JP3465307B2 - Polyalkylene oxide derivative and production method - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel and useful polyalkylene oxide derivative and a method for producing the same, and more particularly to an alkylene oxide derivative having different kinds of functional groups at both ends and a method for producing the same.

[0002]

2. Description of the Related Art Among polyalkylene oxides, polyethylene oxide has properties such as water solubility and non-immunogenicity, and is used as a modifier for physiologically active substances such as proteins and drugs, biology and medical engineering. The application to the field is drawing attention.

Generally, various functional groups such as carboxyl group, amino group, hydroxyl group and mercapto group are present on the surface of proteins. When chemically binding such a protein molecule and polyethylene oxide, what kind of functional group is selected and how much is bonded have a great influence on the properties of the synthesized polyethylene oxide protein conjugate. Exert. Therefore, it is necessary to select the functional group on the polyethylene oxide side according to the functional group existing on the surface of the protein to be modified.

Polyethylene oxide which is industrially synthesized has a non-reactive group such as a methoxy group at one end,
Most of them have a hydroxyl group at the other end, or have a hydroxyl group at both ends, but since the hydroxyl group is poor in reactivity, it is necessary to use it as a protein modifier as described above in terms of reactivity. It's hard to say that we can be satisfied.

Therefore, attempts have been made to convert the hydroxyl group of polyethylene oxide having a hydroxyl group at one end (one end) into another highly reactive functional group (Synt).
h. Commun. , 22 (16), 2417-242
4 (1992)). Attempts have also been made to modify polyethylene oxide having hydroxyl groups at both ends with highly reactive functional groups (J. Bioact. Compat. P.
olym. , 5 (2) 227-231 (1990)).

When selectively binding different types of substances such as proteins to both ends of polyethylene oxide, polyethylene oxide having different functional groups at both ends is required (DE4004296 (1991)). However, in the method of modifying polyethylene oxide having hydroxyl groups at both ends as described above, unreacted hydroxyl groups may remain, and the reaction product has the same functional group at both ends, Since it is obtained as a mixture with those having different functional groups at both ends, purification by column chromatography or the like is required, and there is a problem in yield and purity.

On the other hand, there is an example in which ethylene oxide is polymerized using a potassium salt of an amino group protected by a trimethylsilyl group as a polymerization initiator (Bioconju).
gate Chem. , 3 (4), 275-276 (1
992)). In this method, α-amino-ω-hydro-
Although polyethylene oxide is selectively obtained, there is no example in which other different functional groups are selectively introduced.

Further, a method for selectively producing a polyethylene oxide derivative having different functional groups at both ends has not been established. Therefore, it is desired to establish a selective production method of polyethylene oxide having functional groups having different reactivity at both ends.

[0009]

The object of the present invention is to provide a novel and useful polyalkylene oxide derivative having a carboxyl group at one end and a highly reactive functional group other than the carboxyl group at the other end, and the like. To provide intermediates of various derivatives. Another object of the present invention is to provide a method for producing the above novel and useful polyalkylene oxide derivative selectively, easily and efficiently, and a method for producing an intermediate.

[0010]

The present invention provides the following polyalkylene oxide derivative and a method for producing the same. [1] A polyalkylene oxide derivative represented by the following general formula (1) whose terminal is a carboxyl group.

[Chemical 17] [In the formula, n is an integer of 5 to 10000, m is 0 or 1,
R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, and when m is 1, X ¹ is a hydroxyl group, a mercapto group or an aldehyde group. [2] A polyalkylene oxide derivative represented by the following general formula (2).

