KR101629763B1 - Process for preparation of heterobifunctional poly(ethylene oxide)s using a phthalimide-based functional initiator - Google Patents

Abstract

The present invention provides a process for producing polyethylene oxide in which a functional group is introduced at both chain terminals using a phthalimide functional initiator. According to the production method of the present invention, it is possible to produce polyethylene oxide having amino groups at one end of the chain and various different functional groups at the other end of the chain using a phthalimide functional initiator at a high yield while controlling the molecular weight.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for preparing a poly (ethylene oxide) heteropolifunctional poly (ethylene oxide) using a phthalimide functional initiator,

TECHNICAL FIELD The present invention relates to a process for producing polyethylene oxide having a functional group introduced at both chain terminals using a phthalimide functional initiator. More specifically, the present invention relates to a method for producing polyethylene oxide having different functional groups introduced into both chain terminals at a high yield while controlling molecular weight.

Methods of end-functionalization of polyethylene glycol by various conventional methods and their application fields are well described in the literature [JM Harris, RB Chess, Nature Reviews Drug Discovery, 2003, Vol. 2, pages 214-221 and S Zalipsky, Bioconjugate Chemistry, 1995, Vol. 6, pages 150-165]. In this connection, the synthesis method of polyethylene oxide or polyethylene glycol produced by anionic polymerization is well described in various documents [S. Slomkowski, A. Duda, "Anionic ring-opening polymerization", in Ring-Opening Polymerization: Mechanism, Catalysis, Structure, Utility; Edited by DJ Brunelle, 1993, Chapter 3, pp. 87-128 and RP Quirk, J. Kim, "Macromonomers and Macromonomers", in Ring-Opening Polymerization: Mechanism, Catalysis, Structure, Utility; Editied by DJ Brunelle, 1993, Chapter 9, pages 263-293].

In particular, living polymerization of ethylene oxide with alkali metal initiators combined with various functional groups and their application fields are well documented [W. Li, P. Zhan, ED Clercq, H. Lou, X. Liu, Progress in Polymer Science, 2013, Vol. 40, pages 421-444 and MA Tasdelen, MU Kahveci, Y. Yagci, Progress in Polymer Science, 2011 38, pages 455-567].

Depending on the type of alkali metal of the alkoxide-based initiator used for the production of polyethylene oxide by living polymerization, the control of the reaction conditions is very complicated and difficult to control the molecular weight distribution and molecular weight, and it is very difficult to introduce functional groups at the chain terminals. From this viewpoint, the living polymerization method of ethylene oxide using lithium and potassium alkoxides as initiators is well described in the patent literature (Korean Patent No. 10-122055 and No. 10-1336692).

In addition, polyethylene oxide having an anhydride group is synthesized by a method of functionalizing polyethylene oxide, and an anticancer agent such as folic acid, sulfonamide drug, adenosine, and doxorubicin is added to the purified polyethylene oxide in methanol or aqueous solution To prepare a polyethylene oxide having a functional group and a carboxyl group possessed by the drug itself is well known in the already filed patent [J. Kim, meat. al., WO 2007/007976 A1, Jan. 19, 2007].

However, the conventional double-end chain functionalized polyethylene oxide production process is a process of protecting one end of a diol-type polyethylene glycol (poly (ethylene glycol)) and functionalizing the other end, And there are limitations in its usefulness.

Korean Patent No. 10-122055 Korean Patent No. 10-1336692 WO 2007/007976 A1

DISCLOSURE Technical Problem The present invention has been made to solve the above problems, and an object of the present invention is to provide a method for producing polyethylene oxide having different functional groups at both chain terminals at a high yield.

Another object of the present invention is to provide a method for producing polyethylene oxide having different functional groups introduced into both chain terminals while easily controlling the molecular weight.

The present invention relates to a process for producing polyethyleneimine, which comprises: (a) obtaining polyethyleneimine in which one chain terminal is phthalimidated by living anion polymerization of ethylene oxide with a phthalimide functional initiator;

(b) functionalizing or block copolymerizing the other chain ends of the phthalimidated polyethylene oxide to obtain a chain-terminal functionalized or block copolymerized polyethylene oxide; And

(c) a step of deimidating the chain-terminal functionalized or block-copolymerized polyethylene oxide. The present invention also relates to a method for producing polyethylene oxide in which two functional groups are introduced at both chain terminals.

