JPH0413727A - Polydiorganosiloxane-polyether block copolymer and production thereof - Google Patents

Abstract

PURPOSE:To obtain the title copolymer useful as a medical material to which adaptability with living things is required by reacting an alkali metal salt of a specific polydiorganosiloxane with a pyrrolidinium ring ended polyether and then subjecting a pyrrolidinium base to ring opening by heating, etc. CONSTITUTION:An alkali metal salt of carboxyalkyl-ended polydiorganosiloxane expressed by formula I [R is 1-4C alkyl or phenyl; R<1> is monovalent hydrocarbon or formula II (a is 3-6; q is 10-2000; t is 0 or 1; M is H or alkali metal); p is same as q] is subjected to coupling reaction with a pyrrolidinium ring-ended polyether expressed by formula III (R<2> is 2-6C alkylene; S is 10-200 ; X is negative group[ and the resultant product is separated, dried and subjected to ring opening reaction by heating to provide the aimed copolymer expressed by formula TV or formula V (n is 1-30).

Description

Detailed Description of the Invention [Technical Field of the Invention] The present invention relates to a polydiorganosiloxane-polyether block copolymer and a method for producing the same, and more particularly, to a polydiorganosiloxane-polyether block copolymer and a method for producing the same. Regarding block copolymers with uniform properties.

[Technical background of the invention and its problems] Chain polysiloxanes, which have molecular chains of uniform length and have a reactive functional group at one or both ends, can be grafted together by reacting with various organic polymers. Polymers, block copolymers or crosslinked polymers are obtained, resulting in copolymers with uniform length of siloxane segments.

Such copolymers result in polymeric materials with controlled microdomain structures that exhibit unique properties, such as hemocompatibility, physiological properties such as affinity for a selected range of flagella, and adhesion. Surface properties such as releasability to sensitive substances can be utilized for various purposes.

The present inventors have synthesized a polydimethylsiloxane having a carboxyalkyl group as a linear polysiloxane having uniform molecular chain lengths and a functional group at one or both ends (Patent Application No. No. 102357).

On the other hand, the present inventors obtained a polymer in which a functional group having greater reactivity toward a nucleophilic functional group such as a carboxyl group in a polymer is present at the end of the molecule, and in which the molecular chains are uniform. If possible, block copolymers and crosslinked polymers can be obtained with high reactivity by reacting with polysiloxanes having carboxyalkyl groups, and polymeric materials with controlled microdomain structures can be obtained. I thought so.

By the way, various polytetrahydrofurans having a cyclic quaternary ammonium salt structure at the end are known as polymers having such functional groups [Y, Tezuka,
E., J., Goethals, Makromolek
ulareChemie, Volume 188, No. 783-78
9 pages (1987)].

Polytetrahydrofuran, which has a star-like structure with a similar functional group at the end of the molecule and an aromatic group at the center of the molecule, is also known [Y, Tezuka, E, J, Goethal
s.

Makromolekurare Chemie, 1st
88, pp. 791-797 (1987)]. Furthermore, it is known that a block copolymer can be obtained by an ionic coupling reaction between polytetrahydrofuran having a cyclic quaternary ammonium salt structure at both ends and polybutadiene-bis-carboxylate (sodium salt) [Y, Tezuka, E. J. Goethals,
Polymer Pr1nts.

Volume 22 (No. 2), pages 313-314 (Au
gust 1981), Division of Po
lymer Chemistry Inc, Ame
However, a covalent block copolymer obtained from the aforementioned polysiloxane having a carboxyalkyl group and polytetrahydrofuran or other polyether having a cyclic quaternary ammonium salt structure at the end is not known.

[Purpose of the invention]

The purpose of the present invention is to react a polysiloxane alkali metal salt having a carboxyalkyl group at one or both ends and having a uniform molecular chain length with a polyether having pyrrolidinium rings at both ends of the molecule. A obtained
The object of the present invention is to provide BA-type, (AB)-type, 1-type and (AB+-1A-type boridiorganosiloxane-polyether block copolymers) and a method for producing the same.

