Method for separating racemic lactide

Abstract

The present invention provides a method for separating racemic lactide in high yield and high efficiency without the risk of side reactions, even when the ratio of L-lactide is low.

Description

[Technical field]

[0001] Cross-reference to related applications This application claims the benefit of priority based on Korean Patent Application No. 10-2021-0075600 filed on June 10, 2021, and Korean Patent Application No. 10-2022-0069132 filed on June 7, 2022, and all contents disclosed in the documents of said Korean patent applications are incorporated herein by reference.

[0002] The present invention relates to a method for separating racemic lactide in high yield and efficiency without side reactions. [Background technology]

[0003] Polylactic acid is a biodegradable material with excellent mechanical properties such as tensile strength and elastic modulus, and is widely used in various fields. Although polylactic acid is a homopolymer, it can have various structures depending on its stereoregularity. Polylactic acid is generally produced through ring-opening polymerization of lactide (LT), and since lactide has optical isomers, it is possible to change the properties of polylactic acid by changing the arrangement of these optical isomers in the repeating unit.

[0004] Meanwhile, lactide is a lactic acid dimer, which is a cyclic diester of lactic acid (2-hydroxyptopionic acid, LA). It is produced by the so-called reactive distillation method, in which lactic acid is dehydrated and condensed to obtain a relatively low molecular weight lactic acid oligomer as an intermediate, which is then heated to 180°C or higher in the presence of a catalyst and depolymerized and cyclized under reduced pressure to form lactide, which is then discharged as steam outside the reactor.

[0005] Lactic acid used in the production of lactide is an asymmetric (chiral) molecule having two enantiomers, D-form (or (R)-form) and L-form (or (S)-form), and lactide produced from the lactic acid exists as three optical isomers having two stereocenters, specifically, L-lactide (L-LT) or (S,S)-lactide formed from two molecules of L-lactic acid, D-lactide (D-LT) or (R,R)-lactide formed from two molecules of D-lactic acid, and meso-lactide (meso-LT) or (R,S)-lactide formed from one molecule each of L-lactic acid and D-lactic acid. In addition to the mixture of optical isomers, when lactide is produced by the reactive distillation method, unreacted lactic acid and lactic acid derivatives may also exist as impurities.

[0006] Therefore, when producing lactide, a selective synthesis method can be used to produce a lactide mixture with an optical purity of 90% or more, i.e., containing 90% or more of L-lactide or D-lactide, but it is difficult to produce a high purity of 99% or more. In addition, since meso-lactide contained in the product has a faster hydrolysis rate than L-lactide or D-lactide, if the content of meso-lactide in the product is high, the overall hydrolysis is promoted. In addition, lactic acid and lactic acid oligomers increase the acidity and inhibit the formation of high-quality polylactide. Therefore, a purification method that removes meso-lactide, lactic acid, and lactic acid derivatives while containing L-lactide or D-lactide at high purity depending on the purpose of use is required.

[0007] Recently, various methods for utilizing meso-lactide, which is produced during the production of lactide from lactic acid, have been researched and developed.

[0008] One example is a method of converting meso-lactide to L-lactide and D-lactide through racemization. However, the lactide converted through racemization is a racemate with a 1:1 ratio of L-lactide and D-lactide, and these have the same physical and chemical properties, making it difficult to separate them.

[0009] As a method for separating the racemate, melt-crystallization, simultaneous crystallization using seed injection, chiral solvent use, etc. have been proposed. However, the melt-crystallization method has a limitation that it is only possible when the L-lactide ratio is 80% or more. In addition, there is a method using seed injection and ethanol solvent, in which L-lactide is injected as a seed and then L-lactide is separated using ethanol solvent, which is also effective when the L-lactide ratio is 60% or more.

[0010] Therefore, there is a need to develop a method for separating racemic lactide in high yield and high efficiency without the risk of side reactions even when the ratio of L-lactide is low. Summary of the Invention [Problem to be solved by the invention]

[0011] The present invention provides a method for separating racemic lactide in high yield and high efficiency without the risk of side reactions, even when the ratio of L-lactide is low. [Means for solving the problem]

[0012] In order to solve the above problems, the present invention provides a method for separating racemic lactide, comprising the steps of: preparing a mixture by adding and mixing L-lactide racemic solution (Step 1); and adding an extraction solvent to the mixture to selectively extract L-lactide from the lactide racemate (step 2); The extraction solvent comprises an amine compound or an amide compound; Method for isolating racemic lactide.

