JP3288362B2 - Polyhydroxycarboxylic acid and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to polyhydroxycarboxylic acid which is a biodegradable polymer useful as a substitute for medical materials and general-purpose resins, and to produce the polyhydroxycarboxylic acid by direct dehydration condensation from hydroxycarboxylic acid. On how to do it. Among hydroxycarboxylic acids, lactic acid is particularly harmless to animals and plants and humans and is widely distributed in nature, and its polylactic acid is relatively easily hydrolyzed in the presence of water, Since it is hydrolyzed and absorbed even in the living body, it is attracting attention as a polymer that can be used for the above-mentioned applications.

[0002]

2. Description of the Related Art Polylactic acid or polyglycolic acid, which is a polyhydroxycarboxylic acid, is generally obtained by ring-opening polymerization of lactide or glycolide, which is a cyclic dimer of lactic acid or glycolic acid.

In US Pat. No. 2,703,316, D, L-lactic acid is oligomerized once, and then under reduced pressure.
Lactide is isolated at 200 to 250 ° C., and is further recrystallized from ethyl acetate several times to obtain a racemic lactide having a melting point of 120 ° C. or more, which is subjected to ring-opening polymerization to obtain a logarithmic viscosity number (η) of 0.45 dl / g. It is described that the above poly D, L-lactic acid can be obtained and can be made into a tough film or yarn. It also states that a polymer obtained by direct condensation from lactic acid is brittle and cannot be stretched.

US Pat. No. 2,758,987 discloses that L, L-lactide having a melting point of 94 ° C. or higher obtained from L-lactic acid in a similar manner has a logarithmic viscosity number (η) of 0.4 d.
A method for producing 1 / g or more of poly L-lactic acid is shown.

However, the production of lactide and glycolide suitable for the raw material of the polymer requires enormous labor and cost such as distillation and recrystallization, so that it is not economical. Further, the production of cyclic lactone such as lactide and glycolide is not possible. This method cannot be used when copolymerizing a hydroxy carboxylic acid which is not used.

On the other hand, the direct polycondensation reaction of a hydroxycarboxylic acid such as lactic acid or glycolic acid is a sequential reaction like the esterification reaction between a dibasic acid and a polyhydric alcohol, and the molecular weight increases with the reaction time. In addition, since the water generated at this time has an action of reducing the molecular weight of the polycondensate by a hydrolysis action, it is necessary to remove the generated water to the outside of the system to obtain a polyhydroxycarboxylic acid such as a high molecular weight polylactic acid or polyglycolic acid. Required to get the acid.

Japanese Patent Publication No. 96,12 / 1984
No. 3 has a reaction temperature of 220 to 260 in the absence of a catalyst.
There is disclosed a technique in which a condensation reaction is carried out at a temperature of 10 ° C. and a pressure of 10 mmHg or less to obtain polylactic acid having a molecular weight of 4,000 or more.

Further, US Pat. No. 4,273,92
No. 0 discloses a copolymer of lactic acid and glycolic acid obtained by removing the catalyst after dehydration condensation using an ion exchange resin as a catalyst, which contains substantially no catalyst and has a logarithmic viscosity number (η) of 0.08. 0.30 dl / g and an average molecular weight of 6,000 to 35,000.

However, in the above method, a high temperature of 180 ° C. or more is required to obtain a high molecular weight polymer, and the polymer obtained under such conditions is colored,
There are problems such as inclusion of impurities due to thermal decomposition.

Furthermore, the molecular weight of the polymer obtained by these methods is limited, and it is not possible to obtain a polymer having sufficient strength as a molded product such as a film or a thread.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to obtain a non-colored polyhydroxycarboxylic acid containing no impurities due to thermal decomposition, which overcomes the above-mentioned disadvantages of the prior art, by direct dehydration condensation of the hydroxycarboxylic acid. It is an object of the present invention to provide a polyhydroxycarboxylic acid having sufficient strength as a molded product such as yarn or yarn and a method for producing the same.

[0012]

SUMMARY OF THE INVENTION The present invention provides a polyhydroxycarboxylic acid by a direct dehydration condensation reaction of a hydroxycarboxylic acid and a method for producing the same. That is, the present invention provides a method for producing a polyhydroxycarboxylic acid, which comprises condensing a hydroxycarboxylic acid or an oligomer thereof in an organic solvent substantially in the absence of water, and a method for producing a polyhydroxycarboxylic acid produced by the method. A hydroxycarboxylic acid and an average molecular weight of at least 50,000, or a logarithmic viscosity number (η) of at least 0.40 dl / g, and at least about 16 in a ¹³ C-NMR spectrum.
9.27 ppm, about 169.31 ppm, about 169.4
2 ppm, about 169.49 ppm, about 169.66 pp
It is a polyhydroxycarboxylic acid composed of D-lactic acid units and L-lactic acid units, having five absorptions per m.

A feature of the production method of the present invention is that a thermal dehydration condensation reaction of hydroxycarboxylic acids is carried out in an organic solvent,
The generated water is distilled out of the reaction system together with the organic solvent.However, it is preferable to carry out a thermal dehydration condensation reaction of the hydroxycarboxylic acid in the organic solvent and distill the generated water out of the reaction system together with the organic solvent. The reaction is carried out while charging the organic solvent having an amount of water less than or equal to the amount of water dissolved in the distilled organic solvent as an additional solvent into the reaction system.

The organic solvent which can be used in the production method of the present invention includes, for example, hydrocarbon solvents such as toluene, xylene and mesitylene, chlorobenzene, bromobenzene, iodobenzene, dichlorobenzene, 1,1,2,2-tetrachlorobenzene. Halogen solvents such as chloroethane and p-chlorotoluene,
Ketone solvents such as 3-hexanone, acetophenone and benzophenone; dibutyl ether, anisole, phenetole, o-dimethoxybenzene, p-dimethoxybenzene, 3-methoxytoluene, dibenzylether, benzylphenylether, methoxynaphthalene Ether solvents, phenyl sulfide, thioether solvents such as thioanisole, methyl benzoate, methyl phthalate,
Ester solvents such as ethyl phthalate, diphenyl ether, or alkyl-substituted diphenyl ethers such as 4-methylphenyl ether, 3-methylphenyl ether, 3-phenoxytoluene, or 4-bromophenyl ether, 4-chlorophenyl ether, 4-bromo Halogen-substituted diphenyl ethers such as diphenyl ether and 4-methyl-4'-bromodiphenyl ether, or 4-methoxydiphenyl ether, 4-methoxyphenyl ether, 3-methoxyphenyl ether, 4-
Examples thereof include alkoxy-substituted diphenyl ethers such as methyl-4'-methoxydiphenyl ether and diphenyl ether solvents such as cyclic diphenyl ethers such as dibenzofuran and xanthene, and these may be used as a mixture. A solvent that can be easily separated from water as a solvent is preferable.Especially, in order to obtain a polyhydroxycarboxylic acid having a high average molecular weight, an ether solvent, an alkyl-aryl ether solvent and a diphenyl ether solvent are more preferable. -Aryl ether solvents and diphenyl ether solvents are particularly preferred.

