jp06-279435(1994)-PURIFICATIONOFLACTIDE制备丙交酯的方法.doc

PATENT ABSTRACTS OF JAPAN(11)Publication number : 06-279435(43)Date of publication of application : 04.10.1994(51)Int.Cl. C07D319/12 C07B 63/00 C07C 31/02 (21)Application number : 05-073466(71)Applicant : DAINIPPON INK & CHEM INC(22)Date of filing : 31.03.1993(72)Inventor : KUBOTA KAZUOMI(54) PURIFICATION OF LACTIDE(57)Abstract:PURPOSE: To obtain in high yield and purity a lactide useful as a raw material for biodegradable polymers. CONSTITUTION: The characteristic of this method for purifying a lactide is recrystallizing a crude lactide using (A) a poor solvent and (B) at least one kind of good solvent selected from aliphatic t-alcohols, ketones and esters.CLAIMS Claim(s) Claim 1A refining method of lactide making rough lactide recrystallize using one or more sorts of good solvents (B) chosen from a group which consists of a poor solvent (A), aliphatic series tertiary alcohol, ketone, and ester species. Claim 2The refining method according to claim 1 whose solubility to a good solvent (B) of rough lactide solubility in 23 * to a poor solvent (A) of rough lactide is 1 or less % of the weight, and is 5 % of the weight or more. Claim 3The refining method according to claim 2 whose poor solvent (A) is aliphatic hydrocarbon with 5-12 carbon atoms and whose good solvent (B) is aliphatic series tertiary alcohol. Claim 4A refining method of lactide characterized by making it recrystallize further using an aromatic hydrocarbons solvent (C) and aliphatic hydrocarbons with 5-12 carbon atoms (D) after making rough lactide recrystallize using aliphatic series tertiary alcohol. Claim 5The refining method tertiary alcohol / aliphatic series according to claim 4 using aliphatic hydrocarbon with 5-12 carbon atoms. DETAILED DESCRIPTION Detailed Description of the Invention 0001 Industrial ApplicationLactide useful as a raw material of biodegradable polymer is made to * from rough lactide in this invention using a poor solvent and a specific good solvent.Therefore, it is related with the refining method of the lactide obtained with a high grade and high yield.0002 Description of the Prior ArtBeing obtained by generally lactide carrying out the pyrolysis of the lactic acid oligomer is known. These lactide attracts attention as a raw material of Toshio Kon resolvability polymer. Since the rough lactide obtained by the pyrolysis of the lactic acid oligomer contains impurities, such as lactic acid, as it is, it is unsuitable in a polymer polymerization raw material, and is refined by methods, such as recrystallization. For example, the recrystallizing method from diethylether/petroleum ether of lactide is stated to * Angew.Chem., an Int.Ed.Engl. magazine, 18 volumes, and 310 pages (1979). * To British JP,1122229,B, the recrystallization by 1, such as toluene, 2, and 3 substituted benzene is indicated. In * JP,51-6673,B, the refining method which adds this alcohol to the slurry which is excellent in the storage stability acquired by adding melting rough lactide to t-amyl alcohol (30 * - 50 *) or t-butyl alcohol, and is recrystallized is indicated. 0003 Problem(s) to be Solved by the InventionHowever, each method indicated in the publication etc. which were mentioned above has a recovery rate as low as 70% order, moreover, by the method of *, since diethylether is used for it, its flash point is as low as -45 *, and the industrial method cannot say it easily. 0004 Means for Solving the ProblemWholeheartedly, as a result of examination, by making rough lactide recrystallize using a poor solvent and a specific good solvent, this invention person finds out that refining of lactide can be performed in a high recovery rate, and came to complete this invention. This invention rough lactide Namely, a poor solvent (A) and aliphatic series tertiary alcohol, A refining method row and also a recrystallization thing of lactide recrystallizing using one or more sorts of good solvents (B) chosen from a group which consists of ketone and ester species, A refining method of lactide recrystallizing using an aromatic hydrocarbons solvent (C) and aliphatic hydrocarbons with 5-12 carbon atoms (D) is provided. 0005Raw materials, such as lactic acid, are contained as rough lactide used for a method of this invention, including lactide as the main ingredients. Each can also use rough lactide immediately after manufacture, or rough lactide in which it is refined selectively and a little raw materials remain. This rough lactide is manufactured by various kinds of reaction processes, for example in accordance with a publicly known method. A method of cyclizing ester obtained from alpha-halo carboxylic acid halide and alpha-hydroxycarboxylic acid under a basic condition like a method of carrying out the pyrolysis of the lactic acid oligomer obtained by drying of lactic acid under existence of a catalyst as a typical manufacturing method or * is mentioned. 0006Although each thing to rough lactide which have low solubility can use it as a poor solvent (A) in this invention, 1 or less % of the weight of a solvent has preferred solubility to lactide at 23 *. A not less than 50 * thing has the preferred boiling point at a point that can take a large temperature gradient at the time of heating and cooling, and operation at the time of recrystallization becomes easy especially. If an example is given, there are hydrocarbon system solvents, such as cyclohexane, a methylcyclohexane, hexane, heptane, octane, ligroin, and 2,2,4-trimethylpentane. Although these hydrocarbon system solvent can be used without special restriction, an alkane especially ligroin, heptane, or 2,2,4-trimethylpentane of the carbon numbers 5-12 can use it preferably especially. 