KR101809663B1 - A preparation of lactide with improved optical purity using mixed solvent of alkyl propionate and water - Google Patents

Abstract

The present invention relates to a process for producing optical purity-enhanced L- or D-lactide comprising recrystallizing a lactide sample mixed with an optical isomer in a mixed solvent containing alkyl propionate and water will be.
Since the production method of the present invention can selectively provide a lactide with high optical purity and low acidity, the high purity lactide produced by the above production method can be useful for the production of high molecular weight polylactide having a high molecular weight .

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a method for preparing lactide having improved optical purity using alkyl propionate and water,

The present invention relates to a process for producing optical purity-enhanced L- or D-lactide comprising recrystallizing a lactide sample mixed with an optical isomer in a mixed solvent containing alkyl propionate and water will be.

Lactide is a dimeric cyclic ester of lactic acid. It is useful as a raw material of polylactide which is widely used as a biodegradable polymer. It has recently been used as a preservative, a pH regulating agent, a coagulant such as tofu and dairy products coagulating agent, acidulant, and auxiliary expanding agent.

Conventional lactide production methods include dehydration condensation of lactic acid to obtain a lactic acid oligomer having a relatively low molecular weight as an intermediate, heating it to 180 DEG C or higher in the presence of a catalyst, depolymerizing it to depolymerize to form lactide, Called < / RTI > reactive distillation.

In such a production method, the lactide vapor collected contains impurities such as a lactic acid monomer, a low molecular weight lactic acid derivative such as a lactic acid oligomer, and water. Therefore, the lactide obtained by cooling and collecting the lactide requires an additional purification process depending on the use purpose.

Since lactic acid forming lactide has two isomers, L-type and D-type, the lactide produced from the mixture of the two isomers is L-lactide formed from two molecules of L-lactic acid, D-lactide formed from two molecules of D-lactic acid, and meso-lactide formed from one molecule of each of L-lactic acid and D-lactic acid. At this time, an appropriate synthesis method can be selected to mainly include L-lactide or D-lactide. By the selective synthesis method, a lactide mixture having 90% or more optical purity, that is, a lactide mixture containing 90% or more of L-lactide or D-lactide can be prepared, but it is difficult to produce a lactide mixture with a purity of 99% or more . In addition, the lactide mixture includes meso-lactide, lactic acid and lactic acid derivatives in addition to L-lactide or D-lactide. Since the hydrolysis rate of the double meso-lactide is higher than that of L-lactide or D-lactide, the hydrolysis is promoted as a whole when the content of meso-lactide is high. In addition, lactic acid and lactic acid oligomers increase the acidity and inhibit the formation of high quality polylactide. Accordingly, there is a need for a purification method for removing meso-lactide, lactic acid and lactic acid derivatives while containing L-lactide or D-lactide in a high purity depending on the purpose of use.

(Or L-) lactide from a mixture of low molecular weight lactic acid monomers such as lactic acid monomers and lactic acid oligomers, water, meso-lactide and D- (or L-) lactide mixture by solvent recrystallization Has been reported. Specifically, a method using ethanol as a solvent (U.S. Patent No. 6,313,319; Japanese Patent Laid-Open No. 10-279577), a method using a mixed solvent of water and acetone (U.S. Patent No. 5,502,215, WO 92/00974 ) And a method using benzene or an alkyl-substituted benzene as a solvent (JP-A-1994-006560). However, these methods are insufficient to purify lactide of high purity and high yield.

The present inventors have relatively by a simple purification method of using a solvent, recrystallization method to find a way to improve the optical purity of lactide intensive research efforts result, the alkyl propionate in an organic solvent (wherein alkyl is C ₁ to C ₄ Of lower alkyl) and a water-based solvent, the purity of L-lactide or D-lactide is increased to 99% or more, impurities such as meso-lactide are removed, and the acidity is significantly reduced To provide a high purity lactide for the production of high quality polylactide, and completed the present invention.

An object of the present invention is to provide a process for producing optical purity-enhanced L- or D-lactide comprising recrystallizing a lactide sample mixed with an optical isomer in a mixed solvent containing alkyl propionate and water .

In order to accomplish the above object, the present invention provides an optical isomer comprising an optically pure lactide sample, which comprises recrystallizing a lactide sample mixed with an alkyl propionate represented by the following general formula (1) and water, A process for the preparation of improved L- or D-lactide is provided:

[Chemical Formula 1]

In the above formula R ₁ is C ₁ to C ₄ being lower alkyl.

