JPH10130256A - Production of lactide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for continuously producing lactide, having a high lactide content and capable of lactide product having a high optical purity. SOLUTION: A lactic acid oligomer or a raw material is continuously introduced into a tubular reactor in a first process and heated to 160-300 deg.C for <=2hr retention time or increase polymerization degree of oligomer (preferably so as to become 2,000 to 30,000 molecular weight). Then, the lactic acid oligomer is continuously introduced into a molecular distillation apparatus in a second process and heated to 160-300 deg.C and depolymerized under 1-50mmHg pressure for <=10min retention time to capture the vaporized lactide. When lactic acid oligomer of the raw material is L-lactic acid oligomer or D-lactic acid oligomer, L- or D-lactide having high optical purity is obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for continuously producing lactide, which is a cyclic dimer of lactic acid, by depolymerizing a lactic acid oligomer. The present invention relates to a method for continuously producing lactide capable of obtaining a pure lactide product.

[0002] Lactide is particularly useful as a raw material for producing polylactic acid, a biodegradable polymer.

[0003]

2. Description of the Related Art Conventionally, lactide has been produced by dehydrating and condensing lactic acid to obtain a relatively low molecular weight lactic acid oligomer as an intermediate, and then depolymerizing the lactic acid oligomer by heating under reduced pressure in the presence of a catalyst. In this way, lactide is produced, and the lactide is taken out of the reaction system as a vapor.

[0004] There are many known examples of this lactide production method. For example, DE 267 826 describes a method for producing lactide in which lactic acid is heated to 200 ° C. in a vacuum and distilled. Also, German Patent No. 12
No. 34703 describes a method for producing L-lactide from an aqueous L-lactic acid solution in the presence of a titanium tetraalkoxide catalyst. However, these methods are all based on a batch operation and are not suitable for lactide production on an industrial scale. That is, the batch operation has problems such as difficulty in obtaining a stable product and difficulty in mass production, and is not suitable for production on an industrial scale.

On the other hand, Japanese Patent Application Laid-Open No. 63-101378 describes a method for producing lactide on an industrial scale.
However, the method described in the same publication is based on a semi-batch operation, and the purity of the obtained lactide is generally low and requires a purification operation.

[0006] Japanese Patent Publication No. 7-50991 discloses a method for continuously producing lactide from low-molecular-weight lactic acid oligomers using thin-film distillation. However, according to the method described in the same publication, the lactide content in the obtained distillate is as low as about 56 to 84%,
Further, there is a problem that the target L-lactide content in all lactide is about 90 to 92%, and the optical purity is slightly low.

The low lactide content in the distillate taken out of the reaction system is because the distillate contains lactic acid monomers and linear dimers as impurities. The reason that the lactic acid monomer or linear dimer is contained is that the molecular weight of the lactic acid oligomer subjected to thin-film distillation is low (average molecular weight 300 (polymerization degree: about 5) to 1700 (polymerization degree:
About 30)), when the oligomer is depolymerized, a monomer or linear dimer of lactic acid is likely to be generated, and these are taken out of the reaction system faster than cyclization to lactide. it is conceivable that.

Further, since high temperature is required for depolymerization, the optical purity of lactide obtained tends to decrease as the reaction time becomes longer. That is, for example, when an oligomer having L-lactic acid as a structural unit is depolymerized, racemization occurs by heating during the depolymerization, and L-lactide other than the target L-lactide is used.
Meso-lactide and D which are cyclic dimers of lactic acid and D-lactic acid
-D-lactide, which is a cyclic dimer of lactic acid, is generated, and the optical purity is reduced. When an oligomer having D-lactic acid as a constitutional unit is depolymerized, a desired D-lactic acid is used.
In addition to lactide, meso-lactide and L-lactide are produced.

[0009]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to solve the above-mentioned problems of the prior art and to obtain a lactide continuous product having a high lactide content and a high optical purity product. It is to provide a manufacturing method.

[0010]

Means for Solving the Problems As a result of diligent studies, the present inventors have found that instead of depolymerizing low molecular weight lactic acid oligomers as they are, the degree of polymerization of lactic acid oligomers is increased in a tubular reactor, followed by molecular distillation. It has been found that the above object can be achieved by depolymerization in an apparatus, and the present invention has been completed.

