In the Laboratory edited by
Green Chemistry
Mary M. Kirchhoff
Ring-Opening Polymerization of Lactide To Form a Biodegradable Polymer
ACS Education Division Washington, DC 20036
Jennifer L. Robert and Katherine B. Aubrecht*,† Department of Chemistry, The College of the Holy Cross, Worcester, MA 01610; *
[email protected] In this experiment, which is suitable for the second semester of an introductory organic chemistry course, students prepare polylactide, a biodegradable polyester derived from biorenewable, non-petrochemical carbon sources. Polylactide (PLA) has been used as a specialty polymer in medical applications for a number of years, but has been more recently developed as a commodity polymer (1). It is used in a variety of applications such as food packaging materials, disposable utensils, garbage bags, and fibers. Aliphatic polyesters, such as PLA, undergo chemical and microbial hydrolysis much more readily than aromatic polyesters, such as poly(ethylene terephthalate) (PET) (2, 3). PLA can be formed by the condensation polymerization of lactic acid or by the chain growth ring-opening polymerization of lactide (Scheme I). A number of catalysts and initiators can be used to bring about the ringopening polymerization of lactide (4). A commonly used and robust catalyst–initiator is tin(II) bis(2-ethylhexanoate), commonly called Sn(Oct)2, in the presence of an alcohol (ROH). Kinetic and MALDI-MS studies of these polymerizations reveal that tin alkoxides, Sn(OR)2 or (Oct)Sn(OR), are formed as the active initiators–catalysts (5). The mechanism for metal alkoxide-mediated lactide polymerization is thought to be a coordination–insertion process in which the Lewis acidic metal coordinates to the ester carbonyl, boosting its electrophilicity. The alkoxide moiety attacks the carbonyl carbon, forming a tetrahedral intermediate, which collapses by breaking the acyl carbon–OR bond in the ring (Scheme II). Computational studies support the mechanism in Scheme II, including the O H3C n
Summary of Procedure Toluene stock solutions of Sn(Oct)2 and benzyl alcohol are added to l-lactide or d,l-lactide.1 After 1 hour of reflux, the reaction is cooled and quenched with 1 M HCl. The polymer is precipitated by pouring the reaction mixture into heptane. Percent monomer conversion and ratios of stereosequences can be determined by 1H NMR spectroscopy. We acquired spectra on a 400 MHz instrument, though percent monomer conversion could be determined on a lower field strength instrument. Typically 80–90% conversion of lactide and 70–80% yields are obtained. Full experimental details can be found in the online supplement. Hazards
O O
CH3
Tin(II) bis(2-ethylhexanoate) is an irritant to the eyes, respiratory system, and skin. Toluene and heptane are flammable. 1 M HCl is corrosive. Methylene chloride is volatile, toxic, and upon long-term exposure, carcinogenic. Students should wear appropriate gloves and work in a hood if possible.
Sn(Oct)2 ROH
O lactide O
CH3 O CH3
Results and Discussion
O
RO O
H n
Scheme I. PLA formed by the chain growth ring-opening polymerization of lactide. †Current address: Department of Chemistry, St. Anselm College, Manchester, NH 03102.
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two 4-membered cyclic transition structures implied by the arrows in the second and third structures (6). Although lactide is a 6-membered ring, it still has significant enough ring strain (22.9 kJ mol‒1) that ring opening is favored over reversal of the addition of the alkoxide to the carbonyl (7). The Sn(OR)2 or (Oct)Sn(OR) complex acts both as an initiator, the –OR moiety initiates the first ring opening event, and as a catalyst, the Sn(II) complex coordinates and activates each monomer unit. Although it is intramolecular, the coordination–insertion mechanism of ring-opening polymerization of lactide is similar to that of a transesterification reaction and can be used to either introduce or reinforce transesterifications to students studying carboxylic acid derivatives in an introductory organic chemistry course. This experiment also introduces polymer chemistry and the “green” concepts of biodegradable and biorenewable polymers to students taking organic chemistry.
The polymerization can be carried out in an hour and good results can be obtained using standard teaching laboratory (not Schlenk) conditions. The conversion of monomer to polymer can be monitored by 1H NMR spectroscopy; the methine protons have different chemical shifts in the monomer (5.04 ppm) from the polymer (5.13–5.25 ppm). Integration of these two peaks gives the percent conversion. The number-average mo-
Journal of Chemical Education • Vol. 85 No. 2 February 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
In the Laboratory RO
Sn Oct
O H 3C
O O
CH3 O
RO
Sn Oct
Sn Oct
O H3C
RO H3C
O O
CH3 O
CH3
O
O
O
RO
O
CH3
O
O
Sn Oct
O
CH3 O
O H3C n
O O
CH3 O
O RO
CH3 O CH3
O O
CH3
O O CH3
Sn Oct
O O
n
Scheme II. The alkoxide moiety attacks the carbonyl carbon, forming a tetrahedral intermediate, which collapses by breaking the acyl carbonOR bond in the ring.
