JPH072985A - Method for producing polyhydroxycarboxylic acid - Google Patents

Abstract

(57) [Summary] [Structure] Hydroxycarboxylic acids or their oligomers are heated to reflux in the presence of a catalyst in an organic solvent to remove water and low-boiling compounds, and then water is removed from the reaction system at the same time as the solvent is refluxed. A method for producing a polyhydroxycarboxylic acid, which comprises dehydration polycondensation. [Effect] A high molecular weight polyhydroxycarboxylic acid can be industrially obtained in a short time and at low cost by direct dehydration polycondensation from hydroxycarboxylic acids.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a polyhydroxycarboxylic acid useful as a biodegradable biopolymer in place of a medical material or a general-purpose resin.

[0002]

2. Description of the Related Art Polyhydroxycarboxylic acid has excellent mechanical properties, physical properties, and chemical properties, and is decomposed in a natural environment without harming others. It has a biodegradable function of becoming carbon dioxide gas, and in recent years, it has attracted attention in various fields such as medical materials and substitutes for general-purpose resins from the viewpoint of environmental protection, and its demand is expected to grow greatly in the future. Is expected. Usually, as a method for producing a polyhydroxycarboxylic acid, in the case of a hydroxycarboxylic acid such as lactic acid or glycolic acid, dehydration dimerization is performed to obtain a cyclic dimer, and then ring-opening melt polymerization is performed in the presence of various catalysts. It is known that high molecular weight polymers can be obtained. This method is uneconomical because it requires a great deal of labor and cost in the production of lactide, which is a cyclic dimer, or glycolide. Further, some hydroxycarboxylic acids do not form a cyclic dimer, and in this case, this method cannot be used.

On the other hand, several methods for obtaining polyhydroxycarboxylic acid from a hydroxycarboxylic acid and its oligomer by a direct dehydration method have been disclosed (JP-A-59-59).
096123, JP-A-61-028521). However, the intrinsic viscosity of the polymer obtained by these methods is limited to about 0.3 dl / g, which does not have sufficient mechanical properties and cannot be used depending on its application and purpose. As described above, in the present situation, the polyhydroxycarboxylic acid having sufficient mechanical properties is limited in its polymerization method to the melt polymerization method and its polymer composition is also limited.

[0004]

The direct polymerization method of hydroxycarboxylic acids such as lactic acid and glycolic acid is a sequential reaction similar to the esterification reaction between dibasic acid and polyhydric alcohol, and the molecular weight increases with the reaction time. . Further, the water molecules generated at this time have an action of lowering the molecular weight of the polycondensate by the reverse reaction due to the hydrolysis action, so that it is possible to efficiently remove the produced water out of the system in order to obtain a high molecular weight polymer. Was needed for. This method includes a method of increasing the stirring speed during the reaction, a method of increasing the degree of reduced pressure, a method of introducing an inert gas into the reaction system to volatilize water, and the like, but the viscosity of the reaction system remarkably increases as the molecular weight increases. Therefore, these methods have limitations.

[0005]

Means for Solving the Problems The inventors of the present invention have earnestly studied a direct dehydration polymerization method capable of industrially producing a polyhydroxycarboxylic acid efficiently, easily and inexpensively. It is possible to obtain a polymer having a high average molecular weight in a relatively short time by heating and refluxing in an organic solvent in the presence of to remove low boiling point compounds contained in hydroxycarboxylic acid out of the reaction system. The present invention has been found out. That is, hydroxycarboxylic acids or their oligomers in the presence of a catalyst,
A method for producing a polyhydroxycarboxylic acid, which comprises heating and refluxing in an organic solvent to remove water and a low boiling point compound, and then performing dehydration polycondensation while removing water from the reaction system simultaneously with reflux of the solvent.

The present invention provides a method for producing a high molecular weight polyhydroxycarboxylic acid by a direct dehydration condensation reaction of a hydroxycarboxylic acid.