The term " lactide "of the present invention is a lactic acid dimer that is a cyclic di-ester of lactic acid (2-hydroxyptopionic acid). The lactic acid monomer can not form a lactone unlike other hydroxy acids because the hydroxy group is located too close to the carboxy group. Instead, preferentially form dimers similar to 5-hydroxyacid. The lactic acid dimer forms a lactide, which is a 6-membered cyclic di-ester, since it contains a hydroxy group at a suitable distance to form a lactone from a carboxyl group. It is useful as a raw material of polylactide which is widely used as a biodegradable polymer and recently it has been used as a preservative, a pH regulating agent, a coagulating agent such as tofu and dairy product, an acidulant and a secondary swelling agent an auxiliary expanding agent, and the like.

Lactic acid is an asymmetric chiral molecule with two enantiomers: D-form (or (R) -form) and L-form (or (S) form). Thus, the lactide, a dimeric cyclic ester of lactic acid, is present as three optical isomers with two stereocenters. For example, L-lactide (or (S, S) -lactide) formed from two molecules of L-lactic acid (L-lactic acid or S-lactic acid), two molecules of D- Lactide (or (R, S) - lactide) formed from one molecule of L-lactic acid and D-lactic acid is formed from D- Lt; / RTI >

The lactide forms a polylactide or polylactic acid (PLA) by ring-opening polymerization. Polylactide is a thermoplastic aliphatic polyester, a biodegradable polymer that is widely used recently. The polylactide is re-classified according to the asymmetric chirality of the lactide constituting the polylactide. The polylactide mainly used is poly-L-lactide (PLLA) composed of only L-lactide, poly-D-lactide (PDLA) composed of D- And poly (L-lactide-co-D, L-lactide) (PLDLLA) which is a copolymer of L-lactide and D, L- Three species. These polylactides have different crystallinity (or crystallinity), glass transition temperature, melting temperature, tensile modulus, solubility and thermal resistance to solvents resistance and the like, so that they can be selected or combined as needed. In particular, PLLA and PDLA exhibit undesirable characteristics such as exhibiting a significantly lower glass transition temperature when they contain other isomers, so it is very important to use lactide of high optical purity as a raw material for synthesis of high quality polymers Do. Also, in the case of PLDLLA, it is important to use lactide of high optical purity in the production of PLDLLA because the properties of PLDLLA generated by the ratio of PLA and poly-D, L-lactide constituting the PLDLLA are different.

On the other hand, the reactive distillation method, which is a general lactide production method, is a method in which not only L-lactide, D-lactide and meso-lactide are used as products but also lactic acid monomer residues which have not reacted as impurities, low molecular weight linear lactic acid polymers Dimer or trimer, etc.), water, and the like. It may further comprise other impurities derived from lactic acid, such as saccharides, amino acids and fatty acids.

In addition, lactide may be used as a food additive, wherein the lactide initially exhibits a low acidity and the latter shows high acidity as the food ages. When a large amount of meso-lactide, lactic acid, and low molecular weight linear lactic acid polycondensate are contained, the initial acidity may be increased after the addition. Therefore, it is preferable that the concentrations of meso-lactide, lactic acid and low molecular weight linear lactic acid polymer in lactide are as low as possible.

On the other hand, the melting points of L-lactide and D-lactide are all about 98 캜, while the melting point of meso-lactide is about 40 캜. The melting point of the lactic acid is 16 to 25 占 폚, and the low molecular weight linear lactic acid polypolymer exists in a liquid state at room temperature. As a result, when used as a powder or granule in which each meso-lactide, lactic acid and low molecular weight linear lactic acid polypolymer having a melting point close to or not at room temperature is present in high concentration, the lactide exhibits low fluidity and low And causes availability. Therefore, it is preferable that the concentrations of these substances in the lactide are as low as possible.

Preferably, the mixed solvent may contain 5 to 20% by weight of water. When the content of water in the mixed solvent is more than 20% by weight, hydrolysis of lactide produced is promoted, and the yield is greatly reduced, and selective purification is also impossible in terms of purity and acidity. On the other hand, if the content of water is less than 5%, the purity of lactide is low even after purification, and the removal efficiency of lactic acid and lactic acid oligomer is low, which leads to an increase in acidity.