The polyethylene oxide having a different functional group introduced into both of the chain terminals has an amino group at one chain terminal and hydroxyl (-OH), tosyl, methylsulfonyl, sulfonic acid (-SO ₃ H), thiol (-SH), anhydride (-COOCO-), halide, vinyl, azide, ethyl xanthogenate, COOH) and hydrazide. ≪ / RTI >

Hereinafter, the production method of the present invention will be described step by step.

In the step (a), polyethylene oxide in which one chain terminal is phthalimidated is obtained by living anion polymerization of ethylene oxide using a phthalimide functional initiator.

In the step (a), as the phthalimide functional initiator, alkali metal phthalimide can be used, and potassium phthalimide is preferably used.

In the step (a), the molecular weight of the polyethylene oxide can be controlled by living anionic polymerization, and the method for preparing polyethylene oxide by living anion polymerization and the method for controlling the molecular weight are described in detail in the literature [Kim, J .; Choi, S .; Kim, KM; Go, DH; Jeon, HJ; Lee, JY; Park, HS; Lee, CH; Park, HM Macromolecular Research, 2007, Vol. 15, pp. 337-342].

Examples of the reaction solvent include a polar solvent such as tetrahydrofuran (THF), dimethylsulfoxide (DMSO) and dimethylformamide (DMF), or a mixed solution thereof (polarity / polarity = 90/10 to 10/90, Volume ratio) can be used. The polymerization temperature can be controlled in the range of 30 ^° C to 90 ^° C.

The molecular weight of the phthalimidated polyethylene oxide is preferably 500 to 100,000, more preferably 1,000 to 20,000.

One of the chain terminal phthalimidated polyethylene oxides synthesized in the step (a) may be a compound of the following formula (1).

[Chemical Formula 1]

In this formula,

Mt is an alkali metal, preferably potassium or sodium,

and n is an integer of 10 to 500.

In the step (b), the other chain ends of the phthalimidated polyethylene oxide are functionalized or block copolymerized to obtain a chain-terminal functionalized or block-copolymerized polyethylene oxide.

The chain-terminal functionalized polyethylene oxide may be a compound of the following formula (2) or (3).

(2)

(3)

In this formula,

R ₁ is selected from the group consisting of hydrogen, tosyl, methylsulfonyl, trimellitic anhydride, bromopropionyl, bromoisobutyryl, propanesulfonic acid, methacryloyl, or O-ethylxanthropionyl,

R ₂ is thiol, thioacetate, amino, or azide,

and n is an integer of 10 to 500.

Functionalization of other chain ends of the phthalimidated polyethylene oxide can be easily performed according to methods known in the art. Specifically, the phthalimidated polyethylene oxide is dissolved in a solvent such as toluene sulfonyl chloride, methanesulfonyl chloride, methacryloyl chloride, 1,3-propane sultone, 2-bromo The reaction is carried out by reacting with 2-bromoisobutyryl bromide, trimellitic anhydride chloride, 2-bromopropionyl bromide or the like, or by reacting the chain-terminal functionalized polyethylene produced by the above- The functional group of the oxide may be further subjected to a conversion reaction to introduce various functional groups. The conversion reaction is, for example, the phthalimide stylized α produced polyethylene oxide is reacted with toluenesulfonyl chloride-phthalimido even-ω-tosylate PEO (α -phthalimido- ω -tosylate PEO) of sodium dihydro- Sodium thiosulfate (NaSH), potassium thioacetate, sodium amide (NaNH ₂ ), sodium azide (NaN ₃ ) and the like (see FIG. 1).

The block copolymerized polyethylene oxide may be a compound represented by the following formula (4).

[Chemical Formula 4]

In this formula,

n is an integer of 10 to 500,

m is an integer of 1 to 10;

The phthalimide block copolymer of polyethylene oxide has a mid-N for polyethylene oxide said phthalimide screen may be performed by block copolymerization by phenyl maleimide (N -pheneylmaleimide) a continuous monomer addition method (sequential monomer addition) (See Fig. 2).