[0013] Therefore, the present invention will be described in detail step by step.

[0014] (Stage 1) In the method for separating racemic lactide of the present invention, step 1 is a step of adding L-lactide to racemic lactide and mixing them to prepare a mixture.

[0015] The lactide racemate is a mixture of optical isomers in which L-lactide and D-lactide are mixed in equal amounts, specifically, it contains L-lactide and D-lactide in a weight ratio of 1:1.

[0016] The racemic lactide can be produced by racemizing meso-lactide, which is produced as a by-reaction during lactide production using lactic acid. Thus, the present invention may further include a step of producing racemic lactide containing L-lactide and D-lactide by racemizing meso-lactide before step 1 of adding and mixing L-lactide to the racemic lactide.

[0017] The L-lactide added to the racemic lactide acts as a crystal seed during the extraction reaction for separating the racemic lactide.

[0018] The L-lactide can be added in an amount of 10 to 70 parts by weight based on 100 parts by weight of the racemic lactide. More specifically, the L-lactide can be added in an amount such that the content of L-lactide is more than 50% by weight and not more than 80% by weight, more specifically more than 50% by weight, or 52% by weight or more, or 55% by weight or more, and not more than 80% by weight, or 75% by weight or less, or 70% by weight or less, or 65% by weight or less, or 60% by weight or less, or less than 60% by weight, based on the total weight of the mixture obtained after adding L-lactide to the racemic lactide.

[0019] The higher the amount of L-lactide added and the content of L-lactide in the mixture, the higher the purity of L-lactide obtained. Thus, in terms of the effect of improving the extraction selectivity and reducing the content of impurities, the L-lactide can be added in an amount such that the content of L-lactide is 65% by weight or more, or 70% by weight or more, and 80% by weight or less, or 75% by weight or less, based on the total weight of the mixture obtained after adding L-lactide to the lactide racemate. However, in the present invention, since an optimal extraction solvent is used in the subsequent extraction process, it is possible to separate L-lactide even if the content of L-lactide in the mixture is as low as 60% by weight or less, or less than 60% by weight. In terms of such effect, the L-lactide can be added in an amount such that the content of L-lactide in the mixture is more than 50% by weight, or 52% by weight or more, or 55% by weight or more, and 60% by weight or less, or less than 60% by weight, or 58% by weight or less, based on the total weight of the mixture.

[0020] (Stage 2) In the method for separating racemic lactide of the present invention, step 2 is a step of adding an extraction solvent to the mixture prepared in step 1 to selectively extract L-lactide from the racemic lactide.

[0021] The extraction solvent is an amine-based compound or an amide-based compound. The extraction solvent is a non-chiral compound that does not have chiral properties, has polarity, and can exhibit excellent extraction effects due to the shift of the eutectic point in the three-component system of L-lactide, D-lactide, and the extraction solvent. As a result, the extraction solvent exhibits excellent extraction efficiency compared to alcohols used in the separation of conventional lactide racemates, and amine-based compounds such as TEA can exhibit high extraction efficiency even when the L-lactide content in the mixture is low.

[0022] In addition, the extraction solvent may be a polar solvent that exists in a liquid state at room temperature (20±5° C.), has a melting point of 25° C. or less, and a boiling point of 80° C. or more. More specifically, the extraction solvent has a melting point of 25° C. or less, or 10° C. or less, or -150° C. or more, or -120° C. or more, and a boiling point of 80° C. or more, or 100° C. or more, or 300° C. or less, or 250° C. or less. When the melting and boiling point conditions are satisfied, stable and excellent extraction efficiency can be exhibited while minimizing the occurrence of side reactions.

[0023] Specifically, the amine compound may be a tertiary amine represented by the following Chemical Formula 1: [ka] In the above chemical formula 1, R 11 ~R 13 are each independently C 1-20 is a straight or branched chain alkyl.