[Chemical 18] [In the formula, n is an integer of 5 to 10000, m is 0 or 1,
R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² is an alkyl group, an arylalkyl group or a substituted arylalkyl group, A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, and when m is 1, X ¹ is a hydroxyl group or a mercapto group. , An amino group or an aldehyde group. ] [3] General formula (3)

[Chemical 19] [Wherein R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group, a hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (where Y is an alkyl group, a halogenated alkyl group, an aryl group or a halogen). Represents an aryl group). ] The epoxy compound represented by the general formula (4)

[Chemical 20] [In the formula, R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The general formula (5) obtained by polymerizing an alkali metal salt of a hydroxycarboxylic acid ester represented by

[Chemical 21] [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom,
Alkyl group, halogenated alkyl group, hydroxyalkyl group, aryl group, arylalkyl group or -CH ₂
OY (where Y is an alkyl group, a halogenated alkyl group,
An aryl group or a halogenated aryl group is shown. ) Is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The general formula (5a) characterized by acid-treating the intermediate represented by

[Chemical formula 22] [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom,
Alkyl group, halogenated alkyl group, hydroxyalkyl group, aryl group, arylalkyl group or -CH ₂
OY (where Y is an alkyl group, a halogenated alkyl group,
An aryl group or a halogenated aryl group is shown. ) Is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, and B represents an alkylene group. ] The manufacturing method of the polyalkylene oxide derivative represented by these. [4] The general formula (5) obtained by polymerizing the epoxy compound represented by the general formula (3) with an alkali metal salt of a hydroxycarboxylic acid ester represented by the general formula (4) as a polymerization initiator. ), The intermediate represented by the formula (2a) is characterized in that it is chemically modified.

[Chemical formula 23] [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom,
Alkyl group, halogenated alkyl group, hydroxyalkyl group, aryl group, arylalkyl group or -CH ₂
OY (where Y is an alkyl group, a halogenated alkyl group,
An aryl group or a halogenated aryl group is shown. ) Is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, A represents an alkylene group, B represents an alkylene group, and X ² represents a mercapto group, an amino group or an aldehyde group. ] The manufacturing method of the polyalkylene oxide derivative represented by these. [5] The general formula (5) obtained by polymerizing the epoxy compound represented by the general formula (3) with an alkali metal salt of a hydroxycarboxylic acid ester represented by the general formula (4) as a polymerization initiator. ) A compound obtained by chemically modifying an intermediate represented by the formula (4) is hydrolyzed in the presence of an acid or an alkali, and a method for producing a polyalkylene oxide derivative represented by the general formula (1) . [6] General formula (2b)

[Chemical formula 24] [In the formula, n is an integer of 5 to 10000, m is 0 or 1,
R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² is an alkyl group, an arylalkyl group or a substituted arylalkyl group, A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, and when m is 1, X ¹ is a hydroxyl group or a mercapto group. or shows an aldehyde group. ] The compound represented by the formula is hydrolyzed in the presence of an acid or an alkali.

[Chemical 25] [In the formula, n is an integer of 5 to 10000, m is 0 or 1,
R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is when the hydrogen atom, m is 1, X ¹ is hydroxyl group, mercapto Motoma other represents an aldehyde group. ] The manufacturing method of the polyalkylene oxide derivative whose terminal is a carboxyl group represented by these.

R ^{1 in the} general formula (1) is a hydrogen atom or a monovalent organic group. As the organic group, an alkyl group having 1 to 8 carbon atoms such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group and a hexyl group; a hydrogen atom of these alkyl groups is substituted with chlorine, fluorine, bromine or iodine. A halogenated alkyl group; a hydroxyalkyl group in which a hydrogen atom of the alkyl group is substituted with a hydroxyl group; an aryl group such as a phenyl group and a tolyl group; an arylalkyl group such as a benzyl group and a phenethyl group; and Y in the formula —CH ₂ OY Examples thereof include the above alkyl group, halogenated alkyl group or aryl group, or a group in which the hydrogen atom of the above aryl group is a halogenated aryl group substituted with chlorine, fluorine, bromine or iodine. In the present invention, the terms "alkyl" and "arylalkyl" include straight-chain, branched, saturated and unsaturated ones.

