JPH1121342A - Production of polyhydroxycarboxylic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce, industrially easily, a high-mol.-wt. polyhydroxycarboxylic acid useful as a biodegradable polymer by reacting an acid chloride of a hydroxycarboxylic acid and/or its oligomer in the presence of a tert. amine. SOLUTION: One mol of an acid chloride of a hydroxycarboxylic acid and/or its oligomer of the formula (wherein R is an aliph. hydrocarbon group; and n is 1 or higher) is reacted at a temp. of 120 deg.C or lower in the presence of at least 1 mol, pref. 1-6 mol, of at least one tert. amine having a logarithm of the reciprocal of the acid dissociation constant of 4.9 or higher and selected from among quinoline, isoquinoline, quinaldine, 3,5-lutidine, 2,6-lutidine, 4- methylmorpholine, 2,4,6-collidine, tri-n-octylamine, N,N,N',N'- tetramethylethylenediamine, and N-methylpiperidine while the water content of the reaction system is being controlled so as to satisfy the relation: H<=1.8×M×10<-3> (wherein H is the number of moles of water; and M is the number of moles of the hydroxycarboxylic acid monomer).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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.

[0002]

2. Description of the Related Art Plastics are used in all fields of daily life because of their lightness, ease of processing, and availability at low cost, and they greatly contribute to technological progress in various industrial fields. However, disposal has problems such as shortening the life of the landfill, generating harmful gases during incineration, and burning the incinerator at high temperatures. Therefore, in recent years, attention has been focused on aliphatic polyesters having the same basic physical properties as conventional plastics and having biodegradability. Among them, polyhydroxycarboxylic acids, especially polylactic acid, are made from lactic acid in the natural world or the human body, and are decomposed in the natural world without causing any harm, and eventually turn into water and carbon dioxide gas. It is a biodegradable plastic whose use is greatly expected.

[0003] Polyhydroxycarboxylic acids can be produced by ring-opening polymerization via lactide, which is a dimer of lactic acid (JP-A-56-45920), or by directly polycondensing hydroxycarboxylic acid. Method (Japanese Unexamined Patent Publication No.
No. 96123, JP-A-61-028521)
It has been known. However, in the former method, it is necessary to obtain lactide, which is a cyclic dimer, with high purity, a step of recrystallization of lactide is required, and the resulting polylactic acid is expensive. On the other hand, the latter method has a problem that it is necessary to react under conditions such as high temperature and reduced pressure in order to remove water in the system, and thus it is difficult to set optimal polymerization conditions especially in industrial production. And so on.

[0004] The polyhydroxycarboxylic acid in the present invention is a kind of aliphatic polyester. In general, as a method for producing a polyester, a polymerization method from dicarboxylic acid chlorides and diols, or a hydroxycarboxylic acid chloride is known.In general, these methods use an aromatic compound in which an acid chloride compound is relatively stable. In the present case, a polymerization method using an acid chloride compound from an aliphatic carboxylic acid is hardly known. As a known technique using an aliphatic acid chloride compound, for example, a method using thionyl chloride as a chlorinating agent (Makromol.
Chem. 182.681-686 (1981)), but there are no disclosures about aliphatic hydroxycarboxylic acid chlorides, especially aliphatic hydroxycarboxylic acid chlorides such as lactic acid and / or its oligomeric acid chloride. You can say that you haven't. Also, a method (Japanese Patent Publication No. 4-3763) of polymerizing a polymer by reacting lactic acid and glycolic acid with thionyl chloride, oxalyl chloride, succinyl chloride, terephthaloyl dichloride or the like is disclosed. The existence of lactic acid and / or its oligomer was estimated only by estimating the production of acid chloride, and the polymerization rate of the obtained polymer was as low as 84% even at the highest (polymerization rate = (1−average degree of polymerization after completion of reaction / average degree of polymerization of starting material) × 100). Furthermore, the use of phosgene or diphosgene in a method of subjecting a hydroxycarboxylic acid, particularly an α-hydroxycarboxylic acid or an oligomer thereof, to a condensation reaction in the presence of a predetermined binding reagent (JP-A-4-215822) is disclosed. However, there is no description about the method and examples of the method, and what physical properties of the obtained polyhydroxycarboxylic acid is not clarified at all.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for industrially efficiently and easily producing a polyhydroxycarboxylic acid having a high molecular weight.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to achieve these objects, and as a result, the general formula (1)