0007Although each thing to rough lactide which have high solubility can use it as a good solvent (B) in this invention, 5% of the weight or more of a solvent has preferred solubility of lactide at 23 *. A not less than 50 * thing has the preferred boiling point at a point that can take a large temperature gradient at the time of heating and cooling, and operation at the time of recrystallization becomes easy especially. If an example is given, ester species like the aliphatic series tertiary alcohol like t-butyl alcohol and t-amyl alcohol, the ketone like methyl ethyl ketone, ethyl acetate, methyl acetate, and methyl propionate can be used. 0008Aliphatic series tertiary alcohol has an especially high recovery rate, and it is industrially the most desirable at a point that moreover a recrystallization thing of a high grade is obtained by one recrystallization. What is suitable especially as tertiary alcohol, t-amyl alcohol or t-butyl alcohol is mentioned. 0009As the recrystallization method, the heating and dissolving of the rough lactide are carried out in a recrystallization solvent until a solid part of this rough lactide disappears, and subsequently it cools, and a crystal is made to generate. By one recrystallization, when refining is insufficient, recrystallization operation can be repeated and can also be performed. Under the present circumstances, even if it mixes with a good solvent (B) from the start and uses a poor solvent (A) as a recrystallization solvent, it carries out the heating and dissolving of the rough lactide to a good solvent, may add and use it for that solution, and should just be in the state where it was mixed before cooling. Although the cooking temperature of beyond temperature in which a solid part carries out dissolution disappearance should just be the temperature below the boiling point, 50 * - 95 * are especially preferred. As long as cooling temperature is more than a below room temperature coagulating point, any may be sufficient as it, but since a crystal fully deposits especially if it is within the limits of room temperature -0 *, it is preferred. 0010Although there is no special limitation in a weight ratio of lactide and a recrystallization solvent, it is preferred that it is within the limits of 1:1 to 1:5 especially. In a recrystallization solvent, although there is no special restriction in a weight ratio of a poor solvent and a good solvent, a thing of 1:1 to 1:5 is especially preferred. Lactide recrystallized using aliphatic series tertiary alcohol, When aliphatic series tertiary alcohol is used independently, or when it uses together with a poor solvent and uses, lactic acid and its oligomer are hardly contained, but tertiary alcohol is contained although it is the range of about 1000 ppm or less. 0011These tertiary alcohol is incorporated during a crystal and it cannot remove in washing and reduced-pressure-drying operation of a crystal. However, it becomes possible by making it recrystallize further using an aromatic hydrocarbons solvent (C) and aliphatic hydrocarbons with 5-12 carbon atoms (D) to remove an alcohol content incorporated during a crystal by recrystallization of the first rank. 0012As an aromatic hydrocarbons solvent (C), although anything can be used, benzens, for example, benzene, toluene, xylene, ethylbenzene, mesitylene, etc. are used especially preferably. As aliphatic hydrocarbons with 5-12 carbon atoms (D), 1 or less % of the weight of a solvent is mentioned, for example for a part for L-lactide in a saturated solution of lactide at 23 *. A not less than 50 * thing has the preferred boiling point at a point that can take a large temperature gradient at the time of heating and cooling, and operation at the time of recrystallization becomes easy especially. 0013As the example, there are petroleum ether, cyclohexane, a methylcyclohexane, hexane, heptane, octane, ligroin, 2,2,4-trimethylpentane, etc. Although a hydrocarbon system solvent which fulfills these conditions can be used without special restriction, especially ligroin, heptane, or 2,2,4-trimethylpentane can be used especially preferably. 0014Although there is no special limitation in a weight ratio of lactide and a recrystallization solvent, it is preferred that it is within the limits of 1:1 to 1:5 especially. In a recrystallization solvent, although there is no special restriction in a weight ratio of aromatic system hydrocarbon (C) and aliphatic series system hydrocarbon (D), a thing of 4:1 to 1:4 is especially preferred. Furthermore, into raw material lactide, when there are few acidic impurities, such as lactic acid, repeated use of this recrystallization solvent can be carried out. Since an operating condition can be simplified, and also the number of times of solvent recovery could be reduced and lactide is saturated 2nd further henceforth, product loss is lost as a matter of fact. 0015An example and a comparative example are shown below and this invention is explained to it still more concretely. ExampleAlthough the solubility to L-lactide of the solvent used for below by the example and the comparative example is shown, After measurement of this solubility stirs the slurry of the rough lactide actually used for recrystallization at 23 * for about 1 hour, The component analysis of the saturated solution of a supernatant fluid is conducted by which twist tartaric acid in the ODS (octadecylsilane) column used for the internal standard conducting reversed-phase-high-pressure-liquid-chromatography analysis (it abbreviates to HPLC analysis below). 