WO1997042242A1

WO1997042242A1 - Graft polymer and precursor thereof

Info

Publication number: WO1997042242A1
Application number: PCT/JP1997/001493
Authority: WO
Inventors: Kazunori Kataoka; Masao Kato; Teruo Okano; Yukio Nagasaki; Takahiko Kutsuna; Ryutaro Ogawa
Original assignee: Kazunori Kataoka; Masao Kato; Teruo Okano; Yukio Nagasaki; Takahiko Kutsuna; Ryutaro Ogawa
Priority date: 1996-05-09
Filing date: 1997-05-01
Publication date: 1997-11-13
Also published as: JP3345826B2; JPH09302048A

Abstract

A macromonomer comprising a principal chain of polyoxyethylene having a vinyl group at its one end and having an aldehyde or acetal group at the other end, a process for producing the same, and a graft polymer obtained by copolymerizing (or homopolymerizing) the macromonomer and another vinyl monomer in a ratio of 100 to 1 : 99 to 0.

Description

Specification

Graph polymer and its precursor

Technical field

The present invention relates to a graft polymer having, as a branch polymer, a polymer containing a polyoxetylene main chain having acetal and / or aldehyde groups at its free terminals. Further, the present invention relates to a heterotelechelic polymer which is also a precursor of the graft polymer and a method for producing a heterotelechelic polymer having an aldehyde group at one end thereof. Background art

The graft polymer is a branched polymer composed of a backbone polymer and a branch polymer, and is known to have various functions depending on the properties of both polymers. For example, to control or combine functions due to higher-order structure when forming domains with unique orientation, or functions due to the properties of both the branch polymer and the trunk polymer by adjusting the proportion of the branch polymer. Is possible.

Certain types of graft polymers that have already been proposed focus on emulsification, for forming emulsions, and for improving interface adhesion, for bonding composites, and even more hydrophilic. Paying attention to the action of imparting, it is being applied as a medical polymer or its application is being studied.

The present inventors have previously found efficient production of polyoxyethylene having an aldehyde group at one end and a different functional group at the other end, and have already disclosed (for example, Japanese Patent Application No. Hei 6—1 1 1 7 2 6 2). On the other hand, using the reactivity of the aldehyde group to modify proteins, etc. Also, polymers containing aldehyde groups for providing new functional materials are known. The use of these functional materials is one of the fields to which the polymers disclosed in the specification of Japanese Patent Application No. 6-117172 are used.

If a graft polymer having such a polymer containing an aldehyde group at one end as a branch polymer could be provided, it would be possible to provide a new functional polymer having the functions of the graft polymer itself. Would. However, an aldehyde polyoxyethylene macromonomer (hereinafter referred to as APM) having an aldehyde group at one end and a polymerizable functional group at the other end has not been published in the prior art literature, or at least has not been disclosed. There is no known efficient manufacturing method for such APM. Therefore, an object of the present invention is to provide a block polymer carrying an APM-derived branch polymer and to provide a precursor useful for a method for efficiently producing them.

Disclosure of the invention

When the present inventors contemplate the production of APM via hydrolysis and deacetalization of the aldehyde group from the acetal-protected APM to provide the APM, there are accompanying side reactions that cannot sufficiently achieve the purpose. I confirmed that For example, in the case of a methacrylic ester group as a polymerizable functional group, the ester group is eliminated together with the elimination of the acetal, and in the case of a vinylbenzyl group, the polymerization reaction occurs simultaneously with the elimination of the acetal. It was confirmed. Further, when the content of the deprotected aldehyde group increases, side reactions of the APM itself due to aldol condensation or the like occur during the deprotection.

However, surprisingly, the acetal-protected A Μ 、 It has been found that when treated in an acetic acid solvent containing, the acetal protecting group can be eliminated up to 100% without the side reaction as described above and the side reaction of the generated APM itself. Thus, it has now become possible for the first time to provide a macromonomer with an arbitrarily variable acetal protecting group content.

