JPH072983A - Method for producing polyhydroxycarboxylic acid - Google Patents

Abstract

(57) [Summary] [Structure] In a method for producing polyhydroxycarboxylic acid by dehydration polycondensation of hydroxycarboxylic acids in the presence of a catalyst or in the absence of an organic solvent, polycondensation is carried out in a tank reactor. The reaction is carried out, the resulting reaction solution of polyhydroxycarboxylic acid is supplied to a thin film type evaporator, and the concentrated polyhydroxycarboxylic acid is returned to the tank reactor again, while distilling from the thin film type evaporator. The method for producing a polyhydroxycarboxylic acid, which comprises treating the solvent with a desiccant, or distilling and purifying the solvent, and then returning it to the reactor. [Effect] In the direct dehydration polycondensation of a high molecular weight polyhydroxycarboxylic acid useful as a biodegradable polymer, a target product having a target high molecular weight could be obtained in a shorter time.

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, in the case of producing a hydroxycarboxylic acid, for example, in the case of a hydroxycarboxylic acid such as lactic acid or glycolic acid, it is dehydrated and dimerized to obtain a cyclic dimer, and then in the presence of various catalysts. It is known that a high molecular weight polymer can be obtained by ring-opening melt polymerization. This method
The production of the cyclic dimer lactide or glycolide requires a great deal of labor and cost and is not economical. Further, some hydroxycarboxylic acids do not form a cyclic dimer, and in this case, this method cannot be used.

On the other hand, some 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 about 0.3 dl / g as a limit, and the polymer does not have sufficient mechanical properties and cannot be used depending on its application and purpose.

Further, the present applicant has previously azeotropically dehydrated hydroxycarboxylic acid or an oligomer thereof in an organic solvent in the presence of a catalyst in an inert gas atmosphere, and dried the solvent distilled at this time. A method for obtaining a polyhydroxycarboxylic acid having an average molecular weight of at least 30,000 by applying the agent and then returning it into the system was filed (Japanese Patent Application No. Hei 3).
-336820). However, even in this method, it takes 17 to 50 hours under reflux to obtain a polyhydroxycarboxylic acid having an average molecular weight of 120,000 or more, which is not efficient.

The direct polycondensation reaction of a hydroxycarboxylic acid such as lactic acid or glycolic acid is a sequential reaction similar to the esterification reaction between a dibasic acid and a polyhydric alcohol, and the molecular weight increases with the reaction time. However, this reaction is a reversible reaction, and the presence of water as a by-product in the reaction system causes a decrease in the molecular weight of the polycondensate due to the hydrolysis action. Therefore, it is necessary to remove the generated water to the outside of the system in order to obtain high molecular weight polylactic acid, polyglycolic acid, or the like.
As a means of removing water from the reaction mixture, a method of distilling a solvent and entraining or azeotropically distilling water is adopted, and the amount of distillate of the solvent is increased as much as possible to produce more water. It can be removed to the outside of the system more quickly.

By the way, the polycondensation reaction has hitherto been carried out using a tank reactor equipped with a stirring blade. In order to distill off the solvent, it is necessary to supply heat to the inside of the reactor, but as a general method, external heating using a reactor jacket or a coil can be mentioned. However, as the polycondensation reaction nears completion, the viscosity of the reaction mixture becomes extremely high, resulting in poor thermal conductivity, the distillate amount of the solvent is significantly reduced, and low-boiling substances such as by-product water are reduced. There is a problem that it becomes difficult to remove it efficiently from the reaction mixture.

As a countermeasure, there are a mechanical method of increasing the stirring speed, a method of increasing the temperature of external heating, a method of carrying out the reaction under reduced pressure or while blowing an inert gas, and the like. However, there is a problem in that the stirring speed is limited, and if the temperature of the external heating of the reactor is raised too much, thermal degradation of the polymer and catalyst will occur. Further, in the case of blowing an inert gas, the contact efficiency between the inert gas and the reaction product is low, and in the tank reactor, the reaction product accompanying the scale-up even when the degree of pressure reduction is increased. However, there is a problem that the expected solvent distilling effect cannot be obtained due to the increase of the liquid depth.

[0009]

DISCLOSURE OF THE INVENTION The present inventors completed the present invention as a result of intensive studies on a direct dehydration polycondensation method capable of industrially producing a polyhydroxycarboxylic acid efficiently, easily and inexpensively. Came to. The present inventor, as a result of repeated various studies in view of the problems of the prior art as described above,
By increasing the amount of solvent distilled using a thin-film distillation device while polymerizing in a tank reactor, low boiling components can be effectively removed, resulting in shorter reaction time and higher molecular weight. It was found that a polyhydroxycarboxylic acid of

That is, the present invention provides a method for producing polyhydroxycarboxylic acid by dehydration polycondensation of hydroxycarboxylic acids in the presence of a catalyst or in the presence of an organic solvent in the absence of a catalyst. While carrying out the polycondensation reaction in a tank-type reactor provided, the solvent to be distilled off is treated with a desiccant, or after being purified by distillation, it is returned to the reactor again, and the polycondensation reaction obtained above is carried out. The reaction solution of hydroxycarboxylic acid is supplied to a thin-film type evaporator, and while distillate such as solvent and water is evaporated and condensed polyhydroxycarboxylic acid is returned to the above-mentioned tank reactor, the solvent to be distilled is The present invention relates to a method for producing a polyhydroxycarboxylic acid, which comprises treating with a desiccant, or purifying by distillation, and then returning to the inside of a reactor.