In the step (c), the polyethylene oxide having the functional groups introduced at both chain ends is prepared by subjecting the chain-terminal functionalized or block-copolymerized polyethylene oxide to a deimidation reaction.

The deimidation of the chain-terminal functionalized polyethylene oxide can be carried out using hydrazine and an acid. It is preferable to use hydrazine monohydrate as the hydrazine and hydrochloric acid as the acid.

The polyethylene oxide having different functional groups introduced into both chain terminals prepared from the deimidation reaction of the chain-terminal-functionalized polyethylene oxide may be a compound represented by the following formula (5) or (6).

[Chemical Formula 5]

[Chemical Formula 6]

In this formula,

R ₁ is selected from the group consisting of hydrogen, tosyl, methylsulfonyl, trimellitic anhydride, bromopropionyl, bromoisobutyryl, propanesulfonic acid, methacryloyl, or O-ethylxanthropionyl,

R ₂ is thiol, thioacetate, or azide,

and n is an integer of 10 to 500.

The de-imidation reaction of the block copolymerized polyethylene oxide can be carried out using hydrazine and an acid or a base. As the hydrazine, it is preferable to use hydrazine monohydrate, hydrochloric acid as the acid, and sodium hydroxide as the base.

The polyethylene oxide having different functional groups introduced into both chain ends prepared from the deimidation reaction of the block copolymerized polyethylene oxide may be a compound represented by the following general formula (7).

(7)

In this formula,

R < ₃ > is a carboxylic acid or hydrazide,

n is an integer of 10 to 500,

m is an integer of 1 to 10;

When the de-imidation reaction of the block copolymerized polyethylene oxide is carried out using hydrazine and a base, a compound wherein R ₃ is a carboxylic acid is prepared. When hydrazine and an acid are used, R ₃ is hydrazide (See Fig. 2).

According to the production method of the present invention, it is possible to produce polyethylene oxide having amino groups at one end of the chain and various different functional groups at the other end of the chain using a phthalimide functional initiator at a high yield while controlling the molecular weight. Therefore, it is possible to mass-produce polyethylene oxide having a variety of different functional groups introduced at both chain ends, which can be usefully used for the delivery system of anticancer drugs, at low cost.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a manufacturing process diagram according to one embodiment of polyethylene oxide having various kinds of functional groups introduced at both chain ends of the present invention. FIG.
2 is a manufacturing process diagram according to another embodiment of the polyethylene oxide in which various kinds of functional groups are introduced at both chain ends of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are for illustrative purpose only and that the scope of the present invention is not limited to these embodiments.

≪ Example 1 >

Ampoules of various reactants were adhered with a hand torch in a 1 L round bottom flask under high vacuum and then attached to a vacuum line to completely remove air. 0.925 g of potassium phthalimide (FW = 185.23 g) was injected into the reactor under an argon stream. The valve of the reactor was closed and the argon gas was completely removed using a vacuum pump. Again, 200 mL of purified dimethylsulfoxide (DMSO) was distilled and injected into the reactor. The temperature of the reactor was gradually raised to room temperature, completely dissolved in DMSO in the reactor, and changed to a solution containing an initiator. Again, 25 mL (22.1 g) of ethylene oxide (EO) purified at -78 ^° C using a dry ice / propanol bath was injected into the reactor via distillation in a vacuum line. Again, the reactor was heated to 50 ^o C using a water bath and allowed to react for 24 hours with stirring. After completion of the reaction, the reaction solution was lowered to 25 ^° C, the solvent was partially removed using Rotavap ^™ , and the remaining solution was precipitated in an excess of diethyl ether to obtain polyethyleneimine (poly (ethylene oxide: PEO). The molecular weight of the obtained polymer was 4,200 g / mol. The conversion of EO to the polymer was 95 mol%.

≪ Example 2 >

Toluenesulfonyl chloride (2.12 g; FW = 190.65) was added to a 100 mL aliquot ([POK] = 2.22 mmol) of the polymeric alkoxide solution obtained in Example 1 in 20 mL of tetra Dissolved in hydrofluoric acid (THF), introduced into the reactor using a breakseal technique, and allowed to react for 24 hours while stirring at room temperature. After the reaction was completed, the solvent was partially removed using Rotavap ^™ , and the remaining solution was precipitated in diethyl ether to obtain a powder. The polymer thus prepared had a molecular weight of 4,400 g / mol by gel permeation chromatography (GPC) and a yield of chain end tosylation by ¹ H NMR spectroscopy was 97 mol% or more.

