JP2002128777A - Method for purifying glycolide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for efficiently purifying a glycolide produced by a solution depolymerization method. SOLUTION: This method for purifying the glycolide is characterized by subjecting a glycolic acid oligomer to a thermal depolymerization reaction in a state that a substantially homogeneous phase is formed from the glycolic acid oligomer, a specific polyalkylene glycol ether-based depolymerization solvent having a boiling point of 230 to 450 deg.C and a mol.wt. of 150 to 450, and, if necessary, a solubilizing agent having such a boiling point as substantially not distilling out together with the glycolide on the depolymerization reaction, cooling the distillate to deposit the glycolide, separating the solid material from the liquid, and then washing the filtered cakes with an organic solvent compatible with the depolymerization solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for purifying glycolide, which is a cyclic dimer ester of glycolic acid.
More specifically, the glycolic acid oligomer was heated and depolymerized in a specific polyalkylene glycol ether (depolymerization solvent), and the formed glycolide was distilled off together with the depolymerization solvent, and then cooled to 80 ° C. or lower to precipitate. The present invention relates to an economical and efficient method for purifying glycolide, in which a filter cake obtained by solid-liquid separation of glycolide and a depolymerization solvent is washed with a specific organic solvent to obtain high-purity glycolide. The glycolide purified according to the present invention can be used as a starting material or comonomer of polyglycolic acid useful as a biodegradable polymer or a medical polymer.

[0002]

[Related Art] Polyglycolic acid is glycolic acid (α-
(Hydroxyacetic acid) formed by dehydration polycondensation.

Embedded image

[0003] Polyglycolic acid is hydrolyzed in the living body and metabolized into water and carbon dioxide by microorganisms in a natural environment.
Decomposed. For this reason, it has attracted attention as a biodegradable polymer or the like that substitutes for medical materials and general-purpose resins. But,
It is difficult to obtain high molecular weight polyglycolic acid using glycolic acid directly as a starting material. For this reason, as a method for producing polyglycolic acid, the following formula, which is a cyclic dimer of glycolic acid, is used.

Embedded image Is known, a ring-opening melt polymerization is carried out in the presence of a catalyst (for example, tin octoate or the like) after the synthesis of glycolide represented by

In order to produce polyglycolic acid from glycolide as a raw material on an industrial scale, it is unavoidable to economically supply high-purity glycolide. Glycolide is a cyclic ester in which two molecules of water are eliminated from two molecules of glycolic acid. In the esterification reaction of glycolic acid,
Usually, oligomers are formed and glycolide cannot be obtained. As a related technique for obtaining glycolide, the following methods have been conventionally known.

[0005] US Patent No. 2,668,162 discloses that glycolic acid oligomer is ground into a powder and is supplied to a reactor in small portions (about 20 g / h) while being subjected to ultra-vacuum (12 to 15 t).
Orr (1.6 to 2.0 kPa)), a method of depolymerizing by heating at 270 to 285 ° C. and collecting vapor of cyclic esters containing glycolide generated in a trap is disclosed. Although this method can be implemented on a small scale, it is difficult to scale up and is not suitable for mass production. Moreover, in this method, the oligomer is converted into a heavy substance during heating depolymerization and remains in the reaction vessel as a large amount of residue, resulting in a poor yield.
The cleaning operation of the residue is complicated. In addition, glycolide (melting point: 82 to 83 ° C.) and by-products are deposited in the pipe of the recovery line, which easily causes blockage and the like.

[0006] US Pat. No. 4,727,163 discloses a method for obtaining glycolide by heating and depolymerizing a block copolymer obtained by using a polyether having excellent thermal stability as a substrate and then copolymerizing block acid with glycolic acid. Is disclosed. However, the operation of this block copolymerization process is complicated and the production cost is high. Also, in this method, glycolide having a melting point of 80 ° C. or more and by-products are deposited in the pipe of the recovery line, which easily causes blockage and the like.

In US Pat. Nos. 4,835,293 and 5,023,349, cyclic esters formed by heating and depolymerization are entrained with an inert gas (such as nitrogen) and stripped and recovered in a low boiling point solvent such as isopropyl alcohol. A method is disclosed. This method tends to increase production costs, such as requiring preheating to blow a large amount of inert gas.

[0008] French Patent 2692663-A1 discloses a method in which an oligomer of α-hydroxycarboxylic acid (which may be an ester or a salt thereof) is added to a solvent to which a catalyst has been added, followed by stirring under heating and catalytic decomposition. This method is carried out at normal pressure or under pressure using a solvent suitable for entraining the cyclic dimer ester in a gaseous state, and condensing the gaseous phase to recover the ester and the solvent. As a specific example,
Only an example using a lactic acid oligomer as a raw material and dodecane (boiling point: about 214 ° C.) as a solvent is shown. However, when the present inventors performed additional tests using the glycolic acid oligomer and dodecane under the same conditions as those of the example of this patent, heavy materialization proceeded simultaneously with the start of the depolymerization reaction, and very little glycolide was produced. At that point, the production of glycolide was stopped, and the reaction residue was viscous, requiring a great deal of labor for cleaning.

In addition, in these conventional glycolide production methods, when the obtained glycolide is used as a raw material for the polymerization of polyglycolic acid, recrystallization purification with an organic solvent was necessary to remove impurities such as glycolic acid.