Embedded image

(Wherein, R is an aliphatic hydrocarbon group, and n is an integer of 1 or more). The acid chloride of the hydroxycarboxylic acid and / or their oligomer is represented by the logarithmic value of the reciprocal of the acid dissociation constant. It has been found that a high-molecular-weight polyhydroxycarboxylic acid can be industrially efficiently and easily produced by reacting in the presence of a tertiary amine having a pKa of at least 4.9 (hereinafter abbreviated as pKa), and completed the present invention. It led to.

That is, the present invention provides a compound represented by the general formula (1):

Embedded image (Wherein, R is an aliphatic hydrocarbon group, and n is an integer of 1 or more). The logarithmic value of the reciprocal of the acid dissociation constant is 4. A method for producing a polyhydroxycarboxylic acid, comprising reacting in the presence of a tertiary amine having 9 or more.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The acid chloride of a hydroxycarboxylic acid or an oligomer thereof according to the present invention is represented by the general formula (1). In the general formula (1), R
Is an aliphatic hydrocarbon group, and its form is not particularly limited.

Further, n in the formula represents an average degree of polymerization,
It is an integer of 1 or more. The range of n is not particularly limited, and an arbitrary degree of polymerization can be selected.

The acid chloride is obtained by reacting a hydroxycarboxylic acid and / or an oligomer thereof with a haloiminium salt. The hydroxycarboxylic acid used is specifically glycolic acid, lactic acid, 2-hydroxybutyric acid, -Hydroxyvaleric acid, 2-hydroxycaproic acid, 2-hydroxyheptanoic acid, 2-hydroxyoctanoic acid, 2-hydroxy-2-methylpropionic acid, 2-hydroxy-2-methylbutyric acid, 2-hydroxy-2-ethylbutyric acid 2-hydroxy-2-methylvaleric acid, 2-hydroxy-2-ethylvaleric acid, 2-hydroxy-2-propylvaleric acid, 2-hydroxy-
2-butylvaleric acid, 2-hydroxy-2-methylcaproic acid, 2-hydroxy-2-ethylcaproic acid, 2
-Hydroxy-2-propylcaproic acid, 2-hydroxy-2-butylcaproic acid, 2-hydroxy-2-pentylcaproic acid, 2-hydroxy-2-methylheptanoic acid, 2-hydroxy-2-methylheptanoic acid, 2 -Hydroxy-2-ethylheptanoic acid, 2-hydroxy-2-
Propylheptanoic acid, 2-hydroxy-2-butylheptanoic acid, 2-hydroxy-2-pentylheptanoic acid, 2
-Hydroxy-2-hexylheptanoic acid, 2-hydroxy-2-methyloctanoic acid, 2-hydroxy-2-ethyloctanoic acid, 2-hydroxy-2-propyloctanoic acid, 2-hydroxy-2-butyloctanoic acid, 2 -Hydroxy-2-pentyloctanoic acid, 2-hydroxy-2
-Hexyloctanoic acid, 2-hydroxy-2-heptyloctanoic acid, 3-hydroxypropionic acid, 3-hydroxybutyric acid, 3-hydroxyvaleric acid, 3-hydroxycaproic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxy-3-methylbutyric acid, 3-
Hydroxy-3-methylvaleric acid, 3-hydroxy-
3-ethylvaleric acid, 3-hydroxy-3-methylcaproic acid, 3-hydroxy-3-ethylcaproic acid, 3
-Hydroxy-3-propylcaproic acid, 3-hydroxy-3-methylheptanoic acid, 3-hydroxy-3-ethylheptanoic acid, 3-hydroxy-3-propylheptanoic acid, 3-hydroxy-3-butylheptanoic acid, 3 -Hydroxy-3-methyloctanoic acid, 3-hydroxy-3-
Ethyl octanoic acid, 3-hydroxy-3-propyloctanoic acid, 3-hydroxy-3-butyloctanoic acid, 3-
Hydroxy-3-pentyloctanoic acid, 4-hydroxybutyric acid, 4-hydroxyvaleric acid, 4-hydroxycaproic acid, 4-hydroxyheptanoic acid, 4-hydroxyoctanoic acid, 4-hydroxy-4-methylvaleric acid,
-Hydroxy-4-methylcaproic acid, 4-hydroxy-4-ethylcaproic acid, 4-hydroxy-4-methylheptanoic acid, 4-hydroxy-4-ethylheptanoic acid,
4-hydroxy-4-propylheptanoic acid, 4-hydroxy-4-methyloctanoic acid, 4-hydroxy-4-ethyloctanoic acid, 4-hydroxy-4-propyloctanoic acid, 4-hydroxy-4-butyloctanoic acid, 5-hydroxyvaleric acid, 5-hydroxycaproic acid, 5-
Hydroxyheptanoic acid, 5-hydroxyoctanoic acid, 5
-Hydroxy-5-methylcaproic acid, 5-hydroxy-5-methylheptanoic acid, 5-hydroxy-5-ethylheptanoic acid, 5-hydroxy-5-methyloctanoic acid,
5-hydroxy-5-ethyloctanoic acid, 5-hydroxy-5-propyloctanoic acid, 6-hydroxycaproic acid, 6-hydroxyheptanoic acid, 6-hydroxyoctanoic acid, 6-hydroxy-6-methylheptanoic acid, 6- Hydroxy-6-methyloctanoic acid, 6-hydroxy-6
-Ethyloctanoic acid, 7-hydroxyheptanoic acid, 7-
It is an aliphatic hydroxycarboxylic acid such as hydroxyoctanoic acid, 7-hydroxy-7-methyloctanoic acid, 8-hydroxyoctanoic acid and / or an oligomer thereof, and one or a mixture of two or more thereof may be used. Among these hydroxycarboxylic acids and their oligomers, there are optical carbons, which may take the form of D-form, L-form and D / L-form, respectively. However, in the method of the present invention, the form is not limited at all. .