≪ Example 3 >

Methanesulfonyl chloride (13 mL; FW = 114.55) was added to 100 mL ([POK] = 0.0225 mol) of the polymer alkoxide solution obtained in Example 1 and reacted for 24 hours while stirring at room temperature. After the reaction was completed, the solvent was partially removed using Rotavap ^™ , and the remaining solution was precipitated in diethyl ether to obtain a powder. The polymer thus prepared had a molecular weight of 4,400 g / mol by GPC, and a yield of chain end methanesulfonation by ¹ H NMR spectroscopy was 96 mol% or more.

<Example 4>

Methacryloyl chloride (0.0225 mol) was added to 100 mL of the polymer alkoxide solution obtained in Example 1 and reacted at room temperature for 24 hours to synthesize a phthalimide PEO macromonomer. Since the solution thus synthesized contained DMSO, it was precipitated in diethyl ether and then recrystallized from ethanol to obtain a polymer. The molecular weight of the polymer thus prepared was 4,300 g / mol, and the yield of methacryloylation at the chain terminal by ¹ H NMR spectroscopy was 98 mol% or more.

&Lt; Example 5 >

Propane sultone / THF solution ([POK] / [Sultone] = 1/5, mol / mol) was added to 100 mL of the polymer alkoxide solution obtained in the same manner as in Example 1 so that the molecular weight was 4,500 g / Was added and reacted at room temperature for 24 hours to synthesize ω - sulfonated PEO. A portion of the solvent in the solution was distilled and then precipitated in diethyl ether to remove the solvent. It was dissolved again in THF and re-precipitated in diethyl ether to obtain a powder. The molecular weight of the polymer thus prepared was 4,700 g / mol, and the yield of chain end sulfonation was 99 mol% or more.

&Lt; Example 6 >

2-bromoisobutyryl bromide ([POK] / [R-Br] = 1) was added to 100 mL of the polymer alkoxide solution obtained in the same manner as in Example 1 so that the molecular weight was 4,500 g / mol. / 5, mol / mol) was introduced into the reactor and reacted for 24 hours under high vacuum at room temperature to introduce a bromine group at the terminal of the chain. This was precipitated in dimethyl ether, recovered, redissolved in THF and recrystallized in ethanol to obtain a powder. The molecular weight of the prepared chain endbrominated polyethylene oxide was 4,700 g / mol, and the polymer was again obtained by re-precipitation in diethyl ether. The molecular weight of the prepared polymer was 4,700 g / mol, and the yield of chain terminal bromination by ¹ H NMR spectral analysis was 98 mol% or more.

&Lt; Example 7 >

Trimellitic anhydride chloride (98%) was refined in a high vacuum to a polymer alkoxide solution ([POK] = 0.05 mol) obtained in the same manner as in Example 1 so that the molecular weight was 4,600 g / mol 0.5 mol was introduced into the ampoule and 60 mL of THF was distilled and attached to the reactor and introduced into the reactor using the break seal technique. The reactants were reacted at 5 ^° C for 1 hour and at 35 ^° C for 15 hours, precipitated in dimethyl ether to remove the solvent, and again the precipitate was dissolved in THF and re-dissolved in diethyl ether to obtain a chain end anhydride polyethylene oxide ( ω- anhydride poly (ethylene oxide)). The yield of chain anhydride was 98 mol% based on the initially used polymer solution concentration and the molecular weight was 4,800 g / mol.

&Lt; Example 8 >

Bromo group was introduced at the end of the chain using 2-bromopropionyl bromide in the same manner as in Example 6. The molecular weight was 4,700 g / mol and the reaction yield was more than 98 mol% based on the PEO used.

&Lt; Example 9 >

Example 2 obtained from α - phthalimido also - ω - tosylate PEO (α -phthalimido- ω -tosylate PEO) (M n = 4,400 g / mol, 1 g) and sodium hydro sulfide hydrate (NaSH; FW = 56.06) were reacted in 50 mL of THF or 50 mL of DMSO at room temperature for about 24 hours, respectively. They were redeposited again in diethyl ether to obtain a solid which was then dissolved in THF and reprecipitated in diethyl ether to give a yellow powder (Phthalimido-PEO-SH). The molecular weight was 4,400 g / mol, and the reaction yield was 92 mol% or more based on PEO by ¹ H NMR spectrum analysis.

