WO2018207806A1 - Polymer and methods for producing polymers - Google Patents

Abstract

The purpose of the present invention is to provide: a method for producing a polymer (ii) which is a polymer of an anionically polymerizable monomer and which has an amino group introduced in a given amount at a terminal of said polymer; a polymer (i) which has a pyrrole ring structure at a terminal and is for use in producing the polymer (ii); and a method for producing the polymer (i). The polymer (i) has a pyrrole ring structure at a terminal thereof and has a constituent unit derived from an anionically polymerizable monomer. The polymer (i) is usually obtained by polymerizing an anionically polymerizable monomer by living anionic polymerization using a polymerization initiator having a pyrrole ring structure.

Description

POLYMER AND METHOD FOR PRODUCING POLYMER

The present invention relates to a polymer having a pyrrole ring structure at the end of the polymer, a method for producing the polymer, and a method for producing a polymer having an amino group at the end using the polymer.

A polymer having an amino group at the end of the polymer chain can be reacted with various substances because the amino group is a highly reactive functional group. For example, since an amino group forms an amide by reaction with a carboxy group, a property derived from the substance can be imparted to the end of the polymer by reacting with a substance having a carboxy group.

By the way, poly (ethylene oxide) (PEO) or poly (ethylene glycol) (PEG) is a polymer for which biological application is expected, and coating of implant material, plate for cell sheet preparation, drug delivery system (DDS) construction It is the material used suitably for etc.

In order to use PEG or PEO for such various uses, it is necessary to introduce a functional group quantitatively at the end of the polymer chain. In particular, PEG or PEO having a primary amino group at the terminal is useful because a fluorescent probe, peptide, antibody or the like can be introduced into the terminal of the polymer chain via the amino group. Also, PEG or PEO having a primary amino group at the terminal forms a block copolymer with poly (amino acid) by initiating polymerization of α-amino acid N-carboxylic acid anhydride (NCA) from the amino group. can do.

A method for obtaining PEO or PEG having a primary amino group at the terminal, which can be used for various applications as described above, has already been reported (for example, see Non-patent Document 1 and Patent Document 1).

Non-Patent Document 1 discloses a method of aminating the ω end of PEG. Specifically, by polymerizing ethylene glycol as the first step, isolating the obtained PEG, and by reacting the terminal hydroxy group in the presence of methanesulfonic acid chloride and triethylamine for one hour as the second step. A PEG having a mesyl group at the end is obtained. As a third step, conversion to an amino group is disclosed by treating in ammonia water for several days.

In Patent Document 1, ethylene oxide is polymerized using N, N-dibenzyl-2-aminoethanol as an initiator to obtain PEG having N, N-dibenzylamine at the α-terminus. It is disclosed that this dibenzyl protecting group is deprotected by reaction with hydrogen in the presence of a palladium catalyst to give an amine terminus.

US Patent Application Publication No. 2013/0281639

Shigehiro Hiki, Kazunori Kataoka, "A Facile Synthesis of Azido-Terminated Heterobifunctional Poly (ethylene glycol) s for" Click "Conjugation" Bioconjugate Chem., 2007, 18, 2191-2196

In the production method disclosed in Non-Patent Document 1, PEG or PEO in which an amino group is introduced at the end of the polymer chain can be obtained. In order to obtain such a polymer, a three-step reaction is performed. It was necessary.

In the production method disclosed in Non-Patent Document 1, an amino group is introduced by modifying the end of a polymer chain. However, it is difficult to obtain a high amino conversion rate due to the property of modifying the end of a polymer chain. It was.

Therefore, in the production method disclosed in Non-Patent Document 1, after an amino group is introduced, a column or the like is used to separate PEG or PEO having an amino group introduced at the terminal and other PEG or PEO. It was necessary to purify using For this reason, practically, the manufacturing method disclosed in Non-Patent Document 1 requires a four-step reaction.

In the production method disclosed in Patent Document 1, an amino group protector is used as an initiator, but conversion to an amino group is not described. If a polymer having an amino group is obtained by converting the amino group-protected body of a polymer having an amino group-protected body disclosed in Patent Document 1 into an amino group, obtain it in two steps. Although it is considered that the conversion rate to the final amino group is high, it is necessary to remove the palladium catalyst used for deprotection of the amino protecting group, and the actual number of steps is three.

In the present invention, a method for producing a polymer (ii) in which an amino group is quantitatively introduced at the end of a polymer of an anion polymerizable monomer such as PEG or PEO, is used for producing the polymer (ii). It aims at providing the polymer (i) which has a pyrrole ring structure at the terminal of a polymer, and the manufacturing method of this polymer (i).

As a result of intensive studies to achieve the above problems, the present inventors synthesized a polymer (i) having a pyrrole ring structure at the end of the polymer, and obtained a pyrrole ring structure possessed by the polymer (i). It has been found that by converting to an amino group, the polymer (ii) having an amino group at the terminal can be obtained with high efficiency, that is, the above-mentioned problems can be solved, and the present invention has been completed.

That is, the present invention relates to the following [1] to [15].
[1] A polymer (i) having a pyrrole ring structure at the terminal of the polymer and having a structural unit derived from an anionic polymerizable monomer.

[2] The polymer (i) according to [1], wherein the pyrrole ring structure is a structure represented by the following general formula (α).

　（一般式（α）において、Ｒ^A～Ｒ^Dは、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基である。）

(In the general formula (α), R ^A to R ^D may be the same or different and are a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

[3] The anion polymerizable monomer is at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohols. ] Or polymer (i) according to [2].

[4] The polymer (i) according to [1] or [2], wherein the anionically polymerizable monomer is a cyclic ether having 3 to 4 members.

[5] Using a polymerization initiator having a pyrrole ring structure, living anion polymerization of an anion polymerizable monomer,
The manufacturing method of polymer (i) which has the process (I) which has a pyrrole ring structure at the terminal of a polymer, and obtains the polymer (i) which has a structural unit derived from an anion polymerizable monomer.

[6] The polymerization initiator is at least one compound selected from a compound having a structure represented by the following general formula (A) and a compound having a structure represented by the general formula (B): [5 ] The manufacturing method of the polymer (i) of description.