[0024] Specific examples of the amine-based compound include trimethylamine, triethylamine, tri-n-propylamine, tri-n-butylamine, tri-n-octylamine, tridodecylamine, trioctadecylamine, triisopropylamine, triisobutylamine, tri-t-butylamine, tris(2-ethylhexyl)amine, N,N-dimethyloctylamine, N,N-dimethyldodecylamine, N,N-dimethyl-n-octadecylamine, and N,N-diethyldodecylamine, and any one or a mixture of two or more of these can be used.

[0025] Among these, when considering the remarkable separation effect, the amine-based compound is R 11 ~R 13 are each independently C 1-9 More specifically, the amine compound may be triethylamine or tri-n-octylamine.

[0026] Specifically, the amide compound may be a compound represented by the following Chemical Formula 2: [ka] In the above chemical formula 2, R 21 ~R 23 are each hydrogen or each independently C 1-20 is a straight or branched chain alkyl.

[0027] The amide compound represented by the formula 2 is R 21 ~R 23 Compared with dimethylformamide, which does not satisfy the substituent conditions of R, it can show a better separation effect. 21 ~R 23 are each hydrogen or each independently C 1-8 and more specifically each may be hydrogen or each may be methyl.

[0028] Specific examples of the amide-based compound include formamide and dimethylacetamide, and any one or a mixture of two or more of these can be used.

[0029] The extraction solvent can be used in an amount of 1 to 10 parts by weight per part by weight of L-lactide present in the mixture. If the amount of the extraction solvent used is too small, the extraction efficiency is insufficient, and if the amount of the extraction solvent used is too large, the processability may be reduced, such as requiring a subsequent process for removing the extraction solvent. When used within the above range, lactide racemate can be separated with excellent extraction efficiency without an additional process for removing the extraction solvent. More specifically, the extraction solvent can be used in an amount of 1 part by weight or more, or 2 parts by weight or more, or 2.5 parts by weight or more, or 3 parts by weight or more, or 3.1 parts by weight or more, or 3.2 parts by weight or more, and 10 parts by weight or less, or 8 parts by weight or less, or 6.5 parts by weight or less, or 5 parts by weight or less, or 4 parts by weight or less, or 3.6 parts by weight or less, or 3.5 parts by weight or less, per part by weight of L-lactide present in the mixture.

[0030] In addition, after adding the extraction solvent to the mixture, a mixing process may be optionally performed to increase uniform mixing and therefore separation efficiency.

[0031] At this time, the mixing process can be carried out by a conventional mixing method using a stirrer, mixer, etc., and the mixing speed, time, etc. can be appropriately selected and carried out.

[0032] Furthermore, the step 2 can be carried out at a temperature of 10 to 40° C. Specifically, the step can be carried out at a temperature of 10° C. or higher, or 15° C. or higher, and 40° C. or lower, or 30° C. or lower, or 25° C. or lower, and more specifically, at room temperature of 20±5° C. When the step is carried out within the above temperature range, sufficient extraction efficiency can be achieved without the risk of side reactions occurring.

[0033] As a result of the reaction, L-lactide is extracted from lactide racemate.

[0034] Specifically, after the introduction of the extraction solvent and the subsequent selective mixing steps are completed, the precipitated solids in the resulting reaction product are separated and removed by filtration to obtain a filtrate.

[0035] The precipitated solid is D-lactide that is not dissolved in the extraction solvent and the remaining L-lactide, which can be separated by a conventional method, specifically, by filtration.