Some commercially available hydroxycarboxylic acids contain water, but may be used as they are. In the case of using an oligomer which is subjected to dehydration by heat or azeotropic dehydration as a pretreatment, or is subjected to dehydration using a desiccant such as calcium chloride, molecular sieves, mordenite, ion exchange resin, silica gel, and condensed,
This is preferable because the amount of the acid chloride agent used and the amount of generated hydrogen chloride gas are reduced.

Examples of the acid chloride agent used for synthesizing the acid chloride used as a raw material in the method of the present invention include thionyl chloride, phosphorus pentachloride, phosphorus trichloride, phosphonyl chloride, and the like.
Phosgene, and the following general formula (2)

Embedded image Is a compound containing the structure represented by in the molecule,
A haloiminium salt which does not have any problem as long as it is a compound having the above structure, whether or not a cyclic compound, can be mentioned.

Common haloiminium salts include N,
N-dimethylchloromethyleneiminium chloride,
N, N-diphenylcyclohexylmethyleneiminium chloride, N, N-diphenylchloro-p-methoxyphenylmethyleneiminium chloride, N, N,
N ', N'-tetramethylchloroformamidinium chloride, 2-chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-diethylimidazolinium chloride, 2-chloro-1,3- Dipropylimidazolinium chloride, 2-chloro-1,3-
Dibutyl imidazolinium chloride, 2-chloro-
1,3-dihexylimidazolinium chloride, 2-
Chloro-1,3-dicyclohexylimidazolinium chloride, 2-chloro-1,3-diphenylimidazolinium chloride, 2-chloro-1,3-dimethyl-
3,4,5,6-tetrahydropyrimidinium chloride and the like.

These acid chloride agents can be used as solids or liquids, and can be used without any problem even when dissolved or suspended in an appropriate solvent. Also, several kinds of acid chloride agents can be used in combination.