Specific examples of the hydroxycarboxylic acid used in the present invention include the following. Glycolic acid, lactic acid, 2-hydroxybutanoic acid, 2
-Hydroxypentanoic acid, 2-hydroxyhexanoic acid, 2-hydroxyheptanoic acid, 2-hydroxyoctanoic acid,
2-hydroxy-2-methylpropanoic acid,
2-hydroxy-2-methylbutanoic acid, 2
-Hydroxy-2-ethylbutanoic acid, 2-
Hydroxy-2-methylpentanoic acid, 2-
Hydroxy-2-ethyl pentanoic acid, 2-
Hydroxy-2-propyl pentanoic acid, 2
-Hydroxy-2-butyl pentanoic acid, 2
-Hydroxy-2-methylhexanoic acid, 2
-Hydroxy-2-ethylhexanoic acid, 2
-Hydroxy-2-propylhexanoic acid,
2-hydroxy-2-butylhexanoic acid,
2-hydroxy-2-pentylhexanoic acid, 2-hydroxy-2-methylheptanoic acid, 2-hydroxy-2-methylheptanoic acid, 2-hydroxy-2-ethylheptanoic acid, 2- Hydroxy-2-propyl heptanic acid, 2-hydroxy-2-butyl heptanoic acid, 2-hydroxy-2-pentyl heptanoic acid, 2-hydroxy-2-hexyl heptanoic acid, 2-hydroxy-2 -Methyl octanoic acid, 2-hydroxy-2-ethyl octanoic acid, 2-hydroxy-2-propyl octanoic acid, 2-hydroxy-2-butyl octanoic acid, 2-hydroxy-2-pentyl Octanoic acid, 2-hi Roxy-2-hexyl octanoic acid, 2-hydroxy-2-heptyl octanoic acid, 3-hydroxypropanoic acid, 3-hydroxybutanoic acid, 3-hydroxypentanoic acid, 3-hydroxyhexa Noic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxy-3-methylbutanoic acid, 3-hydroxy-3-methylpentanoic acid, 3-hydroxy-3- Ethyl pentanoic acid, 3-hydroxy-3-methylhexanoic acid, 3-hydroxy-3-ethylhexanoic acid, 3-hydroxy-3-propylhexanoic acid, 3-hydroxy-3-methylhepta Neuqua Acid, 3-hydroxy-3-ethylheptanoic acid, 3-hydroxy-3-propylheptanoic acid, 3-hydroxy-3-butylheptanoic acid, 3-hydroxy-3-methyloctanoic acid. , 3-hydroxy-3-ethyloctanoic acid, 3-hydroxy-3-propyloctanoic acid, 3-
Hydroxy-3-butyloctanoic acid, 3-
Hydroxy-3-pentyl octanoic acid, 4
-Hydroxybutanoic acid, 4-hydroxypentanoic acid, 4-hydroxyhexanoic acid, 4-hydroxyheptanoic acid, 4
-Hydroxyoctanoic acid, 4-hydroxy-4-methylpentanoic acid, 4-hydroxy-4-methylhexanoic acid, 4-hydroxy-4-ethylhexanoic acid, 4-hydroxy-4-methyl Heptanoic acid, 4-hydroxy-4-ethyl heptanoic acid, 4-hydroxy-4-propyl heptanoic acid, 4-hydroxy-4-methyloctanoic acid, 4-hydroxy-4-ethyloctano Ic acid, 4-hydroxy-4-propyloctanoic acid, 4-hydroxy-4-butyloctanoic acid, 5-hydroxypentanoic acid, 5-hydroxyhexanoic acid, 5-hydroxyheptanoic acid , 5-hydroxy Octanoic acid, 5-hydroxy-5-methylhexanoic acid, 5-hydroxy-5-methylheptanoic acid, 5-hydroxy-5-ethylheptanoic acid, 5-hydroxy-5-methyloctano Ic acid, 5-hydroxy-5-ethyloctanoic acid, 5-hydroxy-5-propyloctanoic acid, 6-hydroxyhexanoic acid, 6-hydroxyheptanoic acid, 6-hydroxyoctanoic acid , 6-hydroxy-6-methylheptanoic acid, 6-hydroxy-6-methyloctanoic acid, 6-hydroxy-6-ethyloctanoic acid, 7-hydroxyheptanoic acid, 7-
Hydroxy octanoic acid, 7-hydroxy-
Examples thereof include aliphatic hydroxycarboxylic acids such as 7-methyloctanoic acid and 8-hydroxyoctanoic acid. These may be used alone or in combination of two or more. Particularly preferably used hydroxycarboxylic acids are lactic acid, glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid and 3
-Hydroxyvaleric acid, or a mixture thereof.

In the method of the present invention, the above-mentioned oligomer derived from hydroxycarboxylic acid can be used as a raw material. And, they may be used as one kind or as a mixture of two or more kinds.

These hydroxycarboxylic acids and their oligomers each have an optically active carbon and have D-form and L-form, respectively.
The form may be a body or a D / L form, but the form is not limited in the present invention.

Examples of the catalyst used in the present invention include metals of Group I, II, III, IV and V of the Periodic Table of the Elements, or salts or hydroxides or oxides thereof.