In view of these prior arts, the applicant of the present invention has proposed a high boiling point polar organic solvent (aromatic ester compound) and α-
The hydroxycarboxylic acid oligomer is heated to form a substantially uniform solution phase, and heating is continued in that state to distill off both the cyclic ester and the polar organic solvent, and the cyclic dimer ester from the distillate. A production method for purifying and a purification method have been proposed (JP-A-9-328481). By using this method in the process of producing glycolide from glycolic acid oligomer, it is possible to prevent the oligomer from becoming heavy during the depolymerization reaction, and it is possible to obtain glycolide in high yield. Can be easily cleaned, and mass production of glycolide has become possible. However, the glycolide obtained in this solution depolymerization process contains impurities such as thermal decomposition products of polar organic solvents, and when used as a raw material for polyglycolic acid polymerization, it is necessary to recrystallize and purify it using an organic solvent. It is.

[0011] As a result of subsequent studies, it has been found that aromatic ester solvents having a high boiling point are liable to undergo thermal degradation during the depolymerization reaction, require a purification step for reusing the solvent, and correspond to further deteriorated solvents. It has been found that new amounts need to be added, which is a high cost factor for the entire glycolide manufacturing process. As a result of further study, when a specific polyalkylene glycol ether is used as the depolymerization solvent, thermal degradation hardly occurs during the depolymerization reaction, and the depolymerization solvent can be reused. (Japanese Patent Application 2000-244449)
issue).

As a method for purifying cyclic esters such as glycolide, the present applicant has proposed a method in which countercurrent contact is made between a descending melt of an ascending raw material crystal and a refined crystal component (Japanese Patent Application No. 2002-214,878).
2000-96713). In this method, a raw material crystal of a cyclic ester to which a high boiling point organic solvent is attached is charged from the lower part of a cylindrical purification tower extending in the longitudinal direction, and stirred while being raised, and the melting of the purified crystal component in the purification tower is lowered and melted. The mother liquid and impurities adhering to the surface of the crystal are washed away by the countercurrent contact between the liquid and the ascending raw material crystal, and the mother liquor and impurities taken into the crystal are purified by sweating action. This method has advantages such as not using a solvent, and is suitable for continuous production. However, since it is heated to a temperature higher than the melting point of the crystal, depending on an impurity component, it may react with glycolide and transform the crystal.

[0013]

An object of the present invention is to reduce the number of steps of glycolide produced by the depolymerization reaction in the method described in Japanese Patent Application No. 2000-244449 by the present applicant as compared with the prior art recrystallization method. Another object of the present invention is to provide a method for economically and efficiently purifying glycolide by a process suitable not only for continuous mass production but also for discontinuous small production.

[0014]

Means for Solving the Problems The present inventors have made intensive studies to solve the above problems, and as a result, the mixture of glycolic acid oligomer and a specific depolymerization solvent was heated to depolymerize the oligomer. After glycolide is distilled off together with the depolymerization solvent, the precipitated glycolide obtained by cooling the distillate to 80 ° C. or lower (Japanese Patent Application No. 2000-244449) has high purity, and the depolymerization solvent and glycolide are solid-liquid. After separation, it was found that high-purity glycolide can be easily isolated by removing the depolymerization solvent from the glycolide in the filter cake. Therefore, as a result of examining a method of removing the depolymerization solvent from glycolide, the depolymerization solvent is a high boiling point polar solvent having a boiling point of 230 to 450 ° C. at normal pressure.
After washing the filter cake with an organic solvent having a boiling point of 0 ° C. or less and being compatible with the depolymerization solvent, the depolymerization solvent in the filter cake is replaced with the cleaning organic solvent, and then dried to remove the washing organic solvent. Was found to be the most efficient method.

That is, a specific polyalkylene glycol ether is used as a depolymerization solvent, and a liquid phase composed of an oligomer melt, a depolymerization solvent and, if desired, a solubilizing agent forms a substantially uniform phase. If the depolymerization reaction is allowed to proceed by heating, thermal degradation of the solvent does not occur, and the distillate occupies the majority of the two kinds of substances, glycolide and depolymerization solvent, so that the melting point of glycolide (82 to 83 ° C) ) It was confirmed that high-purity glycolide was obtained as a crystallized product by cooling the distillate to 80 ° C or lower. The crude glycolide obtained by a method such as the conventional method has too many impurities such as glycolic acid, and a large amount of impurities is easily taken into a crystallized product obtained by cooling, and recrystallization is required. The glycolide distilled off by using a superior specific polyalkylene glycol ether as the depolymerization solvent is purified to high purity by crystallization by cooling and subsequent removal of the depolymerization solvent, enabling industrial mass production of glycolide. It was confirmed that the present invention was completed, and the present invention was completed.