The temperature at which the acid chloride agent is allowed to act on the hydroxycarboxylic acid and / or its oligomer is 40 ° C.
The temperature is from 160 ° C to 160 ° C, preferably from 40 ° C to 140 ° C, more preferably from 40 ° C to 120 ° C. 4
At a temperature lower than 0 ° C., it takes a long time to complete the acid chloride reaction. At a temperature higher than 160 ° C., the general formula (3)

Embedded image

Wherein R is an aliphatic hydrocarbon group, n is an integer of 1 or more, and X is a chlorine atom or an OH group (hereinafter abbreviated as Cl-substituted product). C
When the amount of the l-substituted compound increases, the terminal which was originally a hydroxy group is blocked, so that the terminal does not proceed with esterification, and a polyhydroxycarboxylic acid having a high molecular weight cannot be obtained, which is preferable. Absent.

The amount of the acid chloride agent used in the present invention is 0.85 times mol or more, preferably 1.0 to 6.0 times mol, per carboxyl group. It is preferable that the amount of the acid chloride agent used is appropriately selected depending on the reaction temperature, for example, 1.0 to 6.0 times mol at a temperature lower than 120 ° C, and 0.85 mol at 120 ° C or more.
It is preferable to use a mole of about 1.0 times. When water is present in the reaction system, it is preferable to add an acid chloride agent in an equimolar amount with water.

When a hydroxycarboxylic acid and / or its oligomeric acid chloride thus obtained is used as a haloiminium salt, a precursor of a haloiminium salt as a reaction product, for example, dimethylformamide,
N, N, N ', N'-tetrabutylurea, N, N'-
It becomes a reaction mixture with dimethylimidazolidinone or the like, or a reaction solvent, a residual acid chloride agent, by-product hydrogen chloride gas, or the like. When polymerizing the acid chloride, the resulting reaction mixture may be used as it is, but the precursor of the haloiminium salt, by-product hydrogen chloride gas, the reaction solvent and the like are distilled off by evaporation to obtain hydroxycarboxylic acid and And / or the oligomeric acid chloride may be isolated and used.

The polyhydroxycarboxylic acid according to the present invention is obtained by converting the acid chloride of the hydroxycarboxylic acid represented by the general formula (1) and / or its oligomer in the presence of a tertiary amine having a pKa of 4.9 or more. Then, esterification is advanced by dehydrochlorinating the acid chloride to produce a polyhydroxycarboxylic acid.

In the present invention, pKa (logarithm of the reciprocal of the acid dissociation constant) is defined as pKa measured at 25 ° C. in an aqueous solution.
For example, an aqueous solution of tertiary amines or an aqueous alcoholic solution is prepared using a titrant such as hydrochloric acid or iodic acid.
Titration at 5 ° C, or titration of an aqueous solution of a tertiary amine hydrochloride or an alcoholic aqueous solution at 25 ° C with a titrant such as sodium hydroxide or sodium methylate, at which point the sample is 50% neutralized Is a value obtained by a method such as obtaining a pH value in the above. The pKa of each of the tertiary amines determined by this method is, for example, quinoline 4.97, isoquinoline 5.36, quinaldine 5.7.
4,3,5-lutidine 6.14, 2,6-lutidine6.
60, 2,4,6-collidine 7.48, 4-methylmorpholine 7.38, tri-n-octylamine 8.35,
N, N, N ', N'-tetramethylethylenediamine 8.97 and N-methylpiperidine 10.08.

The tertiary amines used in the present invention include, for example, quinoline, isoquinoline, quinaldine, 3,5-lutidine, 2,6-lutidine, 4-methylmorpholine,
2,4,6-collidine, tri-n-octylamine,
N, N, N ', N'-tetramethylethylenediamine,
Examples thereof include N-methylpiperidine and triallylamine. One of these may be used, or a plurality of tertiary amines may be used at the same time. When a tertiary amine having a pKa of 4.9 or more is used, the esterification reaction by dehydrochlorination proceeds smoothly, and a polyester having a high molecular weight is produced.
Can be obtained in a short time under mild conditions. pKa
If 4.9 is less than 4.9, the reaction may be slow or may not react at all because the ability to desorb hydrogen chloride is poor.

