JPH05163332A - Biodegradable, optically active polymer and its production - Google Patents

Abstract

PURPOSE:To obtain the title polymer which is optically active, has enzymatic decomposability and hydrolyzability and is biodegradable. CONSTITUTION:An optically active polymer of formula III (wherein R is 1-5C alkyl and R<1> is H or 1-5C alkyl) is obtained by performing the ring opening polymerization of at least one lactide selected from among those of formula I (wherein R<1> is as defined above) and an optically active 7-substituted-1,4- dioxepan-5-one of formula II (wherein R as defined above) in the presence of at least one catalyst selected from among organotin compounds. This polyether ester is an optically active, biodegradable (enzymatically decomposable), hydrolyzable and thermoplastic resin and can be degraded by microbes living in soil or water. Therefore it is a functional polymer which can be extensively used as a clean plastic free from environmental pollution.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a biodegradable optically active polymer and a method for producing the same. More specifically, 3-
The present invention relates to an optically active polyether ester obtained by ring-opening copolymerization of an optically active 7-substituted-1,4-dioxepan-5-one derivative containing a hydroxybutyric acid unit and a lactide, and a method for producing the same. The polyether ester according to the present invention is a thermoplastic resin having optical activity, biodegradability (enzymatic degradability), and hydrolyzability, and as a clean plastic that does not pollute the environment because it is decomposed by microorganisms existing in soil or water. It is a widely available functional polymer.

[0002]

2. Description of the Related Art A compound of formula (IV) corresponding to the basic skeleton of the polymer of the present invention

[Chemical 7] 1,4-dioxepan-5-one (1,5-
Although it can be named dioxepan-2-one, in the present specification, the former name is used in a unified manner. Is known. For example, in British Patent No. 1272733, ethylene glycol and acrylonitrile are reacted in the presence of 50% caustic soda to give 2- (2-cyanoethoxy) ethanol, which is then cyclized through dry hydrogen chloride in methylene chloride. -Imino-1,4-dioxepan-5-one hydrochloride, then heated to 40 ° C in an aqueous solution to give 1,4-
A method for obtaining dioxepan-5-one (total yield about 5%) is described.

Regarding copolymers of 1,4-dioxepan-5-one with lactides, US Pat. No. 4,470,416 discloses a large amount of lactide (R ¹ in the general formula (II) described later).
A compound having a methyl group) or glycolide and a small amount of 1,4-dioxepan-5-one in the presence of tin octylate is disclosed. However, the 1,4-
The copolymer of dioxepan-5-one and lactide has a problem in that it has no substituent (at the 7-position) and is not optically active and biodegradable.

On the other hand, in recent years, a microorganism has been known which accumulates a polymer of 3-hydroxybutyric acid corresponding to a part of the compound of the present invention in the cells (PA Holmes, Phys. Techno.
l.1985, (16), 32), this polymer has been attracting attention as a new type of functional material because of its biodegradable or enzymatically degradable, hydrolyzable, and biocompatible properties (biodegradable). Polymeric Materials, p. 19, edited by Yoshiharu Dohi, published by Industrial Research Society 1990). In addition, D-(+)-methyl-β
-Ring-opening polymerization of propiolactone is described in Polymer letters, 9,
173 (1970). However, the method that is a microbiological synthesis method uses a microbial or enzymatic reaction,
It requires complicated processes such as separation of polymer from microbial cells, high production cost, and D-(+)-methyl-β
-Propiolactone ring-opening polymerization has many problems in industrialization such as an optical resolution step.

Therefore, an object of the present invention is to biodegrade by optically ring-opening copolymerization of an optically active 7-substituted-1,4-dioxepan-5-one derivative containing a 3-hydroxybutyric acid unit with a lactide. It is intended to provide a polymer excellent in (enzymatic degradability) and hydrolyzability and a method for producing the same.

[0006]

As a result of intensive studies to solve the above problems, the present inventors have found that an optically active 7-substituted-1,4-dioxepane-5 containing a 3-hydroxybutyric acid unit is used. The inventors have found that the on-derivative can be easily subjected to ring-opening copolymerization in the presence of a lactide and a catalyst to give the corresponding optically active polyether ester, and completed the present invention.