　（一般式（Ａ）において、Ｒ¹～Ｒ⁴は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基である。）

(In the general formula (A), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

　（一般式（Ｂ）において、Ｒ⁵～Ｒ⁸は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基であり、
　Ｒ⁹～Ｒ¹¹は、それぞれ同一でも異なっていてもよく、水素原子、炭素数１～３０のアルキル基、ヒドロキシ基、炭素数１～３０のヒドロキシアルキル基、－Ｏ^‐、または、水素原子が－Ｏ^‐で置換された炭素数１～３０のアルキル基であり、
　Ｒ⁹～Ｒ¹¹の少なくとも一つは、－Ｏ^‐、または、水素原子が－Ｏ^‐で置換された炭素数１～３０のアルキル基である。）

(In the general formula (B), R ⁵ to R ⁸ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
R ⁹ to R ¹¹ may be the same or different and each represents a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, a hydroxyalkyl group having 1 to 30 carbon atoms, —O ⁻ , or a hydrogen atom. -O ^- in a substituted alkyl group having 1 to 30 carbon atoms,
At least one of R ⁹ to R ¹¹ is —O ⁻ or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— . )

[7] The anionic polymerizable monomer is at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohols. ] Or the manufacturing method of the polymer (i) as described in [6].

[8] The method for producing the polymer (i) according to [5] or [6], wherein the anion polymerizable monomer is a cyclic ether having 3 to 4 members.

[9] By converting the pyrrole ring structure in the polymer (i) having a pyrrole ring structure at the end of the polymer and having a structural unit derived from an anion polymerizable monomer into an amino group,
The manufacturing method of polymer (ii) which has process (II) which obtains polymer (ii) which has an amino group at the terminal.

[10] By using a polymerization initiator having a pyrrole ring structure, living anion polymerization of the anionic polymerizable monomer,
Step (I) for obtaining a polymer (i) having a pyrrole ring structure at the terminal of the polymer and having a structural unit derived from an anion polymerizable monomer, and converting the pyrrole ring structure in the polymer (i) to an amino group By converting
The manufacturing method of polymer (ii) which has process (II) which obtains polymer (ii) which has an amino group at the terminal.

[11] The polymerization initiator is at least one compound selected from a compound having a structure represented by the following general formula (A) and a compound having a structure represented by the general formula (B). [10 ] The manufacturing method of the polymer (ii).

　（一般式（Ａ）において、Ｒ¹～Ｒ⁴は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基である。）

(In the general formula (A), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

　（一般式（Ｂ）において、Ｒ⁵～Ｒ⁸は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基であり、
　Ｒ⁹～Ｒ¹¹は、それぞれ同一でも異なっていてもよく、水素原子、炭素数１～３０のアルキル基、ヒドロキシ基、炭素数１～３０のヒドロキシアルキル基、－Ｏ^‐、または、水素原子が－Ｏ^‐で置換された炭素数１～３０のアルキル基であり、
　Ｒ⁹～Ｒ¹¹の少なくとも一つは、－Ｏ^‐、または、水素原子が－Ｏ^‐で置換された炭素数１～３０のアルキル基である。）

(In the general formula (B), R ⁵ to R ⁸ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
R ⁹ to R ¹¹ may be the same or different and each represents a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, a hydroxyalkyl group having 1 to 30 carbon atoms, —O ⁻ , or a hydrogen atom. -O ^- in a substituted alkyl group having 1 to 30 carbon atoms,
At least one of R ⁹ to R ¹¹ is —O ⁻ or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— . )

[12] The anionic polymerizable monomer is at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohols. ] To [11] A process for producing the polymer (ii) according to any one of [11] to [11].

[13] The method for producing the polymer (ii) according to any one of [9] to [11], wherein the anionic polymerizable monomer is a cyclic ether having 3 to 4 members.

[14] The method for producing the polymer (ii) according to any one of [9] to [13], wherein hydroxylamine is used when the pyrrole ring structure is converted to an amino group.

[15] The method for producing the polymer (ii) according to any one of [10] to [14], wherein the steps (I) and (II) are performed by one-pot synthesis.

According to the present invention, a method for producing a polymer (ii) in which an amino group is introduced at the terminal of a polymer of an anion-polymerizable monomer, which can be carried out with high efficiency, and a polymer used for producing the polymer (ii) The polymer (i) which has a pyrrole ring structure in the terminal of this, and the manufacturing method of this polymer (i) can be provided.

2 shows an elution curve of DMP-PEG obtained by SEC measurement in Example 1. FIG. 2 shows a mass spectrum of DMP-PEG obtained by MALDI-TOF MS measurement in Example 1, and an enlarged view of the 2600-2750 m / z region of the spectrum. 1 shows the ¹ H-NMR spectrum of DMP-PEG in Example 1. ₂ shows a mass spectrum of NH ₂ -PEG obtained by MALDI-TOF MS measurement in Example 1, and an enlarged view of the 2750 to 2820 m / z region of the spectrum. ₂ shows an elution curve of NH ₂ -PEG by ion exchange chromatography in Example 1. 3 shows an elution curve of NH ₂ -PEG by ion exchange chromatography in Example 2 (one-pot synthesis).

Next, the present invention will be specifically described.
The polymer (i) of the present invention has a pyrrole ring structure at the end of the polymer and has a structural unit derived from an anionic polymerizable monomer. Moreover, the manufacturing method of the polymer (i) of this invention is the process (I) which obtains polymer (i) by carrying out living anion polymerization of an anion polymerizable monomer using the polymerization initiator which has a pyrrole ring structure. Have Furthermore, the method for producing the polymer (ii) of the present invention comprises a step (II) of obtaining a polymer (ii) having an amino group at the terminal by converting the pyrrole ring structure in the polymer (i) into an amino group. Have

In the present invention, the amino group usually means a primary amino group, that is, —NH ₂ . In the present invention, the polymer is not limited to a high molecular weight polymer, but includes a multimer such as a dimer and a trimer.

[Polymer (i)]
The polymer (i) of the present invention has a pyrrole ring structure at the end of the polymer and has a structural unit derived from an anionic polymerizable monomer.

The pyrrole ring structure of the polymer (i) is a 5-membered ring composed of C ₄ N, and the pyrrole ring structure is a structure having no substituent in which one hydrogen atom is bonded to each carbon. It may be a structure in which a group other than a hydrogen atom is bonded to each carbon atom, that is, a structure having a substituent.

The pyrrole ring structure is preferably a structure represented by the following general formula (α) from the viewpoint of easily synthesizing the polymer (i).