The amount of the tertiary amine used in the present invention is at least equimolar to the acid chloride of hydroxycarboxylic acid and / or its oligomer, preferably 1 to 6 times, more preferably 2 to 3 times. Good. When the amount of the tertiary amine is smaller than the number of moles of the acid chloride, the amount of the tertiary amine is insufficient with respect to the amount of hydrogen chloride that can be produced, so that a polyhydroxycarboxylic acid having a desired molecular weight may not be obtained. is there. On the other hand, if the tertiary amine is present in excess, it does not affect the polymerization itself, but is not preferred because it is not only uneconomical, but also complicates subsequent purification and recovery.

In carrying out the polymerization in the present invention, the tertiary amines used or the water in the reaction system is converted into a compound of the formula (4)

H ≦ 1.8 × M × 10 ⁻³ (4) (where H is the number of moles of water and M is the number of moles of hydroxycarboxylic acid monomer unit). Is preferred. When a large amount of water is present, the acid chloride terminal is hydrolyzed, and the molecular weight of the obtained polyhydroxycarboxylic acid is low.

In the present invention, when carrying out the polymerization, the reaction is carried out at a temperature of 120 ° C. or less, preferably from 0 ° C. to 100 ° C. At a temperature exceeding 120 ° C., the general formula (3)
In some cases, a Cl-substituted product represented by the formula (1) is generated, and as a result, a polyhydroxycarboxylic acid having a high molecular weight cannot be obtained.

The Cl substituent acts as a terminator when polymerizing the hydroxycarboxylic acid and / or its oligomer. The amount of the Cl-substituted product was 1800 mol pp in the acid chloride or the hydroxycarboxylic acid produced when the resulting polyhydroxycarboxylic acid was hydrolyzed.
It is better to control so as to be not more than m.

In the present invention, a solvent may or may not be used. As the solvent to be used, basically any solvent can be used as long as it does not react with the hydroxycarboxylic acid and / or its oligomer and the produced polyhydroxycarboxylic acid. Specifically, dichloromethane, ethylene dichloride, chloroform, acetone, benzene, toluene, xylene, mesitylene,
Chlorobenzene, dichlorobenzene, hexane, cyclohexane, dimethylacetamide, N, N′-dimethylimidazolidin, dimethylsulfone and the like,
Particularly, aliphatic halogenated hydrocarbons such as dichloromethane, ethylene dichloride, and chloroform are preferable.

When producing and handling the hydroxycarboxylic acid and / or its oligomeric acid chloride, it is needless to say that the control of moisture is strictly controlled, and it is also necessary to use a closed system or an inert gas such as nitrogen or argon. It is preferably performed under an atmosphere of

The polyhydroxycarboxylic acid produced by the above method is isolated by a known method such as, for example, discharging the reaction mixture into a large amount of alcohol, filtering the solid substance of the polymer, and drying. be able to.

Examples will be shown below, but the present invention is not limited to these examples. Incidentally, the average degree of polymerization (n) and the weight average molecular weight (M
w) and the quantification of the Cl-substituted product in the hydroxycarboxylic acid were measured by the following methods.

Weight average molecular weight (Mw) Measured with a chloroform solvent using Shodex GPC system-11 (manufactured by Showa Denko KK). Mw
Is a polystyrene equivalent value.

Number average molecular weight (Mn), average degree of polymerization (n) Determined from the amounts of carboxylic acid and carboxylic acid chloride. The obtained acid chloride (W (g)) was dissolved in dichloromethane / methanol = 70/30 (vol ratio) in nitrogen,
The first inflection point (E ₁ ml) and the second inflection point (E ₂ ml) were determined by titration with a methanol solution of sodium methylate.