That is, the present invention provides the following method for purifying glycolide obtained by depolymerizing a glycolic acid oligomer using a specific depolymerization solvent or, if desired, using a solubilizing agent. . 1. Glycolic acid oligomer melt, boiling point 230-4
At least one polyalkylene glycol ether solvent (depolymerization solvent) having a molecular weight of 150 to 450 ° C. and at least one terminal ether group containing an alkyl group or an aryl group having 2 to 20 carbon atoms at 50 ° C. The glycolic acid oligomer is subjected to a depolymerization reaction by heating at a temperature of 200 to 320 ° C. in a state where a solid phase is formed, and the formed glycolide is distilled off together with a depolymerization solvent.
Cooling to 0 ° C. or less, and washing the glycolide filter cake obtained by solid-liquid separation of the precipitated glycolide and the depolymerization solvent at a boiling point of 200 ° C. or less with an organic solvent compatible with the polyalkylene glycol ether solvent. A method for purifying glycolide, which comprises: 2. The depolymerization reaction is carried out using a solubilizer having a higher boiling point than glycolic acid oligomericity higher than the depolymerization solvent and substantially not distilling out with glycolide during the depolymerization reaction, and the resulting glycolide is used as a depolymerization solvent. 2. The method for purifying glycolide according to the above item 1, wherein the distillate is cooled, the glycolide precipitated is cooled, and a filter cake of glycolide obtained by solid-liquid separation of the precipitated glycolide with a depolymerization solvent is washed with the organic solvent. 3. 3. The method for purifying glycolide according to 1 or 2, wherein the glycolide is washed with an organic solvent having a boiling point of 200 ° C. or less and a solubility of glycolide at 25 ° C. of 20% or less and compatible with a polyalkylene glycol ether solvent. 4. 4. The method for purifying glycolide according to the above item 3, wherein the organic solvent is an alcohol having 1 to 4 carbon atoms. 5. The method for purifying glycolide according to the above 4, wherein the alcohol having 1 to 4 carbon atoms is isopropyl alcohol. 6. Separating and recovering the depolymerization solvent and / or the organic solvent from the washing recovery liquid generated by washing in the above 1 or 2,
3. The method for purifying glycolide according to the above 1 or 2, wherein the glycolide is reused as a depolymerization solvent and / or an organic solvent.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION According to the method for purifying glycolide of the present invention, the depolymerization solvent has a boiling point of 230 to 450 ° C., a molecular weight of 150 to 450 and at least one terminal ether group having 2 to 20 carbon atoms. At least one polyalkylene glycol ether containing a group or an aryl group, and a liquid phase comprising a glycolic acid oligomer melt, a depolymerization solvent and, if desired, a solubilizing agent, in a state of forming a substantially uniform phase. Glycolide generated by the depolymerization reaction heated at a temperature of 320 ° C. is distilled together with the depolymerization solvent, and the distillate is cooled to 80 ° C. or lower, and the precipitated glycolide is separated from the depolymerization solvent by solid-liquid separation. The cake has a boiling point of 200 ° C. or less, a glycolide solubility at 25 ° C. of 20% or less, and a polyalkylene glycol ether (depolymerized). Wherein the washing medium) and at the compatibility of the organic solvent.

Hereinafter, the method of purifying glycolide of the present invention will be described in detail. The method for purifying glycolide of the present invention is effective when purifying glycolide obtained by a method for producing a specific glycolide. Therefore, a method for producing a specific glycolide will be described first.

(A) Glycolic Acid Oligomer The glycolide used as a raw material in the method for purifying glycolide of the present invention can be obtained by depolymerizing a glycolic acid oligomer. The glycolic acid oligomer can be easily synthesized by a conventional method. In the present invention, the glycolic acid oligomer may be added to the reaction vessel all at once before the reaction, or may be added during the reaction by continuous addition, divided addition, or a combination thereof. However, as described below, it is necessary that the oligomer in the reaction tank forms a uniform molten phase (solution phase) with the solvent during the depolymerization reaction. Alternatively, a preliminary reaction tank may be separately provided so that the solution phase of the oligomer and the solvent becomes more uniform, and a uniform layer is formed there, and then introduced into the depolymerization reaction tank.

(B) Polyalkylene Glycol Ether The polyalkylene glycol ether used in the present invention as a solvent for the depolymerization reaction and used to remove the formed glycolide from the reaction system has a boiling point of 230 to 45.
0 ° C. and the molecular weight is in the range of 150 to 450, and has the following structural formula

Embedded image (Wherein, X is a hydrocarbon group, Y is an alkyl group or an aryl group having 2 to 20 carbon atoms, and p and q are integers of 1 or more). That is, it is a polyalkylene glycol ether in which at least one terminal ether group has an alkyl group or an aryl group having 2 or more carbon atoms.

These polyalkylene glycol ethers can be produced by a conventional synthesis method. For example, most commonly, a polyalkylene glycol monoether is obtained by polyaddition of an alkylene oxide with an alcohol, and then the terminal hydroxy group is etherified. Several etherification methods are known and are not particularly limited, but generally, a method of reacting a polyalkylene glycol monoether with an alkyl halide in the presence of sodium metal, sodium hydride, sodium hydroxide, or the like. In this case, a method in which sodium iodide coexists, a method in which an alcohol corresponding to an ether group is used after sulfonyl chloride is used instead of an alkyl halide, and the like are well known.

(C) Depolymerization Reaction The method for producing glycolide used in the purification method of the present invention is most characterized in that the depolymerization of the glycolic acid oligomer is carried out in a solution phase. When most of the oligomer is not dissolved in the solvent and forms a melt phase at a temperature of 200 ° C. or higher at which depolymerization occurs, glycolide hardly distills out, and the melt phase is likely to be heavy. By heating most of the oligomers in the solution phase, the rate of glycolide generation and volatilization is dramatically increased.

Specifically, the glycolic acid oligomer is
If necessary, the mixture is pulverized to an appropriate particle size, charged into a reaction vessel, and mixed with the above-mentioned polyalkylene glycol ether. When a mixture containing a glycolic acid oligomer and a polyalkylene glycol ether is heated to a temperature of 200 ° C. or higher, all or most of the oligomer is dissolved in a solvent to form a solution phase. The operation of melting and dissolving the oligomer is preferably performed in an atmosphere of an inert gas such as nitrogen gas.

The glycolic acid oligomer is preferably in a uniform liquid phase with the polyalkylene glycol ether, but the oligomer melt phase may coexist if the residual ratio of the oligomer melt phase is 0.5 or less. here,
The “residual rate of the melt phase” refers to an oligomer melt formed when oligomer A (g) is added to a solvent having substantially no dissolving power for glycolic acid oligomer such as liquid paraffin and heated. When the volume of the phase is a (ml) and the volume of the oligomer melt phase formed by heating the oligomer A (g) in the solvent actually used is b (ml), b / ml
represents the ratio of a.

In this state, heating is continued to depolymerize the oligomer, and the produced glycolide and the solvent are co-distilled.
The depolymerization is basically a reaction represented by the following reaction formula.