That is, the present invention is: 1) The following general formula (II)

[Chemical 8] (In the formula, R ¹ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms) and at least one lactide selected from the compounds represented by the general formula (III)

[Chemical 9] (In the formula, R represents an alkyl group having 1 to 5 carbon atoms.) Optically active 7-substituted-1,4-dioxepane-5
General formula (I) obtained by ring-opening copolymerization with -one

[Chemical 10] (In the formula, R and R ¹ have the same meanings as described above, and m and n represent natural numbers.), And

2) The following general formula (II)

[Chemical 11] (Wherein R ¹ has the same meaning as described above) and at least one lactide selected from compounds represented by the general formula (III)

[Chemical 12] (Wherein R represents the same meaning as described above), and the optically active 7-substituted-1,4-dioxepan-5-one is represented by
General formula (I) characterized by carrying out ring-opening copolymerization in the presence of at least one catalyst selected from organotin compounds

[Chemical 13] (Wherein R, R ¹ , m and n have the same meanings as described above), and a method for producing an optically active polymer.

The present invention will be described in detail below. The 7-substituted-1,4-dioxepan-5-one derivative, which is one of the raw materials for the polymer of the present invention, can be produced, for example, as follows.

[0010]

[Chemical 14]

(Wherein R has the same meaning as described above, X
Represents an alkyl group having 1 to 6 carbon atoms. In the above step, the optically active 3-hydroxyalkanoic acid ester represented by the formula (IV) as the starting material is prepared by the method disclosed by the applicant in JP-A-63-310847, that is, the general formula (VIII) )

[Chemical 15] (In the formula, R and X have the same meanings as described above.) The β-ketoester acids can be easily obtained by asymmetric hydrogenation using a ruthenium-optically active phosphine complex as a catalyst.

Another raw material of the polymer of the present invention is the following general formula (II)

[Chemical 16] The lactide represented by the formula (wherein R ¹ has the same meaning as described above) is a cyclic diester obtained by heating α-oxy acid under reduced pressure or by allowing a dehydrating agent to act to dehydrate between two molecules. Yes, it can be easily synthesized from the corresponding α-oxy acid.

In the general formula (II), lactides in which R ¹ is an alkyl group include D-form, L-form and racemate, but any of them can be used in the present invention. Among the lactides of the general formula (II), particularly preferred are compounds in which R ¹ represents a methyl group (hereinafter simply referred to as lactide) and glycolides in which R ¹ represents a hydrogen atom. Can be used. As a purification method, for example, a method in which calcium hydride is added and distilled and stored in an inert gas before use can be adopted. In the present invention, the lactides of general formula (II) may be used alone or in combination of two or more.

In the present invention, the ratio of the optically active 7-substituted-1,4-dioxepan-5-one derivative subjected to ring-opening copolymerization to the lactide is 1 in the molar ratio of the former to the latter.
˜99: 99 to 1, preferably 5 to 50:95 to 50.

The ring-opening copolymerization is carried out by using an optically active 7-substituted-1,4-dioxepan-5-one derivative having a 3-hydroxybutyric acid unit and a lactide at a suitable ratio within the above range without solvent or 2 Dissolved in 10 times the amount of an inert organic solvent, for example, an organic solvent such as toluene, benzene, dioxane, or tetrahydrofuran, and charged into a reaction vessel under an inert gas such as nitrogen or argon. It is carried out by random copolymerization to obtain a polymer by reacting at a temperature of ˜180 ° C. for 1 hour to 5 days.

Here, as the catalyst, an organic tin compound, for example, a dialkyl tin oxide represented by dibutyl tin oxide, a trialkyl tin alkoxide represented by tributyl tin methoxide, a tin alkylate such as tin octylate, 1-hydroxy- Distannoxane represented by 3- (isothiocyanate) tetrabutyldistannoxane, stannous chloride, tetraphenyltin, tetraallyltin, etc. are used.

At least one of these catalysts is used, and if necessary, several types can be used in combination. Among these catalysts, dibutyltin oxide, tin octylate and the like are preferably used. The catalyst is used in an amount of about 1/10 to 1/10000 times the molar amount of the raw material monomer.

[0018]

According to the present invention, an optically active 7-substituted-1,4-dioxepan-5-one derivative containing a 3-hydroxybutyric acid unit and a lactide are subjected to ring-opening copolymerization to give an optically active compound. A useful polymer, which is a new functional material having characteristics of enzymatic degradability and hydrolyzability, can be easily produced by an industrially advantageous method.