Mn = W / (E ₂ × 10 ⁻³ × C) n = Mn / MU Amount of carboxylic acid chloride (mol / g) = E ₁ × 10 ⁻³ ×
C / 1000 / W Carboxylic acid amount (mol / g) = (E ₂ −E ₁ ) × 10 ⁻³ ×
C / 1000 / W (where MU is the molecular weight of the hydroxycarboxylic acid unit (for example, MU = 72.06 in the case of polylactic acid), C is the specified concentration (N) of the titrant)

Determination of Cl-substituted product 0.5 g of acid chloride was added to 18% aqueous sodium hydroxide solution 3
g, hydrolyzed with 1.5 g of 36% hydrochloric acid after decomposition,
After making up to a predetermined amount with water, the Cl-substituted product was quantified by HPLC, and the concentration (mol ppm) relative to the hydroxycarboxylic acid unit was calculated. Column: Shodex KC810p + KC811 × 2
Main eluent: 4.8 mM-HClO ₄ aqueous solution Flow rate: 1 ml / min. Measurement absorption wavelength: 225 nm

[0035]

【Example】

Synthesis Example 1 90% lactic acid 30 was placed in a 1000 ml four-necked flask equipped with a thermometer, a distilling tube, a cooling tube, a blowing tube, and a stirring device.
Of lactic acid oligomer 201 having an average degree of polymerization n of 15.3 under a nitrogen stream at 160 ° C. for 8 hours.
g (oligomer 1; 0.182 mol of -COOH groups) was obtained. Next, 600 g of dichloromethane was charged and dissolved, and 36.92 g of 2-chloro-1,3-dimethylimidazolinium chloride (hereinafter abbreviated as DMC) (0.21 g) was added.
8 mol) and reacted at 40 ° C. for 13 hours. The solvent was evaporated from the obtained reaction mass at 40 ° C. and 10 mmHg.
The mixture was dried and returned to normal pressure with nitrogen (acid chloride 1). Mw of the obtained acid chloride 1 was 5,700 and Mn was 1,50.
The concentration of the acid chloride group was 6.67 × 10 ⁻⁴ mol / g, and no carboxylic acid terminal was detected (measurement was carried out under a nitrogen atmosphere). Further, the amount of 2-chloropropionic acid in the lactic acid unit measured by hydrolyzing the obtained acid chloride 1 was 100 mol ppm or less.

Synthesis Example 2 An oligomer was obtained in the same manner as in Synthesis Example 1 except that 385 g of 70% glycolic acid was used instead of 90% lactic acid. 196 g of the obtained glycolic acid oligomer (oligomer 2)
(N = 21.4, 0.158 mol of -COOH group). Next, 600 g of dichloromethane was charged to dissolve the oligomer 2, and then 32.05 g (0.190 mol) of DMC was charged and reacted at 40 ° C. for 13 hours. The obtained reaction mass was evaporated at 40 ° C. and 10 mmHg to dryness of the solvent, and the pressure was returned to normal pressure with nitrogen (acid chloride 2). Mw of the obtained acid chloride 2 was 5,300, Mn was 1810, the concentration of the acid chloride group was 5.52 × 10 ⁻⁴ mol / g, and no carboxylic acid terminal was detected. The chloroacetic acid in glycolic acid units measured by hydrolyzing the obtained acid chloride 2 was 100 mol ppm or less.

Example 1 10 g of the acid chloride 1 obtained in Synthesis Example 1 (6.67 × 10 ⁻³ mol of acid chloride group) and 50 g of dichloromethane were charged and dissolved in a 100 ml screw tube. Then, 2.45 g (0.019 mol) of quinoline was added,
After shaking for about 1 minute, the mixture was left standing at 40 ° C. for 2 hours to carry out polymerization. Note that all the operations up to this point were performed in a nitrogen atmosphere. The obtained reaction mass was discharged into 300 g of isopropyl alcohol (hereinafter abbreviated as IPA), filtered, and then filtered.
After rinsing with 0 g, it was dried at 80 ° C. and 160 mmHg under a nitrogen stream for 8 hours to obtain 9.72 g of polylactic acid. Mw of the obtained polylactic acid was 172,000, Mn was 64,
000. 100 mol ppm of 2-chloropropionic acid in lactic acid units measured by hydrolyzing polylactic acid
It was below.