Therefore, according to the present invention, the repeating units represented by the following formulas (A) and (B)

A vs B force, correlated 100 ~ 1: 99 ~ 0

And a graft polymer, which is included at a ratio of

Equation (A):

Equation (B)

Z

In the above formula, R ¹ and R ² independently represent C _1-6 alkyne, phenyloxy or phenyl C _1-3 alkyloxy, or

R ¹ and R ² may be taken together to form an ethylenedioxy (— 0-CH (R ′) —CH ₂ — 0—), wherein R ′ is a hydrogen atom or d-alkyl. Or R ¹ and R ² together represent an oxy (= 0), R ³ represents a hydrogen atom or C, -6 alkyl,

L is carbonyl, a C Bok ₃ alkylene or C physician ₃ Arukirufu X two Ren and table,

n is an integer from 2 to 10,000,

p is an integer from 1 to 5,

Y represents a hydrogen atom or C _1-e alkyl, and

Z is Fuweniru, C 1 - ₆ alkyl O alkoxycarbonyl, d-6 alkylcarbonyl alkenyl or formula CON (R ") ₂ (where R〃 is hydrogen atom or a C _{1 -6} § alkyl) represents a group of .

Further, according to the present invention, there is provided a heterotelechelic polymer represented by the following formula (I) which can be conveniently used as a precursor of the above-mentioned graft polymer, and which itself can be used for protein modification and the like. Equation (I):

In the above formula, R ¹ and R ² are independently, C -e alkoxy, Fuweniruo alkoxy or phenyl one d -! ₃ or represents Arukiruokishi, or, R ¹ and R ² together, C I _{6 represents} an ethylenedioxin optionally substituted with alkyl (1—CH (R ′) — CH ₂ —0—: where R ′ is a hydrogen atom or alkyl), or R ¹ and R ² are , Together represent an oxy (= 0),

R ³ represents a hydrogen atom or C _{1 -β} alkyl,

L Table carbonyl, a Ci _-3 alkylene or C _{1 -3} alkyl off We two Len And

n is an integer from 2 to 10,000, and

p is an integer of 1 to 5.

Furthermore, according to the present invention, the following formula (I-a)

I

0 = CH- CH ₂ > p-0— (CH ₂ CH ₂ 0) nLC = CIl2 (I-a)

Wherein R ³ represents a hydrogen atom or C _{1 -β} alkyl, L represents carbonyl, C ₃ alkylene or C ₃ alkyl phenylene, η is an integer of 2 to 10,000, and Ρ is an integer from 1 to 5]

A method for producing a heterotelechelic polymer represented by the formula:

Formula (I-Ib):

[Wherein, R ¹ — ¹¹ and R ² — ^b independently represent C, -6 alkoxy, phenyloxy or phenyl-C, _-3 alkyloxy, or

R ¹ and R ² may be taken together to form an ethylenedioxy (1- 0—CH (R ′) — CH ₂ — 0_, optionally substituted with C で₆ alkyl, wherein R ′ is a hydrogen atom or C, - represents a ₆ alkyl as), and R ^3, L, n and P are as defined above

A process characterized by treating the polymer represented by the formula (1) in acetic acid containing a catalytic amount of water to carry out deaeration.

According to this method, substantially no side reaction occurs and the formula (I-b) The compound can be converted to a compound of formula (Ia).

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is the ¹ H-NMR and ¹³ C-NMR spectrum diagrams (1) and (2), respectively, of the polymer obtained according to Example 1: FIG. ¹ H-NMR and ¹³ C-NMR spectrum diagrams ((1) and (2)) of a polymer (an aldehyde group at one end);

FIG. 3 is the ¹ H-NMR and ¹³ C-NMR spectrum diagrams of the polymer obtained according to Example 3 ((1) and (2), respectively); FIG. 4 is the result obtained according to Example 4. ¹ H-NMR and ¹³ C-NMR spectrum diagrams of the polymer (one-end aldehyde group) ((1) and (2), respectively), and

FIG. 5 is an elution curve showing the results of GPC of the polymer obtained in Example 8.

Specific description of the invention

According to the present invention, among the repeating units represented by formulas (A) and (B), (A) may be in a state where one or more kinds are mixed. For example, R ¹ and R ² are Okishi group together (= 0) except Okishi group branch polymer and R ¹ and R ² representing a branch represents a (aldehyde group is protected) polymer to the trunk polymer It may be attached at the same time, or the aldehyde group may be unprotected at all or, conversely, the aldehyde group may be completely protected as an acetal group. Also, the B units derived from the comonomer to the macromonomer that derives the A units may be derived from more than one comonomer (ie, if Y and Z or Z are It means that it is two or more groups), but for production, those derived from one kind of comonomer are preferable.