Metals such as zinc, tin, aluminum, magnesium, antimony, titanium and zirconium. Metal oxides such as tin oxide, antimony oxide, lead oxide, aluminum oxide, magnesium oxide and titanium oxide. Zinc chloride, stannous chloride, stannic chloride, stannous bromide, stannic bromide, antimony fluoride, zinc chloride, magnesium chloride,
Metal halides such as aluminum chloride. Sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, aluminum hydroxide, zinc hydroxide, iron hydroxide, cobalt hydroxide, nickel hydroxide, copper hydroxide, cesium hydroxide, strontium hydroxide, hydroxide barium,
Metal hydroxides such as lithium hydroxide and zirconium hydroxide. Sulfates such as tin sulfate, zinc sulfate and aluminum sulfate.
Carbonates such as magnesium carbonate, zinc carbonate and calcium carbonate. Organic carboxylates such as tin acetate, tin octoate, tin lactate, zinc acetate, aluminum acetate, iron lactate. Examples thereof include organic sulfonates such as tin trifluoromethanesulfonate and tin p-toluenesulfonate.

In addition, organometal oxides of the above metals such as dibutyltin oxide, metal alkoxides of the above metals such as titanium isopropoxide, or alkyl metals of the above metals such as diethylzinc. And ion exchange resins such as Dowex and Amberlite. The amount used is 0.0001 to 10% by weight of the hydroxycarboxylic acid or the oligomer thereof.

Examples of the organic solvent used in the present invention include aromatic hydrocarbons and ether-based aromatic hydrocarbons. Aromatic hydrocarbons include toluene, xylene,
Examples thereof include biphenyl, naphthalene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene and 1-chloronaphthalene. Examples of ether-based aromatic hydrocarbons include alkoxybenzenes and diphenyl ethers. Alkoxybenzenes include anisole, ethoxybenzene, propoxybenzene, butoxybenzene, pentoxybenzene;
2,4-dimethoxybenzene; 2-chloromethoxybenzene; 2-bromomethoxybenzene; 4-chloromethoxybenzene; 4-bromomethoxybenzene; 2,4-dichloromethoxybenzene and the like. Examples of diphenyl ethers include diphenyl ether; 4,4'-dimethyldiphenyl ether; 3,3'-dimethyldiphenyl ether; 3-methyldiphenyl ether; alkyl-substituted diphenyl ethers 4,4'-dibromodiphenyl ether; 4-methyl-4'-bromodiphenyl ether Halogen-substituted diphenyl ether such as 4-methoxydiphenyl ether; 4,4′-dimethoxydiphenyl ether 3,3′-dimethoxydiphenyl ether; alkoxy-substituted diphenylether dibenzofuran such as 4-methyl-4′-methoxydiphenyl ether;
Examples include cyclic diphenyl ethers such as xanthene. Anisole, diphenyl ether, naphthalene and the like are preferable. These may be one kind or a mixture of two or more kinds without any limitation. The amount of the polymer used can be adjusted so that the polymer concentration becomes 3 to 80% by weight.
The range is preferably such that the polymer concentration is 5 to 50% by weight. If the amount is more than 80% by weight, the viscosity of the polymer when heated and dissolved becomes extremely high, which may make it difficult to handle and operate during the reaction such as stirring and subsequent liquid transfer.
On the other hand, when it is less than 3% by weight, there is no problem in reaction and post-treatment, but the volume efficiency is poor and it is disadvantageous in terms of productivity.

In the present invention, hydroxycarboxylic acids or their oligomers are heated and refluxed in an organic solvent in the presence of a catalyst to remove water and low boiling point compounds, and then while the solvent is refluxed, water is removed from the reaction system. It is a method for producing a high molecular weight polyhydroxycarboxylic acid in a short time by dehydration polycondensation. The effect of the present invention is achieved by heating and refluxing the organic solvent, and distilling and removing the impurities derived from the raw material which becomes the terminal stopper in the reaction system together with the refluxing solvent to the outside of the reaction system. Therefore, the refluxed organic solvent containing impurities may be a system in which the impurities are removed once to remove the impurities and then returned to the reaction system again, or an organic solvent containing no impurities is charged, A system in which the organic solvent in the reaction system is replaced may be used. As a method of removing impurities from the organic solvent, for example, the impurities may be removed by distillation, or some impurities may be extracted and removed by contacting with water into an aqueous layer, and those may be removed from the organic solvent returned to the reaction system. Any method may be used as long as it can remove impurities. As a condition for heating and refluxing in an organic solvent, the temperature is 80 to 250 ° C., preferably 110 to 170 ° C. If the temperature is lower than 80 ° C, the effect of removing impurities decreases, which is not preferable.
If the temperature is 50 ° C. or higher, the hydroxycarboxylic acid may be deteriorated by heat, which is not preferable. The pressure may be either normal pressure or reduced pressure, and the pressure for refluxing within the above temperature range is appropriately selected depending on the reaction solvent used. The time for heating and refluxing varies depending on the temperature conditions, scale, etc., but is 0.5 to
60 hours, preferably 2.0 to 30 hours. 0.5H
When it is less than r, the above-mentioned impurity removing effect is not so great, and when it is more than 60 Hr, there is no further impurity removing effect. By performing such an operation, the amount of impurities in the reaction system is extremely reduced, and a polymer having a higher molecular weight can be obtained.