The amount of these solvents used is preferably 10 to 80% in terms of the concentration of the obtained polymer.

In the production method of the present invention, in order to distill the generated water out of the reaction system, it is preferable to use azeotropic distillation of the organic solvent used and water. The organic solvent distilled off by azeotropic distillation may be returned to the reaction system after removing water by liquid separation when the amount of water contained is higher than the solubility of water in the organic solvent. In order to remove dissolved water, it may be treated with a desiccant or reduced in water content by distillation or the like, and then returned to the reaction system. Instead of the organic solvent distilled off by azeotropic distillation, a new organic solvent having a low water content may be charged. In addition, the water content of the reaction mixture can be set to a predetermined value by removing water under reduced pressure at the beginning of the reaction and then removing a part of the organic solvent from the reaction mixture containing the organic solvent.

In the present invention, the condensation reaction is promoted while removing water. In this embodiment, the solvent may or may not be azeotropic with water, and may or may not separate from water. May be. Further, other embodiments include a method in which an excess solvent is charged in advance and dehydration is performed by simply extracting the solvent, a method in which the reaction solvent is dried using another solvent, and the like. As a further modification, moisture may be removed while the reaction solvent itself remains liquid. Regarding the reaction temperature of the present invention, since the solvent azeotropes with water, the reaction may be performed at a predetermined temperature even if the boiling point is lowered.

The average molecular weight of the polyhydroxycarboxylic acid also depends on the water content of the organic solvent charged into the reaction system, and depends on the type of the solvent. The average molecular weight of the resulting polyhydroxycarboxylic acid is between 15,000 and 50,000. However, it is surprising that a polyphenylcarboxylic acid having an average molecular weight of 40,000 to 50,000 can be obtained using a diphenyl ether-based solvent even at the high water content. In order to obtain a polyhydroxycarboxylic acid having a higher average molecular weight, it is desirable that the water content of the organic solvent inserted into the reaction system is low, and the organic solvent distilled off by azeotropic treatment is treated with a desiccant to remove water or The average molecular weight Mw is from 50,000 to 200,000 by reducing the amount of water to be returned to the reaction system or by inserting a new organic solvent having a low water content to reduce the water content to 50 ppm or less.
0 polyhydroxycarboxylic acid can be obtained.

In the production method of the present invention, as a desiccant used to obtain a polyhydroxycarboxylic acid having a high average molecular weight, molecular sieves such as molecular sieve 3A, molecular sieve 4A, molecular sieve 5A, molecular sieve 13X, alumina, etc. , Silica gel, calcium chloride, calcium sulfate, phosphorus pentoxide,
Concentrated sulfuric acid, magnesium perchlorate, barium oxide, calcium oxide, potassium hydroxide, sodium hydroxide, or metal hydride such as calcium hydride, sodium hydride, lithium aluminum hydride, or alkali metal such as sodium can give. Among them, molecular sieves are preferable from the viewpoint of easy handling and regeneration.

The reaction temperature in the production method of the present invention is preferably from 80 to 200 ° C, more preferably from 110 to 170 ° C, in consideration of the rate of polymer formation and the rate of thermal decomposition of the formed polymer. The condensation reaction is usually performed at normal pressure at the distillation temperature of the organic solvent used.
When a high-boiling organic solvent is used in order to keep the reaction temperature within a preferable range, the reaction may be performed under reduced pressure. When a low-boiling organic solvent is used, the reaction may be performed under pressure.

The hydroxycarboxylic acid used in the present invention is an aliphatic carboxylic acid having a hydroxy group in the molecule, such as lactic acid, glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, and 3-hydroxybutyric acid. Examples include hydroxyvaleric acid, 5-hydroxyvaleric acid, and 6-hydroxycaproic acid. In the case of having an asymmetric carbon in the molecule, D-form and L-form
And the compound may be a single compound or a mixture of the D compound and the L compound, that is, a racemic compound. Further, one hydroxycarboxylic acid may be mixed with another hydroxycarboxylic acid, for example, such that a copolymer is produced by using a mixture of lactic acid and glycolic acid.

In the reaction of the present invention, a catalyst may or may not be used, but when a catalyst is used, the reaction rate can be increased. As the catalyst to be used,
Examples include metals of Group II, III, IV, and V of the periodic table, oxides thereof, and salts thereof. Specifically, metals such as zinc powder, tin powder, aluminum and magnesium, tin oxide, antimony oxide, zinc oxide, aluminum oxide, magnesium oxide, metal oxides such as titanium oxide, stannous chloride, stannic chloride Metal halides, such as stannous bromide, stannic bromide, antimony fluoride, zinc chloride, magnesium chloride, aluminum chloride, sulfates such as tin sulfate, zinc sulfate, aluminum sulfate, magnesium carbonate, zinc carbonate, etc. Organic carboxylate such as carbonate, tin acetate, tin octoate, tin lactate, zinc acetate, aluminum acetate, tin trifluoromethanesulfonate, zinc trifluoromethanesulfonate, magnesium trifluoromethanesulfonate, tin methanesulfonate, p -Organic sulfonates such as tin toluenesulfonate. In addition, an organic metal oxide of the above-mentioned metal such as dibutyltin oxide, or a metal alkoxide of the above-mentioned metal such as titanium isopropoxide, or an alkyl metal of the above-mentioned metal such as diethylzinc, or Dowex, Amberlite or the like Ion exchange resins and the like.

The amount used is 0.0001 to 1% of the hydroxycarboxylic acid used or the oligomer thereof.
0% by weight is good, and considering economics, 0.001 to 2% by weight is preferable.

The production method of the present invention is preferably carried out in an inert gas atmosphere so that moisture does not enter from outside the system, and may be carried out while replacing with an inert gas or while bubbling with an inert gas. .

The condensation reaction of the present invention can be carried out by a continuous operation or a batch operation. The dehydration of the solvent and the charging of the solvent can be performed by a continuous operation or a batch operation.

In the production method of the present invention, the reaction can be carried out while distilling water produced by the reaction together with the organic solvent outside the reaction system. Preferably, the produced water is distilled out together with the organic solvent outside the reaction system. At the same time, the reaction can be performed while charging an organic solvent having the same or lower water content as the amount of water dissolved in the distilled organic solvent into the reaction system. L-
It is described below using lactic acid (substantially all of the balance is water).

