Synthesis of Polylactic Acid Monomer-Lactide

Using D,L-lactic acid as the monomer and anhydrous vaporized zinc (ZnO) as the catalyst, D,L-lactide was prepared by first condensation polymerization and then depolymerization of lactic acid under low vacuum conditions. The effects of dehydration temperature, dehydration rate, catalyst dosage, and depolymerization temperature on lactide yield were investigated. The purification method of lactide was improved and the recrystallization yield of lactide was increased. The melting point of the product was determined by capillary melting point method, and the product was analyzed and characterized by infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction analysis. The results showed that the obtained product was highly pure cyclic lactide.

Biodegradable and biocompatible polylactic acid has been widely used as biomedical polymer materials such as drug controlled release carriers, medical surgical sutures, and fracture internal fixation materials. Its synthesis method is divided into two categories, direct method and indirect method. High molecular weight polylactic acid is generally synthesized through an indirect method, that is, lactide is first obtained from lactic acid, and then the lactide is polymerized into polylactic acid. This method requires the use of high-purity lactide monomer, which is synthesized under high temperature and high vacuum conditions, and the cost is high. In order to reduce the cost of polylactic acid and achieve large-scale production, improving the process to increase the yield of lactide has become the primary problem to be solved. Typically, high vacuum conditions are also required for the preparation of lactide. In this study, lactide was produced under low vacuum conditions by gradually increasing the temperature and gradually reducing the pressure, which reduced the difficulty of the reaction and achieved a higher yield. The product was characterized by various methods.

I. Experimental part

1.1 Main raw materials and reagents

D, L-lactic acid (85-90%), zinc oxide (ZnO), ethyl acetate, ethylene glycol, and absolute ethanol. The above raw materials are all of analytical grade.

1.2 Preparation and purification of lactide

Add 100 mL of D,L-lactic acid to a 250 mL three-necked flask, stir magnetically, slowly add a certain amount of anhydrous ZnO as a catalyst, connect the device, confirm that the system is sealed, heat at normal pressure to 120°C, and distill away the raw materials. D,L-moisture in lactic acid. Gradually reduce the pressure, raise the vacuum degree to 0.097MPa, and increase the temperature to 160°C for 4 to 5 hours to generate D,L-lactic acid oligomers, and the reaction system slowly changes from milky white to brown.

Return to normal pressure, continue stirring at high speed, add an appropriate amount of ethylene glycol as a diluent to the flask, replace the receiving device, re-seal the entire reaction system, quickly raise the temperature to above 200°C, and gradually increase the system vacuum to 0.097 while raising the temperature. MPa, a light yellow distillate can be received, and then light yellow crystals appear in the receiving tube. Slowly raise the temperature to 260°C. When the temperature of the distillate begins to drop, stop the reaction and cool to room temperature. This process takes about 4~5h.

The product was filtered, recrystallized multiple times, placed in a vacuum drying oven, and vacuum dried at 40°C for 24 hours to obtain colorless and transparent flaky crystals, which were placed in a P205 desiccator for later use.

1.3 Analysis and characterization

Melting point: measured by capillary method, with a heating rate of 5℃/min at the beginning and 1℃/min near the melting point. Infrared spectrum (IR); coating method, measured by Magna560 infrared spectrometer of Nicolet Company, USA. X-ray diffraction (XRD): Advance-D80.X-ray diffraction analyzer of BRUKER Company, Germany. Thermal analysis (DSC): STA 409PC comprehensive thermal analyzer of NETZSCH Company, Germany, argon atmosphere.

II. Results and Discussion

2.1 Factors Affecting the Lactide Synthesis Process

2.1.1 Effect of Dehydration Conditions on Lactide Yield

Under the conditions of 100mL D,L-lactic acid, 0.8% catalyst content, and 15ml diluent, the dehydration temperature of D,L-lactic acid was changed within 100~180℃ (considering the characteristics of the step-by-step reaction, the temperature was gradually increased and maintained at the final temperature for 1.0h). The relationship between the dehydration temperature and the dehydration rate and the crude yield of D,L-lactide is shown in Figure 1.

