC during the polymerization process In fact, it should be noted that some deactivation, i.e., hydrolysis, might take place during preparation of the polymer/tetrahydrofuran mixture subsequently subjected to GPC analysis [24] Fig 12 shows the influence of monomer conversion on Mn and PDI for the solution polymerization of CL with Catalyst in Dichloromethane at different ratioes It reveals that the Mn determined by GPC gradually increases with the molar ratio between the monomer and catalyst The PDI is quite low through the reaction process The PDI broadens slightly when the ratio is over 200:1 due to the transesterification reaction 35 5,0 60 Mn PDI 4,5 4,0 55 3,0 PDI Kg/mol 3,5 50 2,5 45 2,0 40 1,5 35 1,0 100 200 300 400 500 600 [M]o/[C]o Figure 12 The effect of molar ratio on ROP when using catalyst Figure 13 witnesses the impact of ratio to Mn and PDI for occasions using catalyst Mn also rises with the [M]/[Cat] and follows a linear relationship even at high ratio (expect ratio 100:1) PDI values remain quite low (around 1.5), even decrease with the increase of ratio This is generally observed in systems propagating in aliving manner,e.g, e-caprolactone initiated with aluminum isopropoxide [7] 5,0 150 Mn PDI 4,5 130 4,0 120 3,5 110 3,0 100 2,5 90 PDI Kg/mol 140 2,0 80 1,5 70 1,0 100 200 300 400 500 600 [M]o/[C]o Figure 13 The effect of molar ratio on ROP when using catalyst To summary, catalyst showed a higher productivity in PCL polymerization at the difference in mole ratio between monomer and catalyst The process tend to 36 follow the living polymerization, whose mechanism allows to control synthesis processes and products as well [30] 3.5 Effect of co-initiator, BnOH To determine the effect of BnOH on polymerization of CL, three reactions with catalysts 1, 2, and BnOH in the same ratio and condition were carried out The results in table 10 indicate that obtained PCLs from these processes have closely Mn values and approximately caculated one accoding to theory In addition, the quite low PDI figures shows that the polymerizations were controlled better when using BnOH together with catalysts As concerned in the chapter 1, adding a protic compound such as an alcohol or a carboxylic acid induces a transfer reaction between the protic molecule and the alkoxide: in addition to the basic character due to the lone pair of the oxygen atom, the alcohol function allows the formation of hydrogen bonds with the oxygen atom of the alkoxide group which increases the strength of the coordination complex [13] A new protic moiety is released by this transfer reaction, and therefore can take part in another transfer reaction [19] Provided the transfer frequency is higher From the Mn values of PCL, which were approximately the theoretical Mn, it can partly show that the mechanism of polymerization could be complied the ‘coordination-consertion‘ This will be indicated in part 3.6 37 Table 10 The effect of co-initiator, BnOH Cat t Conv a (m) (%) 180 b BnOH 99 c b Mn obs (kg/mol) Mn calc 11.5 x (kg/mol) PDI BnOH x 52.3 5.75 1.37 1.14 110.0 5.75 1.64 1.74 85.5 5.80 1.57 1.76 (6.44) 120 99 11.9 (6.66) 60 100 11.6 (6.50) Reaction condition: [M]o = 0.045 mol/l, [M]o : [Cat]o : [BnOH] = 200 : : 4, 40 °C, 400 rpm, in 30 ml dichloromethane a Obtained from 1H NMR analysis b Obtained from GPC analysis and calibrated by polystyrene standard (Mn values in parentheses were obtained using a correcting factor: 0.56)* (Labet & Thielemans, 2009) c Calculated from the molecular weight of (ɛ-caprolactone × [M]o/[Cat]× 100% conversion + FwBnOH) x: The respective values for occasion without BnOH 3.6 Proposed mechanism To better understanding the ring opening polymerization of ε-CL catalyzed with n Bu2Mg, the PCL sample with low molecular weight was prepared from the molar ratio of ε-CL to nBu2Mg equaling to 20/1 at 40 °C The mixture was acidically deactivated, and finally characterized by 1H and 13C NMR to analysis its end groups NMR results The signals in the 1H NMR spectrum of the synthetic PCL were assigned (Fig 14) 38 a c b f d e f k h g h e +d c+f b+g CDCl3 a k 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0 ppm Figure 14 1H NMR spectrum of PCL at ratio 20/1 The signals of COCH2CH2CH2CH2CH2O-, the protons of -COCH2(CH2)4O-, -CO(CH2)2CH2(CH2)2O-, -CO(CH2)4CH2OH, - CO(CH2)4CH2O- of ɛ-caprolactone units were detected at δ 1.45-1.33 ppm (g), 1.711.59 ppm (f), 2.35-2.27 (e), 3.67 ppm (k), 4.06 ppm (h), respectively [27] The spectrum also illustrated that signals