A water separator (eg, Dean Stark)
In a reactor equipped with a trap, solvent and a predetermined amount of 90
% L-lactic acid and a predetermined amount of a catalyst are charged, the reactor is heated, and the solvent and water are distilled off by azeotropic distillation and led to a water separator. At first, a large amount of water contained in the raw material L-lactic acid is distilled off together with the solvent. Water having a solubility equal to or higher than the solubility of the solvent is separated by a water separator and removed outside the system, and the solvent containing water for the solubility is returned to the reaction system. At this stage, water contained in the raw material L-lactic acid is distilled out almost completely, and L-lactic acid is oligomerized. The average molecular weight at this stage is 500-1,000,
It may contain a cyclic dimer (ie, lactide), or may have an average molecular weight of up to about 5,000. The reaction time during this period is approximately 0.5 hours to several hours. This oligomerization reaction may be carried out in advance in another reactor without solvent, without catalyst, under reduced pressure,
The reaction may be performed using a solvent without a catalyst. At the distillation temperature of the solvent, the water produced as the reaction proceeds is removed, and the reaction may be continued while returning the solvent saturated with water to the reaction system. According to this, those having an average molecular weight of 15,000 to 50,000 are obtained. In order to obtain a higher molecular weight polymer, the water separator is removed after almost all of the water in the raw material has been distilled off.
Attach a tube filled with a desiccant such as molecular sieve and allow the solvent to be distilled to reflux through this tube, or treat the distilled solvent in another reactor containing a desiccant to react. Return to the vessel or charge the reactor with fresh low water content solvent. According to these methods, the amount of water dissolved in the solvent is reduced to 50 ppm or less, and the reaction is continued for several tens of hours.
-Lactic acid can be obtained. After the completion of the reaction, any method may be used to obtain the desired polylactic acid.For example, methylene chloride is added to the reaction solution, then the mixture is discharged into methanol, and the precipitated crystals are filtered and dried. L-lactic acid is obtained.

The average molecular weight of the polyhydroxycarboxylic acids obtained by the method of the present invention can be determined by changing the type of solvent, the type and amount of catalyst, the reaction temperature, the reaction time, the method of treating the solvent distilled off by azeotropic distillation, and the like. , Various ones are obtained, but it is about 15,000 to 200,000. In addition, since the polyhydroxycarboxylic acid obtained by the method of the present invention can be subjected to a condensation reaction at a low temperature, there is no problem such as coloring or inclusion of impurities due to thermal decomposition, and the use of a polymer having a relatively low molecular weight. Even when used for adhesives, coating materials, etc., there is no external coloring, and there is a merit in appearance such that a desired color can be obtained by dyeing. In the case of a medical use such as a sustained release material, a material having a small content of impurities is required from the viewpoint of safety.

In particular, according to the method of the present invention, a cyclic dimer such as lactide is not used, and the average molecular weight is 50,000.
It is surprising that zero or more polyhydroxycarboxylic acids can be easily obtained, and it has not been known that polyhydroxycarboxylic acids having such a high molecular weight can be obtained directly from monomers. The high-molecular-weight polyhydroxycarboxylic acids thus obtained have sufficient strength and toughness when processed into films, molded products, and the like, and can be used as they are for containers and the like. In particular, when the polymer produced by the production method of the present invention is formed into a film, the average molecular weight is 50,000 (η = 0.4).
If it is lower than 0 dl / g), the tensile strength and elongation are not sufficient, and there is a problem in using it as a film. Therefore, when used as a film, the average molecular weight of this polymer is 50,000 in terms of strength and elongation.
(Η = 0.40 dl / g) or more, preferably 70,000 (η = 0.57 dl / g) or more, more preferably 100,000 (η = 0.78 dl / g) or more. Although required, according to the production method of the present invention, polyhydroxycarboxylic acids having a suitable molecular weight for use in this film can be easily obtained. Furthermore, these high molecular weight polyhydroxycarboxylic acids can be subjected to secondary processing such as stretching, blowing, vacuum forming and the like. Therefore, the high molecular weight polyhydroxycarboxylic acids obtained by the method of the present invention can be used as a medical material or as a substitute for a conventional general-purpose resin such as a foam or a network.

When the polyhydroxycarboxylic acid is a copolymer, a conventional method for producing the copolymer from a cyclic intermediate such as lactide or glycolide (hereinafter, referred to as “copolymer”) is used.
In the case of the lactide method), the sequence of the monomers in the polymer is composed of two identical monomers in pairs, whereas the copolymer obtained by the production method of the present invention has two monomers arranged randomly. With a structure
Their physical properties are also different. For example, poly-D, L-lactic acid which is a random copolymer of D-lactic acid and L-lactic acid which can be produced by the production method of the present invention, and poly D, L-lactic acid which is obtained by a lactide method, are shown in FIGS. As shown in the figure, the carbonyl group has a different ¹³ C-NMR spectrum pattern,
The carbonyl group of poly-D, L-lactic acid, which is a random copolymer of D-lactic acid and L-lactic acid, which can be produced by the production method of the present invention, has at least about 169.27 ppm and about 169.3.
1 ppm, about 169.42 ppm, about 169.49 pp
m and about 169.66 ppm show 5 specific absorptions. A molecular weight of 50,000 (η) showing such a unique absorption
= 0.40 dl / g) or more, a random copolymer of poly D, L-lactic acid was produced for the first time by the production method of the present invention. The poly D, L-lactic acid of this random copolymer is Fi
As is clear from the thermal analysis data in g.4, the melting point is lower than that of the corresponding poly D, L-lactic acid obtained by the lactide method, and there are practical advantages such as good heat sealability and good workability. Have. For example, D-form 10% and L-form 90%
130,000 (η = 0.94 dl /
The melting point of the random copolymer of g) is 115.6 ° C. and the corresponding lactide molecular weight of 130,000 (η =
0.94 dl / g).
In. This difference in melting point produces practical advantages such as good workability, and is used, for example, as a film having significantly improved heat sealability. In addition, since the melting point and crystallinity are low, when used as a soft polymer,
The amount of plasticizer used can be reduced.

Further, poly D, L-lactic acid which can be produced by the production method of the present invention containing 3 to 25% of D-form shows excellent transparency when formed into a film, and the content of D-form is 5%.
~ 20% is preferred.

[0032]

EXAMPLES Examples will be shown below, but the present invention is not limited to these examples.

The average molecular weight (MW) of the polyhydroxycarboxylic acids described in this specification was determined by gel permeation chromatography (column temperature 40 ° C., chloroform solvent) in comparison with a polystyrene standard sample.

The water content in the solvent was measured using a Karl Fischer moisture meter (MKC-210, manufactured by Kyoto Electronics Industry Co., Ltd.). The logarithmic viscosity number (η) of the polyhydroxycarboxylic acids of the present invention was determined using an Ubbelohde viscometer,
It was measured at 20 ° C. using a solution in which 0.1 g of polyhydroxycarboxylic acid was dissolved per 100 ml of methylene chloride, and was obtained from the following equation.