Such a block copolymer has excellent biocompatibility because it is easy to control the microdomain structure, and is expected to have an effect of controlling critical micelle concentration (CMC) as a surfactant.

[Structure of the invention]

Thus, according to the present invention, - formula (I) R or - formula (II) represents an alkyl group having 1 to 4 carbon atoms or a phenyl group, and R ) R2 represents an alkylene group having 2 to 6 carbon atoms, a represents an integer of 3 to 6, p and q each represent an integer of 10 to 2,000, and S represents an integer of 10 to 2,000. (represents an integer of 10 to 200, t represents 0 or l, n represents an integer of 1 to 30, and M represents an alkali metal or a hydrogen atom.) Polydiorganosiloxane-polyether block copolymer Coalescing is provided.

Further, according to the present invention, - formula (A) ) and an alkali metal salt of a carboxyalkyl group-terminated polydiorganosiloxane represented by general formula (B) (wherein R2s is the same as above and X represents a negative group) The chemical equivalent ratio of (A) and (B) to the pyrrolidinium ring-terminated polyether is 1:0.8 to 1:
The resulting product is obtained by dissolving it in an organic solvent at a ratio in the range of 1.2 and adding it to water with stirring to cause a coupling reaction by ionic interaction between the end groups of the polymers. After separation and drying, the polydiorganosiloxane represented by formula (I) or (If) is heated at a temperature range of 60 to 150'C to cause a ring-opening reaction with the pyrrolidinium base. A method of making an ether block copolymer is provided.

The present invention will be explained in detail below.

(Polydiorganosiloxane-polyether block copolymer) The polydiorganosiloxane-polyether block copolymer of the present invention is an ABA type represented by the above-mentioned formula, (A
B), covalent block copolymers including (AB+, A-type block copolymers, etc.).

In the case of an ABA type block copolymer, a monovalent hydrocarbon group (R'=monovalent hydrocarbon group) is present at the end of the molecule.

In this case, R' includes alkyl groups such as methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, and dodecyl group; cyclopentyl group, cyclohexyl group. Cycloalkyl group such as 2-phenylethyl group, 2
-Aralkyl groups such as phenylpropyl; aryl groups such as phenyl and tolyl groups; and alkenyl groups such as vinyl and allyl groups. Butyl group is preferred because it is easy to use and has high reactivity.

When polydiorganosiloxane having an alkali metal salt of a carboxyalkyl group at both ends is used as a raw material [R1 = general formula (■)], R1 represents the presence of a bisphenylene ether structure (-C, H4-0cs H4-) is not necessarily required, that is, t can be 0 or 1, but since it is easier to obtain polysiloxane with uniform molecular chain length in a well-controlled manner, it is better to have a bisphenylene ether structure, that is, when t is 1. It is preferable that there be. The two phenylene groups (-C6H4) are bonded to an ether oxygen atom and a silicon atom, respectively. Although the positions of these bonds can be selected arbitrarily, discrete positions are preferred because raw materials are easily available and synthesis is easy.

When the above-mentioned polysiloxane having alkali metal carboxylates at both ends is used as a raw material, when equimolar moles of pyrrolidinium ring-terminated polyether are used, an (AB) n-type block copolymer is obtained, as is clear from the general formula. moreover,
If this (AB) type block copolymer is reacted with a polysiloxane having an alkali metal carboxylate at one end, an (AB(, A type block copolymer) is obtained.

Next, in the general formula (A), in a single siloxane chain or two siloxane chains separated and bonded to each other via a bisphenylene ether structure, R has 1 to 4 carbon atoms. They are an alkyl group or a phenyl group, and may be the same or different from each other. Specific examples include methyl, ethyl, propyl, butyl, and phenyl groups, but among these, polysiloxane has the best characteristics such as ease of synthesis and flexibility and heat resistance. Therefore, a methyl group is preferable.

pi3 and q are each 10 to 2.0001, preferably 10 to 200 from the viewpoint of ease of synthesis, and since the synthesis of such polysiloxane is by living polymerization,
p and q are substantially equal. Polysiloxanes with p or q of less than 10 or more than 2,000 are difficult to synthesize as monodisperse (synthesized) by living polymerization.

a is an integer from 3 to 6. When a is less than 3, when a block copolymer is formed with an organic polymer, the bonding points of both segments are easily subject to hydrolysis, and conversely, when a is more than 6, it is difficult to synthesize. Such atomic chains include trimethylene group, tetramethylene group, pentamethylene group, and hexamethylene group, among which trimethylene group (a=3) is preferred because of its ease of synthesis.