Non-limiting examples of the alkyl propionate include methyl propionate, ethyl propionate, propyl propionate, iso-propyl propionate, iso- butyl propionate, tertiary-butyl propionate, and combinations thereof.

Preferably, the step of recrystallization with the solvent may be repeated two or more times. In the specific example of the present invention, the same solvent recrystallization was repeated three times to perform solvent recrystallization once on crude L-lactide extract containing 91.0% by weight of L-lactide, and the content of L-lactide was adjusted to 97.2 By weight, and the same procedure was further carried out two more times to improve to 99.8% by weight or more. Further, the crude D-lactide extract containing 92.8% by weight of D-lactide was subjected to solvent recrystallization once to improve the content of D-lactide to 97.8% by weight, and the same procedure was further repeated two times The purity was improved up to 99.8% or more. On the other hand, it was confirmed that the acidity can be lowered to 6 and 5 meq / kg level.

The recrystallization is preferably performed by adding a lactide mixed sample to the solvent, heating the mixture to 50 to 70 캜 to completely dissolve the solution, and then cooling the solution to 10 to 20 캜 to precipitate lactide crystals. However, the recrystallization is not limited thereto.

Further, the production method according to the present invention may further include a step of filtering and drying the lactide crystal.

As described above, the preparation method according to the present invention can provide L- or D-lactide having an optical purity of 99.0% or more and an acidity of 10 meq / kg or less.

The production method of the present invention can provide a high-purity lactide with high optical purity and low acidity, so that the high-purity lactide produced by the above production method is useful for the production of high molecular weight polylactide .

1 shows the yield and purity of purified L-lactide obtained by solvent recrystallization of crude L-lactide.
FIG. 2 is a view showing the acidity of the purified L-lactide obtained by solvent recrystallization of crude L-lactide.
Figure 3 shows the yield and purity of purified D-lactide obtained by solvent recrystallization of crude D-lactide.
4 is a diagram showing the acidity of the purified D-lactide obtained by solvent recrystallization of crude D-lactide.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are for further illustrating the present invention, and the scope of the present invention is not limited by these examples.

Example  1: L- Lactide  synthesis

1,000 g of a 90 wt% lactic acid aqueous solution was charged into a 2 L stainless steel reactor equipped with a thermometer, a stirrer, a condenser, a distillate remover and a temperature controller, and heating dehydration was started. Dehydrated and slowly heated and decompressed so that lactic acid was not discharged. At this time, 730 g of lactic acid oligomer was obtained by heating at 130 ° C reaction temperature, 600 torr reaction vacuum pressure for 2 hours, further 160 ° C reaction temperature and 30 torr reaction vacuum pressure for 2 hours. The lactic acid oligomer thus obtained was analyzed by GPC using a polystyrene standard sample. As a result, it was confirmed that the lactic acid oligomer had a weight average molecular weight of 1,500. After the reaction, 6 g of tin octonate was added, the reaction temperature was raised from 160 ° C. to 200 ° C., the reaction vacuum pressure was reduced to 10 torr, and the mixture was heated and decompressed for 3 hours to obtain crude L- 710 g of tide was recovered in the condenser. The components of the synthesized crude L-lactide were quantitatively analyzed by HPLC (high performance liquid chromatography) to obtain 91.0% by weight of L-lactide, 0.2% by weight of D-lactide, 5.1% by weight of meso-lactide and 3.7 By weight lactic acid and lactic acid oligomer.

Example  2: L- Lactide  refine

To 700 g of crude L-lactide synthesized according to Example 1, 450 g of methyl propionate and 50 g of water were added and the lactide was completely dissolved by heating at 60 ° C. After confirming that the lactide had completely dissolved, it was cooled to 15 DEG C to precipitate lactide crystals. The precipitated crystals were filtered and put into a vacuum drier and dried under reduced pressure at 55 ° C and 4 torr at 55 ° C to obtain 553 g (yield: 79%) of purified lactide. HPLC analysis of the components of the purified lactide showed 97.2% by weight of L-lactide, 0.1% by weight of D-lactide, 1.5% by weight of meso-lactide and 1.2% by weight of lactic acid and lactic acid oligomer Respectively. Also, the free acidity of the purified lactide was 120 meq / kg. In order to obtain polylactide having a molecular weight of 100 kg / mol or more, which is a high-grade polymer, a high-purity lactide of 10 meq / kg or less is required. Therefore, the solvent recrystallization test was further performed twice to achieve the desired purity and acidity. The yield, purity and acidity of L-lactide measured while repeatedly performing solvent recrystallization are shown in FIGS. 1 and 2. FIG.