The dehydration polycondensation conditions in the method of the present invention may be either atmospheric pressure or reduced pressure, and the reaction temperature may be up to the reflux temperature of the solvent used, preferably 50 to 2
The temperature is 50 ° C, more preferably 100 to 170 ° C. Fifty
If the temperature is lower than 0 ° C, the efficiency of removing the water generated by the reaction from the reaction system by azeotroping with the solvent is deteriorated, and the reaction rate is significantly reduced. On the other hand, if the temperature exceeds 250 ° C., the polymer may be deteriorated, and thus the reaction solution may be colored, which may deteriorate the quality of the obtained product.

Regarding the apparatus used for the reaction, the reaction is dehydration polycondensation, and in order to obtain a high molecular weight polymer, an apparatus capable of removing the water produced as the reaction progresses to the outside of the reaction system. There is a need. As a method of removing the generated water, after treating the water-containing solvent distilled under the reflux of the solvent with a desiccant, a system for returning it to the system again, or reacting in a reactor equipped with a device having a distillative separation ability, Any method of a reflux system for removing water by distilling and separating a mixture of a solvent and water to be refluxed and returning only a dehydrated solvent to the system, and a system for returning only a water-containing solvent to be distilled into the reaction system. But it can be used.

When a desiccant is used, for example, molecular sieves (3A, 4A, 5A, etc.), diphosphorus pentoxide, calcium hydride, sodium hydride, metal hydrides such as lithium aluminum hydride, sodium, lithium, etc. Alkali metals and the like.

In the method of the present invention, polycondensation may be carried out by adding a coloring inhibitor in order to suppress coloration due to thermal deterioration during polycondensation. As the coloring inhibitor used, phosphorus compounds such as phosphoric acid, triphenyl phosphate, pyrophosphoric acid, phosphorous acid and triphenyl phosphite are preferable. The amount added is
It is 0.01 to 5% by weight, more preferably 0.5 to 2% by weight, based on the polymer. If it is less than 0.01% by weight, the coloring prevention effect is small, and if it is 5% by weight or more, the further coloring prevention effect is weak and the degree of polymerization may not be increased.

[0019]

EXAMPLES Examples of the present invention will be described below, but the present invention is not limited to the methods and apparatuses described below. The molecular weights of the polymers described herein are determined by gel permeation chromatography (column temperature 2
3 ° C.) in comparison with a polystyrene standard sample.

Example 1 In a 500 ml four-necked flask equipped with a thermometer, a stirring blade and a distillation tube, 83 g of 90% L-lactic acid (pyruvic acid and acetic acid, which are low boiling point compounds in lactic acid, Was 1500 ppm and 300 ppm respectively).
The mixture was heated and stirred at 30 ° C./50 mmHg for 3 hours while removing water out of the system. Next, the distillation pipe was removed, Dean Stack was attached instead, 0.4 g of Sn powder and 325 g of diphenyl ether were added, and 140 ° C / 4Hr / 23
The mixture was heated to reflux with mmHg. At this time, the mixture of the refluxed diphenyl ether and the produced water was separated in the Dean stack, and the aqueous layer was sequentially extracted. The amounts of low boiling point compounds removed to the outside of the reaction system so far were 1290 ppm of pyruvic acid and 295 ppm of acetic acid with respect to lactic acid. Instead of removing Dean Stack, a tube filled with 50 g of molecular sieves was attached, and the solvent distilled out by reflux was returned to the system through the molecular sieves. The reaction conditions were set to 130 ° C./15 to 18 mmHg, and while performing analysis of the lap sample every 5 hours, 20
Reacted for hours. Table 1 (Table 1) shows the time-dependent changes in the molecular weight of the lap samples. After completion of the reaction, 400 ml of chloroform was added to the reaction mass to dissolve it, and suction filtration was performed to remove tin powder. Methanol 1 was added to the obtained chloroform solution.
400 ml was added, and the precipitated white solid polylactic acid was filtered off and dried. The yield was 56.9 g, the yield was 95.2%, and the weight average molecular weight was 270,000 (in terms of polystyrene, the same applies hereinafter).