correspond to the n-butyl end group (CH3CH2CH2CH2CO-), δ = 0.88-0.94 ppm [21] Furthermore, the signals in 1H NMR spectrum are also observed in the 13C NMR spectrum (Fig 14) The carbon signals due to carbons of ɛ-caprolactone units are detected around δ 173.1 ppm (*), 64.1 ppm (h), 34.1 ppm (e), 25.3 ppm (f’), 24.7 ppm (g), 24.5 ppm (f) In addition, the small signals of the ɛ-caprolactone end groups were detected It is noteworthy that the signals at δ 13.8 ppm (a) and 22.2 ppm (b) which were characteristic of the butyl group [28] 39 c a b f‘ f d * k f e g f‘ h e h g CDCl3 * c b a Figure 15 13C NMR spectrum of PCL at ratio 20/1 The above results of polymer end groups analysis strongly confirmed that PCL is quantitatively capped by the n-butyl group at one end, and either a hydroxyl group at the other, which results from the hydrolysis of the growing species or the elimination reaction The aforementioned results have now illustrated that the propagation is unambiguous, which the monomer inserts into the growing chains with the acyl– oxygen bond scission rather than the break of alkyl–oxygen bond [7] Consequently, we indicate that the mechanism of the present ring-opening polymerization of ɛ-caprolactone catalyzed with nBu2Mg is shown in Scheme 15 In initiation step, the carbonyl group of ɛ-CL coordinates with the Mg atom center to form the alkoxide of 6-hydroxyhexanoate The ligand exchange not only aids the monomer’s coordination but also stimulates the nucleophilic attack of the alkoxide toward the carbonyl group Then alkoxy groups attack the activated carbonyl carbon of ɛ-CL 40 The propagation, the insertion of the monomer into the Mg–O bond of the initiator by the acyl–oxygen bond scission rather than the alkyl–oxygen bond break of the lactones, occurs to afford the polymer The PCL with hydroxyl-terminated by acidic deactivation as well as carbon–carbon double bond end groups due to the elimination of butyl magnesium hydroxide are formed in termination step [5, 28] Scheme 15 Proposed mechanism of polymerization without BnOH 41 Scheme 16 Proposed mechanism of polymerization with the presence of BnOH 42 CONCLUSIONS 1) Poly (ɛ-caprolactone) was synthesized successfully using dialkyl magnesium as catalysts in dichloromethane with high molecular weight (~ 106 g/mol) and 2) low distribution ( 1.1 ~ 1.7) The kinetic examination indicated that the ring-opening polymerization was first-order in both monomer ( R2 = 0.9925) and catalyst concentrations ( R2 = 0.9973) 3) The presence of the signals of butyl group from the end group analysis by 1H, 13 4) C NMR suggests that the coordination-insertion mechanism is very appropriate to the process Among catalysts, catalyst 3, (n-butyl) (n-octyl) magnesium is the most effective 5) The presence of BnOH allows the ROPs to proceed with a better control of the molecular weight compared to the occasions using only catalyst 43 OUTLOOK  Examine various solvents for the ROP  Examine the kinetics under different temperatures to obtain thermodynamic parameters (activation energy)  Assess the mechanical properties of the obtained polymers 44 REFERENCES 1) Asghari, F., Samiei, M., Adibkia, K., Akbarzadeh, A., & Davaran, S (2016), Biodegradable and biocompatible polymers for tissue engineering application: a review, Artificial Cells, Nanomedicine, and Biotechnology, 45(2), pp 185-192 2) Ballard, D., & Tighe, B (1967), Reactions of the anhydrosulfites of alpha hydroxy carboxylic acids II Polymerization of glycolic and lactic acid anhydrosulfites J Chem Soc B, 10, pp 976–980 3) Birgid, W., Helmut Keul, K., & Hartwig, H (1992), Dibutylmagnesium-an initiator for the ring‐opening polymerization of 2,2‐dimethyltrimethylene carbonate and ε‐caprolactone, Makromol Chem., Rapid Commun, 13, pp 9-14 4) Bowman, N (1957), Solid composite propellant containing ammonium nitrate and glycolic acid polymer US Patent, 687853 3012867, 1961 19570930 5) Cox, E., & Hostettler F (1972), Ring-Opening Polymerization, U.S Patent, 3021309 6) Dahlmann, R G (1993), J Acta Polym 7) Dubois, P., Ropson, N., Jérôme, R., & Teyssié, P (1996), Macromolecular Engineering of Polylactones and Polylactides 19 Kinetics of Ring-Opening Polymerization of ε-Caprolactone Initiated with Functional Aluminum Alkoxides, Macromolecules, 29 (6), pp 1965-1975 8) Elham, H., Anita Paoniasari, P., & Rob, D (2013), Catalytic Ring-Opening Copolymerization of Limonene Oxide and Phthalic Anhydride: Toward Partially Renewable Polyesters, Macromolecules, 46 (3), pp 631–637 