Considering that the polymerization reaction of the above macromonomer (and possibly the above comonomer) is usually by radical polymerization, or by a predetermined ratio of a branched polymer (or a graph chain) having an aldehyde group at a free end. To be included in the polymer, it is preferable that one end of the macromonomer is an aldehyde group (ie, APM) which is not protected by acetal. Therefore, a preferred graft polymer is a case where R ¹ and R ² of the A unit together represent an oxy group (= 0). This is not bound by theory, especially from the former point of view, but if one end of the macromonomer is an acetal, its methyl

This is because the radical group is likely to cause side reactions during radical polymerization. The ratio of the A units to the B units contained in the graft polymer can be arbitrarily selected according to the intended use of the graft polymer, but for the purpose of the present invention, the A units are the total of the A units and the B units. It needs to account for at least 1%. Such a graft polymer having a low content of the A unit may be advantageously used for immobilizing a bioactive macromolecule, for example, an enzyme or an antibody. In addition, when used for surface coating of articles applied to living bodies, for example, artificial organs, it is advantageous to fix a large amount of anticoagulant proteins such as heparin via free terminal aldehyde groups. Therefore, it is preferable that the A unit derived from APM occupies several tens percent or more in the graft polymer.

The alkyl moiety of the alkyl and alkyne mentioned in the present invention; Kill means a straight or branched alkyl group. Therefore, Kinru the alkyl moiety of the alkyl and alkoxy of C doctor _6, methyl, Echiru, propyl, IS 0- propyl, butyl, se C.- heptyl, ter and one-butyl, pentyl, IS 0- pentyl, 2 —Methylpentyl, 3-methylpentyl and the like. Among them, the alkyl portion of the alkoxy represented by R ¹ and R ² is particularly preferably Ci- ₃ alkyl.

Thus, R ¹ and particularly preferred as the main butoxy as Arukokin referred to in R ^2, Etokin, Purobokishi, isopropoxy Ru mentioned. R ¹ and R ² are preferably phenyl or phenyl C] _-3 alkyl, especially benzyl or phenethyl. These groups may be the same or different, but are preferably the same group. R ¹ and R ² may be taken together to form an ethylenedioxy (one OCH (R ′) — CH ₂₀ —, which may be substituted with C ₆ alkyl: where R ′ is C, alkyl; ), But is preferably ethylenedioxy, propylenedioxy or 1,2-butylenequine.

These groups are treated by the method of another embodiment of the present invention described below, whereby R ¹ and R ² are combined to form an oxy group (= 0), that is, an aldehyde group at one end of the molecule. It is convenient to form the APM of the present invention having

R ³ represents a hydrogen atom or a C _{l -6} alkyl, preferably hydrogen Contact and methyl. Further, L is a carbonyl (= C = 0), C physician ₃ Al Killen or flicking ₃ Arukirufue two Len _{ί ~ (CH 2) ^ ~} , is a q = l~3, preferably carbonyl, methylene and base Njiren N, which is CH ₂ <0 », can be at least one integer from 2 to 100, 000. Accordingly, the term "polymer" as used in the present invention for the term branch polymer or heterotelechelic polymer is used in a concept encompassing an oligomer. As will be described later, when a heterotelechelic polymer (or macromonomer) is produced by so-called riving polymerization, the polyoxyethylene segment has a monomodal molecular weight by adjusting the amount of ethylene oxide used relative to the polymerization initiator. It is possible to have a segment with. Therefore, n can be an extremely narrowly distributed number in the range of 2 to 100.000, and is preferably an integer of any of 10 to 200.

p is any of the integers from 1 to 5. Preferably, integers of 2 and 3 can be mentioned.

Y and Z defining the unit B represented by the formula (B) are specified by the commonomer used. Y is a hydrogen atom or a C ぃ₆ alkyl group, preferably a hydrogen atom or a methyl group. On the other hand, Z is phenyl, C, — ₆ alkyloxycarbonyl, C ぃ 8 alkylcarbonyl or a group represented by the formula CON (R〃) ₂ (where R〃 is a hydrogen atom or C ぃ₆ alkyl) However, preferred examples include phenyl, methyloxycarbonyl, aminocarbonyl and dimethylaminocarbonyl. Therefore, the B unit is preferably derived from styrene, methacrylate, acrylate, methyl acrylamide or acrylamide.