Specific examples of the hydroxycarboxylic acid used in the present invention include the following. Glico
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.

In the method of the present invention, the addition of the polymerization catalyst can be arbitrarily selected depending on the degree of polymerization (intrinsic viscosity, molecular weight) of the desired polymer.
When producing low molecular weight polymers (intrinsic viscosities of about 0.
If less than 3), the target polymer can be easily obtained with or without addition of a catalyst. On the other hand, when producing a polymer having a high molecular weight (intrinsic viscosity of about 0.3 or more),
It is preferable to use a catalyst because of the reaction time (reaction rate).

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, organic metal 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 above-mentioned hydroxycarboxylic acid or oligomer thereof.

In the method of the present invention, dehydration polycondensation reaction is carried out in an organic solvent. Examples of the organic solvent used include aromatic hydrocarbons and ether-based aromatic hydrocarbons.

As aromatic hydrocarbons, toluene, xylene, naphthalene, biphenyl, chlorobenzene, o
-Chlorobenzene, m-chlorobenzene, p-chlorobenzene and the like can be mentioned. Examples of the ether-based aromatic hydrocarbons include alkoxybenzenes and diphenyl ethers.

The alkoxybenzenes include aniso-
, Ethoxybenzene, propoxybenzene, butoxybenzene, pentoxybenzene, 2,4-dimethoxybenzene, 2-chloromethoxybenzene, 2-bromomethoxybenzene, 4-chloromethoxybenzene, 4-bromomethoxybenzene, 2,4- Examples include dichloromethoxybenzene and the like.

The diphenyl ethers include diphenyl ether, 4,4'-dimethyldiphenyl ether,
Alkyl-substituted diphenyl ethers such as 3,3′-dimethyldiphenyl ether and 3-methyldiphenyl ether. 4,4'-dibromodiphenyl ether, 4,4 '
-Halogen-substituted diphenyl ether such as dichlorodiphenyl ether, 4-bromodiphenyl ether, 4-methyl-4-bromodiphenyl ether and the like. 4-methoxydiphenyl ether, 4,4'-dimethoxydiphenyl ether, 3,3'-dimethoxydiphenyl ether, 4
-Alkoxy-substituted diphenyl ethers such as methyl-4'-methoxydiphenyl ether. Examples thereof include cyclic diphenyl ethers such as dibenzofuran and xanthene. These may be used alone or as a mixture of two or more.

The tank reactor is preferably equipped with a vertical rotary shaft and a stirring blade attached to the rotary shaft, and is of a type suitable for medium to high viscosity substances. Specific examples include "Max Blend", "Super Blend" (concentric twin-screw stirring tank) manufactured by Sumitomo Heavy Industries, Ltd., "Twisted Lattice Blade" manufactured by Hitachi, Ltd., Mitsubishi "Advance Ribbon Reactor (A
R) ”,“ Vertical Cone Reactor (VCR) ”,
Examples include "Bister" manufactured by Nissen Corporation.

The thin-film evaporator has a large heat transfer coefficient, can form a thin film to effectively remove low-boiling substances, and forcibly transfers a high-viscosity or ultra-high-viscosity concentrated substance downward. Those having a structure are preferable. Specific examples include "Exeba" manufactured by Shinko Pantech Co., Ltd., "Evarator" manufactured by Sakura Seisakusho Co., Ltd., and "Contro" manufactured by Hitachi Ltd.

The polycondensation reaction in the tank reactor and the removal of low boiling point substances in the thin film distillation apparatus may be carried out either under normal pressure or under reduced pressure. When performing under reduced pressure, connect a vacuum pump. In the polycondensation reaction, stirring is performed while blowing an inert gas and / or under reduced pressure. Examples of the inert gas include nitrogen and argon.

Heating of the tank reactor and the thin film distillation apparatus is
Use heat medium for outer jacket. The reaction temperature varies depending on whether or not an organic solvent is used, the boiling point of the organic solvent when it is used, and the thermal stability of the produced polymer, but is preferably 50 to 250 ° C, more preferably 100 to 250 ° C. It is 200 ° C. If it is less than 50 ° C, the reaction rate is slow and it is not economical. Further, if the temperature exceeds 250 ° C., the polymer may be deteriorated or the quality of the obtained product may be deteriorated, which is not preferable.

In the method of the present invention, polycondensation may be carried out by adding a coloring inhibitor in order to suppress coloring 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.