Embedded image The heating temperature for the depolymerization is 200 ° C. or higher at which the depolymerization of the oligomer occurs. Usually, 210-320 ° C, preferably 215-300 ° C, more preferably 220-29 ° C.
It is in the range of 0 ° C. The heating causes the depolymerization of the oligomer, and the glycolide (boiling point at atmospheric pressure: 240 to 24)
1 ° C.) elutes with the solvent.

A mixed solution containing the oligomer, the polyalkylene glycol ether and, if necessary, the solubilizing agent described below is heated to form a solution phase, and glycolide and the polyalkylene glycol ether are co-distilled by a depolymerization reaction. The temperatures need not necessarily be the same. The heating in any step can be performed under normal pressure or reduced pressure. Preferably, the step of heating the mixed solution containing the oligomer, the polyalkylene glycol ether and the solubilizing agent added as needed to form a solution phase is performed at normal pressure, and then heated under reduced pressure to heat the glycolide and polyether. The alkylene glycol ether is distilled off. Since the depolymerization reaction is a reversible reaction, the glycolide is distilled off from the solution phase, whereby the depolymerization reaction of the oligomer proceeds efficiently. The pressure is within a range where the inside of the system is maintained at a temperature at which the depolymerization reaction of the oligomer proceeds, and is preferably 0.1 to 90.0 kPa. The lower the pressure, the lower the depolymerization reaction temperature and the higher the residual ratio of the solvent.

The polyalkylene glycol ether is used in an amount of usually 0.3 to 50 times (by mass), preferably 0.5 to 20 times (by mass) the glycolic acid oligomer. The polyalkylene glycol ether may be added continuously or dividedly during the depolymerization reaction within a range that forms a homogeneous solution phase.

(D) Solubilizer In the present invention, a solubilizer is used in order to increase the solubility (solubility and / or dissolution rate) of the glycolic acid oligomer in the polyalkylene glycol ether and form a more uniform solution phase. You may use together. The solubilizer may be added continuously or dividedly during the depolymerization reaction.
The solubilizer used in the present invention preferably satisfies the following requirements.

(I) It has a boiling point higher than that of the polyalkylene glycol ether used as a solvent for co-distilling the glycol, ie, it has a boiling point of 450 ° C. or higher, and does not distill at the time of glycolide production or the amount of distilling is negligible. Things. Distillation occurs when the boiling point is lower than 450 ° C., and the solubility of the glycolic acid oligomer decreases, which is not preferable. (ii) Be a non-basic compound. Basic compounds such as amines, pyridines, and quinolines are not preferred because they may react with oligomers or glycolide formed.

(Iii) A higher affinity with the oligomer than with the polyalkylene glycol ether. The affinity for the oligomer is determined by heating the mixture of the oligomer and the polyalkylene glycol to 230 ° C., increasing the oligomer concentration until the mixture no longer forms a homogeneous solution phase, adding a solubilizing agent, and again forming a homogeneous solution phase. Can be confirmed by visual observation. (iv) The polyalkylene glycol ether as a solubilizer has a molecular weight of more than 450. If the molecular weight is low, it co-distills out with glycolide during the depolymerization reaction, and cannot function as a solubilizing agent for maintaining the solubility of the glycolic acid oligomer in the depolymerization reaction system.

Examples of the solubilizer that can be used in the present invention include monohydric or dihydric or higher polyhydric alcohols (including partially esterified and partially etherified), phenols,
Examples thereof include monovalent or divalent or higher polyvalent aliphatic carboxylic acids, aliphatic amides of an aliphatic carboxylic acid and an amine, aliphatic imides, and polyalkylene glycols. In particular, alcohols are effective as solubilizers.

Among the alcohols, the formula (2)

Embedded image (In the formula, R ² represents a methylene group or a linear or branched alkylene group having 2 to 8 carbon atoms, and q is an integer of 1 or more. When q is 2 or more, even when a plurality of R ¹ are the same, A polyalkylene glycol represented by the formula (3):

Embedded image (Wherein, R ³ represents a methylene group or a linear or branched alkylene group having 2 to 8 carbon atoms, X ² represents a hydrocarbon group, r is an integer of 1 or more, and r is 2 or more. In this case, a plurality of R ¹ may be the same or different.), Glycerin, tridecanol, decanediol, and polyalkylene glycol ethers having a molecular weight of more than 450 can be used.

Specific examples of the polyalkylene glycol include polyalkylene glycols such as polyethylene glycol, polypropylene glycol and polybutylene glycol. Specific examples of the polyalkylene glycol monoether include polyethylene glycol monopropyl ether, polyethylene glycol monobutyl ether, polyethylene glycol monohexyl ether, polyethylene glycol monooctyl ether, polyethylene glycol monodecyl ether, and polyethylene glycol monolauryl ether. Examples thereof include alkyl ethers and polyalkylene glycol monoalkyl ethers including polypropylene glycol monoalkyl ether or polybutylene glycol monoalkyl ether in which the ethyleneoxy group is replaced with a propyleneoxy group or a butyleneoxy group in the above compounds. In the present invention, it has been confirmed that when polyalkylene glycol monoether is used as the solubilizing agent, the can wall cleaning effect is particularly excellent.

In the present invention, a polyalkylene glycol ether having a higher affinity for the oligomer and a higher boiling point than the polyalkylene glycol ether used as a co-distilling solvent for depolymerization is preferably used as a solubilizing agent.
Specific examples include polyethylene glycol dimethyl ether # 500 (average molecular weight 500) and polyethylene glycol dimethyl ether # 2000 (average molecular weight 2000).

