JP3154586B2 - Method for producing polyhydroxycarboxylic acid - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a polyhydroxycarboxylic acid useful as a biodegradable polymer as a substitute for a medical material or a general-purpose resin by direct dehydration polycondensation from a hydroxycarboxylic acid. For example, lactic acid is widely distributed in nature and is harmless to animals, plants and livestock, and its polymer is relatively easily hydrolyzed in the presence of water,
In addition, since it is hydrolyzed and absorbed even in a living body, it is attracting attention as the above application.

[0002]

2. Description of the Related Art Polylactic acid or polyglycolic acid, which is a high molecular weight polyhydroxycarboxylic acid, is generally
It is obtained by producing lactide or glycolide from lactic acid or glycolic acid and subjecting it to ring-opening polymerization.
This method is not economical because it requires a great deal of labor and cost in the production of lactide or glycolide.
This method cannot be used when copolymerizing a hydroxycarboxylic acid that does not form a cyclic lactone such as lactide or glycolide. On the other hand, as a method for directly synthesizing polylactic acid or polyglycolic acid from lactic acid or glycolic acid, Japanese Patent Application Laid-Open No. 59-96123 is known. Cannot be obtained.

[0003]

[0004]

The direct polycondensation reaction of a hydroxycarboxylic acid such as lactic acid or glycolic acid is a sequential reaction, similar to the esterification reaction between a dibasic acid and a polyhydric alcohol, and the molecular weight increases with the reaction time. I do. However,
This reaction is a reversible reaction, and when the generated water is present in the reaction system, the molecular weight of the polycondensate is reduced by a hydrolysis action. Therefore, it is necessary to remove generated water out of the system in order to obtain high molecular weight polylactic acid, polyglycolic acid, and the like.

[0005] Usually, as a means for removing water, a method of distilling a solvent and entraining or azeotropically entraining water is adopted.
By increasing the amount of the solvent distilled off as much as possible, the generated water can be removed more quickly and out of the system.

In order to distill off the solvent, it is necessary to supply heat to the inside of the reactor, but a general method includes external heating using a reactor jacket or a coil. However, as the reaction proceeds, the thermal conductivity of the reaction solution deteriorates, and heat is not sufficiently supplied, so that the amount of the solvent distilled off decreases. In addition, since the scale-up reduces the thermal conductivity into the reactor, the distilling amount of the solvent is significantly reduced. As a countermeasure, there are a mechanical method of increasing the stirring speed and a method of increasing the temperature of external heating. However, the stirring speed is limited, and if the temperature of the external heating of the reactor is too high, the polymer and the catalyst may be thermally degraded.

An object of the present invention is to provide a method for producing a high molecular weight polyhydroxycarboxylic acid by a direct dehydration polycondensation reaction of a hydroxycarboxylic acid. An object of the present invention is to provide a method for efficiently removing generated water by increasing the amount and producing a high-molecular-weight polyhydroxycarboxylic acid in a short time.

[0008]

The present inventors have conducted intensive studies to obtain polyhydroxycarboxylic acid. As a result, when introducing a solvent into the system, the solvent was vaporized by a heat exchanger and blown into a reaction solution. By increasing the amount of solvent distilled,
It has been found that a high molecular weight polyhydroxycarboxylic acid can be obtained in a shorter time, and the present invention has been completed.

That is, the present invention provides a hydroxycarboxylic acid,
Alternatively, in a method for producing polyhydroxycarboxylic acid by azeotropically dehydrating an oligomer thereof in the presence or absence of a catalyst in an organic solvent, a distilling solvent is treated with a drying agent, or purified by distillation. Then, when returning to the inside of the system again, the method is characterized by heating with a heat exchanger, vaporizing part or all of the mixture, and blowing the mixture into a reaction solution.

The monomer used in the method of the present invention is a hydroxycarboxylic acid, preferably lactic acid, glycolic acid, 3-hydroxybutanoic acid, 4-hydroxybutanoic acid and the like. Or racemic form.

