Copolymers of Itaconic Anhydride and Methacrylate-Terminated Poly

Biomacromolecules 2000, 1, 174-179

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Copolymers of Itaconic Anhydride and Methacrylate-Terminated Poly(lactic acid) Macromonomers Joshua A. Wallach and Samuel J. Huang* Polymers from Renewable Resources Research Center, Institute of Materials Science, University of Connecticut, Storrs, Connecticut 06269-3136 Received December 9, 1999

In an effort to design cyclic anhydride copolymers that have biodegradable characteristics and are derived from renewable resources, the copolymerization of itaconic anhydride and methacrylate-terminated poly(L-lactic acid) (PLLA) was studied. Polymers with anhydride concentrations from 85 to 15 mol % have been synthesized successfully with retention of the cyclic anhydride. Molecular weights range from 9000 to 70 000 with higher molecular weights for higher concentrations of PLLA macromonomer. High conversions are observed for samples containing 50% and less itaconic anhydride with a slight tendency for the polymer to be enriched in the monomer in smaller concentration. These copolymers show glass transition temperatures between 31 and 73 °C, increasing with increased itaconic anhydride content. No evidence of crystallinity from the PLLA is observed for these copolymers. Introduction The biodegradable nature and availability from renewable resources coupled with its physical properties make poly(lactic acid) (PLA) an attractive alternative to traditional polymers. Effort has been placed in controlling the material properties to fit a wide range of applications within the packaging and biomedical markets. Still, the lack of structural and property variations of these materials limits applications and has prevented its widespread acceptance. Moreover, from a cost perspective PLA is at a severe disadvantage.1 Blending2-6 and composites7-13 containing PLA-based materials have received attention in attempts to control physical properties, as well as providing a means of addition of a lower cost material. Compatibilization becomes an issue in many cases arising from the differences in hydrophobicity of materials and from the positive free energy associated with mixing polymers. Copolymers containing cyclic anhydrides, notably maleic anhydride, have been used successfully for this purpose with many traditional polymeric materials.14-21 Although these copolymers may provide enhanced properties to PLA-containing materials, they do not have biodegradable characteristics nor are the materials derived from renewable resources. A copolymer of itaconic anhydride and methacrylate-terminated poly(L-lactic acid) (PLLA) is proposed as a suitable material for this purpose. These copolymers contain monomers obtained from renewable feedstocks as well as having the biodegradable characteristics of the PLA. In this study the synthesis of these copolymers is investigated. Experimental Section Materials. L-Lactide (LLA) was supplied by Golden Technologies, Inc., and was recrystallized from chloroform. * To whom correspondence should be addressed.

2-Hydroxyethyl methacrylate (HEMA) and stannous 2-ethyl hexanoate (SnOct) were obtained from Sigma and used as received. Itaconic anhydride (ITA), acetic anhydride, ethyl acetate, and 2,2′-azobisisobutyronitrile (AIBN) were obtained from Aldrich. ITA was determined to have no acid residue from FTIR and NMR analysis and therefore used as received. Ethyl acetate was dried over 4 Å molecular sieves, and AIBN was recrystallized from methanol. Synthesis of Poly(L-lactic acid) Monoethyl Methacrylate (PLLA-EMA). A similar procedure to that in the literature22 for producing methacrylate-terminated PLLA using SnOct and HEMA was employed. In this study the time was reduced to 12 h and the catalyst concentration increased to 4 wt % of LLA. Initiator concentration was set to produce a polymer with molecular weight of 800 g/mol. 1H NMR (CDCl ) δ (ppm): 1.4-1.7 [d, 27H, CH , lactic 3 3 acid], 1.9 [d, 3H, CH3, methacrylate], 4.35 [m 4H, CH2CH2, ethyl methacrylate], 4.38 [m, 1H, CH, terminal lactic acid], 5.1-5.3 [m, 9H, CH, lactic acid], 5.6 and 6.1 [s, 2H, CH2, methacrylate]. IR (cm-1): 3520 (OH), 2950 (CH stretch), 1758 and 1722 (CdO stretch), 1640 (CdC stretch). Synthesis of Poly(L-lactic acid) Monoacetate Monoethyl Methacrylate (PLLA-EMA-AC). The product from the previous synthesis of methacrylate-terminated PLLA was dissolved in chloroform at 50 °C to make a solution of 50 wt % PLLA. To this solution an excess of acetic anhydride was added. After 1 h the reaction was cooled to room temperature, the volume was increased 5-fold by addition of chloroform, and the solution was washed with aqueous sodium carbonate. The solution was then washed several times with distilled water, dried over magnesium sulfate for 24 h, filtered twice, and reduced under vacuum, and the product was precipitated in hexanes. The resultant polymer was dried under vacuum at ambient temperature.