The solubilizer is used in an amount of usually 0.1 to 500 parts by mass, preferably 1 to 300 parts by mass, per 100 parts by mass of the oligomer.
Used in parts by weight. If the proportion of the solubilizing agent is too small, the solubilizing effect becomes insufficient. If the proportion of the solubilizing agent is too large, the cost of recovering the solubilizing agent is high, which is disadvantageous from the viewpoint of economy.

(E) Catalyst In the depolymerization method of glycolic acid oligomer used in the method for purifying glycolide of the present invention, the glycolic acid oligomer is dissolved in polyalkylene glycol and the surface area thereof is extremely widened. Generation rate or volatilization rate is high. Therefore, one of the major features is that it is not usually necessary to use a catalyst for depolymerization (such as a tin compound or an antimony compound). In the present invention using a solvent having excellent heat stability, the catalyst may be rather harmful. However, a catalyst can be used within a range that does not essentially impair the “solution phase depolymerization method”.

When the distillate is cooled to 80 ° C. or lower, glycolide precipitates. The major feature of the distillate from the depolymerization reaction of the present invention is that it contains glycolide and a depolymerization solvent at a high concentration and almost no other impurities are mixed.
Therefore, the melting point of pure glycolide is 82 to 83 ° C.
Crystallization of glycolide can be easily performed by cooling below.

(F) Washing The precipitated glycolide is a crystalline substance, and is subjected to solid-liquid separation using a known method such as centrifugation, natural filtration, reduced pressure filtration, centrifugal filtration, and sedimentation. After the separation, the distillate is still attached to the crystal, and is in a filter cake state. In this specification, the term "filter cake" also includes a wet cake separated by a method other than a filtration method such as centrifugation. The distillate is mainly composed of a depolymerization solvent, and the depolymerization solvent has a boiling point of 230 to
It is a solvent having a high boiling point of 450 ° C., and is difficult to remove by drying. For removing the depolymerization solvent, a method of washing and replacing with an organic solvent is preferable. The organic solvent is required to have a boiling point lower than that of the depolymerization solvent, and preferably an organic solvent having a temperature of 200 ° C. or lower, more preferably 150 ° C. or lower, and most preferably 100 ° C. or lower.

The organic solvent used for washing preferably has a solubility of glycolide at 25 ° C. of 20% or less, more preferably 10% or less, and particularly preferably 5% or less. When the solubility is high, a large amount of glycolide is dissolved in the washing solution, and the recovery rate of glycolide decreases. The organic solvent used for washing is preferably compatible with the polyalkylene glycol ether used in the depolymerization reaction of the present invention. If they are not compatible, the washing with the organic solvent is insufficient and the polyalkylene glycol ether tends to remain attached to glycolide. Compatibility can be confirmed by mixing an organic solvent and a polyalkylene glycol ether at room temperature and visually observing whether or not phase separation has occurred.

Preferred organic solvents include ester solvents,
Examples include polar solvents such as ketones and alcohols.
Among them, alcohols having a high affinity for organic acids are preferable since the impurities obtained by the depolymerization method of glycolic acid oligomers used in the glycolide purification method of the present invention are small but often organic acids. Alcohols of formulas 1 to 4 are more preferable because they have higher polarity and are more excellent in cleaning effect than alcohols having more carbon atoms.
In particular, isopropyl alcohol is most preferable because it has low reactivity with glycolide and hardly produces by-products.

The organic solvent is preferably used in an amount of about 0.5 to 10 times the amount of glycolide to which the depolymerization solvent has adhered. If the amount used is small, the cleaning effect is poor, and if it is too large, the effect does not increase significantly. Therefore, an appropriate amount is used from the viewpoint of economy. The number of washings can be performed by a batch operation of about 1 to 10 times, and a continuous washing method is also employed.

The glycolide substituted by the organic solvent is generally removed by an ordinary separation method such as filtration, and the attached organic solvent is generally removed by drying. The removed organic solvent can be reused by being recovered.

Further, a method may be employed in which the organic solvent for replacement with the depolymerization solvent is further replaced with another organic solvent. For example, if glycolide substituted with isopropyl alcohol is further substituted with hexane, drying becomes easier.

At the time of washing, the temperature is not particularly limited, but is required to be lower than the melting point of glycolide (82 to 83 ° C.). Furthermore, if the washing solvent increases the solubility of glycolide with increasing temperature, the temperature must be controlled lower.

When the mother liquor from which glycolide has been separated contains one or more kinds of solvents and another kind of solvent or a solubilizing agent, the separated mother liquor can be recycled and used without purification. It can be recycled using activated carbon after adsorption and purification, or it can be recycled as a solvent and / or a solubilizing agent after simple distillation or fractionation. Since the solubilizing agent is effective in dissolving the heavy material, in the case of depolymerization using the solubilizing agent, cleaning in the reactor can be omitted or reduced.

The depolymerization method of glycolic acid oligomer used in the method for purifying glycolide of the present invention is a method which can be called a "solution phase depolymerization method". According to this production method, glycolide can be produced efficiently for the following reasons. 1. By causing the glycolide to undergo depolymerization in a solution phase, preferably in a homogeneous solution phase, the surface area of the coexisting oligomer is dramatically increased, and the production rate of glycolide generated and volatilized from the oligomer surface is dramatically increased. 2. Since the contact between the oligomers is suppressed by the dilution effect of the solvent, the progress of the polycondensation reaction of the oligomer at the time of heating is suppressed, and the amount of heavies produced is extremely reduced. Accordingly, the yield of glycolide is improved, and the labor for cleaning the inside of the can can be almost eliminated.