As A in the general formula (1) , a methylene group,
Examples thereof include alkylene groups having 1 to 5 carbon atoms such as ethylene group, trimethylene group, tetramethylene group, methylethylene group and dimethylethylene group. B in the general formula (1) is 2
A valent organic group, specifically, a methylene group,
Methylmethylene group, dimethylmethylene group, ethylene group,
Examples thereof include alkylene groups having 1 to 5 carbon atoms such as methylethylene group, dimethylethylene group and tetramethylene group. X ¹ in the general formula (1), if m is 0 is a hydrogen atom, when m is 1 hydroxy group, mercapto Motoma other is an aldehyde group. N in the general formula (1) is 5 to 10000,
It is preferably 5 to 2000.

Specific examples of the polyalkylene oxide derivative having a carboxyl group at the terminal represented by the general formula (1) include the following . In each formula, n is 5
It is 10,000.

[0014]

[Chemical 21]

[0015]

[Chemical formula 26]

R ^{2 in the} general formula (2) is a monovalent organic group, and specific examples thereof include a methyl group, an ethyl group and ter.
Examples include alkyl groups having 1 to 8 carbon atoms such as t-butyl group, cyclopentyl group and cyclohexyl group; arylalkyl groups such as benzyl group and phenethyl group; and substituted arylalkyl groups such as diphenylmethyl group and triphenylmethyl group. .

R ¹ , A, B, X ¹ , m and n in the general formula (2) are the same as those in the general formula (1). Specific examples of the polyalkylene oxide derivative represented by the general formula (2) include the following. In each formula, n is 5 to 10000.

[0018]

[Chemical formula 23]

[0019]

[Chemical formula 24]

[0020]

[Chemical 25]

R ¹ of the general formula (3) is represented by the general formula (1)
Is the same as In the general formula (4), M is an alkali metal such as potassium or sodium, B is the same as in the general formula (1), and R ² is the same as in the general formula (2). General formula (5), (5a), (2a)
R ¹ , B and n in (2b) and (2b) are the same as in the general formula (1), and R ² is the same as in the general formula (2). M in the general formula (5) is the same as that in the general formula (4). X ^{2 of the} general formula (2a)
Is a mercapto group, an amino group or an aldehyde group,
A is the same as that in the general formula (1).

The polyalkylene oxide derivative represented by the general formula (1) is represented by the general formula (3) by using an alkali metal salt of a hydroxycarboxylic acid ester represented by the general formula (4) as a polymerization initiator. It can be produced by polymerizing the epoxy compound.

Specific examples of the epoxy compound represented by the general formula (3) include ethylene oxide, propylene oxide, 1,2-epoxybutane, 1,2-epoxypentane, 1,2-epoxyhexane, 1, 2-epoxyheptane, styrene oxide, epifluorohydrin, epichlorohydrin, epibromohydrin, glycidol, butyl glycidyl ether, hexyl glycidyl ether, allyl glycidyl ether, 1,2-epoxy-3-phenoxypropane, 2- Examples thereof include chloroethyl glycidyl ether and o-chlorophenyl glycidyl ether. These may be used alone or as a mixture of two or more.

Specific examples of the polymerization initiator represented by the general formula (4) include methyl glycolate, ethyl glycolate, isopropyl glycolate, tert-butyl glycolate, phenylmethyl glycolate and diphenylmethyl glycolate. , An alkali metal salt of hydroxyacetic acid ester such as triphenylmethyl glycolate; methyl-2-hydroxypropionate, ethyl-2-hydroxypropionate, isopropyl-2-hydroxypropionate, tert-butyl-2-hydroxy Alkali metal salts of 2-hydroxypropionic acid esters such as propionate, phenylmethyl-2-hydroxypropionate, diphenylmethyl-2-hydroxypropionate and triphenylmethyl-2-hydroxypropionate; -3-hydroxy propionate,
Ethyl-3-hydroxypropionate, isopropyl-3-hydroxypropionate, tert-butyl-
3-hydroxypropionate, phenylmethyl-3-
Alkali metal salts of 3-hydroxypropionic acid esters such as hydroxypropionate, diphenylmethyl-3-hydroxypropionate and triphenylmethyl-3-hydroxypropionate; methyl-2-hydroxyisobutyrate, ethyl-2 -Hydroxyisobutyrate, isopropyl-2-hydroxyisobutyrate, t
2-hydroxyisobutyric acid ester derivatives such as ert-butyl-2-hydroxyisobutyrate, phenylmethyl-2-hydroxyisobutyrate, diphenylmethyl-2-hydroxyisobutyrate and triphenylmethyl-2-hydroxyisobutyrate Alkali metal salts of. Since these compounds act as a polymerization initiator, they are present at all polymer terminals.