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Copolymerization of ITA and PLLA

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Scheme 1. (a) Synthesis of Hydroxy-Terminated PLLA through the Ring-Opening Polymerization of LLA with SnOct and (b) Acetylation of Methacrylate-Terminated PLLA with Acetic Anhydride

a

b

1H

NMR (CDCl3) δ (ppm): 1.4-1.7 [d, 27H, CH3, lactic acid], 1.9 [d, 3H, CH3, methacrylate], 2.1 [s, 3H, CH3, methyl ester end group], 4.35 [m 4H, CH2CH2, ethyl methacrylate], 4.38 [m, 1H, CH, terminal lactic acid], 5.1-5.3 [m, 9H, CH, lactic acid], 5.6 and 6.1 [2 s, 2H, CH2 methacrylate]. IR (cm-1): 2950 (CH stretch), 1758 and 1722 (CdO stretch), 1640 (CdC stretch). Copolymerization of Itaconic Anhydride and Methacrylate-Terminated Poly(L-lactic acid). To a solution of PLLA-EMA-AC in ethyl acetate (1:1 wt:volume), ITA (1:1 molar ratio with PLLA-EMA-AC) and AIBN (1 mol % of total monomers) were added. The reaction was heated at 80 °C under nitrogen with a condenser and stirring for 6 h. The product was freeze-dried with a dry ice/acetone bath. Samples were also precipitated in ethyl ether to remove residual monomer for thermal analysis testing. 1H NMR (CDCl ) δ (ppm): 1.4-1.7 [d, 30H, CH , lactic 3 3 acid and polymerized methacrylate], 1.9-2.2 [m, 4H, CH2, polymerized methacrylate and ITA], 2.1 [s, 3H, CH3, methyl ester of PLLA-EMA-AC], 3.3 [broad 2H, CH2, ITA], 4.35 [m, 4H, CH2CH2, ethyl methacrylate of PLLA-EMA-AC], 4.38 [m, 1H, CH, terminal lactic acid], 5.1-5.3 [m, 9H, CH, lactic acid]. IR (cm-1): 2950 (CH stretch), 1862 and 1785 (CdO stretch, cyclic anhydride),1758 and 1722 (CdO stretch, PLLA). Characterization. NMR analysis was performed with a Bruker DMX 500 instrument at 25 °C using deuterated chloroform as the solvent and TMS as the reference. A Nicolet 560 Magna FTIR spectrometer was used for IR analysis. Samples were cast from solution onto KBr plates for analysis. Size exclusion chromatography (SEC) was performed with a Waters 150C ALC/GPC instrument at 35