[0036] Meanwhile, when the filtrate was analyzed by gas chromatography, it was found to contain a high content of L-lactide, specifically, 90% by weight or more, 92% by weight or more, 93% by weight or more, or 94% by weight or more of the total weight of the filtrate. In addition, the formation of by-products due to side reactions such as hydrolysis was almost nonexistent, being less than 1% by weight or 0.95% by weight or less of the total weight of the filtrate. Effect of the Invention

[0037] As described above, the method for separating racemic lactide according to the present invention can separate racemic lactide in high yield and high efficiency without the risk of side reactions even when the ratio of L-lactide is low. Therefore, high-purity lactide separated by the method can be usefully used for producing high-molecular-weight polylactide. [Brief description of the drawings]

[0038] [Figure 1] 1 is a graph showing the results of evaluating the L-LT extraction selectivity by solvent according to the input seed and L-LT ratio in an experimental example. [Diagram 2] 1 is a graph showing the results of gas chromatography analysis for Example 3. [Diagram 3] 1 is a graph showing the results of gas chromatography analysis for Example 6. [Figure 4] 1 is a graph showing the results of gas chromatography analysis for Comparative Example 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are merely illustrative of the present invention, and the present invention is not limited to the following examples. EXAMPLES

[0040] Example 1 0.16 g of L-LT (L-LT:D-LT weight ratio = 64 parts by weight based on 100 parts by weight of Rac-LT) was added to 0.25 g of Rac-LT (L-LT:D-LT weight ratio = 1:1) and mixed to prepare a mixture with an L-LT:D-LT weight ratio of 7:3 (L-LT content = 70% by weight based on the total weight of the mixture).

[0041] 1.30 ml (corresponding to 3.28 parts by weight based on 1 part by weight of L-lactide present in the mixture) of triethylamine (TEA, melting point: -114.70°C, boiling point: 89.3°C) was added to the mixture and stirred at room temperature for 1 hour. The resulting solution was in an emulsion state, and the solid portion was filtered through a filter to separate and remove it, obtaining a filtrate.

[0042] Example 2 The same procedure as in Example 1 was repeated, except that 0.25 g of Rac-LT (weight ratio of L-LT:D-LT=1:1) was mixed with 0.07 g of L-LT (L-LT content=28 parts by weight based on 100 parts by weight of Rac-LT) to obtain a weight ratio of L-LT:D-LT of 6:4 (L-LT content=60% by weight based on the total weight of the mixture).

[0043] Example 3 The same procedure as in Example 1 was repeated, except that 0.25 g of Rac-LT (weight ratio of L-LT:D-LT=1:1) was mixed with 0.03 g of L-LT (L-LT content=12 parts by weight based on 100 parts by weight of Rac-LT) to give a weight ratio of L-LT:D-LT of 5.5:4.5 (L-LT content=55% by weight based on the total weight of the mixture).

[0044] Example 4 The same procedure as in Example 1 was carried out, except that 0.84 ml (corresponding to 3.31 parts by weight based on 1 part by weight of L-lactide present in the mixture) of formamide (FA, melting point: 2° C., boiling point: 210° C.) was added instead of 1.30 ml of triethylamine.

[0045] Example 5 The same procedure as in Example 2 was carried out, except that 0.84 ml of formamide (corresponding to 4.95 parts by weight based on 1 part by weight of L-lactide present in the mixture) was added instead of 1.30 ml of triethylamine.

[0046] Example 6 The same procedure as in Example 3 was carried out, except that 0.84 ml of formamide (corresponding to 6.18 parts by weight based on 1 part by weight of L-lactide present in the mixture) was added instead of 1.30 ml of triethylamine.

[0047] Example 7 The same procedure as in Example 1 was carried out, except that 1.17 ml (corresponding to 3.31 parts by weight based on 1 part by weight of L-lactide present in the mixture) of tri-n-octylamine (melting point: -34.0°C, boiling point: 367°C) was added instead of 1.30 ml of triethylamine.

[0048] Example 8 The same procedure as in Example 2 was carried out, except that 1.17 ml of tri-n-octylamine (corresponding to 4.87 parts by weight based on 1 part by weight of L-lactide present in the mixture) was added instead of 1.30 ml of triethylamine.

[0049] Example 9 The same procedure as in Example 1 was repeated, except that 1.17 ml of tri-n-octylamine (corresponding to 6.12 parts by weight based on 1 part by weight of L-lactide present in the mixture) was added instead of 1.30 ml of triethylamine.

[0050] Comparative Example 1 The same procedure as in Example 1 was repeated, except that 1.204 ml of ethanol (ethanol, EtOH, melting point: -114.1°C, boiling point: 78.4°C) was used instead of 1.30 ml of triethylamine.