The organic solvent used in the method of the present invention includes hydrocarbon solvents such as toluene, xylene and mesitylene, chlorobenzene, bromobenzene, iodobenzene, dichlorobenzene, dichloroethane, 1,1,2,2
Halogen solvents such as 2-tetrachloroethane and p-chlorotoluene, ketone solvents such as 3-hexanone, aprotic polar solvents such as dimethyl sulfoxide, dibutyl ether, anisole, diphenyl ether, 4,4′-
Dimethyl diphenyl ether, 3,3′-dimethyl diphenyl ether, 3-methyl diphenyl ether, 4,
4'-dibromodiphenyl ether, 4,4'-dichlorodiphenyl ether, 4-bromodiphenyl ether, 4-methyl-4'-bromodiphenyl ether, 4
Ether compounds such as -methoxydiphenyl ether, 4,4'-dimethoxydiphenylether, 3,3'-dimethoxydiphenylether, 4-methyl-4'-methoxydiphenylether, dibenzofuran, and xanthene. , Or a mixture thereof.

The reaction may be carried out under normal pressure at the reflux temperature of the solvent to be used, or under reduced pressure by lowering the reflux temperature to 50 to 250 ° C. Preferably, the temperature is 100 to 170 ° C., which is a condition in which the reaction is fast and the decomposition reaction is small.

As the catalyst to be used, the periodic table II, I
Metals of II, IV, V or salts thereof.
For example, zinc powder, tin powder, aluminum, metal such as magnesium, or tin oxide, antimony oxide, zinc oxide, aluminum oxide, magnesium oxide, metal oxide such as titanium oxide, or stannous chloride, stannic chloride, Metal halides such as stannous bromide, stannic bromide, antimony fluoride, zinc chloride, magnesium chloride, and aluminum chloride;
Or sulfates such as tin sulfate, zinc sulfate and aluminum sulfate, carbonates such as magnesium carbonate and zinc carbonate, or organic carboxylate salts such as tin acetate, tin octoate, tin lactate, zinc acetate and aluminum acetate, and trifluoromethane sulfone Organic sulfonic acid salts such as tin acid tin (hereinafter abbreviated as TFS tin), zinc trifluoromethanesulfonate, magnesium trifluoromethanesulfonate, tin methanesulfonate, and tin p-toluenesulfonate. In addition, an organic metal oxide of the above metal such as dibutyltin oxide, or a metal alkoxide of the above metal such as titanium isopropoxide, or an alkyl metal of the above metal such as diethyl zinc, or an ion exchange resin such as Dowex or Amberlite Is mentioned. The amount of the hydroxycarboxylic acid to be used or the amount of the oligomer thereof may be 0.
0001 to 10% by weight is good.
001 to 2% by weight is preferred.

The reaction is preferably performed in an inert gas atmosphere, and the inert gas may be bubbled.

A preferred embodiment of the method of the present invention will be described with reference to FIG. 1 (FIG. 1). In FIG. 1, reference numeral 1 denotes a reactor equipped with a stirrer and a heating jacket, into which a raw material hydroxycarboxylic acid, a solvent, and a catalyst are charged.
The reaction is carried out with stirring. The reaction consists of three steps: dehydration, oligomerization and polymerization. First, in the dehydration and oligomerization, since most of the distillate is water, it is cooled by the condenser 2 and removed out of the system. In the next polymerization, the solvent is distilled off, cooled in the condenser 2 and recovered. Since the recovered solvent contains water, it is passed through a desiccant to remove water and then returned to the reactor. Examples of the desiccant include molecular sieves (3A, 4A, 5A etc.), diphosphorus pentoxide, metal hydrides such as calcium hydride, sodium hydride and lithium aluminum hydride, and alkali metals such as sodium and lithium. No. In the reaction apparatus shown in FIG. 1, the distilled solvent passes through a column 5 filled with a desiccant and returns to the reactor. If the desiccant cannot be packed in the column, the distilled solvent is refluxed and dehydrated in a separate reactor in the presence of the desiccant to distill a part of the solvent, and returned to the reactor where the condensation reaction is performed. Can be performed in the following manner. Instead of using a desiccant, water may be removed by distillation and returned to the reactor. When the dehydrated solvent is introduced into the reactor, the solvent is heated and vaporized through the heat exchanger 6 and blown into the reaction solution. The temperature of the heat exchanger is preferably equal to or higher than the boiling point of the solvent at the pressure in the reaction system.