°C using THF as the mobile phase and a refractive index detector. Columns used were 105, 500, and 100 Å Ultrastyragel columns. Due to the reactivity of the copolymers toward the SEC columns, samples were reacted with methanol prior to analysis. Calibration was established using polystyrene (PS) standards. Differential scanning calorimetry (DSC) was performed on a Perkin-Elmer DSC 7 equipped with an intercooler. Reported results are for first scans from 0 to 180 °C and are for second scans after rapid cooling to remove any previous thermal history. Results and Discussion Synthesis of Methacrylate-Terminated PLLA. The synthesis of methacrylate-terminated poly(L-lactic acid) oligomers have been studied by several groups.22-26 For this study, we chose a method that was previously studied by our group22 using HEMA and SnOct as the initiator system (Scheme 1a). This system has been shown to efficiently polymerize L-lactide resulting in a macromonomer that was able to undergo free radical polymerization with HEMA. It proceeds through the hydroxyl of HEMA initiating polymerization with SnOct acting as a coordinating catalyst, which allows the reaction to proceed through a coordination insertion reaction of the L-lactide to the growing polymer chain. Modifications performed to the procedure include increasing the SnOct catalyst concentration to 4 wt % of L-lactide. This modification was performed to decrease reaction time from 24 to 12 h in order to inhibit side reactions due to the reactivity of the macromonomer. Since some potential applications of this copolymer are in blends and composites with PLLA, a polymer that is sufficiently long to be both compatible in the amorphous

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Figure 1.

1H

Wallach and Huang

NMR spectra of acetylated (a) and unacetylated (b) methacrylate-terminated PLLA.

and crystalline phases of the PLLA was desired. This is important as cocrystallization may have an important part in adhesion and compatibilization in materials. Further, the molecular weight must be kept low enough to show compatibility in other phases of blends, in addition to PLLA. Lower molecular weight materials show better compatibility due to a lowering of the enthalpy of mixing that is associated with lower molecular weight materials. A molecular weight of 800 was chosen for this study in order to suit these requirements. Molecular weights were determined by proton NMR end group analysis and SEC analysis. The results from the two methods correspond well and are consistent with the expected results for the reaction. NMR analysis comparing the ratio of methacrylate end groups to lactic acid units gives a Mn of 780, while SEC gives similar results with an Mn of 800 with a polydispersity of 1.5 with no signs of bimodality. Acetylation of PLLA-EMA. Polymerization of L-lactide initiated by HEMA results in a polymer with a methacrylate and hydroxyl terminus. Since this study examines the polymerization of PLLA with ITA, it requires the end capping of the free hydroxyl end group, due to the reactivity of ITA toward the hydroxyl end group. This reaction would result in a difunctional oligomer, which upon polymerization would result in gelation. Acetylation was performed by reacting PLLA-EMA with acetic anhydride (Scheme 1b). This is a simple procedure, which produces an acetylated PLLA macromonomer and acetic acid. No catalyst is added for this reaction due to the high reactivity of the acetic anhydride. Acetylation is observed through a change in the chloroform solution from opaque to clear and colorless resulting from the increased solubility of the more hydrophobic oligomer. Removal of the acetic acid side product is achieved by washing the chloroform solution with aqueous sodium carbonate. Drying of the chloroform solution is essential after this step, because any moisture will react with itaconic anhydride forming the acid, which has been shown to be much less reactive to polymerization. Drying was achieved using anhydrous magnesium sulfate.

Structural analysis by NMR shows that the acetylation is quantitative with respect to the methacrylate end group indicating that all chains become acetylated. Figure 1 shows the spectra of this product along with that of the unacetylated product. The difference can be seen in the presence of the peak at 2.1 associated with the methyl end group on the polymer chain. Other notable peaks are associated with the methacrylate end group 6.1 and 5.6 for H2Cd and 1.9 for dC-CH3 as well as the tertiary hydrogen of PLLA at 5.2. Upon acetylation of PLLA-EMA there is no detectable change in the molecular weight from gel permeation chromatography (GPC) analysis due to the lack of precision in the procedure. The NMR end group indicates that no change in molecular weight occurs through the reaction and work up process except for the addition of the acetate group. Physical changes associated with acetylation are observed through a few degrees change in the glass transition temperature from -8 °C for the unacetylated to -5 °C for the acetylated macromonomer. This change arises from the decreased freedom of the end group by making it more hydrophobic and more compatible with the polymer. Copolymerization of ITA with PLLA-EMA-AC. In comparison to the polymerization of maleic anhydride, the use of ITA in free radical polymerizations has been rather small. The bulk of the research has been by the groups of Guile and co-workers27,28 and Cowie and co-workers.29-31 Additionally it has been a subject in the patent literature32-35 though usually only mentioned in the claims as a material similar to and to be used in place of maleic anhydride. This has been the case despite the increased reactivity of ITA in copolymerization with many common monomers.36 Further, the availability of ITA from an abundant renewable resource, citric acid, should make it an attractive alternative to the chemistry involved in the production of maleic anhydride. ITA has been shown to polymerize well under a variety of solution conditions with typical vinyl and acrylic monomers.28-30 In every case the ITA shows greater reactivity resulting in copolymers enriched in ITA. This is also reflected in the determination of reactivity ratios, which show significantly greater values for r(ITA) in relation to the