9) Ej, C., Park, J., & Chang, H (1994), Effect of polymerization catalysts on the microstructure of P(LLA-co-ε-CL), J Polym Sci Part B Polym Phys, 32, 24819 10) Gunatillake , P., & Adhikari R., R (2003), Biodegradable synthetic polymers for tissue engineering Eur Cell Mater, 20 (5), pp 1-16 11) Hench, L (1991), Bioceramics: From Concept to Clinic, Journal of the American Ceramic Society, 74, pp 1487-1510 45 12) Ito, K., Hashizuka, K., & Yamashita, Y (1977), Equilibrium cyclic oligomer formation in the anionic polymerization of iε-caprolactone, Macromolecules, 10, pp 821-824 13) Kamber, E N., Jeong, W., Waymouth, M R., Pratt, C R., Lohmeijer, G B., & Hedrick, L J (2007), Organocatalytic Ring-Opening Polymerization, Chemical Reviews, 107 (12), pp 5813–5840 14) Kang, X., Xie, Y., & Powell, H (2007), Adipogenesis of Murine Embryonic Stem Cells in a Three-Dimensional Culture System using Electrospun Polymer Scaffolds Biomaterials, 28, pp 450–458 15) Kricheldorf, H (2009), Syntheses of Biodegradable and Biocompatible Polymers by Means of Bismuth Catalysts, Chem Rev., 109, pp 5579-5594 16) Kricheldorf, H., & Lee, S (1995), Polylactones: 32 High-molecular-weight polylactides by ring-opening polymerization with dibutylmagnesium or butylmagnesium chloride, Polymer, 36, (15), pp 2995-3003 17) Kricheldorf, H., & Symbol, M (1991), Octoate-initiated polymerization of Llactide, Eur Polym J., 25, 585 18) Krichelhorf, H., & Saunders-Kreiser, (1990), Chem Macromol Symp 19) Kowalski, A., Libiszowski, J., Majerska, K., & Duda, A (2007), Kinetics and mechanism of ε-caprolactone and L,L-lactide polymerization initi- ated with zinc octoate and aluminum tris-acetylace- tonate: the next proofs for the general alkoxide mech- anism and synthetic applications, Polymer, 48, 3952 20) Labet, M., & Thielemans, M (2009), Synthesis of polycaprolactone: a review Chem Soc Rev., 38 (12), pp 3484–3504 21) Lenka, M., & Jiri, B (2014), Ethyl magnesium bromide as an efficient anionic initiator for controlled polymerization of ε-caprolactone, Polym Bull, 71, pp 111-123 22) Li, S (2006), Scaffolding in Tissue Engineering, Taylor & Francis Group, Boca Raton, pp 335–352 23) Ling, J., Zhu, W., & Shen, Z (2004), Controlling Ring-Opening Copolymerization of ε-Caprolactone with Trimethylene Carbonate by 46 Scandium Tris(2,6-di-tert-butyl-4-methylphenolate), Macromolecules, 37 (3), pp 758-763 24) Liu, L.(2009), Ring opening polymerization of e-caprolactone catalyzed with magnesium lactate, Materials Science Forum, pp 1208-1210 25) Löfgren, A., Albertsson, A C., Dubois, P., & Jérôme, R (2006), Recent Advances in Ring-Opening Polymerization of Lactones and Related Compounds, Journal of Macromolecular Science, Part C, pp 379-418 26) Longo, J., DiCiccio, A., & Coates, G (2014), Poly(propylene succinate): A New Polymer Stereocomplex J Am Chem Soc., 136 (45), pp 15897–15900 27) Malinova´, L., & Brozek, J (2014), Ethyl magnesium bromide as an efficient anionic initiator for controlled polymerization of caprolactone, Polymer Bulletin, 71(1), pp 111–123 28) Nejad, E., Paoniasari, A., & Carlo , G (2013), Catalytic Ring-Opening Copolymerization of Limonene Oxide and Phthalic Anhydride: Toward Partially Renewable Polyesters Macromolecules, 46 (3), pp 631-637 29) Ng, K., & Hutmacher, D (2001), Evaluation of ultra-thin poly(epsiloncaprolactone) films for tissue-engineered skin, Tissue engineering, 7, pp 441455 30) Odian, G (2004), Principles of polymerization, John Wiley & Sons, 3, pp 47127400 31) Rong, T (2017), New Chemistry in Functional Aliphatic Polyesters, Industrial & Engineering Chemistry Research, 56 (15), pp 4207–4219 32) Sarazin, Y., Schormann, M., & Bochmann, M (2004), Amido Cations for RingOpening Polymerization Reactions, Organometallics, 23 (13), pp 3296-3302 33) Stefano, M., Fabia, G., & Roberto, C (2006), Neutral and Cationic Heteroscorpionate Aluminum Complexes:  Synthesis, Structure, and RingOpening Polymerization of ε-Caprolactone, Organometallics, 25 (1), pp 266– 274 34) Tokiwa, Y., & Calabia, B (2004), Degradation of microbial polyesters Biotechnol Lett., 26 (15), pp 1181–1189 47 35) Van Natta, F., Hill, J., & Carothers, W (1934), Polymerization and ring formation XXII e-Caprolactone and its polymers J Chem Soc, 56, pp 455– 457 36) Zhang, C (2015)., Biodegradable Polyesters: Synthesis, Properties, Applications Wiley-VCH Verlag GmbH & Co KGaA 48 ... distribution, and the increase in molecular weight during kinetic experiments [24] The theoretical molecular weight (Mn(Theor) ) is calculated as: