JP2826921B2 - Biodegradable optically active polymer and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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 polyetherester 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 polyetherester according to the present invention is a thermoplastic resin having optical activity, biodegradability (enzymatic degradability) and hydrolyzability, and is degraded by microorganisms existing in soil or water, so that it is used as a clean plastic which does not pollute the environment. It is a widely used functional polymer.

[0002]

BACKGROUND OF THE INVENTION The compound of the formula (IV) which is a compound corresponding to the basic skeleton of the polymer of the present invention

Embedded image 1,4-dioxepan-5-one (1,5-dioxane)
Although it may be named dioxepan-2-one, the former name is used in the present specification. Is known. For example, GB 1272733 discloses that ethylene glycol and acrylonitrile are reacted in the presence of 50% caustic soda to give 2- (2-cyanoethoxy) ethanol, which is then cyclized in dry methylene chloride through dry hydrogen chloride. -Imino-1,4-dioxepan-5-one hydrochloride, and 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.

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

On the other hand, in recent years, microorganisms that accumulate 3-hydroxybutyric acid polymer corresponding to a part of the compound of the present invention in cells have been known (PA Holmes, Phys.
l. 1985, (16), 32), this polymer has attracted attention as a new type of functional material because of its biodegradable, ie, enzymatic, hydrolytic, and biocompatible properties (biodegradation). Polymeric Materials, p. 19, edited by Yoshiharu Toi, published by the Industrial Research Council 1990). D-(+)-methyl-β
-Ring-opening polymerization of propiolactone is described in Polymer letters, 9,
173 (1970). However, microbiological methods use microbial or enzymatic reactions,
It requires complicated steps such as separation of the polymer from the cells, requires a high production cost, and requires D-(+)-methyl-β
-There are many problems in industrialization, such as the fact that the ring-opening polymerization method of propiolactone has an optical resolution step.

Accordingly, an object of the present invention is to provide a biodegradable compound by subjecting an optically active 7-substituted-1,4-dioxepan-5-one derivative containing a 3-hydroxybutyric acid unit to ring-opening copolymerization with lactides. (Enzymatic degradability), to provide a polymer excellent in hydrolyzability and a method for producing the same.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that an optically active 7-substituted-1,4-dioxepane-5-containing a 3-hydroxybutyric acid unit is contained. The present inventors have found that an on-derivative easily undergoes ring-opening copolymerization with a lactide in the presence of a catalyst to form a corresponding optically active polyetherester, thereby completing the present invention.

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

Embedded image (Wherein 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):

Embedded image (Wherein, R represents an alkyl group having 1 to 5 carbon atoms.) An optically active 7-substituted-1,4-dioxepane-5 represented by the formula:
General formula (I) obtained by ring-opening copolymerization with -one

Embedded image (Wherein, R and R ¹ have the same meanings as described above, and m and n each represent a natural number), and

2) The following general formula (II)

Embedded image (Wherein R ¹ has the same meaning as described above) and at least one lactide selected from compounds represented by the general formula (III):

Embedded image (Wherein, R represents the same meaning as described above) represented by the following formula:
A ring-opening copolymerization in the presence of at least one catalyst selected from organotin compounds;

Embedded image (Wherein, R, R ¹ , m and n have the same meanings as described above).

Hereinafter, the present invention will be described in detail. 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]

Embedded image

(Wherein R has the same meaning as described above;
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 a starting material can be prepared by the method disclosed by the present applicant in JP-A-63-310847, that is, by the general formula (VIII) )

Embedded image (Wherein R and X have the same meanings as described above) 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 represented by the following general formula (II):

Embedded image (In the formula, R ¹ has the same meaning as described above.) The lactide represented by the formula ( ¹ ) is a cyclic diester obtained by heating α-oxyacid under reduced pressure or by reacting a dehydrating agent to cause a dehydration reaction between two molecules. Yes, and can be easily synthesized from the corresponding α-oxyacid.

In formula (II), lactides in which R ¹ is an alkyl group include D-forms, L-forms and racemic forms, all of which can be used in the present invention. Of 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 glycolide 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, distilled, and stored in an inert gas until use can be adopted. In the present invention, one kind of the lactides of the general formula (II) may be used alone, or two or more kinds may be used simultaneously.

In the present invention, the ratio of the optically active 7-substituted-1,4-dioxepan-5-one derivative and the lactide to be subjected to the ring-opening copolymerization is 1 in a molar ratio of the former to the latter.
９９99: 99〜1, preferably 5９５50: 95〜50.

In the ring-opening copolymerization, an optically active 7-substituted-1,4-dioxepan-5-one derivative having a 3-hydroxybutyric acid unit and a lactide are used in an appropriate ratio within the above-mentioned range without solvent or with lactide. Dissolve in an organic solvent such as 10 to 10 times the amount of an inert organic solvent, for example, toluene, benzene, dioxane, tetrahydrofuran, etc., charge the reaction vessel under an inert gas such as nitrogen or argon, and add a catalyst thereto. It is carried out by random copolymerization in which a polymer is reacted at a temperature of 180 ° C. for 1 hour to 5 days to obtain a polymer.