As shown in Fig. 1, the yield of final L-lactide was 61% after repeating recrystallization three times. The purity of L-lactide increased to over 99.8%, and meso-lactide was completely removed.

Further, as shown in Fig. 2, the acidity of L-lactide was reduced to 6 meq / kg after repeating recrystallization three times.

Example  3: D- Lactide  synthesis

The lactic acid aqueous solution evaporator, the first oligomerization reactor, the second oligomerization reactor and the depolymerization reactor were each prepared in the form of a multi-tube membrane as shown in Table 1, and a pump, a pressure regulator and a level regulator were attached to the reactor To produce a continuous lactide synthesizer. L-lactic acid aqueous solution (concentration 80%) was fed to the lactic acid aqueous solution evaporator at a flow rate of 38 ml / min. While 0.5 wt% of octyl tin catalyst was added to the first oligomerization reactor in terms of lactic acid, The crude D-lactide was continuously synthesized under the conditions. Lactic acid aqueous solution evaporator, and three reactors, respectively. As a result, lactide was continuously produced at a conversion rate of lactic acid of 99% and a yield of D-lactide of 92%. Quantitative analysis of the components of the crude D-lactide synthesized comprised 92.8% by weight of D-lactide, 0.2% by weight of L-lactide, 4.1% by weight of meso-lactide and 2.9% by weight of lactic acid and lactic acid oligomer Respectively.

Specification of multi-tube membrane device used for lactide manufacture Lactic acid aqueous solution evaporator Primary
Small polymerization reactor Secondary
Small polymerization reactor Depolymerization reactor Vertical tube diameter (cm) 2 2 2 2 Straight tube length (cm) 300 300 300 150 Number of vertical tubes 4 18 18 18 The distance (cm) between the downflow membrane and the liquid distributor plate 0.2 0.3 0.3 0.5

Lactide production Evaporation Concentration and reaction conditions Lactic acid aqueous solution evaporator Primary
Small polymerization reactor Secondary
Small polymerization reactor Depolymerization reactor Temperature (℃) 120 160 200 240 Pressure (torr) 50 600 600 10

Example  4: D- Lactide  refine

To 700 g of the crude D-lactide synthesized according to Example 3, 450 g of methyl propionate and 50 g of water were added and the lactide was completely dissolved by heating at 60 캜. After confirming that the lactide had completely dissolved, it was cooled to 15 DEG C to precipitate lactide crystals. The precipitated lactide crystals were filtered and put into a vacuum drier and dried under reduced pressure at 55 ° C and 4 torr for 3 hours to obtain 553 g of purified lactide (yield: 81%). The purified lactide was analyzed by HPLC to be composed of 97.8% by weight of D-lactide, 0.1% by weight of L-lactide, 1.1% by weight of meso-lactide, 1.0% by weight of lactic acid and lactic acid oligomer Respectively. The acidity of the purified lactide was also 105 meq / kg. The above solvent recrystallization test was further performed twice to purify the high purity lactide having an acidity of 10 meq / kg or less. The yield, purity and acidity of L-lactide measured while repeatedly performing solvent recrystallization are shown in FIGS. 3 and 4. FIG.

 As shown in Fig. 3, the final D-lactide yield after the recrystallization was 3 times repeated, was 64%. The purity of D-lactide increased to over 99.8%, and the meso-lactide was completely removed.

Further, as shown in FIG. 4, after repeating the recrystallization three times, the acidity of D-lactide was reduced to 5 meq / kg.

Example  5: ethyl Propionate  The L- Lactide  refine

The crude L-lactide was purified in the same manner as in Example 2 except that 450 g of ethyl propionate and 50 g of water were used as a solvent instead of a mixed solvent of methyl propionate and water. The result of analyzing the components of the lactide purified by repeating the solvent recrystallization three times is shown in Table 3 along with the results of the comparative examples shown below. The results of Example 2 are also shown.

As shown in Table 3, it was confirmed that similar yield, purity and acidity can be achieved when purified by recrystallization using a mixed solvent of methyl propionate or ethyl propionate and water.