[0019]

The present invention will be described in more detail below with reference to examples and test examples, but the present invention is not limited to these examples. The analytical instruments used in the examples and the facilities used in the biodegradability test are as follows. Nuclear magnetic resonance spectrum (NMR): AM-400 type device (400 MHz) (manufactured by Bruker) Infrared absorption spectrum (IR): IR-810 type infrared spectroscopic analyzer (manufactured by JASCO Corporation), molecular weight: D-2520 GPC Integrator (manufactured by Hitachi, Ltd.), optical rotation: DIP-360 type digital polarimeter (manufactured by JASCO Corporation). Biodegradability test: Performed using activated sludge.

Example 1: D-(-)-7-methyl-1,
Synthesis of polyether ester by ring-opening copolymerization from 4-dioxepan-5-one and L-lactide D-(-)-7-methyl-1,4 was added to a 20 ml reaction vessel.
-Dioxepan-5-one (hereinafter abbreviated as MDO) 0.26 g (2 mmol), L-lactide (Tokyo Kasei Co., Ltd.) 2.59 g (18 mmol), 120 ° C under reduced pressure,
0.0167 g (0.10 g) of dibutyltin oxide dried for 24 hours.
(067 mmol) and 5 ml of dry toluene were added, and the mixture was stirred at 120 ° C. for 2 hours under a nitrogen atmosphere. The produced polymer was put in methanol and washed with ether to obtain 2.58 g (yield 90.5%) of the title polyether ester (hereinafter abbreviated as P (MDO) -L-lactide) (MDO part 6.7). %, L-lactide part 93.3%).

¹ H-NMR (400 MHz, CDCl ₃ ) δp
pm: MDO part 1.15 to 1.24 (3H, m), 2.43 to 2.40 (1H, m), 2.55
~ 2.70 (1H, m), 3.58 ~ 3.74 (2H, m), 3.84 ~ 3.95 (1H, m),
4.10 to 4.34 (2H, m); L-lactide part 1.47 to 1.63 (3H, m), 5.08 to 5.23 (2H, m)
m); IR (cm ^-1 ): 2990, 2850, 1760, 1455, 1385, 1185,
1095; weight average molecular weight (hereinafter abbreviated as Mw): 75400; number average molecular weight (hereinafter abbreviated as Mn): 59200; glass transition temperature (hereinafter abbreviated as Tg): 47 ° C; melting point ( Hereinafter, abbreviated as Tm): 154 ° C .; decomposition temperature (hereinafter abbreviated as TG): 269 ° C .; [α] _D : −145.6 ° (c = 1, CHCl ₃ , 20
C).

Example 2: Synthesis of P (MDO (17%)-L-lactide (83%)) 0.52 g (4 mmol) MDO in a 20 ml reaction vessel.
The reaction was performed in the same manner as in Example 1 except that 2.31 g (16 mmol) of L-lactide was used to obtain 2.58 g of the title polymer (yield 90.5%) (MDO part 16.6).
%, L-lactide part 83.4%). Mw: 69500; Mn: 47300; Tg: 38 ° C .; Tm: 136 ° C .; TG: 279 ° C .; [α] _D : −134.5 ° (c = 1, CHCl ₃ , 20,
C), crystallization rate: 33% (by X-ray analysis).

Example 3: Synthesis of P (MDO (29%)-L-lactide (71%)) 0.78 g (6 mmol) of MDO in a 20 ml reaction vessel.
The reaction was carried out in the same manner as in Example 1 except that 2.02 g (14 mmol) of L-lactide was used to obtain 2.37 g (yield 84.6%) of the title polymer (MDO part: 29.3%).
%, L-lactide part 7 0.7%). Mw: 102800; Mn: 26700; Tg: 24 ° C .; Tm: 111 ° C .; TG: 275 ° C .; [α] _D : -118.7 ° (c = 1, CHCl ₃ , 20,
C).

Example 4: Synthesis of P (MDO (17%)-lactide (83%)) 0.52 g (4 mmol) MDO in a 20 ml reaction vessel.
Racemic lactide (Tokyo Kasei Co., Ltd.) 2.31 g (1
The reaction was conducted in the same manner as in Example 1 except that 6 mmol) was used, and 2.17 g of the title polymer (yield 76.7
%) (MDO part 17.3%, lactide part 82.7)
%). Mw: 78800; Mn: 43800; Tg: 13 ° C; TG: 277 ° C.