&Lt; Example 10 >

One embodiment α obtained in Example 2-phthalimido even-ω-tosylate PEO (α -phthalimido- ω -tosylate PEO) (M n = 4,400 g / mol, 1 g) and potassium acetate Bang (potassium thioacetate; FW = 114.21 ) Were reacted in 50 mL of THF or 50 mL of DMSO at room temperature for about 24 hours, respectively. They were redeposited again in diethyl ether to obtain a solid which was then dissolved in THF and re-precipitated in diethyl ether to give a yellow powder (Phthalimido-PEO-SCOCH ₃ ). The molecular weight was 4,400 g / mol, and the reaction yield was 97 mol% or more based on the PEO by ¹ H NMR spectrum analysis.

&Lt; Example 11 >

Example 2 α obtained in-phthalimido even-ω-tosylate PEO (α -phthalimido- ω -tosylate PEO) (M n = 4,400 g / mol, 1 g) and sodium amide (NaNH _2; FW = 39.01, 50 wt% in toluene) were reacted in 50 mL of THF or 50 mL of DMSO at room temperature for about 24 hours. They were redeposited again in diethyl ether to obtain a solid which was then dissolved in THF and re-precipitated in diethyl ether to give a yellow powder (Phthalimido-PEO-NH ₂ ). The molecular weight was 4,400 g / mol and the reaction yields were 87 mol% and 95 mol%, respectively, based on the PEO by ¹ H NMR spectroscopy.

&Lt; Example 12 >

Example 2 α obtained in-phthalimido even-ω-tosylate PEO (α -phthalimido- ω -tosylate PEO) (M n = 4,400 g / mol, 1 g) and sodium azide (NaN _3; FW = 65.01 ) Were reacted in 50 mL of THF or 50 mL of DMSO at room temperature for about 24 hours, respectively. They were redeposited again in diethyl ether to obtain a solid which was then dissolved in THF and reprecipitated in diethyl ether to give a pale yellow powder (Phthalimido-PEO-N ₃ ). The molecular weight was 4,400 g / mol, and the reaction yields were 90 mol% and 95 mol% or more, respectively, based on the PEO by ¹ H NMR spectroscopy.

&Lt; Example 13 >

100 mL ([POK] = 0.0225 mol) of the polymer alkoxide solution obtained in Example 1 was precipitated in an excessive amount of diethyl ether to obtain a powder. Using a 250 mL three-neck round flask reactor, 2 g of powder (M _n = 4,200 g / moL) was dissolved in 100 mL of N, N- dimethylacetamide. The reaction temperature was raised to 70 ^° C. and 0.1 mol hydrochloric acid (HCl) and hydrazine hydrate (H ₂ N- NH ₂ .H ₂ O; FW = 50.06) was dissolved in 20 mL of DMF, and the mixture was reacted for 24 hours. After completion of the reaction, a part of the solvent was removed using Rotavap ^TM , and this was precipitated in an excess amount of dimethyl ether to obtain a white powder. The polymer thus obtained had a molecular weight of 4,100 g / mol determined by GPC, and ¹ H NMR spectroscopy analysis (PE ₂ O-PEO-OH) was carried out at the chain terminal with amine groups on one side and hydroxyl groups on the other side. . Both functionalization yields were 100 mol%.

&Lt; Example 14 >

Example 9 The polymer (Phthalimido-PEO-SH; M n = 4,400 g / moL) obtained from 2 g (0.0455 mmol) was reacted in the same manner as in the embodiment example 13. After completion of the reaction, a part of the solvent was removed using Rotavap ^TM , which was precipitated in an excessive amount of dimethyl ether to obtain a pale yellow powder. The polymer thus obtained had a molecular weight of 4,300 g / mol by GPC, and ¹ H-NMR spectroscopy analysis revealed that the chain terminal was PEO having an amine group on one side and a polyol on the other side (H ₂ N-PEO-SH). Both functionalization yields were 100 mol% for the amine groups and 92 mol% for the cholesteric groups.