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Copolymerization of ITA and PLLA Scheme 2. Copolymerization of Itaconic Anhydride and Methacrylatre-Terminated PLLA Macromonomers

Figure 2. Percent conversion as a function of time in the copolymerization of ITA and PLLA-EMA-AC (1:1 molar ratio). Table 1. Results of the Copolymerization of ITA with PLLA-EMA-AC sample: ITA/PLLA-EMA-AC

c

% conversion

(mol %)

Mna

85/15 70/30 50/50 30/70 15/85

9 000 11 000 13 000 58 000 70 000

% anhydride

PDIa ITA/PLLA-EMA-ACb in copolymerc 1.3 1.1 1.3 6.5 3.0

58/82 82/94 98/95 100/94 100/87

80 67 51 31 17

a From SEC in THF using PS calibration. b From 1H NMR analysis. Calculated from % conversions and feed ratios.

comonomers. Only in the cases of methyl methacrylate and styrene are values for r(ITA) below 1 indicating its preference to react with the other monomers radical. Similar results to that of methyl methacrylate would be expected here due to the similarity of the methacrylate end group of the PLLAEMA-AC macromonomer; however the polymer chain may interfere and compatibility may be an issue (Scheme 2 ). Polymerization conditions were similar to a previous study of ours using ITA.37 In that case, a solution in ethyl acetate at 80 °C using AIBN as the initiator was employed from molecular weight and percent conversion results. Here we used a similar method though increased the amount of ethyl acetate to 1:1 (volume of ethyl acetate:weight of PLLAEMA-AC). Several polymer compositions were studied, and the results are outlined in Table 1. It can be seen that above 50 mol % ITA in the feed that ITA conversions are greatly decreased, and molecular weights are lower compared to compositions with PLLA-EMA-AC being the majority monomer. These may be explained by the inefficiency of the polymerization of ITA in a homopolymerization. Though it has been shown to polymerize better than maleic anhydride, it still shows low molecular weights and low yields and is very susceptible to polymerization conditions.38 Otsu and Yang38 have shown that molecular weights up to 20 000 have been obtained using AIBN in bulk with a yield of 49.1%. However, in a THF

system molecular weights are reduced to 5000 with yields of only 16.6%. In polymerizations with monomer feeds 50% or greater in PLLA-EMA-AC macromonomer, nearly complete conversions and higher molecular weights are observed. There appears to be a correlation between increasing molecular weight with increasing PLLA-EMA-AC macromonomer content. This arises in part due to the greater molecular weight of the PLLA-EMA-AC, though calculations show degree of polymerization does increase with increasing PLLA-EMA-AC content. The consumption of monomers was followed by 1H NMR analysis for the 50/50 monomer feed composition. This was performed in order to observe the relative rates of addition of the monomers to the growing polymer chain and to ensure one monomer was not consumed prematurely followed by homopolymerization of the other. The results in Figure 2 show that the two monomers show similar conversions within the reaction times, and they show similar rates of reaction. Thermal Properties. Thermal properties of the macromonomers were studied for the samples both as polymerized after freeze-drying and after precipitation in ethyl ether to remove residual monomer. The polymerized samples studied have very similar glass transition temperatures around 23 °C. This is similar to the glass transition temperature of the homopolymerized PLLA-EMA-AC macromonomer of 22 °C. After precipitation in ethyl ether the polymers show quite different results (Table 2), indicating that residual monomer, even in cases where near compete conversions occurred, significantly affect the properties of these materials. Here a correlation between increasing anhydride content and increasing Tg is observed. This is expected due to the increased Tg of poly(itaconic anhydride), which is predicted to be above 200 °C.29 Precipitation did not have an affect on the molecular weight of the polymers nor on the IR spectra except for the removal of residual monomer. Peak areas from IR confirmed that the copolymer composition did not change with precipitation.

