PURIFICATION OF LACTIDES BY MELTCRYSTALLIZATION熔融结晶制备丙交酯Word文档格式.docx

1、13.09.1994（51）Int.Cl. C07D319/12 （21）Application number :06-020338（71）Applicant :E I DU PONT DE NEMOURS & CO（22）Date of filing :17.02.1994（72）Inventor :OBRIEN WILLIAM GSLOAN GILBERT J（30）PriorityPriority number :93 28773 Priority date :17.02.1993Priority country :US （54） PURIFICATION OF LACTIDES BY

2、MELT-CRYSTALLIZATION（57）Abstract:PURPOSE: To provide a method for purifying a lactide by melt-crystallization. CONSTITUTION: The method for purifying a lactide comprises （1） cooling a molten mixture of a lactide and impurities to the solidifying point of the lactide or to a temp. slightly below than

3、 the solidifying point of the lactide, then （2） partially crystallizing the molten mixture to form a solid phase having impurity contents lower than those of the molten mixture and to form a liquid phase having impurity contents higher than those of the molten mixture and （3） separating the solid ph

4、ase from the liquid phase.CLAIMS Claim（s） Claim 1（1） A molten mixture of lactide and an impurity is cooled downward more slightly than a coagulating point of lactide, or a coagulating point of lactide, （2） A refining method of lactide which consists of making solid phase of an impurity content lower

5、 than a molten mixture, and the liquid phase of an impurity content higher than a molten mixture form, and making solid phase which separated （3） solid phase by dissociating from the liquid phase form by crystallizing some molten mixtures. Claim 2A method according to claim 1 of consisting of L-lact

6、ide with more molten mixtures than 80%, or D-lactide. Claim 3A way according to claim 1 a molten mixture consists of 20 to 80% of L-lactide, and 20 to 80% of D-lactide. Claim 4A way according to claim 1, 2, or 3 a molten mixture is on 1-5 * from a coagulating point of lactide. Claim 5A method accord

7、ing to claim 1, 2, 3, or 4 of consisting of a stage which makes an additional molten mixture form and repeats （5） stage （1） - （3） about an additional molten mixture by fusing solid phase which furthermore carried out （4） separation. Claim 6A method according to claim 1, 2, 3, or 4 of consisting of m

8、aking the second liquid phase form, and this second liquid phase consisting of some remaining impurities at least, and removing the （5） second liquid phase by warming gradually solid phase which furthermore carried out （4） separation after a stage （3） to a temperature lower than that melting point.

9、Claim 7A method according to claim 1, 2, 3, 4, or 6 of consisting of making a molten mixture recycle the （6） second liquid phase after a stage （5） furthermore. Claim 8（1） A refining method of lactide which consists of carrying away an impurity in a zone-of-melting region by making a zone-of-melting

10、region in said solids-mixing thing, and moving （2） zone-of-melting regions to a solid zone by heating a narrow zone of a solids-mixing thing of lactide and an impurity. Claim 9A method according to claim 8 of consisting of L-lactide with more molten mixtures than 80%, or D-lactide. Claim 10A way acc

11、ording to claim 8 a molten mixture consists of 20 to 80% of L-lactide, and 20 to 80% of D-lactideDETAILED DESCRIPTION Detailed Description of the Invention 0001 Field of the InventionThis invention about melting crystallization refining of lactide including the optical activity gestalt, Lactide is t

12、horoughly separated from other impurities like the impurity containing a hydroxyl impurity, for example, water, the monomer usually generated between that manufacture together with lactide, and oligomeric hydroxycarboxylic acid, a solvent, and a catalyst by this method. Furthermore, one this inventi

13、on relates to the separation and refining of lactide which exist with many isomer gestalten. It is obtained simply and promptly, without using other publicly known physical means in the state of the purity adjusted by such refining and/or lactide was high by fractionation crystallization from an alt

14、ernative solvent and a solvent, distillation, or this technical field. 0002 Explanation of related art Lactide （1,4-dioxane 3,5-dimethyl- 2,5-dione）, Since the by-product which is decomposed by hydrolysis and is physiologically permitted from environment may be produced biologically, it is an interm

15、ediate of the polymers polylactic acid in which the useful thing became clear for a biomedicine and other uses. It is because it is required for lactide not to contain a hydroxyl （hydroxylcarboxyl is included） impurity in realizing the amount of polymers required for such a use substantially, becaus