In order to keep the temperature inside the reactor constant, at least the amount of heat required to raise the temperature of the supplied solvent to the boiling point and the amount of heat required to evaporate the solvent in the liquid state (latent heat of vaporization). A heat quantity equal to the sum must be supplied. That is, the amount of the solvent distilled out is inevitably determined by the amount of heat supplied to the reactor. There is a limit to the temperature of the jacket only by heating with the jacket of the reactor, and the amount of heat that can be supplied is also limited because the heat transfer area is fixed. When the solvent is blown in with the heat exchanger, the amount of heat substantially equal to the amount of heat taken from the reactor when the solvent is distilled can be supplied by itself. .

Thus, the polycondensation of polyhydroxycarboxylic acid could be performed in a short time by increasing the amount of the solvent distilled out and efficiently removing water generated in the reactor.

[0018]

The present invention will be described in more detail with reference to the following examples. The molecular weight of the polymer was determined by gel permeation chromatography (column temperature 40 ° C).
The comparison was performed with a polystyrene standard sample. (Less than,
Abbreviated as polystyrene equivalent. )

Example 1 5 equipped with a stirrer, jacket, thermometer and distilling tube
In a 100-liter glass-lined reactor, 90% L-lactic acid (containing 10% water) was 112.5 kg (1125 mo).
l), 0.405 kg (3.4 mol) of tin powder and 236 kg of diphenyl ether were charged, and stirred.
Water was distilled off at 0 ° C./160 to 130 mmHg for 6 hours. Then, 140 ° C / 110-100mmH
g of lactic acid over 25 hours. The obtained oligomer is continuously heated at 130 ° C./20 to 15 mm
Polycondensation with Hg for 30 hours, average molecular weight 126,000
Polylactic acid-diphenyl ether solution (about 25% by weight)
I got At that time, the distillate was cooled by a condenser, collected in a solvent storage tank, dried through a tower filled with 40 kg of 4A-molecular sieve, and then vaporized by a heat exchanger.
Blown into the reaction. Set the temperature of the heat medium of the heat exchanger to 200
When set at ~ 210 ° C, the temperature of the solvent vapor is 190
~ 200 ° C. Further, the temperature of the reactor jacket was set at 150 ° C. A lap sample of the reaction solution was analyzed to determine the molecular weight. Table 1 (Table 1) shows the change over time in the amount of solvent distilled off and the molecular weight.

Comparative Example 1 The same preparation and method as in the example were carried out except that the solvent was circulated and heating was performed only with the reactor jacket without using a heat exchanger. Reactor jacket temperature is 15
It was set to 0 ° C. A lap sample of the reaction solution was analyzed to determine the molecular weight. Table 1 (Table 1) shows the change over time in the amount of solvent distilled off and the molecular weight. The polycondensation was carried out for 50 hours to obtain a polylactic acid-diphenyl ether solution having an average molecular weight of 126,000 (about 25% by weight).

[0021]

[Table 1]

[0022]

According to the present invention, a high molecular weight polyhydroxycarboxylic acid useful as a biodegradable polymer can be obtained in a shorter time in the direct dehydration polycondensation of a hydroxycarboxylic acid with a target high molecular weight target product. did it.

[Brief description of the drawings]

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

[Explanation of symbols]

 1. Reactor 2. Condenser 3. Solvent storage tank 4. Pump 5. 5. Desiccant packed tower Heat exchanger

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C08G 63/00-63/91

Claims (1)

(57) [Claims] 1. A method for producing a polyhydroxycarboxylic acid by azeotropically dehydrating a hydroxycarboxylic acid or an oligomer thereof in an organic solvent in the presence or absence of a catalyst, wherein a solvent distilled off is dried. Treatment with an agent,
Alternatively, a method for producing a polyhydroxycarboxylic acid, comprising heating by a heat exchanger, vaporizing part or all of the mixture, and blowing the mixture into a reaction solution after returning to the system after distillation purification.