That is, the method for producing lactide of the present invention is a method for producing lactide by depolymerizing a lactic acid oligomer. In the first step, a raw material lactic acid oligomer is continuously introduced into a tubular reactor. Heating to increase the degree of polymerization of the oligomer, and in the second step, the lactic acid oligomer having the increased degree of polymerization is continuously introduced into a molecular distillation apparatus,
The method is characterized in that lactide is vaporized and collected by heating to a depolymerization temperature and reducing the pressure to a pressure lower than the vapor pressure of lactide at the depolymerization temperature.

Hereinafter, the present invention will be described in detail. In the present invention, in the first step, a tubular reactor is used to increase the degree of polymerization of the raw material lactic acid oligomer. The tubular reactor is a reactor in which the raw material lactic acid oligomer is continuously supplied from one end of the tube and the product lactic acid oligomer is discharged from the other end, and the shape of the tube is a straight tube, a U-shape. Any of a curved tube, a coil, and the like may be used.

The tubular reactor may be constituted by a single tube, but may be constituted by a plurality of tubes arranged in parallel.

In the present invention, a double-tube heat exchanger, a multi-tube heat exchanger, or a single-tube heat exchanger can be used as the tube reactor.

The double-pipe heat exchanger comprises an inner pipe and an outer pipe, and allows a reactant to flow through the inner pipe and a heat transfer medium to flow through the outer pipe. The reactants in the inner tube and the heat transfer medium in the outer tube may be co-current, but are generally circulated in countercurrent. Also, to increase the heat transfer area outside the inner tube,
It is also preferable to use a finned tube having fins formed on the outer peripheral surface of the inner tube as the inner tube. The fin includes a vertical fin and a spiral fin.

The multi-tube heat exchanger is of a so-called shell-and-tube type in which a tube bundle composed of a plurality of tubes arranged in parallel is usually housed in a cylindrical body, and a reactant is passed through the tubes. The heat transfer medium is passed through the gap between the body and the tube bundle.
The multi-tube heat exchanger includes a fixed tube plate type, a U-tube type, a floating head type and the like, and any of them can be used. The heat transfer area can be changed depending on the number, diameter, length, and the like of the tubes. The multi-tube heat exchanger can process a large amount of reactants by increasing the number of tubes, and has excellent temperature control performance by increasing the heat transfer area, has a small device volume, and is inexpensive. Is preferred. The length, diameter, and number of tubes of the multi-tube heat exchanger are not limited, but are, for example, 1 to 10 m in length and 0.5 to 1 in diameter.
0 inch, the number is 2 to 100.

The single-pipe heat exchanger has one heat transfer tube installed in a vessel, and performs heat exchange by flowing a heat transfer medium into or out of the tube. There is a tube type and a coil type.

In the present invention, the tubular reactor is
A single-screw or twin-screw extruder or kneader equipped with various shapes of stirring blades can also be used.

These tubular reactors may be installed in any of a horizontal state, a vertical state, and an oblique state.

In these tubular reactors, the flow of the reaction fluid in the reactor is close to the ideal piston flow, and there is no residence time distribution of the reaction fluid. That is, it is considered that all the reactants pass through the reactor with the same residence time. On the other hand, if a continuous tank reactor is used instead of a tube reactor, there is a residence time distribution of the reaction fluid in the continuous tank reactor, so that a reactant having a residence time longer than the average residence time is generated. Exists. As a result, when a material having optical activity is used as a raw material, racemization occurs and causes a decrease in optical purity. When a tubular reactor is used to increase the degree of polymerization of the lactic acid oligomer, the residence time distribution is smaller than that of a continuous tank reactor even in an actual apparatus on an industrial scale. Can be minimized.

In the present invention, in the second step, a molecular distillation apparatus is used for depolymerizing the lactic acid oligomer.
Molecular distillation uses the difference in the evaporation rate of components under a high vacuum, where molecules evaporated from the surface of the liquid are not restrained from migrating with molecules such as self and residual inert gas. This is a non-equilibrium operation in which components are separated from each other, and has the advantage that the operating temperature can be set arbitrarily regardless of the normal boiling point of the substance.