Example 5: Synthesis of polyester by ring-opening polymerization of MDO and glycolide 2.60 g (20 mmol) of MDO in a 20 ml reaction vessel,
2.32 g (20 mmol) of glycolide (manufactured by DuPont) and 0.0167 g (0.067 mmol) of dibutyltin oxide
In a nitrogen atmosphere at 150 ° C. for 2 hours, then 190
All the polymers produced by the reaction at 0 ° C. for 2 hours were used in Example 1.
2.17 g of the title polymer (yield 76.7
%) (MDO part 49.3%, L-lactide part 50.7)
%).

¹ H-NMR (400 MHz, CDCl ₃ ) δp
pm: MDO part 1.15 to 1.32 (3H, m), 2.33 to 2.53 (1H, m), 2.53
~ 2.76 (1H, m), 3.55 ~ 3.77 (2H, m), 3.86 ~ 3.99 (1H, m),
4.10 to 4.33 (2H, m); glycolide portion 4.60 to 4.90 (2H, m); IR (cm ^-1 ): 2970, 1750, 1425, 1170, 1095; Mw: 34000; Mn: 18400; Tg: -7 ° C Tm: 41 ° C; TG: 280 ° C.

Biodegradability Test Test Example 1 The acclimatized species (aerobic sludge) of sludge used at Takasago International Corporation's Hiratsuka Plant was 500 ppm (600 ml), pH 6.0.
A thin film of 1 cm × 2 cm of the polymer obtained in Example 3 and having a thickness of 0.05 to 0.1 mm (the polymer is dissolved in chloroform, poured into a petri dish, and the solvent is evaporated to evaporate the solvent). 20 to 30 mg was put in a 50 ml flask, and the test was conducted using a shaking constant temperature water bath manufactured by Titec Co., Ltd. The residual weight ratio was determined by measuring the weight of the polymer every one week. The result is shown in FIG. From this result, it was found that the polymer film of Example 3 was decomposed by about 5% after 4 weeks.

Test Example 2 The polymer obtained in Example 5 was subjected to a biodegradability test in the same manner as in Test Example 1. The result is shown in FIG.
From this result, it is confirmed that the polymer film of Example 5 was used after 4 weeks.
It was found to have decomposed by 5.9%.

[Brief description of drawings]

FIG. 1 is a graph showing changes over time in the residual polymer weight ratio in Test Examples 1 and 2.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Takashi Imai 1-5-1, Nishi-Hachiman, Hiratsuka City, Kanagawa Prefecture Takasago Research, Inc. Hiratsuka Branch Office (72) Inventor Minzo Sakaguchi Hiratsuka City, Kanagawa Prefecture Nishihachiman 1-5-1 Takasago Research Co., Ltd., Institute Hiratsuka Branch

Claims (5)

[Claims] 1. The following general formula (II): (In the formula, R ¹ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms) and at least one lactide selected from compounds represented by the general formula (III): (In the formula, R represents an alkyl group having 1 to 5 carbon atoms.) Optically active 7-substituted-1,4-dioxepane-5
General formula (I) obtained by ring-opening copolymerization of -one with (In the formula, R and R ¹ have the same meanings as described above, and m and n represent natural numbers.). 2. A glycolide represented by the general formula (II) in which R ¹ represents a hydrogen atom, and an optically active compound 7 represented by the general formula (III).
The optically active polymer according to claim 1, which is obtained by ring-opening copolymerization with -substituted-1,4-dioxepan-5-one. 3. A lactide represented by the general formula (II) in which R ¹ represents a methyl group, and an optically active compound represented by the general formula (III):
The optically active polymer according to claim 1, which is obtained by ring-opening copolymerization with a substituted-1,4-dioxepan-5-one. 4. The following general formula (II): (Wherein R ¹ has the same meaning as in claim 1) and at least one lactide selected from the compounds represented by the general formula (III): (Wherein R has the same meaning as in claim 1), and the optically active 7-substituted-1,4-dioxepan-5-one is present in the presence of at least one catalyst selected from organotin compounds. General formula characterized by ring-opening copolymerization
(I) [Chemical 6] (Wherein R and R ¹ have the same meanings as described above, and m and n have the same meanings as in claim 1.). 5. The optical according to claim 4, wherein the organotin compound is selected from one or more of dibutyltin oxide, stannous chloride, tributyltin methoxide, tin octylate, tin laurate and tetraphenyltin. Process for producing active polymer.