The alkali metal salt of hydroxycarboxylic acid ester can be obtained by a method of adding an alkali metal or an alkali metal hydride to the hydroxycarboxylic acid ester. Further, instead of the alkali metal salt of hydroxycarboxylic acid ester, hydroxycarboxylic acid ester and alkali metal or alkali metal hydride can be used.

The polymerization initiator can be added to the reaction system as it is, but it is preferable to add it in the form of a solution dissolved in an organic solvent. The organic solvent is not particularly limited as long as it has no active hydrogen group, and examples thereof include benzene, toluene, dimethylsulfoxide, dimethylacetamide, dimethylformamide and the like. The concentration of the polymerization initiator solution is desirably 0.1 to 90% by weight, preferably 1.0 to 50% by weight.

The ratio of the epoxy compound represented by the general formula (3) to the polymerization initiator represented by the general formula (4) is usually 1:10 ⁻⁵ to a molar ratio of epoxy compound: polymerization initiator.
It is desirable that the ratio is 1: 0.5, preferably 1:10 ⁻⁴ to 1: 0.2.

The polymerization reaction is carried out by mixing an epoxy compound and a polymerization initiator or a polymerization initiator solution in a non-solvent or an organic solvent. The organic solvent is not particularly limited as long as it does not interfere with the polymerization reaction, and examples thereof include tetrahydrofuran, benzene, toluene, dimethyl sulfoxide, acetonitrile and the like. The polymerization reaction is preferably carried out in a sealed tube glass tube or in an autoclave. The concentration of the reaction solution is 0.1 to 90% by weight, preferably 1.0 to 50% by weight. The reaction conditions are
The temperature is 0 to 180 ° C., preferably 10 to 150 ° C., the pressure is usually 8 to 0 kgf / cm ² G, and the time is usually 0.5 to 1
20 hours is desirable.

By thus polymerizing the epoxy compound represented by the general formula (3), a polyalkylene oxide derivative as the first intermediate represented by the general formula (5) is obtained. By acid-treating the first intermediate, a compound in which m is 0 and X ¹ is a hydrogen atom in the general formula (2), that is, a polyalkylene oxide represented by the general formula (5a) having a hydroxyl group at the ω-terminal is represented. The derivative is obtained.

In order to obtain a polyalkylene oxide derivative having a mercapto group other than a hydroxyl group, an amino group or an aldehyde group at the ω-terminal, a method in which the first intermediate represented by the general formula (5) is reacted with an electrophile And the like.

In order to convert the alkali metal terminal of the first intermediate into a mercapto group, the following method can be adopted. A mercapto group can be introduced by tosylating the terminal with tosyl chloride and then reacting with sodium hydrosulfide.

The following method can be used to convert the alkali metal terminal of the first intermediate into an amino group. N- (2-bromoethyl) phthalimide as an electrophile,
After reacting with N- (3-bromopropyl) phthalimide or the like, an amino group can be introduced by hydrolysis or treatment with hydrazine. The amino group can be introduced also by reacting polyalkylene oxide halogenated with thionyl chloride or the like with sodium azide or the like to form an azide and then reducing the same. The amino group can also be introduced by adding hydrogen after adding acrylonitrile.