As a molecular distillation apparatus, a pot still type,
A falling film type, a centrifugal type and the like can be mentioned, and a continuous film type and a centrifugal type device widely used industrially are exemplified. The centrifugal molecular distillation apparatus uses a centrifugal force to spread the film of the evaporating substance on the heating surface, and the falling film type molecular distillation apparatus causes the evaporating substance to flow down along the heating surface to form a thin film. It is a method of the method. Also in the present invention, these continuous molecular distillation apparatuses can be suitably used.

Next, the operation method of the present invention will be described.
In the present invention, a relatively low molecular weight lactic acid oligomer is used as a raw material. This oligomer can be produced by a conventionally known method. For example, a lactic acid monomer is heated (generally at 120 to 170 ° C.) under reduced pressure (generally about 5 to 20 mmHg) to be dehydrated, thereby obtaining a molecular weight of 400 (polymerization degree: about 7) to 2000 (polymerization degree: about 36).
Can be obtained.

In the present invention, in the first step, the lactic acid oligomer is continuously introduced into the inlet of the tubular reactor and heated to increase the degree of polymerization of the oligomer.

In this reaction, a lactic acid polymerization catalyst can be used. The polymerization catalyst is not particularly limited, but is usually a group IA, a group IIIA,
A catalyst comprising a metal or a metal compound selected from the group consisting of Group IVA, Group IIB, Group IVB and Group VA can be used.

The compounds belonging to Group IA include, for example, hydroxides of alkali metals (eg, sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.) and salts of alkali metals and weak acids (eg, sodium lactate, sodium acetate). , Sodium carbonate, sodium octylate, sodium stearate, potassium lactate, potassium acetate, potassium carbonate, potassium octylate, etc., and alkoxides of alkali metals (eg, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc.) )
And the like.

As members belonging to the group IIIA, for example,
Examples thereof include aluminum ethoxide, aluminum isopropoxide, aluminum oxide, and aluminum chloride.

Examples of those belonging to the IVA group include organotin-based catalysts (for example, tin lactate, tin tartrate, tin dicaprylate, tin dilaurate, tin dipalmitate, tin distearate, tin dioleate, α-tin). Tin naphthoate, beta-tin naphthoate, tin octylate, etc.)
And tin powder, tin oxide, tin halide and the like.

Examples of those belonging to Group IIB include zinc powder, zinc halide, zinc oxide, and organic zinc compounds.

The compounds belonging to the group IVB include, for example, titanium compounds such as tetrapropyl titanate and zirconium compounds such as zirconium isopropoxide.

The compounds belonging to the VA group include, for example, antimony compounds such as antimony trioxide and bismuth oxide.
And bismuth compounds such as (III).

Among these, a catalyst comprising tin or a tin compound is preferred from the viewpoint of activity, and tin octylate is particularly preferred.

The amount of the catalyst used is from 0.01 to 20% by weight, preferably from 0.0 to 20% by weight, based on the starting lactic acid oligomer.
It is about 5 to 15% by weight, more preferably about 0.5 to 10% by weight.

The catalyst may be added to the lactic acid oligomer before it is introduced into the tubular reactor, or may be added near the inlet in the tubular reactor.

The temperature in the tubular reactor is such that the temperature of the lactic acid oligomer obtained at the outlet of the tubular reactor is 160 to 300 ° C.
Preferably from 180 to 260 ° C, more preferably from 200 to 260 ° C.
Set to 250 ° C. If the temperature is lower than 160 ° C., it is difficult to obtain an oligomer having an appropriate molecular weight, and heating is required to reach the depolymerization temperature in the next step.
On the other hand, when the temperature exceeds 300 ° C., racemization and coloring are likely to occur.

The residence time in the tubular reactor is 2
Time or less, preferably 60 minutes or less, more preferably 1 to
30 minutes. If the residence time exceeds 2 hours, the possibility of racemization increases, which is not preferable.