3. Glycolide is generated at the distillation temperature of the polyalkylene glycol ether and distills out together with the solvent, so that it hardly accumulates in the recovery line, so that blockage of the line is prevented, and the collection of accumulated matter in the line is also called. Most of the work can be saved. 4. Since a system similar to a normal distillation system can be used, scale-up is easy, and mass production on an industrial scale is easy. 5. Further, the polyalkylene glycol ether hardly undergoes thermal deterioration due to the depolymerization reaction, and therefore, by using the solvent used for the depolymerization reaction again for the depolymerization reaction, it is possible to minimize the amount of newly introduced solvent. In the case of mass production of glycolide, the cost of the solvent can be greatly reduced, and as a result, glycolide can be mass-produced at low cost.

The factor which led to the completion of the present invention was that the depolymerization solvent used in the depolymerization reaction was extremely chemically stable because of its thermal stability. Is to occupy most of the
Thus, after the precipitated glycolide is subjected to solid-liquid separation, the depolymerization solvent attached to the glycolide solid is washed and replaced with an organic solvent, and the organic solvent is removed to easily purify high-purity glycolide. Can be released. In the depolymerization solvent in the conventional solution depolymerization method, the thermal decomposition products of the solvent are also contained in the distillate, and these are easily taken into the glycolide crystals. It is difficult to obtain.

[0049]

EXAMPLES The present invention will be described more specifically with reference to Reference Examples, Examples and Comparative Examples. In the following examples, the solubility of glycolide in the solvent was measured by the following method. 10 ml of the solvent was placed in a 25-ml stoppered test tube, and glycolide was added thereto so as to slightly exceed the saturated state, and irradiated with ultrasonic waves for 30 minutes. After the irradiation, the mixture was allowed to stand at 25 ° C. overnight, the content of glycolide in the supernatant was quantified by gas chromatography, the dissolved amount B (g) was obtained, and the solubility was calculated by the following equation.

## EQU1 ## Solubility (%) = (B / 10) × 100

Reference Example 1 Synthesis of Glycolic Acid Oligomer Into a 5-liter autoclave, 2500 g of glycolic acid (manufactured by Wako Pure Chemical Industries, Ltd.) was charged, and stirred at normal pressure for 17 hours.
The temperature was raised from 0 ° C. to 200 ° C. over 2 hours, and the condensation reaction was performed while distilling off the produced water. Then, the pressure inside the can
The pressure was reduced to 5.0 kPa, and the mixture was heated at 200 ° C. for 2 hours to distill off low-boiling components such as unreacted raw materials to prepare a glycolic acid oligomer. The melting point (Tm) of the obtained oligomer is 206
At ° C, ΔHmc was 105 J / g. Tm is DSC
(Differential scanning calorimeter) under an inert gas atmosphere.
ＨHmc is the value when heating and heating at a rate of ° C per minute.
Is the melting enthalpy detected at that time.

Reference Example 2: Synthesis of tetraethylene glycol dibutyl ether (TEG-DB) In a flask, 500 ml of toluene and butoxyethanol were placed.
118.2 g and 101.2 g of triethylamine were added, and 115 g of methanesulfonyl chloride was added dropwise under ice cooling. After removing the precipitated triethylamine hydrochloride, 206.3 g of triethylene glycol butyl ether was added. This mixture was charged into a dropping funnel and 40 g of 60% NaH and 20 g of toluene were added.
It was added dropwise to 0 ml of the mixture at 60-70 ° C. Tetraethylene glycol dibutyl ether was obtained from the reaction solution by distillation (boiling point: 140 to 143 ° C, 80 Pa). When the boiling point of this substance (abbreviated as TEG-DB) is converted to normal pressure, it is about 340 ° C. In addition, 25 ℃ of this substance
The solubility of glycolide in was 4.6%.

Reference Example 3: Synthesis of diethylene glycol dibutyl ether (DEG-DB) In 120 g of 60% NaH and 500 ml of toluene, 329 g of bromobutane and 486 g of diethylene glycol butyl ether were added dropwise at 50 ° C. Diethylene glycol dibutyl ether (abbreviated as DEG-DB) was obtained from the reaction product by distillation (boiling point: 256 ° C., normal pressure). Also,
The solubility of glycolide at 25 ° C in this substance is 1.8%
Met. These results are summarized in Table 1.

[0053]

[Table 1]

Example 1 40 g of the glycolic acid oligomer prepared in Reference Example 1 was charged into a 300 ml flask connected to a receiver cooled with cold water, and the polyethylene glycol dibutyl ether prepared in Reference Example 2 was used as a polyalkylene glycol ether. (TEG-DB) is 200
g was added. The mixture of oligomer and solvent was heated to 280 ° C. in a nitrogen gas atmosphere. It was visually confirmed that the oligomer was uniformly dissolved in the solvent and no phase separation occurred. When the pressure in the flask is reduced to 10 kPa while heating is continued,
The co-distillation of glycolide and solvent started by the depolymerization reaction. The depolymerization reaction was completed in about 4 hours. After the end of the co-distillation, all the glycolide precipitated from the distillate was filtered off with a glass filter to obtain 30 g of a filter cake (GC
Analysis showed 27 g of glycolide and 3 g of TEG-DB). 30 g of the filter cake was added to 130 g of cyclohexanone (glycolide (GL) solubility (25 ° C.): 14.7
%) And stirred for 20 minutes to wash and replace. After washing, the mixture was filtered with a glass filter and dried at 30 ° C. in vacuo. After drying, the obtained purified glycolide was 26 g (yield: 65%), and the purity (area method) by gas chromatography (GC) was as high as 99.98%. When TEG-DB in the mother liquor and the reaction solution was quantified by GC, 1
98 g (residual rate: 99%), and it was confirmed that there was almost no loss of the solvent.