The following method can be adopted for conversion into an aldehyde group. 2-bromo-1,1 as an electrophile
-Diethoxyethane, 2-bromo-1,1-dimethoxyethane, 2-chloro-1,1-diethoxyethane, 2-
An aldehyde group can be introduced by reacting a compound such as chloro-1,1-dimethoxyethane and then hydrolyzing it with an acid or an alkali. The aldehyde group can also be introduced by a direct oxidation method using an oxidizing agent such as pyridine / chromium oxide.

By introducing the functional group in this manner, a second intermediate having m of 1 in the general formula (2), that is, a polyalkylene oxide derivative represented by the general formula (2a) is obtained. The second intermediate R ² —O—C (=
Deprotection of the R ² group from the (O) terminal to convert it to a carboxyl group terminal can be carried out by hydrolysis in the presence of an alkali or an acid.

Alkali reagents used for hydrolysis include potassium hydroxide, sodium hydroxide or tert-
Examples include butoxypotassium. Examples of the acid reagent include hydrochloric acid, sulfuric acid, formic acid, trifluoroacetic acid, hydrogen fluoride and the like.

By deprotecting the R ² group in this manner, a polyalkylene oxide derivative represented by the general formula (1), in which one end is a carboxyl group and the other end is a functional group, is selectively formed. Can be obtained. After completion of the reaction, the target polyalkylene oxide derivative can be isolated as a precipitate by introducing the reaction solution into a solution in which the polyalkylene oxide derivative such as diethyl ether, isopropanol, hexane or the like is not dissolved. The polyalkylene oxide derivative thus obtained can be used as a modifier for physiologically active substances such as proteins and drugs, and can impart properties such as water solubility and non-immunogenicity to the modified physiologically active substance.

[0037]

According to the present invention, a novel and useful polyalkylene oxide derivative having a carboxyl group at one end and a highly reactive functional group other than a carboxyl group at the other end, and an intermediate of such a derivative The body is obtained.

According to the production method of the present invention, the general formula (3)
The intermediate of the above polyalkylene oxide derivative can be easily and efficiently and selectively produced from the epoxy compound represented by the formula (4) and the alkali metal salt of the hydroxycarboxylic acid ester represented by the general formula (4) as starting materials.

According to the production method of the present invention, the desired polyalkylene oxide derivative can be produced easily, efficiently and selectively from the intermediate.

[0040]

EXAMPLES The present invention will be described in more detail with reference to examples below, but these examples do not limit the scope of the present invention. Example 1 Tetrahydrofuran 20 m in a glass polymerization tube at -79 ° C
35.2 g of ethylene oxide was dissolved in 1, and 1.6 g of tert-butyl-2-hydroxyisobutyrate and a potassium halide (KH) were used as a polymerization initiator.
Dimethyl sulfoxide (DMSO) in which 0.4 g was dissolved
5.80 ml of solution was added, frozen in liquid nitrogen, degassed in vacuo and sealed. Polymerization was carried out by stirring at 20 ° C. for 3 days. Then, it was added dropwise to 500 ml of diethyl ether at 0 ° C. to reprecipitate, and the precipitate was dried in vacuum and then 0.1 m
200 ml of ol / l hydrochloric acid aqueous solution was added for acid treatment, and α
-(1,1-dimethyl-2-tert-butoxy-2-
Oxoethoxy) -ω-hydro-polyethylene oxide was obtained (yield 28.5 g).

The obtained compound was analyzed by gel filtration type high performance liquid chromatography, and the average molecular weight determined from a standard sample of polyethylene oxide was 3,500, and the weight average molecular weight / number average molecular weight = 1.1. This average molecular weight is calculated from the ratio of ethylene oxide and tert-butyl-2-hydroxyisobutyrate to a molecular weight of 36
Since it is extremely close to 00, it can be seen that one polymer chain per polymerization initiator was obtained as designed.