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Table 2. Glass Transition Temperatures of the Copolymers and the PLLA-EMA-AC Monomer sample: ITA/PLLA-EMA-AC (mol %) 85/15 70/30 50/50 a

Tga (°C)

sample: ITA/PLLA-EMA-AC (mol %)

Tga (°C)

73 62 55

30/70 15/85 0/100

50 32 22

Tg of PLLA-EMA-AC is -5 °C.

presence of the LLA does interfere somewhat. The IR spectrum of the 50/50 copolymer is shown in Figure 3. The peaks at 1758 and 1722 cm-1 are associated with the carbonyls of the PLLA-EMA-AC macromonomer as can be seen in the spectrum of the unpolymerized macromonomer (Figure 4). The presence of the cyclic anhydride is observed at 1862 cm-1, and a shoulder on the PLLA-EMA-AC peak is observed at 1785 cm-1. These peaks are characteristic of cyclic anhydrides39 indicating that the polymerization does not disrupt the anhydride. Conclusions

Figure 3. IR spectra of 50/50 copolymer of ITA and PLLA-EMA-AC with expanded carbonyl region to show the presence of cyclic anhydride (1862 and 1785 cm-1) and PLLA (1758 And 1722 cm-1).

The copolymerization of ITA and methacrylate-terminated PLLA macromonomers has been shown. Copolymerization was successful for varying concentration of ITA; however, those with more than 50% ITA had decreased conversions and lower molecular weights compared to polymers with greater amounts of PLLA-EMA-AC. After polymerization, the cyclic anhydride remains intact as evidenced through IR analysis. PLLA-EMA-AC macromonomers for this study were synthesized through the ring-opening polymerization of L-lactide followed by acetylation of the product to remove the hydroxyl end group, with a molecular weight of 800 being used. Thermal properties of the copolymers show Tg values between 32 and 73 °C with increasing values for increased itaconic anhydride content. No evidence of crystallization of PLLA is observed within these samples under the conditions studied. Acknowledgment. Financial support from the National Corn Growers Association is gratefully acknowledged. References and Notes

Figure 4. IR spectra of PLLA-EMA-AC with carbonyl region expanded to show peaks arising from the PLLA macromonomer at 1758 And 1722 cm-1.

Polymers produced from L-lactide as is the case here typically contains crystallinity that can be observed in a DSC scan irrespective of the previous thermal history due to crystallization of the polymer during the temperature scan. For these samples, although the monomer exhibits crystallinity, the copolymer does not show any crystallinity. Noncrystalline behavior is also observed in the homopolymerization of the PLLA-EMA-AC macromonomer. This indicates that tying down the PLLA-EMA-AC chains through polymerization sufficiently disrupts crystallization within the molecular weight studied. Structural Characteristics. Structural characteristics are difficult to analyze due to the overwhelming presence of the lactic acid units in the copolymer; for example in the case of the 50% ITA copolymer the itaconic anhydride/lactic acid ratio is 9:1. NMR analysis does not provide significant information, respective of the amount of monomer remaining which was used for copolymer composition determination (Table 1), due to overlapping and broadness of peaks from the ITA. IR analysis gives more information though the large

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