Example 2: 40 g of the glycolic acid oligomer prepared in Reference Example 1 was charged into a 300 ml flask connected to a receiver cooled with cold water, and diethylene glycol dibutyl ether (DEG-DEG) prepared in Reference Example 4 as a polyalkylene glycol ether. DB) was added, and 50 g of polyethylene glycol dimethyl ether # 2000 (average molecular weight: 2000, manufactured by Merck, boiling point: more than 280 ° C./10 mmHg) was added as a solubilizing agent. Mix the mixture of oligomer and solvent in a nitrogen gas atmosphere.
Heated to 0 ° C. The oligomer was uniformly dissolved in the solvent, and it was visually confirmed that no phase separation occurred. When the pressure of the mixture was reduced to 10 kPa while heating was continued, co-distillation of glycolide and the solvent was started by a depolymerization reaction.
The depolymerization reaction was completed in about 5 hours. After the end of the joint distillation,
The total amount of glycolide precipitated from the distillate was filtered off with a glass filter to obtain 40 g of a filter cake (33 g of glycolide and 7 g of DEG-DB according to GC analysis). 40 g of the filter cake was added to 200 g of ethyl acetate (GL
Solubility (25 ° C): 12.0%) and stirred for 20 minutes to wash and replace. After washing, filter with a glass filter,
Vacuum dried at 30 ° C. The purified glycolide obtained after drying was 32 g (yield: 80%), and the purity by GC (area method) was as high as 99.98%. When DEG-DB in the mother liquor and the reaction solution was quantified by GC, it was 199 g (residual rate: 99.5%), and it was confirmed that the decomposition of the solvent was small.

Example 3 A depolymerization reaction was carried out in the same manner as in Example 2 except that the solubilizing agent was changed to 60 g of polyethylene glycol # 600 (average molecular weight: 600). After the completion of the co-distillation, all the glycolide precipitated from the distillate was filtered off with a glass filter to obtain 37 g of a filter cake (GC
According to analysis, 33 g of glycolide and 4 g of DEG-DB) 37 g of filter cake were mixed with 180 g of cyclohexanone, stirred for 20 minutes and washed and replaced. After washing
The mixture was filtered through a glass filter and dried at 30 ° C. under vacuum. After drying, the purified glycolide obtained was 32 g (yield:
80%), and the purity by GC (area method) was as high as 99.98%. DEG-DB in mother liquor and reaction solution
It was 199 g (residual rate: 99.5%) determined by C, and it was confirmed that there was almost no loss of the solvent.

Example 4: Polypropylene glycol # 400 (average molecular weight: 400, boiling point: 280 ° C.)
A depolymerization reaction was carried out in the same manner as in Example 2 except that the amount was changed to 40 g (exceeding 10 mmHg). After the end of the co-distillation, the entire amount of glycolide precipitated from the distillate was filtered off with a glass filter to obtain 40 g of a filter cake (34 g of glycolide and 6 g of DEG-DB according to GC analysis). 300 g of dioxane (GL solubility (25
C): 27.3%) and stirred for 20 minutes to wash and replace. After washing, the mixture was filtered with a glass filter and dried at 30 ° C. in vacuo. After drying, the purified glycolide obtained was 33 g (yield: 82.5%), and the purity by GC (area method) was 9
High purity of 9.97%. DE in mother liquor and reaction solution
When G-DB was quantified by GC, 199 g (residual rate: 99.5)
%), And it was confirmed that there was almost no loss of the solvent.

Example 5: The solubilizing agent was polyethylene glycol monomethyl ether # 350 (average molecular weight: 350,
A depolymerization reaction was carried out in the same manner as in Example 2 except that the amount was changed to 50 g (manufactured by Aldrich). After completion of the co-distillation, the entire amount of glycolide precipitated from the distillate was filtered off with a glass filter to obtain 36 g of a filter cake (33 g of glycolide and 3 g of DEG-DB according to GC analysis), and 36 g of a filter cake. Was mixed with 230 g of isopropyl alcohol (GL solubility (25 ° C.): 0.9%), stirred for 20 minutes, and washed and replaced. After washing, filter with a glass filter and remove
Vacuum dried at 0 ° C. After drying, the obtained purified glycolide was 32 g (yield: 80%), and the purity by GC (area method) was as high as 99.99%. When DEG-DB in the mother liquor and the reaction solution was quantified by GC, it was 198 g (residual rate: 99%), and it was confirmed that there was almost no loss of the solvent.

Example 6 Same as Example 2 except that the solubilizing agent was changed to 50 g of polyoxyethylene monolauryl ether (trade name: Newcol 1105, manufactured by Nippon Emulsifier Co., Ltd., boiling point: 280 ° C./10 mmHg). A depolymerization reaction was performed. After the end of the co-distillation, the entire amount of glycolide precipitated from the distillate was filtered off with a glass filter to obtain 38 g of a filter cake (according to GC analysis, glycolide 34).
g, 4 g of DEG-DB).
90 g of cold ethanol (GL in ethanol (25 ° C.)
(Solubility: 2.9%) and mix while cooling in an ice-cooled bath.
The mixture was stirred for 0 minutes, washed and replaced. Further, the filter cake to which cold ethanol was attached was washed with 100 g of hexane, filtered with a glass filter, and dried at 30 ° C. under vacuum. After drying,
The obtained purified glycolide was 33 g (yield: 82.5
%), And the purity by GC (area method) was as high as 99.99%. When DEG-DB in the mother liquor and the reaction solution was quantified by GC, it was 198 g (residual rate: 99%), and it was confirmed that there was almost no loss of the solvent.