　（一般式（α）において、Ｒ^A～Ｒ^Dは、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基である。）

(In the general formula (α), R ^A to R ^D may be the same or different and are a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

Examples and preferred embodiments of R ^A to R ^D are the same as those exemplified and preferred embodiments of R ¹ to R ⁴ and R ⁵ to R ⁸ described later.
The polymer (i), which will be described in detail in the method for producing the polymer (i) described later, is obtained by living anion polymerization of an anion polymerizable monomer using a polymerization initiator having a pyrrole ring structure. Is possible. The pyrrole ring structure which the polymer (i) of the present invention has is derived from a polymerization initiator having a pyrrole ring structure which is usually used in the production method of the polymer (i). That is, the polymer (i) has a pyrrole ring structure at the terminal, but usually has a pyrrole ring structure at the polymerization initiation terminal of the polymer (i).

Since the pyrrole ring structure can be converted to an amino group, the polymer (i) is produced when the polymer (ii) in which an amino group is introduced at the terminal of the polymer of the anionic polymerizable monomer is produced. Can be used.

The polymer (i) of the present invention preferably has a weight average molecular weight (Mw) of, for example, 150 to 1,000,000 measured under the conditions described in the examples, and is 1,000 to 100,000. More preferably, the range is 2,000 to 40,000. The molecular weight of the polymer (ii) depends on the molecular weight of the polymer (i), but is preferably within the above range from the viewpoint of applying the polymer (ii) to a living body and from the viewpoint of using it in the industrial field. Further, the molecular weight distribution (Mw / Mn) determined from the weight average molecular weight and the number average molecular weight is preferably 1 to 2, more preferably 1 to 1.2. The polymer (i) of the present invention can be obtained as a polymer having a narrow molecular weight distribution by being obtained by the production method described later.

The polymer of the present invention usually has a group or atom derived from a polymerization terminator at a terminal other than the terminal having a pyrrole ring structure. The anionically polymerizable monomer, in the case of cyclic ethers 3-4 membered ring which will be described later, the end of when performing a living anionic -O ^- for a which, when the polymerization was terminated by water , —O 2 ^— can be obtained by introducing a hydrogen atom into a polymer having a hydroxy group at the terminal. In the following description, a hydroxy group formed by introducing a hydrogen atom into —O 2 ^— is also included in a group derived from a polymerization terminator.

The terminal having the group or atom means not the polymerization starting terminal of the polymer but the terminal obtained by polymerization and the termination reaction. The polymer (i) obtained by the method for producing the polymer (i) described later can be a polymer having a group derived from a polymerization terminator at the polymer terminal.

Therefore, the polymer (i) of the present invention has a pyrrole ring structure at the polymerization initiation terminal and a polymer having a group derived from a polymerization terminator at another terminal, that is, a polymer having two types of functional groups. Is possible. The polymer (ii) obtained from the polymer (i) can also be a polymer having two types of functional groups.
Since polymers such as PEG having different functional groups are extremely difficult to produce by conventional production methods, the polymers (i) and (ii) can be expected to be used in various applications.

(Polymerization initiator)
The polymerization initiator is not particularly limited as long as it is a polymerization initiator having a pyrrole ring structure and can suitably polymerize an anionic polymerizable monomer, but has a structure represented by the following general formula (A). Examples thereof include at least one compound selected from a compound and a compound having a structure represented by the general formula (B). By using at least one compound selected from a compound having a structure represented by the following general formula (A) and a compound having a structure represented by the general formula (B) as a polymerization initiator, the polymer (i ) Has a pyrrole ring structure represented by the general formula (α).

In addition, as a polymerization initiator, it may be used individually by 1 type, or 2 or more types may be used, but it is preferable to use only 1 type from a viewpoint from which the composition of the polymer obtained becomes uniform.
As the polymerization initiator, it is preferable to use a compound having a structure represented by the following general formula (A) from the viewpoint of solubility of the polymerization initiator.

　（一般式（Ａ）において、Ｒ¹～Ｒ⁴は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基である。）

(In the general formula (A), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

　（一般式（Ｂ）において、Ｒ⁵～Ｒ⁸は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基であり、
　Ｒ⁹～Ｒ¹¹は、それぞれ同一でも異なっていてもよく、水素原子、炭素数１～３０のアルキル基、ヒドロキシ基、炭素数１～３０のヒドロキシアルキル基、－Ｏ^‐、または、水素原子が－Ｏ^‐で置換された炭素数１～３０のアルキル基であり、
　Ｒ⁹～Ｒ¹¹の少なくとも一つは、－Ｏ^‐、または、水素原子が－Ｏ^‐で置換された炭素数１～３０のアルキル基である。）

(In the general formula (B), R ⁵ to R ⁸ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
R ⁹ to R ¹¹ may be the same or different and each represents a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, a hydroxyalkyl group having 1 to 30 carbon atoms, —O ⁻ , or a hydrogen atom. -O ^- in a substituted alkyl group having 1 to 30 carbon atoms,
At least one of R ⁹ to R ¹¹ is —O ⁻ or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— . )

R ¹ to R ⁴ and R ⁵ to R ^{8, which} may be the same or different, are a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. The alkyl group having 1 to 4 carbon atoms preferably has 1 to 2 carbon atoms. Specific examples of the alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, t-butyl group and the like.

R ¹ to R ⁴ and R ⁵ to R ⁸ are preferably a hydrogen atom, a methyl group, or an ethyl group from the viewpoint that polymerization proceeds suitably. More preferably, 1 to 3 of R ¹ to R ⁴ are hydrogen atoms, and 1 to 3 are methyl groups. More preferably, 1 to 3 of R ⁵ to R ⁸ are hydrogen atoms and 1 to 3 are methyl groups. R ¹ and R ⁴ are alkyl groups, R ² and R ³ are hydrogen atoms, R ⁵ and R ⁸ are alkyl groups, and R ⁶ and R ⁷ are hydrogen atoms. It is particularly preferable from the viewpoint that polymerization proceeds suitably.

In the general formula (B), R ⁹ to R ¹¹ may be the same or different and are each a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, a hydroxyalkyl group having 1 to 30 carbon atoms, —O ^-, or a hydrogen atom -O ^- been an alkyl group having 1 to 30 carbon atoms substituted with.