The bond between the A unit and the B unit is determined by their methylene groups (or Or methylene group (or side) may be bonded to face each other, but usually, one methylene group is bonded to the carbon atom side having the other substituent. The following Table I shows examples of the graft polymer of the present invention composed of the above groups or parts.

Table I

Unit of formula (A) 4 Unit of formula (B) Graft polymer No. R ³

1 — C- 70 2 10 90

II

0

2 1 C- 70 2 10 90 3 CH _S C 1 140 2 5 90

13 Cflg one c one 70 2 40 CH ₃ COOCH3 300

The numbers a and b indicate the average number of A units and B units present in the graft polymer, and each unit constitutes a block. The above graft polymer is obtained by polymerizing a hetero telechelic polymer (or macromonomer) represented by the following formula (I) provided as another embodiment of the present invention or the macromonomer and the macromonomer represented by the following formula (II). It can be obtained by copolymerization with a comonomer.

Equation (I):

R ³

R ¹

CH- (CH ₂ > p-0— tCH ₂ CH ₂ 0> nLC = CH2 (I)

R wherein RR ² , R ³ , L, n and p are as defined above, Formula (II):

Y

: C = CH ₂ (Π)

Z In the above formula, Y and Z are as defined above.

In the above polymerization or copolymerization, the monomer of the formula (I) and optionally the monomer of the formula (II) are polymerized at an appropriate ratio according to the ratio of the A unit and possibly the B unit to the target graft polymer. Carry out by a known radical polymerization reaction in an inert solvent, for example toluene, in the presence of an initiator, for example an azo compound or peroxide, or under the action of heat, light or radiation it can.

On the other hand, the macromonomer of the formula (I) [for example, the formulas (Ia) and (Ib)] can be produced according to the following reaction scheme.

R ³

0 = CH— (CH ₂ > p-0- (CH ₂ CH ₂ 0> n- LC = CH ₂

(Water monoacetic acid)

(I -a)

In the above formulas, R'- ^b and R ² - ^b, of the R ¹ and R ² defined, except where R ¹ and R ² represents Okishi groups become Ichi緖, R ¹ and R ^As defined for ² , R ³ , L, n and p are as defined above, X is, for example, a hydroxyl group, a halogen (eg, chlorine or bromine), and M is an alkali metal (eg, Sodium, potassium or cesium).

Production of (i) force, ira (ii):

The metal alkoxide protected alkoxide (i) is reacted with ethylene oxide to obtain a compound (ii) having a polyethylene oxide segment added thereto. Compound (i) is an acetal-protected acetal as a metallizing agent, an alkali metal such as sodium or potassium, an organic metal such as sodium naphthylene, potassium naphthalene, cumyl potassium, cumyl cesium, or sodium hydroxide. Treated with metal hydrogen such as hydrating power P97 / 01493.

The above-mentioned reaction from (i) to (ii) may be carried out in the absence of a solvent or, preferably, in an anhydrous non-protonic solvent at a wide range of temperatures, for example, from 150 ° C to 300 ° C, preferably Can be carried out at 10 ° C to 60 ° C, conveniently at room temperature (20 to 30 ° C). The reaction may be performed under elevated or reduced pressure. Examples of the solvent used include, but are not limited to, benzene, toluene, xylene, tetrahydrofuran, dioxane, and acetonitrile. Although the reaction vessel is not particularly limited, for example, a round bottom flask, an auto-reave, a pressure-resistant sealed tube, or the like is used. It is preferable that the inside of the reaction vessel can be shielded from outside air, and it is more preferable that the inside of the reaction vessel can be filled with an inert gas. The concentration of the reaction solution is desirably 0.1 to 95% by weight, more preferably 1 to 80% by weight, and most preferably 3 to 10% by weight.

Production of (Ii b) from (i i):

Without removing the compound of the formula (ii) from the reaction solution, a compound of the formula X—L—C (R ³ ) = CH ₂ is added to the reaction solution to stop the above polymerization reaction, and C (R ³ ) = CH ₂ is introduced at the ω-terminal.