Figure 1. Effect of dehydration temperature on lactide yield and dehydration rate.

When the temperature is low, the dehydration rate is slow, the dehydration rate is low, and the production of lactic acid oligomers suitable for degradation is small, so the yield of lactide is low; when the temperature is too high, the dehydration rate is accelerated, the molecular weight of the generated lactic acid oligomers is too high, and it is not suitable for degradation. If the polymerization degree is too high, the viscosity of the material is too large, and the lactide vapor generated by the reaction is difficult to break through the encirclement of the viscous material and evaporate, resulting in a decrease in the lactide yield.

Repeated experiments have confirmed that the heating rate should be fast at the beginning of the reaction, and the temperature should be kept constant for 0.5h at 120℃ to remove the original water in the lactic acid solution, and then slowly increase the temperature (heating rate 15℃/h), and then keep the temperature constant for 1.0h after the temperature is raised to 160℃. In this way, distilling water for 4~5h can achieve a relatively ideal dehydration effect, and the dehydration amount reaches about 90% of the theoretical value, and the yield of lactide is high.

2.1.2 Effect of catalyst dosage on lactide yield

The catalysts used for the synthesis of lactide mainly include oxides such as Sb203, P2O5, ZnO and tin compounds such as stannous octoate, tin octoate, stannous sulfate, etc. Considering that zinc compounds are cheap, easy to obtain, easy to store, and harmless to the human body, ZnO was selected as the catalyst for the synthesis of lactide, and the effect of ZnO dosage (100mL D, L-lactic acid 15mL diluent, dehydration temperature 160℃, depolymerization temperature 260℃) on the lactide yield was investigated. The results are shown in Figure 2.

Figure 2. Effect of catalyst dosage on the crude lactide yield.

With the increase of catalyst dosage, the lactide yield first increased and then decreased, indicating that too much or too little catalyst dosage may lead to a decrease in yield. When the catalyst dosage is 1.2%, the lactide yield reaches the maximum. The main reason is that the amount of catalyst affects the reaction rates of the three reactions of lactic acid polymerization, oligomer depolymerization and ring-opening polymerization of lactide. If the catalyst is too little, the reaction rate is slow, the amount of lactic acid oligomers generated is small, and unreacted lactic acid remains in the distilled product, which reduces the yield of lactide. When the amount of catalyst reaches a certain level, the reaction rate is too fast, the molecular weight of the generated lactic acid oligomers is too high, and it is difficult to depolymerize to generate lactide, which will also reduce the yield of lactide. In addition, the increase in the amount of catalyst also leads to an accelerated depolymerization rate of the oligomers, and the generated lactide cannot leave the reaction area in time, and high relative molecular weight polylactic acid is generated, making the depolymerization reaction difficult to occur, which also leads to a decrease in the yield of lactide.

2.1.3 Effect of depolymerization conditions on lactide yield

The factors affecting the lactide yield in the depolymerization stage are mainly vacuum and temperature. Low vacuum conditions were adopted in the study. The system vacuum degree was 0.097MPa under the limit decompression capacity of the circulating water vacuum pump. Complete the pressure reduction process quickly while ensuring that the reactants do not explode.

Under the conditions of 100 mL D,L lactic acid, 1.2% catalyst content, and 160°C dehydration temperature, the relationship between depolymerization temperature and lactide yield is shown in Figure 3.

Figure 3. Effect of depolymerization temperature on lactide yield.

As can be seen from Figure 3, the lactide yield increases with the increase of depolymerization temperature at the beginning. The yield is the highest when the depolymerization temperature is 250℃, and then the lactide yield begins to decrease with the increase of temperature. According to research, the temperature should be raised as quickly and effectively as possible during the depolymerization process to avoid the molecular weight of lactic acid oligomers being too high and difficult to depolymerize. The optimal depolymerization temperature is 250℃.

2.1.4 Effect of diluent ethylene glycol on lactide yield

When no diluent is added, only part of the product is distilled in the early stage of distillation. The reactants are very easy to oxidize and discolor or even carbonize under high temperature conditions. The system is viscous. Only a small amount of lactide is obtained under the extreme decompression capacity of the circulating water vacuum pump. The reactants are dark brown and there are many residues. After adding an appropriate amount of ethylene glycol, the distillation process becomes stable, most of the products are distilled out, the distillation time is significantly extended, and the amount of residue in the bottle is very small.