Further, the carboxyalkyl group-terminated polysiloxane of general formula (A) used as a raw material of the present invention has a ratio of its weight average molecular weight (Mw) to number average molecular weight (Mn) (M w
/Mn) is 1.4 or less, preferably 1.2 or less, and exhibits substantially monodispersity. If this ratio exceeds 1.4, the block copolymer of the present invention cannot provide the effect of controlling the critical micelle concentration (CMC) as a surfactant, which is a feature of the block copolymer of the present invention, and the biocompatibility superior to conventional ones.

The above ratio (M w / M n ) is a value determined by comparing the number average molecular weight determined from a gel permeation chromatography (GPC) chart and a standard sample of polystyrene.

In the general formula (A), examples of the alkali metal represented by M include potassium and sodium, which can be easily replaced with hydrogen atoms by neutralization.

The segment represented by the following formula % derived from the other raw material (B) of the present invention has a polyether skeleton as a main chain. R2 in the formula represents an alkylene group having 2 to 6 carbon atoms. When the number of carbon atoms is less than 2, it is difficult to synthesize and obtain raw materials, and when the number of carbon atoms exceeds 6, the hydrophilicity (derived from the polyether skeleton) is impaired, and the surfactant and biocompatibility, which are the characteristics of the present invention, are impaired. This is not preferable because the effect will be insufficient.

As this more R2, ethylene group, propylene group, trimethylene group, tetramethylene group, pentamethylene group,
Examples include hexamethylene groups. S is 10-200
represents an integer of 20 to 100, preferably 20 to 100. If it is less than 10, the above effects cannot be expected, and if it exceeds 200, the synthesis becomes difficult.

In the block copolymer (If) of the present invention, n is 1 to
It is an integer of 30. Although n may exceed 30, this is not preferable since it may be difficult to synthesize or it may be difficult to obtain the desired effect.

(Manufacturing method) The polydiorganosiloxane-polyether block copolymer of the present invention is manufactured, for example, as follows.

An alkali metal salt of a monodisperse carboalkyl group-terminated polydiorganosiloxane represented by the general formula (A) and a monodisperse pyrrolidinium ring-terminated polyether represented by the general formula (B) (a polyether having pyrrolidinium bases at both ends) ) in a chemical equivalent ratio of (A):(B) of 1:0.
The solution is dissolved in an organic solvent in a ratio ranging from 8 to 1:1.2, usually with a substantially chemical equivalent ratio of 1:1, and the solution is slowly poured into water cooled to below 5°C with vigorous stirring. In addition, a polymer-polymer coupling reaction is performed due to strong ionic interaction between end groups of polymer segments that are incompatible with each other. The product obtained (
The coprecipitate) is filtered off, then dissolved in a small amount of organic solvent and freeze-dried.

When the polymer thus obtained is heated in a temperature range of 60 to 150°C, for example, at 100°C in a vacuum dryer for about 24 hours, the pyrrolidinium base (cyclic onium base) undergoes a ring-opening reaction. A covalent block copolymer is obtained.

Here, the chemical equivalent ratio is the number of terminal alkali metal salts (1 or 2) in the prepolymer of general formula (A), and the number of terminal pyrrolidinium rings (2) in the prepolymer of general formula (B). This is a value calculated based on the respective number average molecular weights (Mn).

The above reaction can be shown by the following reaction formula.

CH8 Co-precipitation in water ↓ -MX CH3 Heating ↓ Ring-opening reaction (polysiloxane + COO + CH, 6N + polyether) CH.

In the present invention, the temperature for the ring-opening reaction is 60 to 150°C.
temperature range, preferably 80 to 120°C. When the temperature is below 60°C, the ring-opening reaction is difficult to occur;
If the temperature exceeds .degree. C., the pyrrolidinium ring will decompose, making it impossible to obtain the desired block copolymer, which is not preferable.