The polymer of the formula (I-b) thus formed can be purified, for example, by converting it into an aqueous solution obtained by adding water to a reaction solution, and then extracting the solution with chloroform or methylene chloride. .

Production of (I-a) from (I-b) (desorption of acetal):

This step can be performed by adding an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, nitric acid, formic acid, or hydrofluoric acid to the aqueous solution of (Ib), and hydrolyzing the acetal. However, under these conditions, the rate of conversion to aldehydes due to acetal elimination is not always good. It should be noted that higher conversions can lead to side reactions, which can be attributed to the aldol condensation of the aldehyde. More preferably, this step can be efficiently performed by the following method, which is another aspect of the present invention. For example, after dissolving the polymer of the formula (I-b) in a mixture of glacial acetic acid and a catalytic amount of water (a few percent to 15% by volume), the mixture is stirred at room temperature (10 to 30 ° C). ) Incubate under several hours. This reaction may be carried out under heating if necessary, but is preferably carried out at room temperature to eliminate any side reaction. The reaction time can be shortened by increasing the reaction temperature.On the other hand, when the reaction is carried out at room temperature, it is possible to convert approximately 100% acetal to aldehyde without side reaction in 3 to 8 hours. it can. The product can be recovered from the reaction mixture according to the above formula (I-b).

Specific examples of the thus obtained heterotelechelic polymer of the formula (I) of the present invention include those shown in Table II below.

9ΐ

0

II

-3- Z = o 02 εΗ0 3- 2 = o

Η 3- on Z = 0 Π

0

II

■ 3- Oiz ⁸ H0 0 ^E HD

; ID

OL z

0

II

-3- OH z

01 0 ^ζ Η0 ^ε Η3 O ^z HD ^e H3 I ε8 ud ON

ー (\ ^

Halla

£ 6n0lL6d £ / lDd Hi ZZW 6 OM The above-described graft polymer provided by the present invention may be used, in particular, by converting at least one aldehyde group at the free end (total or partial hydrolysis of the free end being an acetal group into an aldehyde group, (A copolymer having an acetal group at one end and a monomer having an aldehyde group may be used in the copolymerization by adjusting the use ratio.) Therefore, for example, by coating these polymers on the surface of various articles (for example, medical supplies), the compatibility of living tissue or blood can be increased. In addition, if heparin or the like is bound using a free aldehyde group, it will be possible to further enhance blood compatibility. In addition, since these graft polymers disperse in water to form micelles, they can also be expected to be used as dispersion hardeners for paints and the like.

Hereinafter, the present invention will be described more specifically with reference to specific examples.

Example 1: jet carboxypropyl one poly O key Chez Ji Ren vinylbenzyl (I - b - 1) of the manufacturing CH ₂ (I one b-1)

To the reaction vessel were added 20 ml of THF and 1 mmol of 3,3-diethoxyquinpropanol and 1 mmol of potassium naphthalene (K-Naph), and the mixture was stirred for 10 minutes under an argon atmosphere to obtain 3,3-diethoxypropanol. Potassium chloride (potassium 3,3-dietkinpropanoxide) was produced.

To this solution, ethylene oxide 7 Ommo 1 was added, and the mixture was stirred at 1 atm and room temperature. The reaction was performed for 50 hours. Further add K-Naph to this reaction solution. After 3 mmo 1 was added and the mixture was further stirred for 10 minutes, 1 Ommo 1 was added to p-chloromethylstyrene, and the mixture was stirred at room temperature for 3 hours.

Subsequently, extraction with black-mouthed form, washing with saturated saline, dehydration with anhydrous sodium sulfate, and reprecipitation with dimethyl ether were performed. The polymer obtained after drying under reduced pressure had a molecular weight by gel permeation chromatography (GPC), and was subjected to structural analysis using 'Η and ¹³ C-NMR. Matched. The spectrum diagrams of 'Η-NMR and ¹³ C-NMR are shown in Figs. 1 (1) and (2).