2.1.5 Improvement of receiving deviceice

During the depolymerization stage of lactic acid oligomers, this experiment initially used one receiving bottle. As a result, the receiving tube was easily blocked by the crude lactide product, making the reaction unable to continue. After the improvement, a two-stage receiving bottle was used, and most of the products entered the first receiving bottle, and the experiment went smoothly.

2.2 Purification of lactide

The crude lactide contains a small amount of impurities such as water, lactic acid and lactic acid oligomers. Only after purification can high-purity lactide monomer be obtained for the preparation of high molecular weight polylactic acid. The most commonly used method for purifying lactide is the recrystallization method, and the solvents used are ether, ethyl acetate, butanone, benzene, isopropanol, etc., among which ethyl acetate is the most commonly used. Method 1 of this study uses ethyl acetate as the recrystallization solvent, and the yield is relatively low. Later, method 2 was used, which was first recrystallized twice with anhydrous ethanol and then recrystallized with ethyl acetate to obtain lactide with higher purity. After 4 recrystallizations, the melting point of lactide can meet the requirements, and the recrystallization yield is increased by 8.7%. The comparison of the two methods is shown in Table 1.

Table 1. Comparison of two quantitative crystallization methods.

2.3 Characterization of propylene glycol

2.3.1 Infrared spectrum analysis

The infrared spectrum of the synthetic product is shown in Figure 4. The CH stretching vibration peak is at 3004 cm^(-1), and the CH:-bending vibration peak is at 1446 cm^(-1); the C-H stretching vibration peaks are at 3004, 2950, and 2925 cm^(-1), respectively, and the C-H bending vibration peak is at 1387 cm^(-1); the C-0 stretching vibration peak in the ester group is at 1765 cm^(-1); the C-0-antisymmetric stretching vibration peak is at 1262 cm^(-1); and the O-C-0 exists at 1099 cm^(-1), and the ring skeleton vibration peaks are at 930 cm^(-1) and 652 cm^(-1), which are consistent with the literature spectra.

Figure 4. Infrared spectrum of D,L-lactide.

2.3.2 X-ray diffraction analysis

Figure 5 is the XRD diagram of the product. It can be seen from Figure 5 that the diffraction peak is obviously prominent, which indicates that the prepared lactide has a high purity and does not contain other amorphous substances, which is consistent with the literature value.

Figure 5. XRD diagram of D,L-lactide.

2.3.3 Melting point and DSC analysis of lactide

The crude lactide is white transparent flaky crystals after recrystallization 3~4 times: easy to absorb water. Lactide used as a polymerization monomer must have a high purity. Lactide used as a polymerization monomer must have high purity. The crystal melting point is generally used to control its purity. If the melting point is lower than the standard value and the melting range is long, it indicates that the crystal purity is low. The melting point of lactide after five recrystallizations was determined by capillary method, with a melting range of 125.3~126.2℃, and verified by DSC analysis (see Figure 6), with a melting point of 125.9℃, which is consistent with the value reported in the literature.

Figure 6. DSC diagram of D,L-lactide.

III. Conclusion

(1)With anhydrous ZnO as dehydrating agent and depolymerizing agent, lactic acid was polycondensed at 120~160℃ and depolymerized at 220~250℃ under low vacuum conditions throughout the process to synthesize lactide with a crude yield of 40.2%. The water pump reduced the pressure and reduced the difficulty of the reaction. Under the optimal conditions, the average lactide yield reached 38.6%.

(2) In the process of lactide purification, the combination of anhydrous ethanol and ethyl acetate can increase the yield of lactide after four recrystallizations by 8.7% compared with the use of ethyl acetate alone, and the melting point of the product meets the requirements.

(3) High-purity lactide was obtained through multiple recrystallizations, and was tested by XRD, DSC, etc., confirming that the structure of the synthesized product was consistent with the theoretical structure.

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