[0051] Comparative Example 2 The same procedure as in Example 2 was repeated, except that 1.204 ml of ethanol was used instead of 1.30 ml of triethylamine.

[0052] Comparative Example 3 The same procedure as in Example 3 was repeated, except that 1.204 ml of ethanol was used instead of 1.30 ml of triethylamine.

[0053] Comparative Example 4 The same procedure as in Example 1 was repeated, except that 0.92 ml of 1,4-dioxane (melting point: 11° C., boiling point: 101° C.) was used instead of 1.30 ml of triethylamine.

[0054] Comparative Example 5 The same procedure as in Example 2 was repeated, except that 0.92 ml of 1,4-dioxane was used instead of 1.30 ml of triethylamine.

[0055] Comparative Example 6 The same procedure as in Example 3 was repeated, except that 0.92 ml of 1,4-dioxane was used instead of 1.30 ml of triethylamine.

[0056] Comparative Example 7 Except for not introducing L-LT as a seed for Rac-LT, it was carried out in the same manner as in Example 1 above.

[0057] Specifically, 1.30 ml of triethylamine (corresponding to 7.6 parts by weight based on 1 part by weight of L-lactide present in the mixture) was introduced into Rac-LT (weight ratio of L-LT:D-LT = 1:1), and the mixture was stirred at room temperature for 1 hour.

[0058] However, solid separation corresponding to D-LT in the resulting solution did not occur.

[0059] Experimental Example (1) L-LT extraction selectivity The weight ratio of L-LT:D-LT in the filtrates obtained in the above Examples and Comparative Examples was measured, and the L-LT extraction selectivity was evaluated from the results.

[0060] Specifically, for each of the filtrates obtained in the above Examples and Comparative Examples, about 60 μl each was taken and diluted with 1 ml of acetonitrile (MeCN) to prepare samples for gas chromatography (GC) measurement. GC analysis was performed on the prepared samples under the following conditions. The total peak area and the L-LT peak area were determined from the chromatogram obtained as the GC analysis result, and the L-LT extraction selectivity (%) was calculated by the following formula 1.

[0061] [Formula 1] L-LT extraction selectivity (%) = (L-LT peak area / total peak area) × 100 In the above formula 1, the total peak area and the L-LT peak area were determined through integration for each peak. <GC analysis conditions> GC / FID, Shimadzu Column: CP-Chirasil Dilution solvent: MeCN (acetonitrile) Injection volume: 1 μl Injection port temperature: 200 °C Carrier gas:N 2 FID (flame photometric detector) Temperature: 275℃ Column temperature: Carrier flow rate(ml / min):1.5ml / min Analysis time: 19.60min The results are shown in Table 1 below and in FIGS.

[0062] FIG. 1 is a graph showing the results of evaluating the L-LT extraction selectivity by solvent according to the input seed and L-LT ratio in an experimental example, and FIGS. 2 to 4 are graphs showing the gas chromatography analysis results for Example 3, Example 6, and Comparative Example 3, respectively.

[0063] In the gas chromatography analysis graphs of Figures 2 to 4, the x-axis starts from 0 min when the analysis started, but is expanded from 8 min when peaks began to be observed so that the results can be clearly identified.

[0064] (2) Impurity content (%) From the GC analysis results, the contents of impurities generated during separation of racemic lactide according to the examples and comparative examples were measured.

[0065] Specifically, the areas of peaks corresponding to impurities such as the meso-LT peak and the unknown peak (hereinafter simply referred to as "impurity peaks") in the GC analysis chromatogram were calculated, and the impurity content (%) was calculated according to the following Equation 2.

[0066] [Formula 2] Impurity content (%) = (total area of ​​impurity peaks / total peak area) x 100 In Equation 2, the total peak area and the area of ​​the impurity peaks are calculated by integrating the respective peaks, and the total area of ​​the impurity peaks is the sum of the areas of the respective impurity peaks calculated by integrating the respective impurity peaks.