Η = ln (t / t ₀ ) / C (where t is the outflow time of the solution, t ₀ is the outflow time of the solvent,
C represents the concentration of the solution (g / dl). In the examples, the moisture in the solvent was measured using a Karl Fischer moisture meter (MKC-210, manufactured by Kyoto Electronics Industry Co., Ltd.).

Example 1 Using an apparatus equipped with a Dean Stark trap,
In the presence of 0.1 g of tin trifluoromethanesulfonate (hereinafter abbreviated as TFS tin), 40.2 g of 90% L-lactic acid was added to m-
The azeotropic dehydration was performed at 138 ° C. for 2 hours in 400 ml of xylene. After removing the water accumulated in the Dean Stark trap out of the system, the Dean Stark trap is removed.
p was replaced with a tube filled with 40 g of molecular sieve 3A, so that the distilled solvent returned to the reactor through the molecular sieve layer. Then, at 138 ° C, 4
It was azeotropically dehydrated for 0 hours. The water content of the solvent after passing through the molecular sieve was 3 ppm. About 2 reaction
After concentration twice, 300 ml of methylene chloride was added. afterwards,
The crystals were discharged into 900 ml of methanol, and the precipitated crystals were filtered by suction, followed by washing with methanol. After drying under reduced pressure,
20.3 g (70% yield) of white polylactic acid was obtained. The average molecular weight of the produced polylactic acid was 60,000.

Example 2 Using an apparatus equipped with a Dean Stark trap,
40.2 g of 90% L-lactic acid was added in the presence of 0.1 g of metallic tin,
In 200 ml of mesitylene, azeotropic dehydration was performed at 163 ° C. for 2 hours. After removing the water accumulated in the Dean Stark trap out of the system, the Dean Stark tr
The ap was replaced with a tube filled with 40 g of molecular sieve 5A, and the distilled solvent was returned to the reactor through the molecular sieve layer. Thereafter, azeotropic dehydration was performed at 163 ° C. for 20 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added.
Suction filtration was performed. Thereafter, the mixture was discharged into 900 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol. After drying under reduced pressure, 23.1 g (79% yield) of white polylactic acid was obtained. The average molecular weight of the generated polylactic acid is
60,000.

Example 3 Using an apparatus equipped with a Dean Stark trap,
40.2 g of 90% L-lactic acid was added in the presence of 0.5 g of metal tin,
The azeotropic dehydration was performed at 154 ° C. for 2 hours in 85 ml of anisole. After removing the water accumulated in the Dean Stark trap out of the system, the Dean Stark trap is removed.
p was replaced with a tube filled with 40 g of molecular sieve 3A, so that the distilled solvent returned to the reactor through the molecular sieve layer. Then, at 154 ° C, 4
Azeotropic dehydration was performed for 5 hours. In addition, the water content in the solvent after passing through the molecular sieve was 1 ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added, followed by suction filtration. Thereafter, the mixture was discharged into 900 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol. After drying under reduced pressure, 24.4 g (yield 84%) of white polylactic acid was obtained. The logarithmic viscosity number (η) of the obtained polymer was 0.84. The average molecular weight of the produced polylactic acid was 100,000.

Example 4 Using a device in which a tube containing 40 g of molecular sieve 3A and 40 g was attached, and the distilled solvent was passed through the molecular sieve layer and returned to the reactor, 90% was used in advance.
40.2 g of L-lactic acid was added in the presence of 0.3 g of metallic tin,
30.0 g of lactic acid oligomer obtained by dehydration condensation at 40 ° C. and 40 mmHg for 2 hours was added with 300 ml of o-dichlorobenzene without removing metal tin, and subjected to azeotropic dehydration at 130 ° C./180 mmHg for 45 hours. In addition, the water content in the solvent after passing through the molecular sieve was 1 ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added, followed by suction filtration. Then, discharge into 900 ml of methanol,
The precipitated crystals were subjected to suction filtration and subsequently washed with methanol. After drying under reduced pressure, 18.8 g of white polylactic acid (yield 7)
3%). The average molecular weight of the produced polylactic acid is 5
It was 0000.

Example 5 Using an apparatus equipped with a Dean Stark trap,
32.2 g of 90% L-lactic acid and 8.0% of 90% D, L-lactic acid
g was subjected to azeotropic dehydration for 5 hours at 154 ° C. in 85 ml of anisole in the presence of 0.5 g of metallic tin. Dean S
After water remaining in the trap trap was removed from the system, the Dean Stark trap was replaced with a tube filled with molecular sieve 3A, 40 g, and the distilled solvent was returned to the reactor through the molecular sieve layer. I made it. Thereafter, azeotropic dehydration was performed at 154 ° C. for 50 hours. In addition, the water content in the solvent after passing through the molecular sieve was 1 ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added, followed by suction filtration. Thereafter, the mixture was discharged into 900 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol. After drying under reduced pressure, 23.5 g (81% yield) of white polylactic acid was obtained.
The average molecular weight of the produced polylactic acid was 80,000.

Example 6 Using an apparatus equipped with a Dean Stark trap,
30.0 g of 90% L-lactic acid and 10.0 g of DL-hydroxybutyric acid were subjected to azeotropic dehydration for 2 hours at 163 ° C. in 400 ml of mesitylene in the presence of 0.1 g of metal tin. After removing the water accumulated in the Dean Stark trap to the outside of the system, the Dean Stark trap is replaced with a tube filled with the molecular sieve 3A, 40 g, and the distilled solvent is returned to the reactor through the molecular sieve layer. did. Thereafter, azeotropic dehydration was performed at 163 ° C. for 30 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added. Thereafter, the mixture was discharged into 900 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol. After drying under reduced pressure, 23.5 g (78% yield) of the copolymer was obtained. The average molecular weight of the resulting copolymer was 50,000.

Example 7 A tube in which 40 g of molecular sieve 3A was placed was attached, and a device in which the distilled solvent was returned to the reactor through the molecular sieve layer was used.
30.0 g of L-lactic acid and 5.0 g of 4-hydroxy-n-butylic acid were added in the presence of 0.5 g of tin metal for 150 days.
The oligomer obtained by heating and stirring at 40 ° C and 40 mmHg for 2 hours was used as a raw material, and the catalyst was removed without removing 400 m of mesitylene.
and azeotropic dehydration at 163 ° C. for 25 hours. The amount of water in the solvent after passing through the molecular sieve is 3
ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added. Then, 900m of methanol
The crystals were discharged into the flask, and the precipitated crystals were filtered by suction, followed by washing with methanol. After drying under reduced pressure, the copolymer 20.0
g (78% yield). The average molecular weight of the resulting copolymer was 50,000.