Example 2 Example 1 was followed except that 2.45 g of quinoline was changed to 2.45 g of isoquinoline. M of the obtained polylactic acid
w was 250,000 and Mn was 89,000. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 3 The procedure was as in Example 1, except that 2.45 g of quinoline was changed to 2.72 g of quinaldine. Mw of the obtained polylactic acid
Was 168,000 and Mn was 67,000. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 4 The procedure of Example 1 was followed, except that 2.45 g of quinoline was changed to 2.04 g of 3,5-lutidine. Mw of the obtained polylactic acid was 262,000, and Mn was 94,000. 2 in lactic acid unit measured by hydrolyzing polylactic acid
-Chloropropionic acid was 100 mol ppm or less.

Example 5 The procedure was as in Example 1, except that 2.45 g of quinoline was changed to 2.04 g of 2,6-lutidine. Mw of the obtained polylactic acid was 232,000 and Mn was 83,000. 2 in lactic acid unit measured by hydrolyzing polylactic acid
-Chloropropionic acid was 100 mol ppm or less.

Example 6 2.45 g of quinoline and 1.92 g of 4-methylmorpholine
Example 1 was followed except for changing to. Mw of the obtained polylactic acid was 182,000 and Mn was 67,000. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 7 2.45 g of quinoline and 2.30 g of 2,4,6-collidine
Example 1 was followed except for changing to. Mw of the obtained polylactic acid was 169,000, and Mn was 65,000. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 8 2.45 g of quinoline was added to 6.7 of tri-n-octylamine.
Example 1 was followed except that the amount was changed to 2 g. Mw of the obtained polylactic acid was 195,000 and Mn was 72,000.
Met. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 9 Example 1 was followed except that 2.45 g of quinoline was changed to 2.21 g of N, N, N ', N'-tetramethylethylenediamine. The Mw of the obtained polylactic acid was 166,00
0 and Mn were 66,000. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 10 2.45 g of quinoline was added to 1.88 g of N-methylpiperidine
Example 1 was followed except for changing to. Mw of the obtained polylactic acid was 164,000 and Mn was 65,000. 2-Chloropropionic acid in the lactic acid unit measured by hydrolyzing the polylactic acid was 100 mol ppm or less.

Example 11 A 100 ml screw tube was charged with 10 g of the acid chloride 2 obtained in Synthesis Example 2 (5.52 × 10 ^-3 mol of acid chloride group) and 50 g of dichloromethane, and dissolved therein. Next, 2.07 g (0.016 mol) of quinoline was added,
After shaking for about 1 minute, the mixture was left standing at 40 ° C. for 2 hours to carry out polymerization. Note that all the operations up to this point were performed in a nitrogen atmosphere. The reaction mass obtained was discharged into 300 g of IPA, filtered, rinsed with 150 g of IPA,
It was dried for 8 hours under a stream of mmHg and nitrogen to obtain 9.79 g of polyglycolic acid. Mw of the obtained polyglycolic acid
Was 154,000 and Mn was 56,000. The amount of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid was 100 mol ppm or less.

Example 12 Example 12 was followed except that 2.07 g of quinoline was changed to 2.07 g of isoquinoline. Mw of the obtained polyglycolic acid was 199,000, and Mn was 71,000. The amount of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid was 100 mol ppm or less.

Example 13 Example 12 was followed except that 2.45 g of quinoline was changed to 2.29 g of quinaldine. Mw of the obtained polyglycolic acid was 161,000 and Mn was 54,000. The amount of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid was 100 mol ppm or less.

Example 14 Example 12 was followed except that 2.45 g of quinoline was changed to 1.71 g of 3,5-lutidine. Mw of the obtained polyglycolic acid was 203,000 and Mn was 75,000.
It was 0. 100 mol ppm of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid
It was below.

Example 15 Example 12 was followed except that 2.45 g of quinoline was changed to 1.71 g of 2,6-lutidine. Mw of the obtained polyglycolic acid was 196,000 and Mn was 66,00.
It was 0. 100 mol ppm of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid
It was below.

Example 16 2.45 g of quinoline and 1.62 g of 4-methylmorpholine
Example 12 was followed except for changing to. Mw of the obtained polyglycolic acid was 155,000, and Mn was 67,0.
00. Chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid is 100 mol pp
m or less.