&Lt; Example 15 >

Example 10 A powder of yellow obtained in _{(Phthalimido-PEO-SCOCH 3;} M n = 4,400 g / moL) 2 g (0.0455 mmol) of using a three-necked round flask reactor of 250 mL 100 mL under a stream of argon-dimethyl acetamide ( N, N- dimethylacetamide). The reaction temperature was raised to 70 ^° C, and 0.15 g (2.2 mmol) of sodium ethoxide (FW = 68.05) was injected into the reactor and reacted for 24 hours. The reaction was terminated, the solvent was partially removed and the residue was precipitated in dimethyl ether to give a light purple powder. 1.5 g of the powder thus obtained was deimidated in the same manner as in Example 13 to obtain a pale yellow powder. The molecular weight by GPC was 4,200 g / mol, and ¹ H NMR spectroscopy gave PEO (H ₂ N-PEO-SH) with chain ends with an amine group on one side and a polyol on the other side. Both functionalization yields were 100 mol% for amine groups and 96 mol% or more for chiolated groups.

&Lt; Example 16 >

Example powders _{(PEO-Br; M n =} 4,700 g / moL) having bromine in the chain ends obtained in 6 2 g was dissolved in 100 mL THF in a flask three-necked 250 mL round in a nitrogen atmosphere, 2.1 × 10 ^{- 3} O molar-ethyl xanthic acid potassium salt (O -ethylxanthic acid, potassium salt) (potassium ethyl xanthogenate; FW = 160.30) and was 24 hours at room temperature. After completion of the reaction, the reaction product was precipitated in dimethyl ether and recovered. Then, the product was redissolved in THF, and the polymer was again obtained by re-precipitation in diethyl ether. The molecular weight of the synthesized polymer was 4,800 g / mol, and the yield of the chain terminal functionalization by ¹ H NMR spectral analysis was 98 mol% (RAFT material). 1.5 g of these were injected into the reactor with 0.086 g (2.3 mmol) of sodium hydride boron (NaBH ₄ ; FW = 37.83) in 100 mL DMF and the reaction was reduced at 35 ^° C. This was precipitated again in an excess amount of dimethyl ether to obtain a white powder. 1 g of the powder was deimidated in the same manner as in Example 13 to finally obtain 0.95 g of a pale yellow powder. The molecular weight by GPC was 4,600 g / mol. ¹ H NMR spectroscopy gave PEO (H ₂ N-PEO-SH) chain ends with amine groups on one side and cholate on the other side. Both functionalization yields were 100 mole% for amine groups and 97 mole% or more for polyol.

&Lt; Example 17 >

Example 12 A powder obtained in pale yellow _{(Phthalimido-PEO-N 3;} M n = 4,400 g / mol) 1 g for example by de-imide screen 13 in the same manner to give a light yellow powder, 0.85 g. The molecular weight by GPC was 4,200 g / mol, and ¹ H NMR spectrum analysis gave PEO (H ₂ N-PEO-N ₃ ) having chain ends with an amine group on one side and an azide group on the other side. Both functionalization yields were 100 mol% for amine groups and 95 mol% for azide groups.

&Lt; Example 18 >

Example 1 A polymeric alkoxide solution 100 mL aliquot (aliquot) obtained in ([POK] = 2.22 mmol) in N - phenylmaleimide (N -pheneylmaleimide) (FW = 173.17 ) was added to a high vacuum 1.153 g (6.66 mmol) The block copolymerization was carried out at 30 ^° C for 24 hours. 10 g of a pink powder was obtained (Phthalimido-PEO- b- Poly ( N- phenylmaleimide)). The molecular weight by GPC analysis was 4,800 g / mol, and ¹ H NMR spectrum analysis showed that a block copolymer having a chain terminal with phthalimide group on one side and N - phenyl maleimide block (~3 units) on the other side was prepared .