Example 8 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while flowing water out of the system to obtain 25.3 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g and 150 g of acetophenone were added, and 130 ° C./8
An azeotropic dehydration reaction was performed at 0 mmHg for 1 hour. Dean
After removing the water accumulated in the Stark trap to the outside of the system, the Dean Stark trap was replaced with a tube filled with molecular sieve 3A, 40 g, and the distilled solvent was returned to the reactor through the molecular sieve layer. did. Thereafter, the reaction was performed at 130 ° C./80 mmHg for 55 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 600 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 19.4 g (yield: 75%) of white polylactic acid was obtained. The average molecular weight of the produced polylactic acid was 70,000.

Example 9 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.6 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g and 150 g of phenetole were added, and an azeotropic dehydration reaction was performed at 170 ° C. for 1 hour to remove water, and then Dean
The Stark trap was removed, and a tube filled with Molecular Sieve 3A, 20 g was attached, so that the solvent to be distilled out returned to the system through the Molecular Sieve. The reaction was performed at 170 ° C. for 55 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 600 ml of methanol, and the precipitated crystals were filtered by suction.
Subsequently, methanol washing and hexane washing were performed. 30
After drying under reduced pressure at 5 ° C./5 mmHg, white polylactic acid 18.6 was obtained.
g (72% yield). The average molecular weight of the obtained polylactic acid was 75,000.

Example 10 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while flowing water out of the system to obtain 25.5 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g and 150 g of p-dimethoxybenzene were added, and 15 g
An azeotropic dehydration reaction was performed at 2 ° C./135 mmHg for 1 hour to remove water, then the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 20 g was attached, and the solvent to be distilled out passed through the molecular sieve again. Returned to the system. 152 ° C / 135mm
The reaction was performed at Hg for 50 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 600
and the precipitated crystals are filtered off with suction,
Methanol washing and hexane washing were performed. 30 ℃ / 5m
After drying under reduced pressure at mHg, 18.1 g (yield 70%) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid is 6
It was 0000.

Example 11 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.5 g of an oligomer. To this, 0.141 g of stannous chloride was added, and the mixture was further stirred at 150 ° C./30 mmHg for 2 hours. A Dean Stark trap was attached, 0.666 g of stannous chloride and 150 g of 3-methoxytoluene were added, and an azeotropic dehydration reaction was performed at 175 ° C. for 1 hour to remove water. Thereafter, the Dean Stark trap was removed, and molecular sieve 3A, 20 g Was attached, and the solvent to be distilled was returned to the system again through the molecular sieve. The reaction was performed at 175 ° C. for 50 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 600 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg,
19.1 g (74% yield) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid was 60,000.

Example 12 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while flowing water out of the system to obtain 25.8 g of an oligomer. To this, 0.112 g of tin oxide was added, and the mixture was further stirred at 150 ° C./30 mmHg for 2 hours. Attach Dean Stark trap, add 0.530 g of tin oxide and 450 g of thioanisole, and add 13
An azeotropic dehydration reaction was performed at 0 ° C./150 mmHg for 1 hour to remove water, then the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 20 g was attached, and the solvent to be distilled out passed through the molecular sieve again. Returned to the system. 130 ° C / 150mm
The reaction was performed at Hg for 50 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 600
and the precipitated crystals are filtered off with suction,
Methanol washing and hexane washing were performed. 30 ℃ / 5m
After drying under reduced pressure at mHg, 18.3 g (71% yield) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid is 5
It was 0000.

Example 13 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.9 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. Thereafter, 0.417 g of tin powder and 76.0 g of anisole were added thereto, and anisole dried with a molecular sieve 3A and having a water content of 36 ppm was distilled at 154 ° C. while being charged at 154 ° C. At this time, the charging speed and the outflow speed were adjusted to be equal, and the reaction was carried out by distilling while charging 1800 g of anisole in 130 hours. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 600 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 18.1 g (yield 70%) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid was 70,000.

Example 14 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.3 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g and 75.9 g of diphenyl ether were added, and 130
An azeotropic dehydration reaction was carried out at a temperature of 12 ° C. for 12 hours to remove water. After that, the Dean Stark trap was removed, a tube filled with 20 g of molecular sieve 3A was attached, and the solvent distilled off by reflux was a molecular sieve.
And returned to the system again. 130 ° C / 12
The reaction was performed at mmHg for 48 hours. In addition, the water content in the solvent after passing through the molecular sieve was 1 ppm.
170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 6
The solution was discharged into 00 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol and hexane. 30 ° C /
After drying under reduced pressure at 5 mmHg, 21.5 g of white polylactic acid
(83% yield). The average molecular weight of the obtained polylactic acid was 184,000.

Example 15 40.2 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 28.0 g of an oligomer. 0.098 g of tin powder was added thereto, and the mixture was further stirred at 150 ° C./30 mmHg for 2 hours. 0.378 g of tin powder and 8 parts of diphenyl ether
4.0 g was added thereto, and an azeotropic dehydration reaction was performed at 150 ° C./35 mmHg. At this time, a tube filled with molecular sieve 3A, 20 g was attached, and the solvent distilled out by reflux passed through the molecular sieve again into the system. Back to 1
The reaction was performed for 5 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. The reaction solution was filtered under heating to remove tin powder, and then concentrated under reduced pressure to obtain 27.2 g (yield 94%) of white polylactic acid. The average molecular weight of the obtained polylactic acid was 133,000.

Example 16 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.2 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g, diphenyl ether 38.0 and anisole 3
8.0 g was added, an azeotropic dehydration reaction was performed at 154 ° C. for 1 hour to remove water, and thereafter, Dean Stark tra.
After removing p, a tube filled with 20 g of molecular sieve 4A was attached, and the solvent distilled off under reflux was returned to the system again through the molecular sieve. 154
The reaction was carried out at 50 ° C for 50 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 170 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 600m
The crystals were discharged into the flask, and the precipitated crystals were filtered by suction, followed by washing with methanol and washing with hexane. 30 ℃ / 5mm
After drying under reduced pressure with Hg, 21.2 g of white polylactic acid (yield 8
2%). The average molecular weight of the obtained polylactic acid is 15
It was 0000.

Example 17 Two reaction flasks were arranged in parallel, an azeotropic dehydration reaction was performed in one of the flasks, and the solvent was dried in the other. The apparatus was set up to flow into the flask, and the solvent was circulated between the two reaction flasks. In an azeotropic dehydration flask, a mixture of 30.0 g of a synthesized lactic acid oligomer, 0.3 g of tin powder and 90 g of diphenyl ether was stirred at 150 ° C. and 30 mmHg for 3 hours in the absence of a catalyst in advance at 150 ° C./35 m
Heat and stir at mHg. The drying flask was charged with 10 g of calcium hydride and 400 g of diphenyl ether, and reacted for 30 hours while heating and stirring at 150 ° C./35 mmHg. The amount of water in the solvent returning to the reactor was 1 pp
m. 200 g of chloroform was added to the reaction solution, followed by filtration to remove tin powder. Thereafter, the filtrate was treated with methanol 70
The solution was discharged into 0 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol and hexane. 30 ° C /
After drying under reduced pressure at 5 mmHg, 23.7 g (yield: 82%) of white polylactic acid was obtained. The average molecular weight of the generated polylactic acid is
166,000.