The resulting polymer in this example, by the formula tert-Bu-OC (= O ) C (CH 3) 2 O- (CH 2 CH 2 O) nH (Bu is butyl group, n = 80) Is what is shown. ^{The 13} C-NMR analysis results are as follows. ¹³ C-NMR (CDCl ₃ ) δ (ppm): 28.5
61.1, 71.2, 72.5

Example 2 α- (1,1-dimethyl-2-te obtained in Example 1
rt-Butoxy-2-oxoethoxy) -ω-hydro-
A DMSO solution 5 containing 10 mmol of potassium tert-butoxide and 2 ml of water in 2 g of polyethylene oxide.
After adding 0 ml and further reacting at 20 ° C. for 5 hours to hydrolyze, it was added dropwise to 500 ml of diethyl ether for reprecipitation, vacuum dried and α- (1,1-dimethyloxyethanoic acid) -ω. -Hydro-polyethylene oxide was obtained.

The obtained polymer was analyzed by gel filtration type high performance liquid chromatography as in Example 1. As a result, the average molecular weight was 3,500 and the weight average molecular weight / number average molecular weight was 1.1. Polymer obtained in this example are those of the formula _{HOOC-C (CH 3) 2} O- (CH 2 CH 2 O) nH (n = 80). ^{The 13} C-NMR analysis results are as follows. ¹³ C-NMR (CDCl ₃ ) δ (ppm): 30.5,
61.1, 71.2, 72.8, 172.0

Example 3 Using the same procedure as in Example 1, 1.76 g of ethylene oxide was added.
(0.04 mol) to 1 mmol of tert-butyl-
3% at 20 ° C. in 20 ml of tetrahydrofuran / DMSO solution with potassium salt of 2-hydroxyisobutyrate.
Polymerized for a day. To this reaction solution, a tetrahydrofuran solution containing 1 mmol of N- (2-bromoethyl) phthalimide was added, and the mixture was further reacted at room temperature for 24 hours for chemical modification, and then added dropwise to 500 ml of diethyl ether for reprecipitation and vacuum drying. It was

20 m of a DMSO solution containing 10 mmol of potassium tert-butoxide and 2 ml of water.
In addition to 1, the mixture was reacted at 20 ° C. for 5 hours to hydrolyze both ends, and then added dropwise to 500 ml of diethyl ether for reprecipitation and drying to obtain α- (1,1-dimethyloxyethanoic acid). It was possible to obtain -ω- (2-aminoethyl) -polyethylene oxide. This was analyzed by gel filtration type high performance liquid chromatography as in Example 1. As a result, an average molecular weight of 1800 and a weight average molecular weight /
The number average molecular weight was 1.1.

The polymer obtained in this example is of the formula HOOC-C (CH ₃ ) ₂ O- (CH ₂ CH ₂ O) n-CH ₂ CH ₂ NH ₂ (n = 40). . ^{The 13} C-NMR analysis results are as follows. ¹³ C-NMR (CDCl ₃ ) δ (ppm): 48.2
54.4, 61.3, 70.4, 72.1

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masayuki Yokoyama 3-170 Shin-Matsudo, Matsudo City, Chiba Prefecture (72) Inventor Kazunori Kataoka 4 1072, Omuro, Kashiwa City, Chiba Prefecture (72) Yukio Nagasaki Kashiwa City, Chiba Prefecture Toyoshikidai housing complex 3-1-53-403 (72) Inventor Masao Kato 460-167 Kamihirooka, Tsukuba, Ibaraki (56) References JP-A-5-279469 (JP, A) JP-A-7-48449 ( JP, A) JP-A-6-135889 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) C08G 65/26-65/28 C08G 65/329-65/337 CA (STN )

Claims (6)