〔Effect of the invention〕

The present invention provides a polydiorganosiloxane-polyether block copolymer in which mutually incompatible polymer segments are coupled.

In the block copolymer of the present invention, since polymer segments having the same molecular chain length can be used as raw materials, a microdomain structure can be obtained with good control. Therefore, it has excellent biocompatibility, and not only can the balance between biocompatibility and physical properties be adjusted according to the purpose of use (also, as a surfactant, it is also possible to control the critical micelle concentration (CMC)).

The block copolymer of the present invention is useful as a medical material that requires biocompatibility, a highly safe surfactant, a compatibilizing additive for polymeric materials, and the like.

[Examples] Hereinafter, the present invention will be explained by reference examples and examples, but the present invention is not limited only to these examples. In addition, in these examples, unless otherwise specified, parts and percentages are based on weight.

[Reference Example 1] Synthesis of polydimethylsiloxane (1) having a carboxyalkyl group at one end] 100 parts of hexamethylcyclotrisiloxane was placed in a reaction vessel that had been degassed and replaced with nitrogen gas, and 178 parts of hexamethylcyclotrisiloxane was added. After adding and dissolving tetrahydrofuran, 1.7 parts of n-butyllithium previously dissolved in hexane was added to initiate polymerization. After continuing stirring at 20°C for 3 hours, 34 parts of 3-(dimethylchlorosilyl)butyric acid trimethylsilyl ester was added as a reaction terminator, and the mixture was immediately transferred to a constant temperature bath at 50°C to carry out the reaction for 42 hours.

After the reaction, the product solution was poured into a large amount of methanol to precipitate the polymer, which was then washed with methanol and heated to remove low-boiling components to obtain 104 parts of a colorless, transparent, viscous oil. Obtained.

A 270 MHz IH-NMR and IR spectrum and a GPC chart were obtained for this oily substance. The lH-NMR spectrum, IR spectrum, and GPC chart using the refractive index as a parameter of the polymer obtained in Reference Example 1 are shown in FIGS. 1 to 3, respectively. 'H-NMR δ values and IR characteristic absorptions are shown in Table 1 along with their assignments.

Analysis of these measurement results confirmed that the obtained oil was polydimethylsiloxane having a 3-carboxypropyl group at one end.

The yield of polysiloxane based on the theoretical amount was 83%, and the number average molecular weight was 3,300 based on GPC. When these carboxyl group-terminated polysiloxanes were left to stand for one month and then subjected to GPC again, exactly the same charts were obtained, indicating good stability.

The GPC chart showed an extremely narrow molecular weight distribution as shown in Figure 3 (1). And, compared to the standard sample of polystyrene, the ratio of weight average molecular weight (Mw) to number average molecular weight (Mn-) (M w / M n ) is 1.
．． It was 1 or less.

Table 1 a) b) c) d) d) c) e) f) C
Hs CHs [Reference Example 2] [Synthesis of polydimethylsiloxane (2) having sodium carboxylate at the end] Polydimethylsiloxane (1) having a carboxyalkyl group at one end obtained in Reference Example 1 (Mn = 3.300 )1
Dissolve 4 parts in 140 parts of diethyl ether and add 1
．． In a separatory funnel at 000 mA, add 1N-NaOH aqueous solution 5
00 parts and was thoroughly shaken to emulsify. After washing this with saturated brine until it became neutral, diethyl ether was distilled off, benzene was added and freeze-dried to obtain 13.3 parts of an oily substance (2).

For comparison with raw material (1) (Figure 2), the obtained sodium carboxylate-containing polydimethylsiloxane (2
) is shown in Figure 4. A GPC chart of the oily substance (2) is also shown in conjunction with FIG. 3 (2).

From the above results, it is clear that the desired monodisperse polymer was obtained.