At least one of R ⁹ to R ¹¹ is —O ⁻ or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— .
When two to three of R ⁹ to R ¹¹ are —O ⁻ , or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— , the structure represented by the general formula (B) It is possible to initiate the polymerization of the compound having 2 or 3 places.

The alkyl group having 1 to 30 carbon atoms in R ⁹ to R ¹¹ is preferably an alkyl group having 1 to 4 carbon atoms. The alkyl group having 1 to 30 carbon atoms may be a linear alkyl group or a branched alkyl group. Among the alkyl groups having 1 to 30 carbon atoms, examples of the alkyl group having 1 to 4 carbon atoms include those exemplified as the alkyl groups for R ⁵ to R ⁸ .

The hydroxyalkyl group having 1 to 30 carbon atoms in R ⁹ to R ¹¹ is preferably a hydroxyalkyl group having 1 to 4 carbon atoms. The hydroxyalkyl group having 1 to 30 carbon atoms is a group in which at least one, preferably 1 to 2, more preferably one of the hydrogen atoms of the alkyl group having 1 to 30 carbon atoms is substituted with a hydroxy group Is mentioned. From the viewpoint of reactivity, a group in which a hydrogen atom at the terminal of an alkyl group having 1 to 30 carbon atoms is substituted with a hydroxy group is preferable.

At least one of R ⁹ ~ R ¹¹ are -O ^-, or a hydrogen atom is -O ^- but have been certain alkyl group having 1 to 30 carbon atoms substituted with, the structure is respectively hydroxy group, or Obtained by elimination of protons (H ⁺ ) from a hydroxyalkyl group having 1 to 30 carbon atoms.

As the polymerization initiator, a compound having a structure represented by the general formula (A) is used, and R ¹ and R ⁴ are alkyl groups, the solubility viewpoint of the polymerization initiator, and the pyrrole ring structure. From the viewpoint that it can be easily converted to an amino group and the polymer (ii) can be obtained efficiently, it is particularly preferable.

Although the structure represented by the general formula (A) and the structure represented by the general formula (B) are anions, the compound having the structure represented by the general formula (A) used as a polymerization initiator and Each compound having a structure represented by the general formula (B) has a counter cation. Examples of the counter cation include a cation derived from a base described later, and examples thereof include an alkali metal cation.

The compound having a structure represented by the general formula (A) can be obtained by reacting a compound represented by the following general formula (A ′) with a base, and the general formula (B) The compound having a structure represented by can be obtained by reacting a compound represented by the following general formula (B ′) with a base.

　（一般式（Ａ'）において、Ｒ¹～Ｒ⁴は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基である。）

(In the general formula (A ′), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

　（一般式（Ｂ'）において、Ｒ⁵～Ｒ⁸は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基であり、
　Ｒ⁹～Ｒ¹¹は、それぞれ同一でも異なっていてもよく、水素原子、炭素数１～３０のアルキル基、ヒドロキシ基、または、炭素数１～３０のヒドロキシアルキル基である。）

(In the general formula (B ′), R ⁵ to R ⁸ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
R ⁹ to R ¹¹ may be the same or different and are each a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, or a hydroxyalkyl group having 1 to 30 carbon atoms. )

As the base, a structure represented by the general formula (A) by extracting the proton (H ⁺ ) of the compound represented by the general formula (A ′) or the compound represented by the general formula (B ′) There is no particular limitation as long as it is possible to obtain a compound having a compound or a compound having a structure represented by the general formula (B).

Examples of the base include alkali metal compounds, alkaline earth metal compounds, and strong bases (excluding alkali metal compounds and alkaline earth metal compounds). Although a base may be used individually by 1 type or may be used 2 or more types, it is normally used individually by 1 type.

Alkali metal compounds include lithium naphthalene (lithium naphthalenide), sodium naphthalene (sodium naphthalenide), potassium naphthalene (potassium naphthalenide), cesium naphthalene, benzyl lithium, benzyl sodium, benzyl potassium, benzyl cesium, diphenylmethyl Examples include lithium, diphenylmethyl sodium, diphenylmethyl potassium, diphenylmethyl cesium, triphenylmethyl lithium, triphenylmethyl sodium, triphenylmethyl potassium, triphenylmethyl cesium, sodium hydroxide, potassium hydroxide, cesium hydroxide and the like.

Examples of the alkaline earth metal compound include calcium hydroxide and magnesium hydroxide.
Examples of strong bases (excluding alkali metal compounds and alkaline earth metal compounds) include tetramethylammonium hydroxide, tetraethylammonium hydroxide, and guanidine.

As the base, an alkali metal compound is preferable from the viewpoint of reactivity, and sodium naphthalene and potassium naphthalene are more preferable.
When the compound represented by the general formula (A ′) is reacted with a base, it is usually different depending on the valence of the base, but is usually 0.001 per mole of the compound represented by the general formula (A ′). 2 to 1.1 mol of base is used.

When the compound represented by the general formula (B ′) is reacted with the base, the general formula (B ′) usually varies depending on the number of hydroxy groups and the valence of the base. 0.2 to 1.1 mol of base is used per mol of the compound represented by ').

When the compound represented by the general formula (A ′) is reacted with an alkali metal compound, usually 0.5 to 1.1 mol of alkali is used per 1 mol of the compound represented by the general formula (A ′). Metal compounds are used, preferably 0.8 to 1.0 mole of alkali metal compound.

(Anionic polymerizable monomer)
The anion polymerizable monomer is not particularly limited as long as it is a monomer capable of living anion polymerization using the aforementioned polymerization initiator.

The anionic polymerizable monomer is preferably at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohol.

As the 3- to 4-membered cyclic ethers, cyclic ethers having 2 to 6 carbon atoms are preferable, and cyclic ethers having 2 to 4 carbon atoms are more preferable. Cyclic ethers may be cyclic monoethers or cyclic diethers, but cyclic monoethers are preferred. Examples of the cyclic monoether include ethylene oxide, propylene oxide, and oxetane.
As the olefins, olefins having 2 to 4 carbon atoms are preferable. Examples of olefins include ethylene, propylene, n-butene, and isobutene.

The conjugated diene compound is preferably a conjugated diene compound having 4 to 6 carbon atoms. Examples of the conjugated diene compound include 1,3-butadiene, isoprene, and 2,3-dimethyl-1,3-butadiene.