Comparative Example 1 83 g of 90% L-lactic acid was charged into a 500 ml four-necked flask equipped with a thermometer, stirring blades, and a distillation tube, and 130 ° C./5.
The mixture was heated and stirred while removing water from the system at 0 mmHg for 3 hours. The amount of low boiling point compounds removed to the outside of the reaction system up to here is
Pyruvic acid 390ppm, acetic acid 150pp against lactic acid
It was m. To this, 0.4 g of Sn powder and 325 g of diphenyl ether were added, and the solvent distilled off by reflux was allowed to return to the system through the molecular sieves. The reaction conditions were set to 130 ° C./15 to 18 mmHg, and the reaction was performed for 50 hours while analyzing the lap sample every 5 hours. Table 1 (Table 1) shows the time-dependent changes in the molecular weight of the lap samples. After completion of the reaction, chloroform 40 in the reaction mass
0 ml was added and dissolved, and suction filtration was performed to remove tin powder. Methanol 1400m in the obtained chloroform solution
1 was added, and the precipitated white solid polylactic acid was filtered off and dried. Yield 55.6 g, yield 93.0%, weight average molecular weight 120,000 (in terms of polystyrene, the same applies hereinafter).
Met.

[0022]

[Table 1]

Example 2 Instead of 83 g of 90% L-lactic acid, 75% of 90% L-lactic acid was used.
g and D / L lactic acid 15 g were used, and the same procedure as in Example 1 was carried out to obtain a copolymer of L-lactic acid and D / L lactic acid. Yield 93.4%, dehydration polycondensation time 15Hr,
The weight average molecular weight was Mw 255,000.

Example 3 Instead of 83 g of 90% L-lactic acid, 75% of 90% L-lactic acid was used.
g and glycolic acid 9.6 g were used, the same procedure as in Example 1 was carried out. As a result, a white solid copolymer of L-lactic acid and glycolic acid was obtained. The yield was 90.6%, the dehydration polycondensation time was 15 hours, and the weight average molecular weight was Mw 185,000.

Example 4 Instead of 83 g of 90% L-lactic acid, 75% of 90% L-lactic acid was used.
g and DL-4-hydroxybutanoic acid 6.8
As a result of performing the same method as in Example 1 except that g was used,
A copolymer of L-lactic acid and DL-4-hydroxybutanoic acid was obtained. The yield was 86.1%, the dehydration polycondensation time was 17 hours, and the weight average molecular weight was Mw 177,000.

Example 5 Instead of 83 g of 90% L-lactic acid, 75% of 90% L-lactic acid was used.
g and DL-3-hydroxybutanoic acid 6.8
As a result of performing the same method as in Example 1 except that g was used,
A copolymer of L-lactic acid and DL-3-hydroxybutanoic acid was obtained. The yield was 83.7%, the dehydration polycondensation time was 20 hours, and the weight average molecular weight was Mw 1910,000.

[0027]

INDUSTRIAL APPLICABILITY The method of the present invention is a method which makes it possible to industrially obtain a high molecular weight polymer from a hydroxycarboxylic acid or an oligomer thereof by dehydration polycondensation, in a short time, and at a low cost.

Claims (4)

[Claims] 1. Hydroxylcarboxylic acids or their oligomers are heated to reflux in an organic solvent in the presence of a catalyst to remove water and low-boiling compounds, and then dehydration weight is removed while simultaneously refluxing the solvent and removing water from the reaction system. A method for producing a polyhydroxycarboxylic acid, which comprises condensation. 2. An organic solvent containing the produced water distilled under reflux during dehydration polycondensation is treated with a desiccant and dried, or dehydrated by distillation separation and then returned to the reaction system again. The method for producing a polyhydroxycarboxylic acid according to claim 1, which is characterized in that. 3. The method according to claim 2, wherein the desiccant used is a molecular sieve, diphosphorus pentoxide, a metal hydrogen compound, or an alkali metal. 4. The hydroxycarboxylic acid is lactic acid, glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 3-hydroxyvaleric acid, or a mixture thereof. [3] The manufacturing method according to any one of [3] to [3].