Example 18 Two reaction flasks were arranged side by side, an azeotropic dehydration reaction was performed on one side, and the solvent was dried on the other side. The apparatus was set up to flow into the flask, and the solvent was circulated between the two reaction flasks. In an azeotropic dehydration flask, a mixture of 30.0 g of a synthesized lactic acid oligomer, 0.3 g of tin powder and 90 g of diphenyl ether was stirred at 150 ° C. and 30 mmHg for 3 hours in the absence of a catalyst in advance at 150 ° C./35 m
Heat and stir at mHg. In a drying flask, put 10 g of diphosphorus pentoxide and 400 g of diphenyl ether,
The reaction was carried out for 30 hours while heating and stirring at 0 ° C./35 mmHg. The amount of water in the solvent returned to the reactor was 3 ppm. 200 g of chloroform was added to the reaction solution, followed by filtration to remove tin powder. Then, the filtrate was treated with 700 m of methanol.
The crystals were discharged into the flask, and the precipitated crystals were filtered by suction, followed by washing with methanol and washing with hexane. 30 ℃ / 5mm
After drying under reduced pressure with Hg, 22.8 g of white polylactic acid (yield 79)
%). The average molecular weight of the produced polylactic acid is 12
It was 0000.

Example 19 36.0 g of 90% L-lactic acid, 9.0% of 90% D, L-lactic acid
g was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 31.6 g of an oligomer. Then, 0.158 g of tin powder was added, and 150 ° C./30 mmHg was added.
And further stirred for 2 hours. Dean Stark t
rap, 0.743 g of tin powder and 95.0 g of diphenyl ether were added, and an azeotropic dehydration reaction was carried out at 150 ° C./35 mmHg for 1 hour to remove water, and then Dean
The Stark trap was removed, and a tube filled with 25 g of molecular sieve 3A was attached, so that the solvent distilled off by reflux returned to the system through the molecular sieve. The reaction was performed at 150 ° C./35 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. To this reaction solution, 220 g of chloroform was added, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 750 ml of methanol, and the precipitated crystals were filtered by suction, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 26.9 g (83% yield) of white polylactic acid was obtained.
The average molecular weight of the obtained polylactic acid was 160,000.

Example 20 32.4 g of 90% L-lactic acid, 3.9 of 70% glycolic acid
g was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 27.4 g of an oligomer. Then, 0.158 g of tin powder was added, and 150 ° C./30 mmHg was added.
And further stirred for 2 hours. Dean Stark t
rap, 0.743 g of tin powder and 95.0 g of diphenyl ether were added, and an azeotropic dehydration reaction was carried out at 150 ° C./35 mmHg for 1 hour to remove water, and then Dean
The Starktrap was removed, a tube filled with 25 g of molecular sieve 3A was attached, and the solvent distilled off under reflux was returned to the system again through the molecular sieve. The reaction was performed at 150 ° C./35 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. To this reaction solution, 220 g of chloroform was added, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 750 ml of methanol, and the precipitated crystals were filtered by suction, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 22.0 g (yield 85%) of the copolymer was obtained. The average molecular weight Mw of the obtained copolymer was 140,000.

Example 21 32.4 g of 90% L-lactic acid, DL-3-hydroxy-n
3.75 g of butyric acid at 150 ° C./50 mm
The mixture was heated and stirred at Hg for 3 hours while distilling water out of the system to obtain 27.4 g of an oligomer. 0.158 g of tin powder was added thereto, and the mixture was further stirred at 150 ° C./30 mmHg for 2 hours. Attach Dean Stark trap, add 0.743 g of tin powder and 95.0 g of diphenyl ether,
An azeotropic dehydration reaction was carried out at 150 ° C./35 mmHg for 1 hour to remove water. After that, the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 25 g was attached, and the solvent distilled off by reflux was a molecular sieve. I passed through the system again. 150 ° C /
The reaction was performed at 35 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. To this reaction solution, 220 g of chloroform was added, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 750 ml of methanol, and the precipitated crystals were filtered by suction.
Subsequently, methanol washing and hexane washing were performed. 30
21.5 g of copolymer after drying under reduced pressure at 5 ° C./5 mmHg
(83% yield). The average molecular weight of the obtained copolymer was 100,000.

Example 22 32.4 g of 90% L-lactic acid and 3.75 g of 4-hydroxy-n-butylic acid were heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system. 4 g were obtained. To this, add tin powder 0.158g,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin powder 0.7
43 g and 95.0 g of diphenyl ether were added,
An azeotropic dehydration reaction was carried out at ℃ / 35 mmHg for 1 hour to remove water, then the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 25 g was attached, and the solvent distilled off by reflux was a molecular sieve.
And returned to the system again. 150 ° C / 35
The reaction was performed at mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm.
To this reaction solution, 220 g of chloroform was added, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 7
The solution was discharged into 50 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol and hexane. 30 ° C /
After drying under reduced pressure at 5 mmHg, 21.0 g (yield 81%) of the copolymer was obtained. The average molecular weight of the obtained copolymer is
105,000.

Example 23 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. To this, add 0.108g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin powder 0.5
10 g and 92.2 g of 3-phenoxytoluene were added, and 1
An azeotropic dehydration reaction was carried out at 50 ° C./20 mmHg for 2 hours to remove water. After that, the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 20 g was attached, and the solvent distilled off by reflux was a molecular sieve. And returned to the system again. 150 ° C /
The reaction was performed at 20 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 200 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 700 ml of methanol, and the precipitated crystals were filtered by suction.
Subsequently, methanol washing and hexane washing were performed. 30
After drying under reduced pressure at 5 ° C./5 mmHg, 26.2 white polylactic acid was obtained.
g (83% yield). The average molecular weight of the obtained polylactic acid was 150,000.

Example 24 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. To this, add 0.108g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin powder 0.5
10 g and 92.2 g of 4-bromodiphenyl ether were added, and an azeotropic dehydration reaction was performed at 150 ° C./6 mmHg for 2 hours to remove water, and thereafter, Dean Stark tra.
After removing p, a tube filled with 20 g of molecular sieve 3A was attached, and the solvent distilled off by reflux was returned to the system again through the molecular sieve. 150
The reaction was carried out at a temperature of 6 ° C./6 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 200 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 700 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane.
After drying under reduced pressure at 30 ° C./5 mmHg, white polylactic acid 2
5.6 g (81% yield) was obtained. The average molecular weight of the obtained polylactic acid was 140,000.