[Reference Example 3] [Synthesis J of polydimethylsiloxane (3) having carboxyalkyl groups at both ends and its carboxylate (4) 100 parts of hexamethyltrisiloxane was placed in the same reaction vessel as used in Reference Example 1, 355 parts of tetrahydrofuran and 82.8 parts of N-methylpyrrolidine were added and uniformly dissolved. To this was added a solution prepared by suspending 4.4 parts of bis[p-(hydroxydimethylsilyl)phenyl]ether dilithium salt in 111 parts of n-hexane, and
Polymerization was carried out at ℃ for 3 hours. Then, 20 parts of 3-(dimethylchlorosilyl)butyric acid trimethylsilyl ester was added as a reaction terminator, and the mixture was reacted at 50°C for 1 hour. After the reaction was completed, purification was carried out in the same manner as in Reference Example 1 to obtain 84.3 parts of a colorless, transparent, viscous oil (yield: 71%). This polymer (3) was analyzed in the same manner as in Reference Example 1.

As a result of the above analysis, the number average molecular weight was 6.200 from GPC.
Met. The GPC chart showed an extremely sharp and narrow molecular weight distribution as in Reference Example 1, and the weight average molecular weight (Mw)/number average molecular weight (Mn) ratio compared with the polystyrene standard sample was 1.1 or less.

For reference, the 'H-NMR δ values and IR characteristic absorptions are shown in Table 2 along with their attributions.

Using the above-obtained polydimethylsiloxane having carboxyalkyl groups at both ends, its sodium carboxylate (4) was synthesized in the same manner as in Reference Example 2.

Table 2 a) b) c) d) d) e)
f) [Reference Example 4] (Synthesis of polytetrahydrofuran having pyrrolidinium bases at both ends) A magnetic cooler was placed in a 100 ml round-shaped flask, a three-way cock was attached, and the flask was degassed and replaced with nitrogen. In it, after drying with metallic sodium,
0.12 g of (CFs S
on )-0 was added via syringe to initiate polymerization. After stirring for 30 minutes, 0.92 mj2 of N-methylpyrrolidine was added as a stopper, and the mixture was stirred for an additional 15 minutes. After the reaction solution was concentrated to about half using an evaporator, it was poured into 142-liter cold water to precipitate a product.

This product was further reprecipitated and purified with THF/water,
Finally, it was freeze-dried from a benzene solution.

The obtained product was in the form of a white powder, and the yield was 4.15 g. Its number average molecular weight was 3.600 from GPC analysis. Its chemical formula is expressed as follows.

[For the synthesis method of the polymer, see Y.

Tezuka et al-, Makromolec
ulare Chemie, Volume 188, No. 783-7
Details are given on page 89 (1987). ] (S: about 50) [Example 1] (Synthesis of a type block copolymer (AB) consisting of polytetrahydrofuran having a pyrrolidinium base at both ends and polydimethylsiloxane having a sodium carboxylate at both ends) Reference example Polytetrahydrofuran (polytetrahydrofuran) having virolidinilam bases at both ends obtained in the same manner as in 4.
Molecular weight: 2,800) 5.2 parts and both terminal carboxylate (4) obtained according to Reference Example 3 (molecular weight: 6.2QQ)
11.5 parts of the solution were dissolved in 317.3 parts of THF, and the solution was added dropwise to 5,000 parts of water cooled to 5° C. or lower with vigorous stirring. The chemical equivalent ratio was approximately 1:1. After continuing stirring for 1 hour, the coprecipitate was suction filtered through a glass filter. The obtained polymer was dissolved in a small amount of benzene and lyophilized to obtain 12.0 parts of a white powder product.

Take 2.0 parts of the product obtained above in a flask and
When the ring-opening reaction was carried out by heating at 0° C. for 24 hours, 1.9 parts of a waxy product with a white appearance was obtained.

Regarding this waxy material, 'H-NM of 270MHz
R and IR spectra and GPC charts were obtained.

The 'H-NMR1IR spectrum of the polymer and the GPC chart using the refractive index as a parameter are shown in FIGS. 5 to 7, respectively. The GPC chart in FIG. 7 also shows the polydimethylsiloxane component PDMS and the polytetrahydrofuran component PTHF as raw materials.