0016(HPLC analysis result of rough lactide) L-lactide: 89.6% meso lactide: 4.0% lactic acid monomer : 2.2% lactic acid dimer : 0.2% lactic acid trimer : 0.2% 0017 0018(Example 1) Dissolved 20.07 g of rough lactide in the partially aromatic solvent 50.88g of t-butyl alcohol/heptane (weight ratio 1:2) at 77 *, separated the crystal after cooling to 4 *, it was made to dry under decompression, and the recrystallization thing of a 18.18-g colorless columnar crystal was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0019 0020(Example 2) 19.84 g of rough lactide was dissolved in the partially aromatic solvent 49.84g of t-amyl alcohol / 2,2,4-trimethylpentane (weight ratio 1:2) at 83 *, and to 4 *, the crystal was separated, it dried under decompression after cooling, and the recrystallization thing of a 18.11-g colorless needle shape crystal was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0021 0022(Example 3) 20.13 g of rough lactide was dissolved in the partially aromatic solvent 50.13g of t-butyl alcohol/2,2,4-trimethylpentane (weight ratio 1:2) at 77 *, and to 2 *, the crystal was separated, it dried under decompression after cooling, and the recrystallization thing of a 18.21-g colorless needle shape crystal was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0023 T-butyl alcohol in a recrystallization thing was 310 ppm as a result of measurement by capillary gas chromatography. The acid value of the recrystallization thing was 1.96 mg/g. 0024(Example 4) 12.26 g of rough lactide is dissolved in the partially aromatic solvent 30.66g of t-butyl alcohol/2,2,4-trimethylpentane (weight ratio 1:2) at 78 *, Several mg refining L-lactide was supplied as a seed crystal in the place cooled to 69 *, and when it dissociated and the crystal was dried under decompression after cooling to 21 *, the recrystallization thing of a 10.55-g colorless columnar crystal was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0025 0026(Example 5) After adding 30.1 g of rough lactide to the partially aromatic solvent 69.2g of t-butyl alcohol/2,2,4-trimethylpentane (weight ratio 1:2) and carrying out temperature up to 78 *, it cooled to 22 *. When it dissociated and the crystal was dried under decompression, the recrystallization thing of a 28.0-g white solid was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0027 0028T-butyl alcohol in a recrystallization thing was 720 ppm as a result of measurement by capillary gas chromatography. After adding this recrystallization thing 12.5g to the partially aromatic solvent 19.9g of toluene/2,2,4-trimethylpentane (weight ratio 1:0.593) furthermore and carrying out temperature up to 50 *, it cooled to 24 *. When it dissociated and the crystal was dried under decompression, the recrystallization thing of a 10.6-g white solid was obtained. T-butyl alcohol was not detected in the recrystallization thing as a result of measurement by capillary gas chromatography. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0029 0030(Example 6) After adding 40.35 g of rough lactide to the partially aromatic solvent 100.89g of t-butyl alcohol/2,2,4-trimethylpentane (weight ratio 1:2) and carrying out temperature up to 76 *, it cooled to 24 *. When it dissociated and the crystal was dried under decompression, the recrystallization thing of a 33.89-g white solid was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0031 Presentation: Rough lactide Recrystallization thing L-lactide: 4.6% 96.5% meso lactide: 85.0% 0.5% lactic acid monomer : 5.9% 0.1% Lactic acid dimer : 1.4% 0.2% Lactic acid trimer : 0.6% 0% recovery rate: 84.0%0032T-butyl alcohol in a recrystallization thing was 310 ppm as a result of measurement by capillary gas chromatography. After adding this recrystallization thing 16.05g to the partially aromatic solvent 32.02g of toluene/2,2,4-trimethylpentane (weight ratio 1:1) furthermore and carrying out temperature up to 95 *, it cooled to 24 *. When it dissociated and the crystal was dried under decompression, the recrystallization thing of a 15.35-g white solid was obtained. T-butyl alcohol was not detected in the recrystallization thing as a result of measurement by capillary gas chromatography. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0033 0034(Example 7) 12.61 g of rough lactide was dissolved in the partially aromatic solvent of 31.60 g of t-butyl alcohol/ligroin (weight ratio 1:2) at 55 *, and when it dissociated and the crystal was dried under decompression after cooling to 18 *, a 10.83-g recrystallization thing was obtained. The presentation and recovery rate of a recrystallization thing in the reversed-phase-high-pressure-liquid-chromatography analysis by the ODS (octadecylsilane) column which used tartaric acid for the internal standard are shown below. 0035 T-butyl alcohol in a recrystallizat