Examples of the catalyst include organotin compounds, for example, dialkyltin oxides typified by dibutyltin oxide, trialkyltin alkoxides typified by tributyltin methoxide, tin alkylates such as tin octylate, 1-hydroxy- Distannoxane represented by 3- (isothiocyanate) tetrabutyldistannoxane, stannous chloride, tetraphenyltin, tetraallyltin and the like are used.

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

[0018]

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

[0019]

The present invention will be described in more detail with reference to the following 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 apparatus (400 MHz) (manufactured by Bruker) Infrared absorption spectrum (IR): IR-810 type infrared spectroscopic analyzer (manufactured by JASCO Corporation), molecular weight: D-2520GPC Integrator (manufactured by Hitachi, Ltd.), Optical rotation: DIP-360 digital polarimeter (manufactured by JASCO Corporation). Biodegradability test: Performed using activated sludge.

Example 1: D-(-)-7-methyl-1,
Synthesis of polyetherester 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 (manufactured by Tokyo Chemical Industry Co., Ltd.) 2.59 g (18 mmol), 120 ° C. under reduced pressure,
0.0167 g of dibutyltin oxide (0.
(067 mmol) and 5 ml of dry toluene, and stirred at 120 ° C. for 2 hours under a nitrogen atmosphere. The resulting polymer was placed in methanol and washed with ether to obtain 2.58 g (yield 90.5%) of the title polyetherester (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 section 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; 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%)) In a 20 ml reaction vessel, 0.52 g (4 mmol) of MDO,
The reaction was carried out 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 (yield 90.5%) of the title polymer (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 70.7%). 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%)) In a 20 ml reaction vessel, 0.52 g (4 mmol) of MDO,
Racemic lactide (Tokyo Kasei Co., Ltd.) 2.31 g (1
The reaction was carried out 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 g) was obtained.
% (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 from MDO and Glycolide In a 20 ml reaction vessel, 2.60 g (20 mmol) of MDO, 2.32 g (20 mmol) of glycolide (manufactured by Dupont) and 0 g of dibutyltin oxide 0.0167 g (0.067 mmol) was added under a nitrogen atmosphere at 150 ° C. for 2 hours, and then at 190 ° C.
The resulting polymer was treated in the same manner as in Example 1 to give 2.17 g of the title polymer (yield 7).
6.7%) (49.3% of MDO part, 50.7% of glycolide part ).

¹ H-NMR (400 MHz, CDCl ₃ ) δp
pm: MDO section 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 part 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 1 500 ppm (600 ml) of sludge acclimatized (aerobic sludge) used at Hiratsuka Plant of Takasago International Corporation, pH 6.0
The polymer obtained in Example 3 was used under the conditions of 7.07.0 and 30 ° C., and a thin film of 1 cm × 2 cm and a thickness of 0.05 to 0.1 mm was prepared by dissolving the polymer in chloroform, flowing the solution into a petri dish, and evaporating the solvent. 20 to 30 mg was placed in a 50 ml flask, and a test was performed using a shaking water bath manufactured by Taitec Corporation. The residual weight percentage was determined by measuring the weight of the polymer every 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, the polymer film of Example 5 was obtained after 4 weeks.
It turned out that it decomposed 5.9%.

[Brief description of the drawings]

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

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Akio Yamaguchi 5-36-31 Kamata, Ota-ku, Tokyo Inside Takasago Research, Inc. (72) Inventor Takashi Imai 1-5 Nishi-Hachiman, Hiratsuka-shi, Kanagawa Prefecture No. 1 Takasago Research Co., Ltd., Institut Hiratsuka Branch (72) Inventor Tamzo Sakaguchi 1-5-1, Nishihachiman, Hiratsuka-shi, Kanagawa Prefecture Takasago Research, Inc. Hiratsuka Branch (56) References U.S. Pat. No. 4,470,416 (US, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C08G 63/00-63/91

Claims (5)

(57) [Claims] 1. A compound represented by the following general formula (II): (Wherein 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): (Wherein, R represents an alkyl group having 1 to 5 carbon atoms.) An optically active 7-substituted-1,4-dioxepane-5 represented by the formula:
Formula (I) obtained by ring-opening copolymerization of -one with (Wherein, R and R ¹ have the same meanings as described above, and m and n each represent a natural number). 2. A glycolide represented by the formula (II) wherein R ¹ represents a hydrogen atom, and an optically active compound represented by the 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 wherein R ¹ in the general formula (II) represents a methyl group, and a lactide 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. 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 represents the same meaning as in claim 1), wherein the optically active 7-substituted-1,4-dioxepan-5-one is used in the presence of at least one catalyst selected from organotin compounds. General formula characterized by ring-opening copolymerization
(I) (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 device 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. Method for producing active polymer.