From these measurement results, it was confirmed that the wax-like material obtained was a type block copolymer (AB) consisting of polydiorganosiloxane segments and polytetrahydrofuran segments. The number average molecular weight determined by GPC was 118.000, and the degree of polymerization n was about 13.

[Example 2] (Synthesis of ABA type block copolymer of polytetrahydrofuran having a pyrrolidinium base at both ends and polydimethylsiloxane having a sodium carboxylate at one end) The copolymer having a pyrrolidinium base at both ends obtained in Reference Example 4 1.6 parts of polytetrahydrofuran (molecular weight 3,600) and polydimethylsiloxane having sodium carboxylate at one end obtained in Reference Example 2 (molecular weight 3,300)
3.0 parts were dissolved in 87.4 parts of tetrahydrofuran. The chemical equivalent ratio was approximately 1:1. 5,000 parts of water was cooled to below 5° C. and the solution was slowly added with vigorous stirring. After the addition, stirring was continued for an additional hour, and then the coprecipitate was suction filtered using a glass filter (G4). The obtained polymer was dissolved in a small amount of benzene and freeze-dried. The yield was 3.1 parts.

1.5 parts of the obtained polymer was placed in a sample bottle and heated at 100° C. for 24 hours in a vacuum dryer to obtain 1.4 parts of a colorless viscous oil.

Regarding this oil, the 270 MHz 'H-NMR and IR spectra and GPC chart were determined in the same manner as in Example 1.

Analysis of these measurement results confirmed that the obtained oil was an ABA block copolymer consisting of polydiorganosiloxane segments at both ends and a polytetrahydrofuran segment at the center.

[Brief explanation of the drawing]

Figures 1 and 2 show polydimethylsiloxane (polydimethylsiloxane) having a carboxyalkyl group at one end obtained in Reference Example 1.
1) 'H-NMR spectrum (Figure 1) and IR
Q spectrum (Figure 2). FIG. 3 is a GPC chart of polydimethylsiloxane (1) having a carboxyalkyl group at one end obtained in Reference Example 1 and polydimethylsiloxane (2) having sodium carboxylate obtained in Reference Example 2. . FIG. 4 is an IR spectrum of polydimethylsiloxane (2) containing sodium carboxylate obtained in Reference Example 2. Figures 5 to 7 show the 'H-NMR spectrum (Figure 5), IR spectrum (Figure 6) and GPC chart (Figure 7) of the block copolymer obtained in Example 1.
It is. In addition, FIG. 7 also shows the GPC chart of the raw material prepolymer as well as the block copolymer, as shown below. copolymer diblock copolymer, PDMS: polydimethylsiloxane having sodium carboxylate at both ends, PTHF: polytetrahydrofuran having pyrrolidinium bases at both ends. Applicant: Toshiba Silicone Corporation

Claims (1)

[Claims] 1. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) or general formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R ^ may be the same or different from each other and represents an alkyl group or phenyl group having 1 to 4 carbon atoms,
R^1 represents a monovalent hydrocarbon group or a group represented by the general formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III), and R^2 represents an alkylene group having 2 to 6 carbon atoms. , a represents an integer of 3 to 6, p and q each represent an integer of 10 to 2,000, s represents an integer of 10 to 200, t represents 0 or 1, and n represents 1 to 30. M represents an alkali metal or a hydrogen atom. )
A polydiorganosiloxane-polyether block copolymer represented by: 2. General formula (A) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (A) (In the formula, R, R^1, p, and a are the same as above, and M represents an alkali metal.) General formula (B) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (B) (In the formula, R^2, s are the same as above, represents a negative group) and the pyrrolidinium ring-terminated polyether represented by (A):(B) in a chemical equivalent ratio of 1:0.8 to 1:
Dissolve the solution in an organic solvent at a ratio within the range of 1.2, add it to water with stirring, perform a coupling reaction by ionic interaction between the end groups of the polymers, and separate the resulting product. - After drying, the polydiorganosiloxane-polyether block compound represented by the general formula (I) or (II) is characterized by heating at a temperature range of 60 to 150°C to cause a ring-opening reaction with a pyrrolidinium base. Method for producing polymers.