Under these operating conditions, the molecular weight of the lactic acid oligomer in the tubular reactor is 2,000.
To 30,000, preferably 10,000 to 25,000, and more preferably 12,000 to 20,000. If the molecular weight is less than 2000,
In the depolymerization in the molecular distillation apparatus in the next step, lactic acid monomers and linear dimers are likely to be generated, and the lactide fraction contains many of these impurities. On the other hand, in order to obtain an oligomer having a molecular weight exceeding 30,000, a high internal temperature and a long residence time of the tubular reactor are required, which is not preferable.

Further, by attaching a vent near the outlet of the tubular reactor and reducing the pressure inside the reactor, the dehydration reaction can be promoted to increase the degree of polymerization of the oligomer. In this case, the internal temperature and residence time of the tubular reactor can be appropriately selected.

Thus, from the outlet of the tubular reactor,
A lactic acid oligomer having an increased degree of polymerization is obtained in a molten state. In the first step, since a tubular reactor is used, the residence time distribution is small even in an actual device on an industrial scale, and a decrease in optical purity can be minimized.

In the present invention, the lactic acid oligomer thus obtained from the outlet of the tubular reactor is continuously introduced into a molecular distillation apparatus in the second step, and is heated to the depolymerization temperature and the depolymerization is carried out. The pressure is reduced to a pressure below the vapor pressure of lactide at the temperature to produce lactide continuously. The introduction into the molecular distillation apparatus is preferably performed while maintaining the molten state of the lactic acid oligomer.

Effective temperature in molecular distillation apparatus (depolymerization temperature)
Is 160 to 300 ° C, preferably 180 to 260 ° C,
More preferably, the temperature is set to 200 to 250 ° C. If this temperature is lower than 160 ° C., it is difficult to distill lactide, and a considerably high degree of vacuum is required. On the other hand, the temperature is 300 ° C
If it exceeds, racemization and coloring are likely to occur. Further, from the viewpoint of operation efficiency, it is preferable to set the temperature to the same level as the temperature of the lactic acid oligomer obtained at the outlet of the tubular reactor.

The surface of the heating zone of the molecular distillation apparatus can be heated by any means. The heating zone is preferably made of a thermally conductive material, and supplies heat from outside the wall of the heating zone toward the internal evaporation surface to heat the lactic acid oligomer introduced into the molecular distillation apparatus. Heat can be supplied, for example, by electrically wrapping the outside of the heating area with a heating tape, or by covering the heating area with an electric heating mantle. Alternatively, a jacket may be provided in the heating area, and a heating medium may be circulated through the jacket to heat the internal heating surface. In order to accurately control the temperature of the surface of the heating area, a thermocouple may be provided on the outer surface of the heating area to monitor the temperature of the surface of the heating area.

The pressure in the molecular distillation apparatus is a pressure equal to or lower than the vapor pressure of lactide at the above-mentioned depolymerization temperature.
It is about 50 mmHg. A lower pressure is preferable because the heating temperature can be lowered, and therefore it is preferably 1 to 20 mmHg, more preferably 1 to 10 mmHg.
g, more preferably 1 to 5 mmHg.

The residence time in the molecular distillation apparatus is as follows:
It is 10 minutes or less, preferably 3 minutes or less, more preferably 1 minute or less. If the residence time exceeds 10 minutes, the possibility of racemization increases, which is not preferable.

Under such operating conditions, the generated lactide can be taken out of the depolymerization reaction system as vapor and continuously collected. The collection of lactide can be easily performed by a condenser attached to the molecular distillation apparatus.

In the second step, since the lactic acid oligomer having an increased degree of polymerization is depolymerized, the production of lactic acid monomers and linear dimers is very small, and the lactide content is high (for example, Lactide content in lactide fraction: 85-9
5%) of the lactide fraction. Further, the residence time can be short, racemization does not occur during depolymerization, and when an L- or D-lactic acid oligomer synthesized from optically active L- or D-lactic acid is used as a raw material,
L- or D-lactide of high optical purity (for example, L-lactide having an optical purity of 90 to 98% ee) can be obtained.