Example-2: Conversion of acetal (I—b—1) to aldehyde (I—a—1) CH = CH ₂ (I—a—1)

Jetoxypropyl-polyoxyethylenevinylbenzyl 0.1 lmmo 1 was dissolved in 10 ml of THF at room temperature under air. Thereafter, 5 ml of 1N—HC1 was added, and the mixture was stirred for 1 hour to deprotect the terminal. After that, form extraction with black mouth, washing with saturated saline, dehydration with anhydrous sodium sulfate, and reprecipitation of getyl ether were performed. After drying under reduced pressure, structural analysis was performed using iH, ¹³ C-NMR. As a result, the obtained polymer was found to have an acetal at one end (see formula (I-b-1)) as shown in the above formula. It was confirmed that the compound was hydrolyzed and converted into an aldehyde group (see formula (I-a-1)). ¹ H and ¹³ C-NMR spectrograms are shown in Figures 2 (1) and (2), respectively.

Example 3: 3.3-diethoxy-1-1propanol as initiator, terminator Preparation of heterobifunctional polyoxetylene (PE 0) represented by formula (I-b-2) using acrylyl bromide

CH ₃ CH ₂ 0.

CHCH ₂ CH ₂ 0 CH ₂ CH ₂ 0 n-CH ₂ CH = CH ₂ (I_b—2)

At room temperature under CHsCHzO and argon atmosphere, 3,3-diethoxy-11-propanol 1 mmo 1 and KNaph 1 mmo 1 were added as initiators in 15 ml of solvent THF at room temperature, and the mixture was stirred for 10 minutes to perform metallization. Thereafter, ethylene oxide (E0) was added in an amount of 7 Ommo 1 and the mixture was stirred for 50 hours to carry out polymerization. Before the termination reaction, 2.Ommo 1 of K-Naph was added again, and the mixture was stirred for 30 minutes. Then, 1 Ommo 1 of aryl bromide was added as a terminator, and the mixture was stirred at room temperature for 4 hours to perform a termination reaction. Then, the title polymer was obtained by extraction with black hole form, washing with saturated saline, dehydration with anhydrous sodium sulfate, and reprecipitation with getyl ether. After drying under reduced pressure, the molecular weight was analyzed by GPC and the structure was analyzed using ¹ H, ¹³ C-NMR.

The molecular weight of the obtained polymer is about 2,500,

'Η-NMR and ¹³ C-NMR spectrumgrams are shown in (1) and (2) of FIG. 3, respectively.

Example 4: Conversion of acetal (I-b-2) to aldehyde (I-a-2)

The reaction solution after termination reaction prepared according to Example 3 was added with 1 N—HC I 5 m 1 was added and stirred for 1 hour. Next, the solution was subjected to form extraction with black-mouthed mouth, washing with saturated saline, dehydration with anhydrous sodium sulfate, and reprecipitation of getyl ether. After drying under reduced pressure, molecular weight analysis was performed by GPC and structural analysis was performed using ¹ H. ¹³ C-NMR.

The molecular weight of the obtained terminal aldehyde-containing polymer (I_a-2) was not substantially changed from the starting material. 'Η-NMR and' ³ C-NMR spectra are shown in Fig. 4 (1) and (2), respectively. Examples 5 to 8: Production of heterobifunctional polyoxetylenes represented by the following general formula (Ib-3, 4, 5 and 6: n is different from each other)

Under an argon atmosphere, at room temperature, in a receiver, 3,3-diethoxy-1-propanol was added to the solvent THF. Next, potassium naphthalene was added and metallized for 10 minutes. Thereafter, ethylene oxide was added and polymerization was carried out for 50 hours. After completion of the polymerization, methacrylic anhydride was added as a terminator, and a termination reaction was performed for 24 hours.

The charged amounts, purification and recovery methods were performed as shown in Table III-11 below. Benzene was used for lyophilization.

Table m-1 _: PEO charge, purification and recovery method

: THF

Polymerization temperature: room temperature

After recovery, molecular weight analysis was performed by GPC. Structural analysis by 'Η-NMR and ¹³ C-NMR was also performed. Structural analysis revealed that the ester in which the methacryloyl group was bonded to the other hydroxyl group at the terminal of the acetanol was obtained as represented by the general formula (I-b-3, 4, 5, and 6). It was confirmed that. The yield and other results are summarized in Table III-12 below.