Example 25 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. To this, add 0.108g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin powder 0.5
10 g and 92.2 g of dibenzofuran were added, and 154 ° C. /
An azeotropic dehydration reaction was performed at 20 mmHg for 2 hours to remove water, then the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 20 g was attached, and the solvent distilled off by reflux was a molecular sieve.
And returned to the system again. 154 ° C / 20
The reaction was performed at mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm.
200 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 7
The solution was discharged into 00 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol and hexane. 30 ° C /
After drying under reduced pressure at 5 mmHg, 26.2 g of white polylactic acid
(83% yield). The average molecular weight of the obtained polylactic acid was 150,000.

Example 26 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. To this, 0.173 g of stannous chloride was added, and the mixture was further stirred at 150 ° C./30 mmHg for 2 hours. A Dean Stark trap was attached, 0.816 g of stannous chloride and 92.2 g of diphenyl ether were added, an azeotropic dehydration reaction was performed at 130 ° C./12 mmHg for 2 hours to remove water, and thereafter, a Dean Stark tr.
The ap was removed, a tube filled with 20 g of molecular sieve 3A was attached, and the solvent distilled off by reflux was returned to the system again through the molecular sieve. 13
The reaction was carried out at 0 ° C./12 mmHg for 40 hours. The amount of water in the solvent after passing through the molecular sieve was 2 ppm
Met. 200 g of chloroform was added to the reaction solution,
Suction filtration was performed to remove tin powder. The chloroform solution was discharged into 700 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 24.9 g (yield 79%) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid was 110,000.

Example 27 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. 0.386 g of tin octoate
Was added, and the mixture was further stirred at 150 ° C./30 mmHg for 2 hours. Attach a Dean Stark trap, 1.821 g of tin octoate and 92.2 g of diphenyl ether
, And an azeotropic dehydration reaction is performed at 130 ° C./12 mmHg for 2 hours to remove water, and then Dean Stark is added.
The trap was removed, and a tube filled with 20 g of molecular sieve 3A was attached, so that the solvent distilled by reflux returned to the system again through the molecular sieve.
The reaction was performed at 130 ° C./12 mmHg for 55 hours. The amount of water in the solvent after passing through the molecular sieve is 2
ppm. 200 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 700 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 23.9 g (yield: 76%) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid was 70,000.

Example 28 36.0 g of 90% L-lactic acid and 0.505 g of tin powder were heated and stirred at 130 ° C./100 mmHg for 5 hours in a solvent of 76.0 g of diphenyl ether while distilling water out of the system.
After that, diphenyl ether dehydrated with a molecular sieve 3A and having a water content of 10 ppm in advance at 130 ° C. /
Distillation was performed while charging at 12 mmHg. At this time, the charging speed and the distilling speed were adjusted to be equal, and the reaction was performed while distilling while charging 3,900 g of diphenyl ether in 130 hours. Chloroform 17 was added to this reaction solution.
After adding 0 g, the mixture was subjected to suction filtration to remove tin powder. The chloroform solution was discharged into 600 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 19.4 g (yield: 75%) of white polylactic acid was obtained. The average molecular weight of the obtained polylactic acid was 100,000.

Example 29 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. To this, add 0.108g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin powder 0.5
10 g and 92.2 g of diphenyl ether were added, and 150
An azeotropic dehydration reaction was carried out at a temperature of 35 ° C./35 mmHg for 2 hours to remove water. Thereafter, the Dean Stark trap was removed, a tube filled with 20 g of molecular sieve 3A was attached, and the solvent distilled off by reflux was a molecular sieve.
And returned to the system again. 150 ° C / 35
The reaction was performed at mmHg for 40 hours. In addition, the water content in the solvent after passing through the molecular sieve was 1 ppm.
200 g of chloroform was added to the reaction solution, and suction filtration was performed to remove tin powder. This chloroform solution was added to methanol 7
The solution was discharged into 00 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol and hexane. 30 ° C /
After drying under reduced pressure at 5 mmHg, 26.8 g of white polylactic acid
(85% yield). The average molecular weight of the obtained polylactic acid was 147,000.

Example 30 Using an apparatus equipped with a Dean Stark trap,
40.2 g of 90% L-lactic acid was subjected to azeotropic dehydration for 40 hours in 400 ml of m-xylene in the presence of 0.1 g of TFS tin. The amount of water in m-xylene circulating between the Dean Stark trap and the reactor is finally 4
It was 39 ppm. After concentrating the reaction solution about twice, 300 ml of methylene chloride was added. Then, methanol 90
The solution was discharged into 0 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol. After drying under reduced pressure, 11.6 g (yield: 40%) of white polylactic acid was obtained. The average molecular weight of the produced polylactic acid was 15,000.

Example 31 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.3 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g and 75.9 g of diphenyl ether were added, and 130
An azeotropic dehydration reaction was performed at 30 ° C./12 mmHg for 30 hours to carry out the reaction while removing water to be separated. The amount of water in the solvent that separated water and returned to the reactor was 450 ppm.
600 g of chloroform was added to the reaction solution, and the mixture was subjected to suction filtration to remove tin powder. This chloroform solution was added to methanol 6
The solution was discharged into 00 ml, and the precipitated crystals were filtered by suction, followed by washing with methanol and hexane. 30 ° C /
After drying under reduced pressure at 5 mmHg, 18.7 g of white polylactic acid
(72% yield). The average molecular weight of the obtained polylactic acid was 48,000.

Comparative Example 1 43.8 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.7 g of an oligomer. To this, add 0.108g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. 0.510 g of tin powder was added, and a dehydration reaction was performed at 150 ° C./1 mmHg for 30 hours. Add chloroform 170 to this reaction solution.
g was added thereto, and suction filtration was performed to remove tin powder. The chloroform solution was discharged into 600 ml of methanol, and the precipitated crystals were subjected to suction filtration, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 11.4 g (36% yield) of polylactic acid was obtained. The average molecular weight Mw of the obtained polylactic acid was 8,000.

Reference Example 1 L-polylactic acid having an average molecular weight of 100,000 obtained in Example 3 was dissolved in chloroform, and a film was formed from the solution by a casting method. The physical properties of the produced film are shown below.

[0069]

Reference Example 2 L-polylactic acid having an average molecular weight of 75,000 obtained in Example 9 was dissolved in chloroform, and a film was prepared from the solution by a casting method. The prepared film is non-colored, and its physical properties are shown below.

[0071]

Reference Example 3 L-polylactic acid having an average molecular weight of 60,000 obtained in Example 10 was dissolved in chloroform, and a film was prepared from the solution by a casting method. The prepared film is non-colored, and its physical properties are shown below.

[0073]

Reference Example 4 D, L- having an average molecular weight of 120,000 obtained in Example 18
Polylactic acid was dissolved in chloroform, and a film was formed from the solution by a casting method. The prepared film is non-colored, and its physical properties are shown below.

[0075]

Reference Example 5 L-polylactic acid having an average molecular weight of 147,000 obtained in Example 29 was dissolved in chloroform, and a film was prepared from the solution by a casting method. The prepared film is non-colored, and its physical properties are shown below.