As the aromatic vinyl compound, an aromatic vinyl compound having 8 to 10 carbon atoms is preferable. Examples of the aromatic vinyl compound include styrene, p-methylstyrene, α-methylstyrene, vinylethylbenzene, and vinylxylene.

The protected vinyl alcohol is a monomer in which keto-enol tautomerism does not occur by replacing the hydrogen atom of the hydroxy group of vinyl alcohol (CH ₂ ═CH—OH) with another group. Examples of the vinyl alcohol protector include vinyl acetate and benzyl vinyl ether. When a vinyl alcohol protector is used as the anion polymerizable monomer, the main chain of the polymer is converted to polyvinyl alcohol by saponification or the like in the obtained polymer (i) or polymer (ii). be able to.

As the anion polymerizable monomer, one kind may be used alone, or two or more kinds may be used.
The anionic polymerizable monomer is preferably at least one monomer selected from 3- to 4-membered cyclic ethers and aromatic vinyl compounds, although it varies depending on the use of the polymer (ii). Ethylene oxide, propylene oxide More preferred is at least one monomer selected from oxetane, styrene, p-methylstyrene, and α-methylstyrene. In addition, it is preferable that the anionic polymerizable monomer is a 3- to 4-membered cyclic ether because polymerization proceeds rapidly.

[Method for Producing Polymer (i)]
The production method of the polymer (i) of the present invention has a pyrrole ring structure at the end of the polymer by living anion polymerization of an anionically polymerizable monomer using a polymerization initiator having a pyrrole ring structure, and A step (I) of obtaining a polymer (i) having a structural unit derived from an anionically polymerizable monomer;

In the present invention, living anionic polymerization includes not only the case where a chain group such as a vinyl group is polymerized but also the case where a cyclic monomer such as a cyclic ether is subjected to ring-opening polymerization. That is, in the present invention, living anion polymerization includes living anion ring-opening polymerization.

In step (I), the anionic polymerizable monomer may be subjected to living anion polymerization using the polymerization initiator having the pyrrole ring structure, and other conditions are not particularly limited.

Examples of the method of living anion polymerization include a method of living anion polymerization of an anion polymerizable monomer in a solvent using the polymerization initiator. The living anionic polymerization is usually carried out while stirring.

When two or more anionic polymerizable monomers are used, the monomers may be added to the reaction system simultaneously or sequentially. When the monomers are sequentially added, the polymer (i) can be obtained as a block copolymer.

As the solvent, it is preferable to use an aprotic solvent. Examples of aprotic solvents include cyclohexane, acetonitrile, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMA), N-methylpyrrolidone (NMP), tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), Examples include cyanobenzene, phenylacetonitrile, chlorobenzene, benzene, nitromethane and the like. The amount of the solvent used is usually 50 to 1000 parts by mass with respect to 100 parts by mass of the anionic polymerizable monomer.

The amount of the polymerization initiator having a pyrrole ring structure is usually 0.0001 to 0.1 mol, preferably 0.001 to 0.1 mol, per 1 mol of the anionic polymerizable monomer.

The temperature at the step (I) (polymerization temperature) is usually −100 to 100 ° C., preferably 4 to 50 ° C.
The time for performing step (I) (polymerization time) is usually 0.1 to 100 hours.

Step (I) (polymerization) may be performed under any of reduced pressure, increased pressure, and normal pressure, but is preferably performed at normal pressure from the viewpoint of manufacturing cost.
Step (I) is usually performed in an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere from the viewpoint of suppressing the occurrence of side reactions.

The manufacturing method of the polymer (i) of this invention should just have the above-mentioned process (I), and may have processes (other processes) other than process (I).
Examples of other steps include a step (α) for performing a living anion polymerization termination reaction.

In step (i), the end of the polymer is ionized to perform living anion polymerization. In the present invention, the termination reaction can be carried out using a reagent that generates electrophilic species as a polymerization terminator. The polymerization terminator may be used in combination, or two or more polymerization terminators may be used.

Examples of the polymerization terminator include water, alkyl halide (for example, iodomethane), aryl halide, p-toluenesulfonic acid ester, methanesulfonic acid ester, trifluoromethanesulfonic acid ester and the like.

In addition, when performing stop reaction with water, you may carry out by adding water to a reaction system, and after performing process (I) in inert gas atmosphere, by putting a reaction system in air | atmosphere. You may carry out by mixing in the reaction system of the water in the air which arises. In addition, when the stop reaction is carried out by adding water to the reaction system, water may be added directly to the reaction system, or a mixture of alcohol such as methanol or ethanol, ether such as diethyl ether, and water. You may add to a reaction system as a liquid.

In addition, it has the group or atom derived from the polymerization terminator used for termination | terminus reaction at the terminal of the polymer of this invention. When the anionic polymerizable monomer is a 3- to 4-membered cyclic ether, the terminal of the polymer during living anionic polymerization is —O 2 ^— . For this reason, a specific group can be introduce | transduced into the terminal of polymer (i) or polymer (ii) by selecting suitably the reagent used for termination reaction. For example, when water is used for the termination reaction, it is possible to obtain a polymer (i) or polymer (ii) having a hydroxyl group at the terminal, and when other polymerization terminators are used. It is possible to obtain a polymer (i) or a polymer (ii) having a group or atom (structure) derived from the polymerization terminator.
Examples of other steps other than the step (α) include a step of recovering the polymer (i) after performing the step (α), and other purification steps.

[Production Method of Polymer (ii)]
The method for producing the polymer (ii) of the present invention comprises the step (II) of obtaining a polymer (ii) having an amino group at the terminal by converting the pyrrole ring structure in the polymer (i) to an amino group. Have.
As process (ii), what is necessary is just to be able to convert the pyrrole ring structure in polymer (i) into an amino group.

Examples of a method for converting a pyrrole ring structure to an amino group include a method using hydroxylamine. Hydroxylamine may be used as a salt such as hydroxylamine hydrochloride.

Examples of the method using hydroxylamine include a method in which the polymer (i) is reacted in the presence of water and hydroxylamine to convert the pyrrole ring structure into an amino group. Specifically, for example, the polymer (i) is dissolved in water or a mixed solvent of water and an alcohol such as ethanol, and hydroxylamine is added to react. The reaction solution for producing the polymer (i) is added with water. And a method in which hydroxylamine is added and reacted.
In carrying out the above method, a hydroxylamine salt or an aqueous solution of hydroxylamine is usually used from the viewpoint of handleability.

