JPH06306149A - Production of polyhydrocarboxylic acid - Google Patents

Abstract

PURPOSE:To produce a high-molecular polyhydroxycarboxylic acid industrially in a short time at a low cost from a hydroxycarboxylic acid or its oligomer directly by polycondensation by dehydration. CONSTITUTION:A hydroxycarboxylic acid is polycondensed by dehydration in the presence or absence of a catalyst and/or a solvent under the condition that a thin-film evaporation apparatus is used to separate and remove low- boiling components in the whole or a part of the polycondensation process.

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 polyhydroxycarboxylic acid useful as a biodegradable polymer as a substitute for medical materials and general-purpose resins.

[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, dehydration dimerization is carried out to obtain a cyclic dimer, and then ring opening is carried out in the presence of various catalysts. It is known that high molecular weight polymers can be obtained by 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 a 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. Further, the present applicant has azeotropically dehydrated hydroxycarboxylic acid or an oligomer thereof in an organic solvent in the presence of a catalyst in an inert gas atmosphere, treated the solvent distilled at this time with a desiccant, and then again. An application for a method of obtaining a polyhydroxycarboxylic acid having an average molecular weight of at least 30,000 by applying the method of returning to the system (Japanese Patent Application No. 3-336820). However, even in this method, the average molecular weight of 40,000-
It takes 17 to 50 hours under reflux to obtain 60,000 polyhydroxycarboxylic acid, which is not efficient.

In a kettle-type reactor equipped with an ordinary stirring blade, a low-boiling component (water in the case of polyhydroxycarboxylic acid production) that causes a reaction delay is removed under reduced pressure or an inert gas. It is performed under the blowing of. However, in a kettle-type reactor equipped with a stirring blade, the contact efficiency between the inert gas and the reactant is low, and even when the degree of pressure reduction is increased, the depth of the reactant is expected, The effect of removing low-boiling components as much as the above cannot be achieved.

[0006]

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 has conducted various studies in view of the problems of the prior art as described above, and as a result, when using a thin film evaporator, a higher molecular weight polyhydroxycarboxylic acid can be obtained in a shorter reaction time. I found it.

That is, according to the present invention, hydroxycarboxylic acids are added in the presence of a catalyst or in the absence of an organic solvent,
Alternatively, in the method of dehydration polycondensation in the absence of the compound, in a whole dehydration polycondensation step or a part of the dehydration polycondensation step, a thin film evaporator is used to perform thermal polycondensation while separating and removing low boiling point components. And a method for producing a polyhydroxycarboxylic 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 heptanoic acid, 2-hydroxy-2-butyl heptanoic acid, 2-hydroxy-2-pentyl heptanoic acid, 2-hydroxy-2-hexyl heptanoic acid, 2-hydroxy- 2-methyloctanoic acid, 2-hydroxy-2-ethyloctanoic acid, 2-hydroxy-2-propyloctanoic acid, 2-hydroxy-2-butyloctanoic acid, 2-hydroxy-2- Pentyl octanoic acid, 2- Droxy-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 Noic Cyd, 3-hydroxy-3-ethyl heptanoate dichroic acid, 3-hydroxy-3-propyl heptanoate dichroic acid, 3-
Hydroxy-3-butyl heptanoic acid, 3-
Hydroxy-3-methyloctanoic acid, 3-
Hydroxy-3-ethyl octanoic acid, 3-
Hydroxy-3-propyl octanoic 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-methyl octanoic acid, 4-hydroxy-4-ethyl octa Noic acid, 4-hydroxy-4-propyloctanoic acid, 4-hydroxy-4-butyloctanoic acid, 5-hydroxypentanoic acid, 5-hydroxyhexanoic acid, 5-hydroxyheptanoic Acid, 5-hydro Cyoctanoic acid, 5-hydroxy-5-methylhexanoic acid, 5-hydroxy-5-methylheptanoic acid, 5-hydroxy-5-ethylheptanoic acid, 5-hydroxy-5-methylocta Noic acid, 5-hydroxy-5-ethyloctanoic acid, 5-hydroxy-5-propyloctanoic acid, 6-
Hydroxy hexanoic acid, 6-hydroxy heptanoic acid, 6-hydroxy octanoic acid, 6-hydroxy-6-methyl heptanoic acid, 6-hydroxy-6-methyl octanoic acid, 6-hydroxy- 6-Ethyloctanoic acid, 7-Hydroxyheptanoic acid, 7
And aliphatic hydroxycarboxylic acids such as -hydroxyoctanoic acid, 7-hydroxy-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, glyco-acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid,
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 a D form and an 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 a low molecular weight polymer (intrinsic viscosity of about 0.
(Less than 3), the target polymer can be easily obtained with or without the 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. For example zinc,
Metals such as tin, aluminum, magnesium, antimony, titanium and zirconium. Tin oxide, antimony oxide,
Metal oxides such as lead oxide, aluminum oxide, magnesium oxide, and titanium oxide. Metal halides such as zinc chloride, stannous chloride, stannic chloride, stannous bromide, stannic bromide, antimony fluoride, zinc chloride, magnesium chloride and 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 Metal hydroxides such as barium, 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.