In the figure, reference numeral 1 is a tank reactor equipped with a vertical rotary shaft, a stirring blade attached to this rotary shaft, and a heating jacket, and a raw material hydroxycarboxylic acid, a solvent, and a catalyst are charged and stirred. While doing the reaction. The reaction is
It consists of three steps: dehydration, oligomerization and polymerization.
First, in dehydration and oligomerization, most of the distillate is water, so it is cooled in the condenser 2 and removed outside the system. In the next polymerization, the solvent is distilled off, cooled in the condenser 2 and collected in the storage tank 4. Simultaneously with the polymerization reaction, the reaction mixture is continuously supplied to the thin film distillation apparatus 3 by the liquid feed pump 6 to distill off the solvent, cool it by the condenser 2 and collect it in the storage tank 4. The concentrate is returned to reactor 1. Since the recovered solvent contains water, it is returned to the reactor 1 after removing water through a desiccant. Further, instead of using a desiccant, water may be removed by distillation and returned to the reactor 1. In the reactor shown in the figure, the distilled solvent passes through the column 5 filled with the desiccant and returns to the reactor 1. If the desiccant cannot be packed in the column 5, the distillate solvent is refluxed and dehydrated in another reactor in the presence of the desiccant to distill a part of the solvent to carry out a polycondensation reaction. It can be carried out by a method such as returning to.

As described above, when the polycondensation reaction is carried out in the tank reactor, the thin film distillation apparatus is used to increase the evaporation surface area per unit amount of the reaction mixture.
Since the amount of solvent distilled increases and the water produced by polycondensation can be efficiently removed, polycondensation of polyhydroxycarboxylic acid can be carried out in a short time.

[0029]

EXAMPLES The present invention will be described in more detail below with reference to examples.
The molecular weight of the polymer was determined by gel permeation chromatography (column temperature: 40 ° C.) in comparison with a polystyrene standard sample. (Hereinafter abbreviated as polystyrene conversion.) Example 1 5 equipped with a stirring blade, jacket, thermometer and distilling pipe
In a 001 glass-lined tank reactor, 90% L-lactic acid (containing 10% water) 112.5 kg (1125 mo)
l), 0.405 kg (3.4 mol) of tin powder and 236 kg of diphenyl ether were charged, and the jacket was set at 14
Heat to 0 ° C and stir at 130 ° C / 160-130
Water was distilled off over 6 hours at mmHg. After that, the jacket temperature was raised to 150 ° C and 140 ° C / 110-10
Lactic acid was oligomerized at 0 mmHg for 25 hours. The obtained oligomer is continuously heated at 130 ° C / 20 ~
Polycondensation at 15 mmHg for 20 hours, average molecular weight 128
000 polylactic acid-diphenyl ether solution (about 25 weight percent) was obtained. At that time, the distillate of the reactor was cooled by a condenser and collected in a solvent storage tank.
-Dried through a column packed with molecular sieves and then returned to the reactor. At this time, the jacket temperature of the reactor was maintained at 150 ° C. On the other hand, the polycondensation reaction is carried out, and the polymerization liquid is supplied from the reactor to the thin film distillation apparatus made of stainless steel having a heat transfer area of 1 m2 at a flow rate of 160 kg / h and the concentrate is returned to the reactor again. did. The jacket temperature of the thin film distillation apparatus was set to 160 ° C. Diphenyl ether was distilled at 15 mmHg, and the distillate was cooled in the same condenser as above, collected in a solvent storage tank, dried through the above molecular sieve packed column, and then returned to the reactor. Lap analysis of the reaction solution was performed to measure the molecular weight. Table 1 shows the changes over time in the solvent distillation amount and the molecular weight.

Comparative Example 1 The polycondensation reaction was carried out in the same manner as in Example 1 except that the thin film distillation apparatus was not used and only the reactor jacket was used for heating. The temperature of the reactor jacket was set to 150 ° C. Lap analysis of the reaction solution was performed to measure the molecular weight. Table 1 shows the changes over time in the solvent distillation amount and the molecular weight. 50 hours polycondensation, average molecular weight 12600
A polylactic acid-diphenyl ether solution of 0 (about 25 weight percent) was obtained.

[0031]

[Table 1]

[0032]

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

[Brief description of drawings]

FIG. 1 is an example of a schematic view of a preferred method of the present invention.

[Explanation of symbols]

 1. Tank type reactor 2. Condenser 3. Thin film distillation apparatus 4. Solvent storage tank 5. Drying agent packing tower 6. Feed pump

Claims (2)

[Claims] 1. A method for producing a polyhydroxycarboxylic acid by dehydration polycondensation of a hydroxycarboxylic acid in the presence of an organic solvent in the presence or absence of a catalyst,
The polycondensation reaction is carried out in a tank reactor, the resulting reaction solution of polyhydroxycarboxylic acid is supplied to a thin film evaporator, and the concentrated polyhydroxycarboxylic acid is returned to the tank reactor again, A process for producing a polyhydroxycarboxylic acid, which comprises treating a solvent distilled from a thin film type evaporator with a desiccant, or distilling and refining and then returning the solvent to the reactor again. 2. The hydroxycarboxylic acid is lactic acid, glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 3-hydroxyvaleric acid, or a mixture thereof. Item 2. A method for producing a polyhydroxycarboxylic acid according to Item 1.