(57) [Claims] 1. A polyalkylene oxide derivative represented by the following general formula (1) , wherein the terminal is a carboxyl group. [Chemical 1] [In the formula, n is an integer of 5 to 10000, m is 0 or 1, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, and when m is 1, X ¹ is a hydroxyl group, a mercapto group or an aldehyde group. ] 2. A polyalkylene oxide derivative represented by the following general formula (2). [Chemical 2] [In the formula, n is an integer of 5 to 10000, m is 0 or 1, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² is an alkyl group, an arylalkyl group or a substituted arylalkyl group, A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, when m is 1, X ¹ is a hydroxyl group or a mercapto group. , An amino group or an aldehyde group. ] 3. A compound represented by the general formula (3): [Wherein R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group, a hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (where Y is an alkyl group, a halogenated alkyl group, an aryl group or a halogen). Represents an aryl group). ] The epoxy compound represented by the general formula (4) [In the formula, R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The compound of general formula (5) obtained by polymerizing an alkali metal salt of a hydroxycarboxylic acid ester represented by the following as a polymerization initiator: [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The intermediate represented by the formula [5a] is characterized by acid treatment. [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, and B represents an alkylene group. ] The manufacturing method of the polyalkylene oxide derivative represented by these. 4. A compound represented by the general formula (3): [Wherein R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group, a hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (where Y is an alkyl group, a halogenated alkyl group, an aryl group or a halogen). Represents an aryl group). ] The epoxy compound represented by the general formula (4) [In the formula, R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The compound of general formula (5) obtained by polymerizing an alkali metal salt of a hydroxycarboxylic acid ester represented by the following as a polymerization initiator: [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The general formula (2a) characterized by chemically modifying the intermediate represented by the following formula: [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² is an alkyl group, an arylalkyl group or a substituted arylalkyl group, A is an alkylene group, B is an alkylene group, and X ² is a mercapto group, an amino group or an aldehyde group. ] The manufacturing method of the polyalkylene oxide derivative represented by these. 5. A compound represented by the general formula (3): [Wherein R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group, a hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (where Y is an alkyl group, a halogenated alkyl group, an aryl group or a halogen). Represents an aryl group). ] The epoxy compound represented by the general formula (4) [In the formula, R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. ] The compound of general formula (5) obtained by polymerizing an alkali metal salt of a hydroxycarboxylic acid ester represented by [In the formula, n is an integer of 5 to 10000, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² represents an alkyl group, an arylalkyl group or a substituted arylalkyl group, B represents an alkylene group, and M represents an alkali metal. A compound obtainable intermediates by chemical modification represented by], general formula, which comprises hydrolyzing under the presence of an acid or alkali (1) embedded image [In the formula, n is an integer of 5 to 10000, m is 0 or 1, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, and when m is 1, X ¹ is a hydroxyl group, a mercapto group or an aldehyde group. ] The manufacturing method of the polyalkylene oxide derivative represented by these. 6. A compound represented by the general formula (2b) : [In the formula, n is an integer of 5 to 10000, m is 0 or 1, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. R ² is an alkyl group, an arylalkyl group or a substituted arylalkyl group, A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is a hydrogen atom, when m is 1, X ¹ is a hydroxyl group or a mercapto group. or shows an aldehyde group. ] The compound represented by the following formula is hydrolyzed in the presence of an acid or an alkali. [In the formula, n is an integer of 5 to 10000, m is 0 or 1, R ¹ is a hydrogen atom, an alkyl group, a halogenated alkyl group,
A hydroxyalkyl group, an aryl group, an arylalkyl group or —CH ₂ OY (wherein Y represents an alkyl group, a halogenated alkyl group, an aryl group or a halogenated aryl group) is shown. R ^{1 s} in each repeating unit may be the same or different. A is an alkylene group, B is an alkylene group, when m is 0, X ¹ is when the hydrogen atom, m is 1, X ¹ is hydroxyl group, mercapto Motoma other represents an aldehyde group. ] The manufacturing method of the polyalkylene oxide derivative whose terminal is a carboxyl group represented by these.