The lactide produced by the method of the present invention is of high purity, but can be further purified, if necessary, and then used for the polymerization reaction to polylactic acid. Purification can be performed according to the methods described in, for example, JP-A-6-256340, “Lactide Melt Crystallization Purification”, and JP-A-7-118259, “Lactide Purification Method and Polymerization Method”.

In the present invention, at least a part of the lactic acid oligomer which has not been converted into lactide in the molecular distillation apparatus can be recycled by recycling to a tubular reactor or a molecular distillation apparatus.

Alternatively, it is also possible to hydrolyze at least a part of the lactic acid oligomer not converted into lactide in the molecular distillation apparatus into lactic acid, and use the obtained lactic acid as a raw material of the lactic acid oligomer. Hydrolysis to lactic acid can be performed by a conventional method.

When the lactic acid oligomer which has not been converted into lactide is reused, it is necessary to consider the amount of catalyst contained in the oligomer, the degree of deactivation, and the material balance in the entire reaction system. is required.

The preferred embodiment of the present invention will be described below. An L- or D-lactic acid oligomer having a molecular weight of 400 to 2,000 is used as a raw material, and this is continuously introduced into a tubular reactor. The lactic acid oligomer obtained at the outlet of the reactor is heated so that the temperature thereof is 160 to 300 ° C, preferably 180 to 260 ° C.
The time is not more than 60 minutes, preferably not more than 60 minutes, to increase the degree of polymerization of the oligomer to continuously obtain a lactic acid oligomer having a molecular weight of 2,000 to 30,000, preferably 10,000 to 25,000. The lactic acid oligomer is continuously introduced into a molecular distillation apparatus, and the depolymerization temperature is 160 to 300 ° C, preferably 180 to 300 ° C.
260 ° C., pressure 1-20 mmHg, preferably 1-10
The lactide is continuously produced by depolymerization at mmHg and a residence time of 10 minutes or less, preferably 3 minutes or less. This lactide is taken out of the depolymerization reaction system as vapor and collected.

By this operation, the lactide content was 85 to 9
5%, optical purity of L- or D-lactide 9 depending on the raw material
A lactide fraction of 0-98% ee can be obtained.

In a more preferred embodiment of the present invention, an L- or D-lactic acid oligomer having a molecular weight of 400 to 2,000 is used as a raw material, and this is continuously introduced into a tubular reactor, and is reacted in the presence of a tin octylate catalyst. The temperature of the lactic acid oligomer obtained at the outlet of the tubular reactor is 200 to 250 ° C.
And the residence time is from 1 to 30 minutes to increase the degree of polymerization of the oligomer and to increase the molecular weight from 12,000 to 20,000.
Is continuously obtained. This lactic acid oligomer is continuously introduced into a molecular distillation apparatus, and the depolymerization temperature is 200 to
Depolymerization is performed at 250 ° C., a pressure of 1 to 5 mmHg, and a residence time of 1 minute or less to continuously produce lactide. This lactide is taken out of the depolymerization reaction system as vapor and collected.

By this operation, the lactide content was 90 to 9
5%, optical purity of L- or D-lactide 9 depending on the raw material
A lactide fraction of 5 to 98% ee can be obtained.

[0055]

The present invention will be described more specifically with reference to the following examples. <Weight average molecular weight of lactic acid oligomer> GP under the following conditions
It was determined by C (gel permeation chromatography) in comparison with a polystyrene standard sample. Detector: RID-6A, Pump: LC-9A, Column oven: GT
O-6A, Column: Shim-pack GPC-801C, -804C, -806C, -8
025C in series (manufactured by Shimadzu Corporation) Mobile phase: chloroform, flow rate: 1 ml / min, sample amount: 200 μl (dissolved in chloroform so that the sample concentration becomes 0.5 w / w%), column temperature: 40
° C.

[Example] L-lactic acid (purac) having a concentration of 87% and an optical purity of 98.6% was continuously supplied to a glass flask having a capacity of 2 l at a rate of 1000 [g / hr]. The temperature in the flask is 160 ° C and the pressure is 5mmHg
And a dehydration reaction was performed. By this operation, lactic acid oligomer having a weight average molecular weight of about 2,000
It was obtained at 30 [g / hr].