Comparative Example 1: 40 g of the glycolic acid oligomer prepared in Reference Example 1 was charged into a 300 ml flask connected to a receiver cooled with cold water, and 170 g of di (2-methoxyethyl) phthalate (DMEP) was added. The mixture of oligomer and solvent was heated to 280 ° C. in a nitrogen gas atmosphere. It was visually confirmed that the oligomer was uniformly dissolved in the solvent and did not undergo phase separation. When the pressure of the mixture was reduced to 13 kPa while heating was continued, co-distillation of glycolide and the solvent was started by a depolymerization reaction. The depolymerization reaction was completed in about 4 hours. After the completion of the co-distillation, the entire amount of glycolide precipitated from the distillate was filtered off with a glass filter to obtain 30 g of a filter cake (26 g of glycolide and 3 g of DMEP according to GC analysis), and 130 g of 30 g of the filter cake. Mixed with cyclohexanone of
The mixture was stirred for 20 minutes and washed and replaced. After washing, the mixture was filtered with a glass filter and dried at 30 ° C. in vacuo. After drying, 25 g of purified glycolide was obtained (yield: 62.5%).
The purity by C (area method) was 96.85%. The amount of DMEP in the mother liquor and the reaction solution was determined by GC to be 125 g.
(Residual rate: 73%) was confirmed. In addition, the presence of phthalic anhydride and 2-methoxyethanol was confirmed in the mother liquor and the washed glycolide.

Comparative Example 2: A depolymerization reaction was carried out in the same manner as in Comparative Example 1. After completion of the co-distillation, all the glycolide precipitated from the distillate was filtered off with a glass filter to obtain 35 g of a filter cake. (According to GC analysis, glycolide 24
g, 9 g of DMEP).
g of isopropyl alcohol and stirred for 20 minutes to wash and replace. After washing, filter with a glass filter,
Vacuum dried at 30 ° C. After drying, the purified glycolide obtained was 23 g (yield: 57.5%), and the purity by GC (area method) was 97.8%. The amount of DMEP in the mother liquor and the reaction solution was determined by GC to be 124 g (residual rate: 73%).
%) Was confirmed. In addition, the presence of phthalic anhydride and 2-methoxyethanol was confirmed in the mother liquor and the washed glycolide.

Comparative Example 3: According to the method described in Example A of US Pat. No. 2,668,162, 100 g of glycolic acid oligomer obtained by condensing glycolic acid was pulverized into powder and 1 g of trioxide After mixing with antimony,
Heat to 270-280 ° C and further 10-15 mmHg
The mixture was thrown into the container under reduced pressure of 5 times 20 g per hour. The yellow distillate was cooled to give 87 g of crude glycolide (87% yield). This crude glycolide (GC
(Purity: 97% by area method) 40 g was mixed with 200 g of isopropyl alcohol, stirred for 20 minutes, and washed and replaced. After washing, the mixture was filtered with a glass filter and dried at 30 ° C. in vacuo. After drying, the glycolide obtained was 35 g (total yield: 76%), and the purity by GC (area method) was
97.5%.

[0063]

According to the method for purifying glucolide of the present invention,
Glycolide produced by depolymerizing the glycolic acid oligomer in the solution phase using a specific polyalkylene glycol ether (depolymerization solvent) and, if desired, a solubilizing agent, is distilled together with the solvent, and the distillate is recovered. After cooling to below ℃ and separating the precipitated glycolide and solid-liquid from the depolymerization solvent,
By washing the filter cake with an organic solvent having a boiling point of 200 ° C. or less and compatible with the depolymerization solvent,
Highly pure glycolide can be easily and economically obtained.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Hoshimoto 16 Nishimachi, Nishikicho, Iwaki-shi, Fukushima Prefecture

Claims (6)

[Claims] 1. A glycolic acid oligomer melt and at least one kind of a compound having a boiling point of 230 to 450 ° C., a molecular weight of 150 to 450 and at least one terminal ether group containing an alkyl group or an aryl group having 2 to 20 carbon atoms. In a state where a polyalkylene glycol ether solvent (depolymerization solvent) and a substantially uniform phase are formed, the glycolic acid oligomer is subjected to a depolymerization reaction by heating at a temperature of 200 to 320 ° C. to decompose the formed glycolide. Distilled together with the polymerization solvent,
The distillate was cooled to 80 ° C. or less, and the glycolide filter cake obtained by solid-liquid separation of the precipitated glycolide and the depolymerization solvent was converted to an organic solvent compatible with the polyalkylene glycol ether solvent at a boiling point of 200 ° C. or less. And purifying the glycolide. 2. A depolymerization reaction is performed by using a solubilizing agent having a higher glycolic acid-oligomeric property than the depolymerization solvent and having a boiling point that does not substantially distill together with glycolide during the depolymerization reaction. The glycolide is distilled off together with the depolymerization solvent, the distillate is cooled, and the glycolide filter cake obtained by solid-liquid separation of the precipitated glycolide and the depolymerization solvent is washed with the organic solvent according to claim 1. A method for purifying glycolide. 3. The method for purifying glycolide according to claim 1, wherein the glycolide is washed with an organic solvent having a boiling point of 200 ° C. or less and a glycolide solubility of 20% or less at 25 ° C. and compatible with a polyalkylene glycol ether solvent. 4. The method for purifying glycolide according to claim 3, wherein the organic solvent is an alcohol having 1 to 4 carbon atoms. 5. The method for purifying glycolide according to claim 4, wherein the alcohol having 1 to 4 carbon atoms is isopropyl alcohol. 6. The method according to claim 1, wherein a depolymerization solvent and / or an organic solvent is separated and recovered from the washing and recovery liquid generated by the washing in claim 1 or 2 and reused as a depolymerization solvent and / or an organic solvent. 2. The method for purifying glycolide according to 1. above.