When using a salt such as hydroxylamine hydrochloride, the reaction is preferably performed in the presence of a tertiary amine such as triethylamine or a base such as sodium hydroxide.
The amount of hydroxylamine used is usually 1 to 100 mol, preferably 5 to 100 mol, per 1 mol of the pyrrole ring structure of the polymer (i).

In the case where the polymerization initiator is a compound having a structure represented by the general formula (A), and the polymerization initiator is a compound having a structure represented by the general formula (B), and- O ^- when the structure having one, usually a number of moles of the polymerization initiator used in step (I), and the number of moles of the pyrrole ring structure a polymer (i) has to match.

The amount of water used is not particularly limited and is usually used in such an amount that hydroxylamine can be dissolved.
When a mixed solvent of water and alcohol is used, usually 0.1 to 10 mol of alcohol is used per 1 mol of water.
The temperature at which the step (II) is carried out is usually 4 to 100 ° C., preferably 10 to 50 ° C.

The reaction time in step (II) is usually 6 to 72 hours, more preferably 12 to 48 hours.
Step (II) may be performed under any of reduced pressure, increased pressure, and normal pressure, but is preferably performed at normal pressure from the viewpoint of manufacturing cost.
Further, although the step (II) can be performed in the air, it may be performed in an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere from the viewpoint of suppressing the occurrence of side reactions.

Moreover, it is preferable that the polymer (i) used by process (II) is a polymer obtained by the manufacturing method of polymer (i) which has the above-mentioned process (I).
That is, the production method of the polymer (ii) of the present invention has a pyrrole ring structure at the end of the polymer by living anion polymerization of an anionically polymerizable monomer using a polymerization initiator having a pyrrole ring structure. And (I) to obtain a polymer (i) having a structural unit derived from an anion polymerizable monomer, and a polymer having a pyrrole ring structure at the end of the polymer and having a structural unit derived from an anion polymerizable monomer ( It is preferable to have the process (II) which obtains the polymer (ii) which has an amino group at the terminal by converting the pyrrole ring structure in i) into an amino group.

In the production method of the polymer (ii), after performing the step (I), the step (II) may be performed as it is, and other steps such as those described above may be performed between the step (I) and the step (II). The step (α) may be included.

In addition, after performing process (I), when performing process (II) as it is, living anion polymerization termination reaction is performed with the water etc. which are used for process (II).
The manufacturing method of the polymer (ii) of this invention may have processes (other processes) other than the above-mentioned process (I), (II), ((alpha)).

Other steps include a step of recovering the polymer (ii) by dialysis, lyophilization, etc. after performing the step (II), a step of purification by extraction, reprecipitation, etc.

In the method for producing the polymer (ii) of the present invention, the steps (I) and (II) may be performed by one-pot synthesis. One-pot synthesis is a method in which raw materials are sequentially charged into a reactor without changing the reactor in the middle. In the production method of the polymer (ii), after performing the step (I), after removing the polymerization (i) by isolation or the like, the step (II) may be performed. Even if II) is carried out by one-pot synthesis, the polymer (ii) can be obtained with high efficiency.

[Polymer (ii)]
The polymer (ii) obtained by the production method of the polymer (ii) of the present invention is a polymer (ii) having an amino group at the terminal. Since the polymer (ii) is obtained by converting the pyrrole ring structure in the polymer (i) to an amino group, the polymer (ii) is a polymer having a structural unit derived from an anion polymerizable monomer as in the polymer (i). is there.

The weight average molecular weight (Mw) and molecular weight distribution (Mw / Mn) of the polymer (ii) mainly depend on the Mw and Mw / Mn of the polymer (i). The polymer (ii) preferably has a weight average molecular weight (Mw) measured under the conditions described in the examples, for example, of 100 to 1,000,000, more preferably 1,000 to 100,000. It is particularly preferably 2,000 to 40,000.

Within the above range, it is preferable from the viewpoint of applying the polymer (ii) to a living body. Further, the molecular weight distribution (Mw / Mn) determined from the weight average molecular weight and the number average molecular weight is preferably 1 to 2, more preferably 1 to 1.2.

Usually, the polymer (ii) and the polymer (i) have the same end. For example, when the anionic polymerizable monomer is a 3- to 4-membered cyclic ether and water is used as a terminator, it has a hydroxy group at the terminal.

When it is desired to introduce a group different from the polymer (i) to the terminal of the polymer (ii), the terminal of the polymerization (i) is converted into another group between the step (I) and the step (II). A process may be provided. Moreover, after obtaining polymer (ii), you may convert a terminal into another group as needed.

The polymer (ii) has an amino group at the terminal, and a functional group can be introduced at another terminal by appropriately selecting the type of anion polymerizable monomer and the polymerization terminator used for the termination reaction. . That is, a polymer having two types of functional groups can be obtained.
Polymers such as PEG having different functional groups are extremely difficult to produce by conventional production methods, and the polymer (ii) can be expected to be used in various applications.

Next, a preferred example of the present invention will be described. When ethylene oxide is used as the anionic polymerizable monomer, the compound represented by the general formula (A) is used as the polymerization initiator, and the terminal of the polymer is a hydroxy group or an alkoxy group, for example, the polymer (i ) Is represented by general formula (X), and polymer (ii) is represented by general formula (Y). In particular, the hydroxy group is highly polar and excellent in reactivity, so it can be used for various applications such as conversion to other functional groups, compounding with other materials, and use in biological applications. Highly useful. Alkoxy groups can be converted into other functional groups and combined with other materials by subsequent reactions, but alkoxy groups such as methoxy groups and ethoxy groups are extremely inactive, so construction of biointerface materials Can be used. In addition, it is possible to make the terminal of a polymer into a hydroxy group by using water or the like for the termination reaction of polymerization, and to make the terminal of the polymer an alkoxy group by using an alkyl halide or the like for the termination reaction. It is possible.

　（一般式（Ｘ）において、Ｒ¹～Ｒ⁴は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基であり、Ｒは、水素原子または炭素数１～４のアルキル基であり、ｎは、好ましくは２０～２３００である。）

(In general formula (X), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R is a hydrogen atom or 1 to 4 carbon atoms; And n is preferably 20 to 2300.)