Table III-12: Number average molecular weight, polydispersity, yield of PEO Example Mn (X 1 O— ³ ) yield

Sample name M w / M n

No.Theoretical value Measured value (%)

.5 P EO (l) 3300 6000 1.10 94

6 P E 0 (2) 3300 3000 1.04 57

7 P E 0 (3) 3300 3600 1.01 70

8 P EO (4) 4100 4500 1.06 99 FIG. 5 shows the results of GPC of the polymer of Example 8.

Implementation: Conversion of acetal (I-b-6) to aldehyde (I-a-6)

The polymer obtained in Example 8 was dissolved in INHC150m] and stirred at room temperature for 6 hours. The polymer was obtained by extraction with chloroform and precipitation into ether, followed by drying under reduced pressure. As a result of ¹ H NMR analysis of the obtained polymer, a new signal of aldehyde proton appeared around 9.7 ppm, and it was confirmed that the conversion of acetal to aldehyde was progressing. Was about 85%.

Example 10: Conversion of acetal (I-b-3) to aldehyde (I-a-3)

The same procedure as in Example 9 was carried out except that the polymer (0.5 g) obtained in Example 5 was dissolved in 0.1 N HC1 (20 ml) and the reaction was carried out for 4 hours. The conversion of acetal to aldehyde by the method of this example was about 61%.

Example 11 1: Conversion of acetal (I-ti-I5) to aldehyde (I-a-5)

The same procedure as in Example 9 was carried out except that the polymer (0.5 g) obtained in Example 7 was dissolved in 0.1 N HC1 (20 ml), and the reaction was carried out for 3 hours. The conversion of acetal to aldehyde by the method of this example was about 70%.

Example 12:

The polymer (Ib-6) (0.5 g) obtained in Example 8 was dissolved in 20 ml of glacial acetic acid, 2 ml of water was added, and the mixture was stirred at room temperature for 1 hour. Implementation Recover the polymer as in Example 9, and! H NMR and ¹³ C NMR analysis revealed that the conversion of acetal to aldehyde was approximately 89%.

Example 13:

Example 12 was repeated except that the reaction time was 5 hours. The conversion from acetal to aldehyde was confirmed to be 100%. From the results of the GPC analysis, it was confirmed that there was no change from the precursor acetal polymer, and that no by-product was generated.

Example 14: Production of graft polymer

3.65 g of the polymer obtained in Example 13, 4 g of methyl methacrylate (MMA) and 0.015 g of azobisisobutyronitrile were dissolved in 35 ml of toluene, degassed in an ampoule, and then sealed. Thereafter, polymerization was carried out at 50 ° C. for 45 hours. After the polymerization, the polymer was subjected to GPC analysis, dispersed in water, and centrifuged to precipitate the polymer. The obtained polymer was dried under reduced pressure and analyzed by NMR. The yield was 85%, and it was confirmed that the obtained polymer had 5 branch polymer units and 260 MMA units.

Ή NMR (δ, p pm):

0.8 (derived from R ³ (= CH ₃ ) in unit A)

2.2 (derived from —CH ₂ — in the trunk polymer of units A and B)

2.8 (derived from one CH ₂ — adjacent to the free terminal aldehyde group of unit A) 3.5-4.0 (derived from — O— CH ₂ — of unit A and — C 00 CH ₃ of unit B)

4.2 (derived from one COOCH of unit A) 9.8 (derived from one CHO of unit A)

Example 15: Production of graft polymer

As in Example 14, 4.51 g of the polymer obtained in Example 13 and 2.0 g of MMA 0.015 g of azobisisobutyronitrile were dissolved in toluene (35 ml) and reacted at 60 ° C. for 24 hours. Was. The yield of the obtained polymer was 70%, and the molecular weight of the polymer was 3.3 × 10 ⁴ . From the analysis results of 'Η ΝΜ R, it was confirmed that polyoxyethylene 鑲 was 5 and MM unit was 100 in the polymer.

Industrial applicability

ADVANTAGE OF THE INVENTION According to the present invention, there is provided a graft polymer having a free end containing an aldehyde group (or a protected aldehyde group) and having a polyoxyquinethylene segment as a branched polymer, and an efficient production method thereof. Also provided is a heterotelechelic polymer that can be used as a precursor in its manufacture. Therefore, the present invention can be used in the manufacturing industry of functional polymers, particularly, in biologically applicable polymers and in the processing industry of medical supplies.