In the method of the present invention, either a method using an organic solvent or a method not using an organic solvent can be adopted in the dehydration polycondensation step. When an organic solvent is used, 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-
Examples include chlorobenzene.

Examples of ether aromatic hydrocarbons include alkoxybenzenes and diphenyl ethers. The alkoxybenzenes include anisole, ethoxybenzene, propoxybenzene, butoxybenzene, pentoxybenzene, 2,4-dimethoxybenzene, 2-chloromethoxybenzene, 2-bromomethoxybenzene, 4-chloromethoxybenzene, 4-bromomethoxy. Examples thereof include benzene and 2,4-dichloromethoxybenzene. Examples of the diphenyl ethers include alkyl-substituted diphenyl ethers such as diphenyl ether, 4,4'-dimethyldiphenyl ether, 3,3'-dimethyldiphenyl ether and 3-methyldiphenyl ether. 4,4'-dibromodiphenyl ether, 4,
Halogen-substituted diphenyl ether such as 4′-dichlorodiphenyl ether, 4-bromodiphenyl ether, 4-methyl-4-bromodiphenyl ether. Alkoxy-substituted diphenyl ethers such as 4-methoxydiphenyl ether, 4,4′-dimethoxydiphenyl ether, 3,3′-dimethoxydiphenyl ether and 4-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 thin film evaporation device is not particularly limited as long as it forms a thin film of a polymer solution or a polymer melt, but the following may be mentioned. It consists of a rotatable vertical cylindrical reactor, a raw material supply port in the upper part, a reaction product outlet in the lower part, and the feedstock was heated in the cylindrical reactor by the centrifugal force due to the rotation of the vertical cylindrical reactor. It is attached to the inner wall so that it can move downward. A stirring blade is fixed radially to a rotating shaft that penetrates the cylindrical or conical body, and the raw material fed into the body is centrifugally generated by the stirring blade to form a thin film on the inner wall of the body. A tower in which a part is filled with a packing, in which the raw material supplied from the upper part travels down the surface of the packing and is made to flow down in a thin film form. A polymer solution or polymer melt in the form of a filament or a film, which is allowed to flow down under an inert gas flow atmosphere or under reduced pressure. Provide a multi-stage taper roll in the casing, scrape the reaction product adhering in a thin film on the surface of the taper roll every rotation, and let the taper roll feed action sequentially send the reaction product to the taper roll surface of the next stage. What Any of the above mechanisms may be used.

In the method of the present invention, the thin film evaporator may be used throughout the dehydration polycondensation process, or may be used during a part of the dehydration polycondensation process. Also,
In the present invention, the reaction may be carried out batchwise or continuously.

The reaction may be carried out under normal pressure or under reduced pressure. When the reaction is carried out under reduced pressure, a vacuum pump is connected. Stirring is carried out while blowing in an inert gas and / or under reduced pressure. As the inert gas, nitrogen,
Argon etc. are illustrated.

At the time of reaction, the inside of the thin film evaporator is heated using a heating medium or by electric heating. The reaction temperature depends on whether or not an organic solvent is used, and when an organic solvent is used, the boiling point of the solvent. Further, although it depends on the thermal stability of the produced polymer, it is preferably 50 to 250 ° C.,
More preferably, it is 100 to 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 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.

[0021]

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 weight of the polymer described in this example was determined by gel permeation chromatography (column temperature: 23 ° C.) in comparison with a polystyrene standard sample.