　（一般式（Ｙ）においてＲは、水素原子または炭素数１～４のアルキル基であり、ｎは、好ましくは２０～２３００である。）

(In the general formula (Y), R is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n is preferably 20 to 2300.)

The polymers represented by the general formula (X) and the general formula (Y) are polymers obtained when ethylene oxide is used as the anionic polymerizable monomer, and the anionic polymerizable monomer is converted into styrene. By changing, it is possible to obtain the polymer represented by the general formula (x) as the polymer (i) and the polymer represented by the general formula (y) as the polymer (ii).

　（一般式（ｘ）において、Ｒ¹～Ｒ⁴は、それぞれ同一でも異なっていてもよく、水素原子、または炭素数１～４のアルキル基であり、Ｒは、水素原子または炭素数１～４のアルキル基であり、ｎは、好ましくは２０～２３００である。）

(In the general formula (x), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R is a hydrogen atom or 1 to 4 carbon atoms. And n is preferably 20 to 2300.)

　（一般式（ｙ）においてＲは、水素原子または炭素数１～４のアルキル基であり、ｎは、好ましくは２０～２３００である。）

(In general formula (y), R is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n is preferably 20 to 2300.)

In general formula (X), general formula (Y), general formula (x), and general formula (y), R is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n is more preferably 40. ~ 910.

The use of the polymer (ii) varies depending on the type of anion polymerizable monomer and is not particularly limited. For example, when the anion polymerizable monomer is ethylene oxide, the polymer (ii) Application is possible. As specific examples, it can be suitably used for implant material coating, cell sheet preparation plate, drug delivery system (DDS) construction material and the like. As another example, when the anionic polymerizable monomer is styrene, the polymer (ii) can be used for various applications in which polystyrene is used, and various molding methods such as injection molding, blow molding, and the like. Molding, vacuum molding, extrusion molding, and foam molding can be used for various purposes.

EXAMPLES Next, although an Example is shown and this invention is demonstrated further in detail, this invention is not limited by these.
[material]
2,5-dimethylpyrrole (DMP) and triethylamine purchased from Wako Pure Chemical Industries, Ltd. were used after being distilled in the presence of calcium hydride.
The calcium hydride used was purchased from Wako Pure Chemical Industries.
Metal sodium purchased from Nacalai Tesque was used.
The hydroxyamine hydrochloride used was purchased from Wako Pure Chemical Industries.

Ethylene oxide was purchased from 3M and distilled in the presence of calcium hydride.
Tetrahydrofuran (THF) was purchased from Wako Pure Chemical Industries and distilled in the presence of sodium.

The potassium naphthalene solution was prepared by dissolving a recrystallized naphthalene purchased from Sigma-Aldrich in THF and adding potassium.
Diethyl ether was purchased from Showa Ether and used as it was.

[Example 1]
Synthesis of amine-terminated polyethylene glycol Amine-terminated polyethylene glycol was synthesized according to the following scheme (S1).

<Production of dimethylpyrrole-terminated polyethylene glycol (DMP-PEG)>
Under an argon atmosphere, DMP (171 μL, 1.67 mmol) was dissolved in 25 mL of THF, 5.6 mL of a 0.3 mol / L potassium naphthalene solution was added, and the mixture was stirred for 5 minutes. Ethylene oxide (4.5 mL, 90.67 mmol) was added thereto, and the mixture was stirred at 20 ° C. for 3 days.

After stirring for 3 days, the reaction solution was added to 200 mL of diethyl ether to precipitate the polymer. The argon atmosphere was maintained until 3 days of stirring were completed.
The obtained polymer was analyzed as described below, and it was confirmed that dimethylpyrrole-terminated polyethylene glycol (DMP-PEG) was obtained.

The obtained polymer was SEC (size exclusion chromatography) measurement (eluent: flow rate 0.8 mg / mL, concentration 10 mM) by GPC TOSOH HLC 8220 system (Tosoh Corporation) equipped with G4000HHR and G3000HHR as columns. N, N-dimethylformamide dissolved in LiCl), ¹ H-NMR measurement (400 MHz) by JEOL ECS 400 (JEOL Ltd.), and MALDI-TOF MS (matrix-assisted laser by JMS-S3000 (JEOL Ltd.)) Desorption ionization time-of-flight mass spectrometer) analysis (1,8,9-trihydroxyanthracene as a matrix and sodium trifluoroacetate as an ionizing agent) was used for analysis.

From the SEC measurement, it was found that the polymerization of ethylene oxide using DMP as an initiator proceeded well, with Mn of 2,856, Mw of 3,118, and molecular weight distribution Mw / Mn of 1.092 (see FIG. 1).

If dimethylpyrrole-terminated polyethylene glycol (DMP-PEG) proceeds according to the reaction scheme, a sodium-added ion of DMP-PEG-H (in MALDI-TOF MS measurement using sodium trifluoroacetate as an ion additive ( Mass value = 22.99 + 94.07 + 44.03 × degree of polymerization + 1.01) will be detected. When the MALDI-TOF MS measurement was actually performed on the obtained polymer, the main molecular weight spectrum coincided with that of the sodium added ion of DMP-PEG-H, and dimethylpyrrole-terminated polyethylene glycol (DMP-PEG) was polymerized. (FIG. 2).

^{From the 1} H-NMR measurement, it was found that the introduction of DMP was almost quantitative (FIG. 3), and a method for producing a novel compound, PEG terminated with DMP, was established.
In this production method, it is considered that water contained in diethyl ether or water mixed in the reaction system from the atmosphere after eliminating the argon atmosphere acted as a polymerization terminator.

<Production of amino group-terminated polyethylene glycol (NH ₂ -PEG)>
The pyrrole ring structure (dimethylpyrrole end) of the dimethylpyrrole-terminated polyethylene glycol (DMP-PEG) was converted to an amino group by the following method.

DMP-PEG (300 mg, about 0.1 mmol) was dissolved in 2.4 mL of ethanol and 0.6 mL of water, 350 μL of triethylamine and hydroxyamine hydrochloride (350 mg, 5 mmol) were added, and the mixture was stirred at 95 ° C. for 10 hours. .

Thereafter, the reaction solution was dialyzed and freeze-dried to recover the polymer.
The obtained polymer was analyzed as described below, and it was confirmed that amine-terminated polyethylene glycol (NH ₂ -PEG) was obtained.