[0077]

Reference Example 6 The L-polylactic acid obtained in Example 29 and the plasticizer triacetin were dissolved in chloroform at a weight ratio of 4: 1, and a film was formed from the solution by a casting method. The prepared film is non-colored, and its physical properties are shown below.

[0079]

Reference Example 7 The polylactic acid having an average molecular weight of 15,000 obtained in Example 30 was dissolved in chloroform, and an attempt was made to form a film from the solution by a casting method, but no film could be formed.

Example 32 36.0 g of 90% L-lactic acid, 9.0% of 90% D, L-lactic acid
Example 19 except that the reaction time was 20 hours using g
Oligomerization and polymerization were carried out in the same manner as described above. To this reaction solution, 220 g of chloroform was added, and suction filtration was performed to remove tin powder. This chloroform solution was washed with 1N hydrochloric acid (100 ml), further washed with water (100 ml) twice, discharged into methanol (750 ml), and the precipitated solid was filtered by suction, followed by methanol washing and hexane washing.
After drying under reduced pressure at 30 ° C./5 mmHg, 28.9 g of polylactic acid
(89% yield). The average molecular weight of the obtained polylactic acid was 130,000. The obtained polymer was subjected to ¹³ C-NMR analysis using heavy chloroform as a solvent.
The overall diagram is shown in Fig. 1, and the enlarged carbonyl carbon signal is shown in Fig. 2. The polymer of the present invention has at least about 169.27 ppm, about 169.31 ppm, about 16
9.42 ppm, about 169.49 ppm, about 169.6
It is characterized by having five signals at 6 ppm. In addition, differential thermal analysis (DSC: differentialenci)
The results of all scanning calorimetry are shown in the upper part of FIG. The polymer of Example 32 obtained by the method of the present invention has an endothermic peak at 115.6 ° C. corresponding to a melting point.

Comparative Example 2 172 g (1.2 mol) of L-lactide, 44 g (0.3 mol) of D, L-lactide and 0.1 g of tin octoate.
01% by weight and 0.03% by weight of lauryl alcohol
It was sealed in a thick cylindrical stainless steel polymerization vessel equipped with a stirrer, degassed under vacuum for 2 hours, and then replaced with nitrogen gas. The mixture was heated at 200 ° C. for 3 hours with stirring under a nitrogen atmosphere. While maintaining the temperature as it was, the air was gradually degassed by a vacuum pump through an exhaust pipe and a glass receiver, and the pressure inside the reaction vessel was reduced to 3 mmHg. One hour after the start of degassing, the distillation of the monomer and low-molecular-weight volatiles disappeared, so the inside of the container was replaced with nitrogen, and the polymer was pulled out from the lower part of the container into a string and pelletized to obtain white poly L-lactic acid. Was. The average molecular weight of this polymer was 130,000 and the yield was 96%.

The obtained polymer was analyzed by ¹³ C-NMR using heavy chloroform as a solvent. The enlarged carbonyl carbon signal is shown in FIG. These are described in Example 3.
Compared with the signal of the polymer obtained in 2, it can be seen that the pattern is significantly different. At the carbonyl carbon, the polymer of Example 32 is at least about 169.27 pp
m, about 169.31 ppm, about 169.42 ppm, about 169.49 ppm, and about 169.66 ppm. The signals of Comparative Example 2 synthesized from lactide have about 169.20 ppm and about 169.66 ppm. 36
ppm, about 169.40 ppm, about 169.45 pp
m, there are five signals at about 169.66 ppm, which can be easily distinguished. In addition, differential thermal analysis (DSC: differential scanning)
calorimetry) is shown at the bottom of FIG. The polymer of Example 32 obtained by the method of the present invention has an endothermic peak corresponding to the melting point at 115.6 ° C., whereas the polymer of Comparative Example 2 has a main endothermic peak at 130.9 ° C. Is high.

REFERENCE EXAMPLE 8 One having an average molecular weight of 130,000 and 1 obtained in Example 32
Two 150 mm × 150 mm, 40 μm thick films obtained from a polymer having an endothermic peak corresponding to a melting point at 15.6 ° C. were sandwiched between two heating plates having a width of 5 mm to perform a welding test. Heating plate temperature 102 ° C, pressure 0.5kg /
Welding was possible by pressing for 0.5 seconds at cm ² .

Reference Example 9 13 with an average molecular weight of 130,000 obtained in Comparative Example 2.
A welding test was performed in the same manner as in Reference Example 8 using two 150 mm × 150 mm, 40 μm thick films obtained from a polymer having a main endothermic peak at 0.9 ° C.
As a result, the heating plate temperature was 102 ° C. and the pressure was 0.5 kg / cm.
^At 0.5, it was pressed for 0.5 seconds, but could not be welded. In order to perform welding at a pressure of 0.5 kg / cm ² and a pressing time of 0.5 second, a heating plate temperature of 115 ° C. was required.

[0086]

According to the production method of the present invention, a white and colorless polyhydroxycarboxylic acid containing no impurities useful as a biodegradable polymer can be obtained directly from hydroxycarboxylic acids by dehydration condensation. Further, according to the method of the present invention, polyhydroxycarboxylic acids having sufficient strength can be easily obtained as a molded product such as a film or a thread.

[Brief description of the drawings]

FIG. 1 is an overall view of ¹³ C-NMR spectrum of a random copolymer of 90% L-lactic acid and 10% D-lactic acid obtained in Example 32.

FIG. 2 shows the carbonyl groups of the random copolymer of 90% L-lactic acid and 10% D-lactic acid obtained in Example 32.
It is a < ¹³ > C-NMR spectrum.

FIG. 3 shows L-lactide 90% obtained in Comparative Example 2.
When the D- lactide 10% of a copolymer of a carbonyl group ¹³
It is a C-NMR spectrum.

FIG. 4 is a diagram showing a result of a thermal analysis by DSC, in which 90% of L-lactic acid and D-lactic acid 1 obtained in Example 32 are shown.
Thermal analysis results of 0% random copolymer are shown on the top, 90% of L-lactide and D-lactide 10 obtained in Comparative Example 2.
The results of thermal analysis of the% copolymer are shown below.

(56) References UK Patent Application Publication 779291 (GB, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C08G 63/00-63/91

Claims (3)

(57) [Claims] 1. 169.27 ppm, 169.31 pp
m, 169.42 ppm, 169.49 ppm and 16
A polyhydroxycarboxylic acid having a weight average molecular weight of 50,000 or more, having at least five ¹³ C-NMR absorption spectra at 9.66 ppm and having D-lactic acid units and L-lactic acid units. 2. The polyhydroxycarboxylic acid according to claim 1, which has a weight average molecular weight of 70,000 or more. 3. The polyhydroxycarboxylic acid according to claim 2, which has a weight average molecular weight of 100,000 or more.