Synthesis Example 1 100 parts by weight of 90% L-lactic acid was charged into a kettle-type reactor equipped with a normal stirring blade (anchor type) and a reflux condenser, and 130 ° C.
The mixture was heated and stirred while removing water to the outside of the system at / 50 mmHg for 3 hours. To this was added 70 parts by weight of diphenyl ether and 0.5 parts by weight of tin powder, and further molecular sieve 3A10.
A column filled with 0 parts by weight was prepared, and the solvent distilled out by reflux was allowed to return to the system through the molecular sieve column. The reaction conditions were set to 130 ° C./15 mmHg, stirring was continued for 3 hours, and the weight average molecular weight (Mw) was about 10,000.
Low molecular weight polylactic acid was obtained.

Example 1 A portion of the low molecular weight polylactic acid obtained in Synthesis Example 1 was heated to 100 ° C.
The film was heated to 150 ° C. and heated to 150 ° C. by the heating medium and supplied to the thin film evaporator by a supply pump. The thin film evaporator is a vertical type, the raw material supply port is at the bottom, and the reaction product is extracted from the upper part of the evaporator. In addition, the residence time can be controlled by the amount of liquid feed. 150 ° C
/ 15 mmHg, while distilling diphenyl ether and water were removed, the operation was carried out under the conditions of an average residence time of 30 minutes, whereby polylactic acid having a weight average molecular weight of 120,000 was continuously obtained. 70 parts by weight of chloroform was added to 10 parts by weight of the obtained reaction mass to dissolve it, and the tin powder was removed by filtration. 250 parts by weight of methanol was added to a chloroform solution of this polymer, and the precipitated white-yellow solid polylactic acid was separated by filtration and dried. The dried polylactic acid powder was white and had a weight average molecular weight of 120,000.

Comparative Example 1 A portion of the low-molecular-weight polylactic acid obtained in Synthesis Example 1 was continuously reacted in the kettle type reactor used in Synthesis Example 1. 150 ° C / 1
The reaction was continued under the condition of 5 mmHg, sampling was performed at 2 hour intervals, and the weight average molecular weight was measured. The results are shown in Table 1.

[0025]

[Table 1]

Example 2 100 parts by weight of 90% L-lactic acid was charged into a kettle type reactor equipped with a normal stirring blade (anchor type) and a reflux condenser, and the mixture was heated to 130 ° C.
The mixture was heated and stirred while removing water to the outside of the system at / 50 mmHg for 3 hours. 0.8 parts by weight of stannous chloride was added thereto, the reaction conditions were set to 130 ° C./15 mmHg, and stirring was continued for 5 hours to obtain polylactic acid having a weight average molecular weight (Mw) of about 40,000. Using the same thin-film evaporator as in Example 1, the medium-molecular-weight polylactic acid was heated to 100 ° C., and heated with a heating medium.
It was supplied by a supply pump to a thin film evaporator heated to 0 ° C. When water was distilled off at 170 ° C./15 mmHg and operated under an average residence time of 30 minutes, polylactic acid having a weight average molecular weight of 150,000 was continuously obtained. The same treatment as in Example 1 was performed to obtain white powder of polylactic acid.

Example 3 Three thin film evaporators similar to those used in Example 1 were connected in series to carry out the reaction. A solution was prepared by adding 70 parts by weight of diphenyl ether and 0.8 parts by weight of stannous chloride to 100 parts by weight of 90% L-lactic acid, and continuously supplying the solution to the first evaporator. In the first and second evaporators, 130
℃ / 50mmHg condition, the third evaporator is 1
Diphenyl ether and water distilled off under the condition of 70 ° C./15 mmHg were removed. The average residence time in each evaporator was 30 minutes each, and the total average residence time was 90 minutes. The weight average molecular weight was measured by sampling at intervals of 2 hours after the reaction product polymer was discharged from the third evaporator. The results are shown in Table 2.

[0028]

[Table 2]

[0029]

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

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hiroyuki Ito 30 Asmuta-cho, Omuta-shi, Fukuoka Mitsui Toatsu Chemical Co., Ltd.

Claims (2)

[Claims] 1. A method of dehydration polycondensation of a hydroxycarboxylic acid in the presence or absence of a catalyst, in the presence or absence of an organic solvent, in the entire dehydration polycondensation step or a part of the dehydration polycondensation step. 2. A method for producing polyhydroxycarboxylic acid, which comprises subjecting a low-boiling point component to thermal polycondensation while separating and removing the low-boiling point component, using a thin film evaporator. 2. The hydroxycarboxylic acid is lactic acid, glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 3-hydroxyvaleric acid, or a mixture thereof. A method for producing the described polyhydroxycarboxylic acid.