[0067] [Table 1]

[0068] As a result of the experiment, Examples 1-9, which used TEA, FA or Tri-n-octylamine as the extraction solvent, showed a significantly reduced impurity content along with excellent L-LT extraction selectivity.

[0069] Specifically, when the ratio of L-LT in the mixture after the addition of L-LT was high at 60% by weight or more, Examples 1, 2, 4, 5, 7, and 8, in which TEA, FA, or Tri-n-octylamine was used as the extraction solvent, showed excellent L-LT extraction selectivity at the same level or higher than that of Comparative Examples 1, 2, 4, and 5, in which EtOH or 1,4-dioxane was used as the extraction solvent.

[0070] In addition, when the L-LT content in the mixture after the addition of L-LT was less than 60%, specifically 55%, the L-LT extraction selectivity of the conventional extraction solvent EtOH was reduced to 86.547%, whereas the extraction selectivity of TEA and Tri-n-octylamine was still high at 92.045% and 92.884%, respectively.

[0071] Meanwhile, in the case of Example 6, in which FA was used as the extraction solvent, the L-LT extraction selectivity was 66.069%, which was lower than that of Comparative Example 3, in which EtOH was used. However, the amount of impurities generated during separation of lactide racemate using FA was 0.928%, whereas the content of impurities generated during separation of lactide racemate using EtOH was significantly higher at 5.227%. From this, it can be seen that when the L-LT content is low, the L-LT extraction selectivity is somewhat lower when FA is used as the extraction solvent than EtOH, but the amount of impurities generated can be significantly reduced, so that L-LT can be obtained with even higher purity.

[0072] In addition, as shown in the GC analysis graphs in Figures 2 to 4, in Example 3 using TEA, there were no peaks other than L-LT and D-LT in the GC analysis graph. On the other hand, in the case of Comparative Example 3 using EtOH solvent, an unknown peak was observed in the GC analysis graph other than L-LT and D-LT, which confirmed the possibility of a side reaction of lactide such as hydrolysis.

[0073] In addition, in the case of Example 6 using FA, a very small meso-LT peak was observed in the GC analysis graph at retention times of 10 minutes or more, confirming the presence of side reactions. However, the ratio was very low, and the amount of side reaction products was also very small.

Claims

1. preparing a mixture by adding L-lactide to racemic lactide and mixing; and adding an extraction solvent to the mixture to selectively extract L-lactide from the lactide racemate; The extraction solvent comprises an amine compound or an amide compound; A method for separating racemic lactide, comprising the steps of: The amine compound is a tertiary amine represented by the following formula 1: 【Chemistry 1】 (In the above chemical formula 1, R 11 to R 13 are each independently a C 1-9 linear alkyl group; The amide compound is a compound represented by the following formula 2: 【Chemistry 2】 (In the above chemical formula 2, R 21 to R 23 are each hydrogen or each independently C 1-8 straight chain alkyl), the method.

2. 2. The method according to claim 1, wherein the extraction solvent is a polar solvent that is liquid and has a melting point of 25° C. or lower and a boiling point of 80° C. or higher.

3. 2. The method of claim 1, wherein the extraction solvent is a non-chiral compound.

4. 2. The method according to claim 1, wherein the amine compound is trimethylamine, triethylamine, tri-n-propylamine, tri-n-butylamine, or tri-n-octylamine.

5. 2. The method according to claim 1, wherein the amine compound is triethylamine or tri-n-octylamine.

6. The method according to claim 1, wherein the amide compound is formamide or dimethylacetamide.

7. 2. The method according to claim 1, wherein the extraction solvent is used in an amount of 1 to 10 parts by weight per 1 part by weight of L-lactide present in the mixture.

8. 2. The method according to claim 1, wherein the L-lactide is added in an amount of 10 to 70 parts by weight based on 100 parts by weight of the racemic lactide.

9. 2. The method according to claim 1, wherein the L-lactide is added in an amount such that the content of L-lactide in the mixture is more than 50% by weight and not more than 80% by weight based on the total weight of the mixture.

10. 2. The method of claim 1, wherein the L-lactide is added in an amount such that the content of L-lactide in the mixture is greater than 50% by weight and less than 60% by weight based on the total weight of the mixture.

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