16、e it bars that such an impurity reaches a desired molecular weight. As for the acid content of lactide, it is preferred that it is lower, for example than 10 milliequivalent （meq/kg） per kg and much more preferably lower than 5 meq/kg. 0003Other important factors are the stereoisomerism gestalten of

17、 lactide. While lactic acid exists with both D and L stereoisomerism gestalt, lactide has meso form voice further. Similarly the racemic mixture of important D and L lactide is pointed out commercially, and DL lactide is called. Such isomer lactide has different stability, and since polymer with sub

18、stantially different character is produced, for the use of a certain kind of polymer, it is necessary to adjust the ratio of each isomer gestalt in a final product. These ratios can be adjusted using the method of making only a single isomer, or by refining the mixture of an isomer. Since an isomer

19、has an approximate physical property, the refining method publicly known at this technical field is extremely troublesomely difficult. 0004Lactide polymerizes corresponding lactic acid in the polylactic acid of low molecular weight （oligomer） comparatively, Subsequently, oligomer is heated under exi

20、stence of the catalyst which this technical field may generally be sufficient as, and was known, it is depolymerized in lactide, and it is made with the most sufficient convenience by subsequently collecting these as an ingredient of the flow of steamy output. Gruter etc., U.S. Pat. No. 1,095,205 （1

21、914）; Lowe, U.S. Pat. No. 2,668,162 （1954）;Bhatia, U.S. Pat. No. 4,835,293 （1989）;DeVries, U.S. Pat. No. 4,797,468 （1989）;. And please refer to Muller and U.S. Pat. No. 5,053,522 （1991）. These patents are included in this specification by reference. 0005These this steamy product stream not only incl

22、uding lactide but including a volatile hydroxyl impurity always Water, Since it is much more volatile monomer lactic acid and a polymerization chain terminator in which these all bar the arrival to a desired molecular weight including oligomer of lactic acid of a high boiling point often more, it is

23、 not more desirable than lactide. They may include a small amount of the solvents or catalysts which remain from a former processing stage. Typically, a steamy product stream contains more lactide than 90% and impurities fewer than 10% containing arbitrary isomers. 0006The typical technical procedur

24、e of separation of the lactide from a steamy product stream and recovery includes crystallization from scrubbing or a solvent which generally uses a solvent. However, a hydroxyl impurity especially water, and lactic acid have the capability to start the ring opening reaction of lactide, under such c

25、onditions, and, as a result, reduction of the amount of lactide acquisition and the increase in the acidity of output are produced. Such a reaction much more such is likely to occur that the temperature of the recovery process to be used is high. In order to collect cyclic ester, that it is moreover

26、 dependent on a solvent a steamy product stream by carrying out scrubbing That, or the thing for which recrystallization refines it - be - a solvent is stored, it is used, it is refined, the equipment for preventing it being emitted and polluting environment is needed, and these all are disadvantage

27、ous things from becoming the load to the investment in a process, and operation expense remarkably. 0007Refining and recovery of lactide by the distillation and condensation which are options fall into the fault that the loss of a remarkable output often arises, easily, and this depends them on a re

28、action with the lactide of the water at distillation temperature, and other hydroxy acid impurities clearly. In an elevated temperature, a metal ion may arise as a result of the corrosion by the acidic environment of a distillation apparatus, and, subsequently this may carry out the catalysis of a p

29、remature lactide polymerization into the device itself. Separation of the lactide which exists with more isomer gestalten than one kind is still much more complicated, and often needs the combination of much solvent recrystallization and fractionation distillation. 0008The melting crystallizing meth

30、od was often used for refining of an organic compound of a certain kind. However, it cannot predict feasibility of this method easily. It depends for the structure of the crystal by whether the output, eutectic mixture, or solid solution which it should refine that it is dependent on the coagulating

31、 point of a desired output, its impurity, and a mixture with those output, i.e., an impurity, is formed formed, therefore an impurity also on the tendency which carries out occlusion. Moreover, it depends for the size and productivity of a crystallizing device on the speed which can form a suitable

32、crystal into a crystal structure without the occlusion of an impurity happening. The latest total theory of this art Wynn, separation of the organic substance by melting crystallization （Separate Organics by Melt Crystallization）, it is stated to Chemical Engineering Progress （March, 1992） and 52-60 pages - as -