lecular weight (Mn) and polydispersion index (Mw∙Mn, where Mw is the weight-average molecular weight) can be determined using size exclusion chromatography (SEC) (8), though we do not include this analysis as part of the lab for organic chemistry students. The stereochemistry of the polymerization is examined. Lactide has two asymmetric carbons and is commercially available in the enantiomerically pure form, (S,S )-lactide (l-lactide), or as the racemic mixture of (S,S )-lactide and (R,R)-lactide. (d,l-lactide).1 The meso form, (R,S )-lactide, is not commercially available. If no epimerization occurs during the polymerization of l-lactide, a single peak (a quartet) is seen for the methine protons of the polymer. Poly(l-lactide) is crystalline and has a melting range of 170–180 °C. The methine region of poly(d,l-lactide) is more complex. The chemical shift of the methine proton depends upon the configurations of the asymmetric centers near it. While chemical shifts for sequences of up to eight asymmetric centers have been differentiated, chemical shift assignments for all possible stereosequences have
been made only on the tetrad level, for which there are three pairwise relationships (9). If adjacent asymmetric carbons have the same configuration, their relationship is termed isotactic (i). If adjacent asymmetric carbons have opposite configurations, their relationship is termed syndiotactic (s). For example, an (R,R,S,S ) tetrad is denoted isi. The methine region for poly(d,l-lactide) displays several superimposed quartets corresponding to the different stereosequences. The quantity of the various stereosequences can be analyzed by single-frequency decoupled 1H NMR spectroscopy. Single-frequency decoupling of the methyl protons causes the methine quartets to collapse to singlets. A single-frequency decoupled 1H NMR spectrum of poly(d,l-lactide) formed using Sn(Oct)2/ROH displays all of the possible stereosequences expected for a polymer of racemic lactide (Figure 1), demonstrating that this catalyst–initiator displays little stereocontrol, though catalysts with high degrees of stereocontrol have been developed (10). A single-frequency decoupled 1H NMR spectrum of poly(llactide) formed using Sn(Oct) 2/ROH displays primarily
© Division of Chemical Education • www.JCE.DivCHED.org • Vol. 85 No. 2 February 2008 • Journal of Chemical Education
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In the Laboratory A
C
5.25
5.20
5.15
5.10
5.25
Chemical Shift (ppm) isi
B
sis
5.20
5.15
5.10
Chemical Shift (ppm) iii
D
iii sii iis
5.25
5.20
5.15
5.10
5.25
Chemical Shift (ppm)
5.20
5.15
5.10
Chemical Shift (ppm)
Figure 1. 1H NMR spectra of the methine region of PLA. Decoupled peaks are labeled with corresponding stereosequences: (A) poly(d,l-lactide), (B) homonuclearly decoupled poly(d,l-lactide), (C) poly(l-lactide), and (D) homonuclearly decoupled poly(l-lactide).
the iii resonance (Figure 1), indicating that the existing (S ) asymmetric centers are nearly completely retained during the polymerization. Conclusion This experiment is appropriate for students studying carboxylic acid derivatives in an introductory organic chemistry lab. While the experiment reinforces the concept of nucleophilic acyl substitution, it also introduces students to polymers and green chemistry. Stereochemistry and its affect on NMR chemical equivalence, concepts typically introduced in the first semester of an introductory organic chemistry course, are applied in this laboratory. Acknowledgments The authors thank the Donors of the American Chemical Society Petroleum Research Fund for partial support of this research. Becton, Dickinson, and Company is acknowledged for a summer research fellowship for JLR. Note 1. l-Lactide is (S,S )-lactide and d,l-lactide is a racemic mixture of the (S,S)-lactide and (R,R)-lactide.
Literature Cited 1. NatureWorks LLC Home Page. http://www.natureworksllc.com (accessed Oct 2007).
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2. Amass, A.; Amass, A.; Tighe, B. Polym. Int. 1998, 47, 89–144. 3. Müller, R.-J.; Kleeberg, I.; Deckwer, W.-D. J. Biotechnol. 2001, 86, 87–95. 4. Dechy-Cabaret, O.; Martin-Vaca, B.; Bourissou, D. Chem. Rev. 2004, 104, 6147–6176. 5. Kowalski, A.; Duda, A.; Penczek, S. Macromolecules 2000, 33, 7359–7370. 6. Ryner, M.; Stridsberg, K.; Albertsson, A.-C.; von Schenk, H.; Svensson, M. Macromolecules 2001, 34, 3877–3881. 7. Duda, A.; Penczek, S. Macromolecules 1990, 23, 1636–1639. 8. Snyder, D. M. J. Chem. Educ. 1992, 69, 422–423. 9. Zell, M. T.; Padden, B. E.; Paterick, A. J.; Thakur, K. A. M.; Kean, R. T.; Hillmyer, M. A.; Munson, E. J. Macromolecules 2002, 35, 7700–7707. 10. Chamberlain, B. M.; Cheng, M.; Moore, D. R.; Ovitt. T. M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2001, 123, 3229–3238.
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2008/Feb/abs258.html Abstract and keywords Full text (PDF) Links to cited URLs and JCE articles Supplement Student instructions, including pre- and postlab questions
Instructor notes
Discussion on the effect of adventitious water on the rate of the polymerization and the number-average molecular weight, Mn, of the resulting polymer
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