The obtained polymer was measured by MALDI-TOF MS by JMS-S3000 (JEOL Ltd.) (1,8,9-trihydroxyanthracene as a matrix, sodium trifluoroacetate as an ionizing agent), and TOSOH TSKgel SP- as a column. Analysis was performed by ion exchange chromatography (eluent: flow rate 0.5 mg / mL, 1 mM phosphate buffer (pH 7.4)) using HPLC system (JASCO Corporation) equipped with 5PW (Tosoh Corporation).

When the obtained polymer was measured by MALDI-TOF MS, its mass spectrum was consistent with the sodium-added ion of NH ₂ -PEG-H (mass value = 29.99 + 16.02 + 44.03 × polymerization degree + 1.01) ( FIG. 4). From this result, it was found that the pyrrole ring structure (dimethylpyrrole end) of DMP-PEG was well converted to amine.

Further, GPC measurement using an ion exchange column revealed that the terminal amine introduction rate was 89% (FIG. 5).
That is, it was shown that the amine terminal can be introduced into PEG almost quantitatively by the production method of the present invention.

[Example 2]
One-pot synthesis of amine-terminated polyethylene glycol Under an argon atmosphere, DMP (103 μL, 1 mmol) was dissolved in 60 mL of THF, and 3.3 mL of a 0.3 mol / L potassium naphthalene solution was added and stirred for 5 minutes.

Ethylene oxide (13.5 mL, 272 mmol) was added thereto, and the mixture was stirred at 25 ° C. for 3 days. The argon atmosphere was maintained until 3 days of stirring were completed.
15 mL of water and hydroxyamine hydrochloride (4.65 g, 67.5 mmol) were added to the reaction solution, and the mixture was stirred at 50 ° C. for 24 hours.

Thereafter, the reaction solution was dialyzed and freeze-dried to recover the polymer.
The obtained polymer was analyzed as described below, and it was confirmed that amine-terminated polyethylene glycol (NH ₂ -PEG) was obtained.

The obtained polymer was ion-exchange chromatography (eluent: flow rate 0.5 mg / mL, 1 mM phosphate buffer (pH 7.7)) equipped with TOSOH TSKgel SP-5PW (Tosoh Corporation) and HPLC system (JASCO Corporation). 4)).

GPC measurement using an ion exchange column revealed that the terminal amine introduction rate was 90% (FIG. 6). That is, the production method of the present invention can produce DMP-PEG and NH ₂ -PEG by converting the pyrrole ring structure of DMP-PEG into an amino group in one pot.

Claims (15)

Polymer (i) having a pyrrole ring structure at the end of the polymer and having a structural unit derived from an anionic polymerizable monomer. The polymer (i) according to claim 1, wherein the pyrrole ring structure is a structure represented by the following general formula (α).

(In the general formula (α), R ^A to R ^D may be the same or different and are a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.) 3. The anionic polymerizable monomer is at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohols. (I). The polymer (i) according to claim 1 or 2, wherein the anionic polymerizable monomer is a cyclic ether having 3 to 4 members. By using a polymerization initiator having a pyrrole ring structure, living anion polymerization of the anionic polymerizable monomer,
The manufacturing method of polymer (i) which has the process (I) which has a pyrrole ring structure at the terminal of a polymer, and obtains the polymer (i) which has a structural unit derived from an anion polymerizable monomer. The polymerization initiator is at least one compound selected from a compound having a structure represented by the following general formula (A) and a compound having a structure represented by the general formula (B). The manufacturing method of polymer (i).

(In the general formula (A), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

(In the general formula (B), R ⁵ to R ⁸ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
R ⁹ to R ¹¹ may be the same or different and each represents a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, a hydroxyalkyl group having 1 to 30 carbon atoms, —O ⁻ , or a hydrogen atom. -O ^- in a substituted alkyl group having 1 to 30 carbon atoms,
At least one of R ⁹ to R ¹¹ is —O ⁻ or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— . ) 7. The anionic polymerizable monomer is at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohols. A process for producing the polymer (i) described in 1. The method for producing a polymer (i) according to claim 5 or 6, wherein the anionic polymerizable monomer is a cyclic ether having 3 to 4 members. By converting the pyrrole ring structure in the polymer (i) having a pyrrole ring structure at the terminal of the polymer and having a structural unit derived from an anion polymerizable monomer into an amino group,
The manufacturing method of polymer (ii) which has process (II) which obtains polymer (ii) which has an amino group at the terminal. By using a polymerization initiator having a pyrrole ring structure, living anion polymerization of the anionic polymerizable monomer,
Step (I) for obtaining a polymer (i) having a pyrrole ring structure at the terminal of the polymer and having a structural unit derived from an anion polymerizable monomer, and converting the pyrrole ring structure in the polymer (i) to an amino group By converting
The manufacturing method of polymer (ii) which has process (II) which obtains polymer (ii) which has an amino group at the terminal. 11. The polymerization initiator according to claim 10, wherein the polymerization initiator is at least one compound selected from a compound having a structure represented by the following general formula (A) and a compound having a structure represented by the general formula (B). The manufacturing method of polymer (ii).

(In the general formula (A), R ¹ to R ⁴ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

(In the general formula (B), R ⁵ to R ⁸ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
R ⁹ to R ¹¹ may be the same or different and each represents a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, a hydroxy group, a hydroxyalkyl group having 1 to 30 carbon atoms, —O ⁻ , or a hydrogen atom. -O ^- in a substituted alkyl group having 1 to 30 carbon atoms,
At least one of R ⁹ to R ¹¹ is —O ⁻ or an alkyl group having 1 to 30 carbon atoms in which a hydrogen atom is substituted with —O 2 ^— . ) The anionic polymerizable monomer is at least one monomer selected from 3- to 4-membered cyclic ethers, olefins, conjugated diene compounds, aromatic vinyl compounds, and protected vinyl alcohols. The manufacturing method of the polymer (ii) as described in any one of these. The method for producing a polymer (ii) according to any one of claims 9 to 11, wherein the anion polymerizable monomer is a cyclic ether having a 3- to 4-membered ring. The method for producing a polymer (ii) according to any one of claims 9 to 13, wherein hydroxylamine is used when the pyrrole ring structure is converted to an amino group. The method for producing a polymer (ii) according to any one of claims 10 to 14, wherein the steps (I) and (II) are carried out by one-pot synthesis.

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