&Lt; Example 19 >

2 g of the block copolymer obtained in Example 18 was treated in the same manner as in Example 13 with 0.12 g of 0.1 mol hydrochloric acid (HCl) and hydrazine hydrate (H ₂ N-NH ₂ .H ₂ O; FW = 50.06) And the mixture was reacted for 24 hours to be deimidated. A mixed solution of 2 g / L LiNO ₃ dissolved in THF / DMF (90/10, vol / vol) as a solvent for GPC analysis was used. The molecular weight was 4,400 g / mol and analyzed by ¹ H NMR spectroscopy (-NH-NH ₂ ) (~ 6 units) was prepared on one side and on the other side by an amine group on the other side.

&Lt; Example 20 >

2 g of the block copolymer obtained in Example 18 was dissolved in 20 mL of 0.12 g of 0.1 molar sodium hydroxide (NaOH) and hydrazine hydrate (H ₂ N-NH ₂ .H ₂ O; FW = 50.06) Dissolved in DMF, injected into the reactor, and allowed to react for 24 hours for deimidation. A mixed solution of 2 g / L LiNO ₃ dissolved in THF / DMF (90/10, vol / vol) as a solvent for GPC analysis was used. The molecular weight was 4,400 g / mol and analyzed by ¹ H NMR spectroscopy (- COOH) (~ 6 units) was produced on one side and on the other side with an amine group on the other side.

Claims (10)

(a) obtaining polyethyleneimine in which one chain terminal is phthalimidated by living anion polymerization of ethylene oxide with potassium phthalimide;
(b) functionalizing or block copolymerizing the other chain ends of the phthalimidated polyethylene oxide to obtain a chain-terminal functionalized or block copolymerized polyethylene oxide; And
(c) a step of deimidating the chain-terminal-functionalized or block-copolymerized polyethylene oxide, wherein the functional groups are introduced at both terminal ends of the chain. The polyethylene oxide according to claim 1, wherein the polyethylene oxide having a different functional group at both terminal ends thereof has an amino group at one end of the chain and hydroxyl (-OH), tosyl, methylsulfonyl, , sulfonate (-SO ₃ H), chiol (-SH), anhydride (-COOCO-), halide (halide), vinyl (vinyl), azide (azide), ethyl xanthosine claim carbonate (ethyl xanthogenate), A carboxylic acid (-COOH), and a hydrazide. delete 2. The process according to claim 1, wherein in step (a), one of the chain ends of the phthalimidated polyethylene oxide is a compound of the formula (1)
[Chemical Formula 1]

In this formula,
Mt is an alkali metal,
and n is an integer of 10 to 500. The process according to claim 1, wherein, in step (b), the chain-terminal functionalized polyethylene oxide is a compound of the formula (2) or (3)
(2)

(3)

R ₁ is selected from the group consisting of hydrogen, tosyl, methylsulfonyl, trimellitic anhydride, bromopropionyl, bromoisobutyryl, propanesulfonic acid, methacryloyl, or O-ethylxanthropionyl,
R ₂ is thiol, thioacetate, amino, or azide,
and n is an integer of 10 to 500. 4. The process of claim 1, wherein in step (b), the block copolymerized polyethylene oxide is a compound of formula 4:
[Chemical Formula 4]

In this formula,
n is an integer of 10 to 500,
m is an integer of 1 to 10; The process according to claim 1, wherein in step (c), the deimidation reaction of the chain-terminal functionalized polyethylene oxide is carried out using hydrazine and an acid. The process according to claim 1, wherein the polyethylene oxide having a different functional group introduced into both chain terminals is a compound represented by the following formula (5) or (6):
[Chemical Formula 5]

[Chemical Formula 6]

In this formula,
R ₁ is selected from the group consisting of hydrogen, tosyl, methylsulfonyl, trimellitic anhydride, bromopropionyl, bromoisobutyryl, propanesulfonic acid, methacryloyl, or O-ethylxanthropionyl,
R ₂ is thiol, thioacetate, or azide,
and n is an integer of 10 to 500. The process according to claim 1, wherein in step (c), the de-imidation reaction of the block copolymerized polyethylene oxide is carried out using hydrazine and an acid or base. 2. The process according to claim 1, wherein the polyethylene oxide having different functional groups introduced into both chain terminals is a compound represented by the following formula (7): &lt; EMI ID =
(7)

In this formula,
R &lt; ₃ &gt; is a carboxylic acid or hydrazide,
n is an integer of 10 to 500,
m is an integer of 1 to 10;

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