To this lactic acid oligomer, tin octylate was added as a catalyst at a rate of 73 g / hr, and the internal temperature was 240 ° C.
Was introduced continuously to the inlet of a twin-screw kneading extruder (S-1, manufactured by Kurimoto Iron Works Co., Ltd.), which was mixed with the catalyst while heating the oligomer. The residence time was 20 minutes. By this operation, a lactic acid oligomer having a weight average molecular weight of about 15,000 was continuously obtained from the outlet of the extruder.

The lactic acid oligomer, while in a molten state, is continuously introduced into a falling-type thin-film distillation apparatus (WFE2-03, manufactured by Shinko Pantec Co., Ltd.).
Depolymerization was performed at mHg and a residence time of about 1 minute, and the generated lactide fraction was collected by a condenser. Lactide fraction 59
0 [g / hr].

The lactide content in this lactide fraction is 8
9% by weight, and the composition of lactide was determined by high performance liquid chromatography (HPLC) to be L-lactide:
97.6, D-lactide: 0.3%, LD-lactide (meso): 2.1%, and the optical purity of L-lactide was 97.3% ee.

[0060]

According to the lactide production method of the present invention, as described above, in the first step, the degree of polymerization of the lactic acid oligomer as the raw material is increased using the tubular reactor, so that the residence time distribution is small and the A decrease in purity can be minimized. Then, in the second step, since the lactic acid oligomer having an increased degree of polymerization is depolymerized using a molecular distillation apparatus, the production of lactic acid monomers and linear dimers is extremely small,
A lactide fraction with a high lactide content can be obtained.
Further, the residence time in the molecular distillation apparatus is short, and the decrease in optical purity is very small.

The lactide production method of the present invention is a continuous operation, and lactide having stable quality can be mass-produced.

As described above, according to the lactide producing method of the present invention, high-purity lactide can be produced industrially stably. In particular, when an optically active lactic acid oligomer is used as a raw material, lactide having high optical purity can be produced. Furthermore, the tubular reactor is a low-cost equipment, and the method is economically excellent.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Takashi Kawabe 1 Shiwazu Works Sanjo Plant, Nakagyo-ku, Kyoto-shi, Kyoto, Japan Inside the Sanjo Plant (72) Inventor Yasumasa Horibe 1 Nishinokyo Kuwahara-cho, Nakagyo-ku, Kyoto, Kyoto Shimadzu Sanjo Plant

Claims (7)

[Claims] 1. A method for producing lactide by depolymerizing a lactic acid oligomer. In a first step, a raw material lactic acid oligomer is continuously introduced into a tubular reactor and heated to reduce the degree of polymerization of the oligomer. In the second step, the lactic acid oligomer having an increased degree of polymerization is continuously introduced into a molecular distillation apparatus, heated to a depolymerization temperature and reduced to a pressure equal to or lower than the vapor pressure of lactide at the depolymerization temperature. A method for producing lactide, comprising vaporizing and collecting lactide. 2. The method for producing lactide according to claim 1, wherein in the first step, the degree of polymerization of the lactic acid oligomer is increased such that the molecular weight of the lactic acid oligomer becomes 2000 to 30,000. 3. The method for producing lactide according to claim 1, wherein the residence time in the tubular reactor is 2 hours or less. 4. The method for producing lactide according to claim 1, wherein the residence time in the molecular distillation apparatus is 10 minutes or less. 5. The method for producing lactide according to claim 1, wherein the lactic acid oligomer as a raw material is an L-lactic acid oligomer or a D-lactic acid oligomer. 6. At least a part of the lactic acid oligomer not converted into lactide in the molecular distillation apparatus,
The method for producing lactide according to any one of claims 1 to 5, wherein the lactide is recycled to a tubular reactor or a molecular distillation apparatus. 7. The method according to claim 1, wherein at least a part of the lactic acid oligomer not converted into lactide is hydrolyzed to lactic acid in the molecular distillation apparatus, and the obtained lactic acid is used as a raw material of the lactic acid oligomer. Item 7. The method for producing lactide according to any one of Items 1 to 6.