3 times tablets lactide yield(%) water(%) Acidity (meq / kg) Example 2
(450 g of methyl propionate + 50 g of water) 61 99.8 6 Example 5
(450 g of ethyl propionate + 50 g of water) 59 99.8 7 Comparative Example 1
(Methyl propionate 500 g) 65 98.3 95 Comparative Example 2
(500 g of water) 42 98.9 45 Comparative Example 3
(350 g of methyl propionate + 150 g of water) 53 99.1 35 Comparative Example 4
(500 g of ethanol) 55 99.3 30 Comparative Example 5
(500 g of methyl acetate) 46 99.1 35

Comparative Example  One: methyl Propionate  The L- Lactide  refine

Crude L-lactide was purified in the same manner as in Example 3 except that 500 g of methyl propionate was used as a solvent. The results of analysis of the constituents of the three-times purified lactide are shown in Table 3 above.

As shown in Table 3, when the solvent containing no water was used as the recrystallization solvent, the purified lactide yield was increased but the lactide purity was lowered, and the removal of lactic acid and lactic acid oligomer was not efficient and the acidity .

Comparative Example  2: Reaction of L- Lactide  refine

Crude L-lactide was purified in the same manner as in Example 3, except that 500 g of water was used as the solvent. The results of analysis of the constituents of the three-times purified lactide are shown in Table 3 above.

As shown in Table 3, when pure water not containing methyl propionate, which is an organic solvent, was used as the recrystallization solvent, hydrolysis of lactide was promoted, and the yield of lactide was greatly reduced, and in terms of purity of lactide and acidity It was confirmed that no selective purification was performed.

Comparative Example  3: methyl Propionate and  Purification of L-lactide by recrystallization using water-mixed solvent

Crude L-lactide was purified in the same manner as in Example 3 except that 350 g of methyl propionate and 150 g of water were used as a solvent. The results of analysis of the constituents of the three-times purified lactide are shown in Table 3 above.

As shown in Table 3, when the content of water exceeds 20 wt% (150 g / (150 g + 350 g) = 30 wt%) in the ratio of methyl propionate to water, the purified lactide yield and purity And the acidity was increased.

Comparative Example  4: Recrystallization by ethanol using L- Lactide  refine

Crude L-lactide was purified in the same manner as in Example 3 except that 500 g of ethanol was used as a solvent. The results of analysis of the constituents of the three-times purified lactide are shown in Table 3 above.

As shown in Table 3, when methanol was used, the yield and purity of the purified lactide were low and the acidity was somewhat higher than that of methyl propionate or ethyl propionate and water mixed solvent.

Comparative Example  5: methyl  The L- Lactide  refine

Crude L-lactide was purified in the same manner as in Example 3 except that 500 g of methyl acetate was used as a solvent. The results of analysis of the constituents of the three-times purified lactide are shown in Table 3 above.

As shown in Table 3, when methyl acetate was used, the yield and purity of the purified lactide was low and the acidity was somewhat higher than that in the case of using methyl propionate or ethyl propionate and water mixture solvent.

Claims (7)

Comprising recrystallizing a lactide sample mixed with an optical isomer in a mixed solvent containing 80 to 95% by weight of alkyl propionate represented by the following formula (1) and 5 to 20% by weight of water, A method for purifying L- or D-
[Chemical Formula 1]

In the above formula R ₁ is C ₁ to C ₄ being lower alkyl.
delete The method according to claim 1,
Wherein the alkyl propionate is selected from the group consisting of methyl propionate, ethyl propionate, propyl propionate, isopropyl propionate, isobutyl propionate, tacyl butyl propionate, and combinations thereof Lt; RTI ID = 0.0 > L-or < / RTI > D-lactide.
The method according to claim 1,
And the step of recrystallization with the solvent is repeated two or more times.
The method according to claim 1,
The recrystallization is achieved by adding a lactide mixed sample to the solvent, heating it to 50 to 70 캜 to completely dissolve it, and then cooling the solution to 10 to 20 캜 to precipitate lactide crystals. Method for purifying L- or D-lactide .
6. The method of claim 5,
And then filtering and drying the lactide crystal. ≪ RTI ID = 0.0 > 15. < / RTI >
The method according to claim 1,
To provide L- or D-lactide with an optical purity of at least 99.0% and an acidity of 10 meq / kg or less.

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