Example 17 2.45 g of quinoline was added to 1.94 g of 2,4,6-collidine
Example 12 was followed except for changing to. Mw of the obtained polyglycolic acid was 156,000, Mn was 52,
000. Chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid is 100 mol p
pm or less.

Example 18 2.45 g of quinoline was added to 5.6 of tri-n-octylamine.
Example 12 was followed except that the amount was changed to 5 g. Mw of the obtained polyglycolic acid was 170,000 and Mn was 5
It was 8,000. The amount of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid was 100 mol ppm or less.

Example 19 The procedure of Example 12 was followed, except that 2.45 g of quinoline was changed to 1.86 g of N, N, N ', N'-tetramethylethylenediamine. Mw of the obtained polyglycolic acid was 156,000 and Mn was 53,000. The amount of chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid was 100 mol ppm or less.

Example 20 2.45 g of quinoline was added to 1.59 g of N-methylpiperidine.
Example 12 was followed except for changing to. Mw of the obtained polyglycolic acid was 154,000, Mn was 53,
000. Chloroacetic acid in glycolic acid units measured by hydrolyzing polyglycolic acid is 100 mol p
pm or less.

Comparative Example 1 Example 1 was followed except that 2.45 g of quinoline was changed to 2.16 g of 2-chloropyridine having a pKa of 0.72, and the polymerization time was changed to 24 hours. Mw of the obtained polylactic acid was 5,700 and Mn was 1,500, and polymerization did not proceed at all.

Comparative Example 2 Except that 2.16 g of 2-chloropyridine was changed to 1.79 g of 2-methylpyrazine having a pKa of 1.50.
Based on Comparative Example 1. The Mw of the obtained polylactic acid was 5, 7
00 and Mn were 1,500, and polymerization did not proceed at all.

Comparative Example 3 Comparative Example 1 was followed except that 2.16 g of 2-chloropyridine was changed to 2.30 g of N, N-dimethylaniline having a pKa of 4.75. Mw of the obtained polylactic acid was 22,000, Mn was 7,000, and the polymerization rate was very slow.

Comparative Example 4 Comparative Example 1 was followed except that 2.16 g of 2-chloropyridine was changed to 2.66 g of hexamethylenetetramine having a pKa of 4.85. Mw of the obtained polylactic acid was 19,000 and Mn was 6,400, and the polymerization rate was very slow.

[0061]

EFFECT OF THE INVENTION It has been clarified that a high molecular weight polyhydroxycarboxylic acid can be easily produced by polymerizing a hydroxycarboxylic acid and / or an acid chloride of an oligomer thereof in the presence of a tertiary amine having a specific pKa. did.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Kenichi Goto, inventor, 30 Asamutacho, Omuta-shi, Fukuoka Prefecture Mitsui Toatsu Chemical Co., Ltd. Inside the corporation

Claims (4)

[Claims] 1. The hydroxycarboxylic acid represented by the general formula (1) and / or an acid chloride of an oligomer thereof is represented by the following formula: (In the formula, R is an aliphatic hydrocarbon group, and n is an integer of 1 or more.) 3. The logarithm of the reciprocal of the acid dissociation constant is 4.9 or more.
A method for producing a polyhydroxycarboxylic acid, comprising reacting in the presence of a secondary amine. 2. The method according to claim 1, wherein the reaction is carried out at a temperature of 120 ° C. or lower. 3. A tertiary amine having a logarithm of the reciprocal of the acid dissociation constant of 4.9 or more is quinoline, isoquinoline, quinaldine, 3,5-lutidine, 2,6-lutidine, 4-methylmorpholine, And at least one tertiary amine selected from the group consisting of 1,4,6-collidine, tri-n-octylamine, N, N, N ', N'-tetramethylethylenediamine and N-methylpiperidine. 2
The manufacturing method as described. 4. The method of claim 1, wherein the acid chloride of hydroxycarboxylic acid and / or its oligomer is lactic acid, glycolic acid,
The production method according to claim 1, which is at least one or more hydroxycarboxylic acids selected from -hydroxybutyric acid, 4-hydroxybutyric acid, 3-hydroxyvaleric acid, and 5-hydroxyvaleric acid and / or an acid chloride of an oligomer thereof. .