Claims

The scope of the claims

1. The repeating units represented by the following formulas (A) and (B)

A vs B ^^ correlated 100 ~ 1: 99 ~ 0

Graph polymer contained in the ratio of

Equation (A):

Equation (B):

Z

In the above formula, R ¹ and R ² are independently, de alkoxy, or represents Fuweniruo alkoxy or Fuweniru one C I ₃ Arukiruokishi, or,

R ¹ and R ² together such connexion, C, - ₆ alkyl substituted optionally it may also Echirenjiokishi (an _{0- CH (R ') -CH 2} -0-: wherein R' is a hydrogen atom or represent a C _{1 -6} alkyl), or R ¹ and

R ² together represent an oxy (= 0),

R ³ represents a hydrogen atom or a C _{1 -6} alkyl,

L represents carbonyl, C ₃ -alkylene or C, _-3 alkylphenyl Xylene;

n is an integer from 2 to 10,000,

p is an integer from 1 to 5, Y represents a hydrogen atom or C ₆ alkyl, and

Z is Fuweniru, C physician ₆ alkyl O alkoxycarbonyl, C physician ₆ alkylcarbonyl alkenyl or formula C ON (R ") ₂ (where R〃 is hydrogen atom or a C Bok ₆ § alkyl) represents a group of.

,

2. The graft polymer according to claim 1, wherein R ¹ and R ² together represent oxy (= 0).

3. R ¹ and R ^{2 taken} together represent oxy (= 0), R ³ represents a hydrogen atom or methyl, and L represents carbonyl, methylene or benzylene (one CH ₂ <G> ~) The graft polymer according to claim 1.

4. A pair B is correlated to 9 9 to 1: is in the ratio of 1 to 9 9, Y represents a hydrogen atom or methyl, and Z is C physician ₆ alkyl O alkoxycarbonyl, phenyl, § amino carbonyl or The graft polymer according to any one of claims 1 to 3, which represents dimethylaminocarbonyl.

5. A heterotelechelic polymer represented by the following formula (I).

Equation (I):

In the above formula, R ¹ and R ² independently represent alkoxy, phenyloxy or phenyl-C ₃ alkyloxy, or R ¹ and R ² together form C ₆ -alkyl in but it may also be substituted Echirenjiokishi (an 0- CH (R ') - CH 2 - 0-: wherein R' is hydrogen atom or a C _{1 -6} alkyl) or represents, or R ¹ and R ² together represents an oxy (= 0),

R ³ represents a hydrogen atom or a C _{1 -6} alkyl,

L represents carbonyl, C, _-3 alkylene or C! _-3 alkylphenylene,

n is an integer from 2 to 10,000, and

p is an integer of 1 to 5.

6. The heterotelechelic polymer of claim 5, wherein R ¹ and R ² together represent oxy (= 0) and represents carbonyl or benzylene ( ^1-2 (^>") ~.

7. The following formula (I-a):

R ³

0 = CH— (CH ₂ > p-0— (CH ₂ CH ₂ 0 i LC = CH ₂ (I—a) wherein R ³ represents a hydrogen atom or C 原子₆ alkyl, L represents carbonyl, C _{1 -3} alkylene or C, - ₃ alkyl phenylene, n is an integer from 2 to 10 000, and p is an integer of 1 to 5]

A method for producing a heterotelechelic polymer represented by the formula:

Equation (I_b):

; CH- (CH ₂ ) p-0- CHzCHzO LC = CH ₂ (I -b)

[In the formula, R ¹ and R ² - ^b are independently C I ₆ alkoxy, or represents Fueniruo alkoxy or Fuweniru one C physician ₃ Arukiruokishi, or, R ¹ and R ² may be taken together to form an ethylenedioxy (1- 0—CH (R ′) — CH ₂ —0—: optionally substituted with C ぃ₆ alkyl, wherein R ′ is a hydrogen atom or Cぃ₆ alkyl), and R ³ , L, n and P are as defined above]

A process characterized by treating the polymer represented by the formula (1) in acetic acid containing a catalytic amount of water to perform deacetylation.