Block copolymer

Abstract

To provide a temperature-responsive block copolymer with a narrow composition distribution and a method of producing the same.SOLUTION: In a block copolymer according to the present invention, among repeating units constituting the block copolymer, a repeating unit with the highest constituent ratio has a standard deviation of 3.0 mol% or less.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a block copolymer and a method for producing the same.

Background Art

[0002] A polymer compound is an aggregate of polymer chains with different degrees of polymerization, resulting in a broad molecular weight distribution. However, it is known that the molecular weight distribution can be narrowed by controlled polymerization. For example, Non-Patent Document 1 introduces the controlled polymerization of poly(styrene-acrylonitrile) random copolymer, and it has been shown that the molecular weight distribution can be narrowed compared to general radical polymerization by using reversible addition-fragmentation chain transfer reaction.

[0003] As an application of controlled polymerization, there is the polymerization of block copolymers. A block copolymer refers to a polymer in which two or more types of segments composed of repeating units are bonded in one chain. Since the combined properties of each segment of the block copolymer are likely to be exhibited and molecular design is easy, applications in various fields have been studied. Patent Document 1 discloses a block copolymer composed of a temperature-responsive segment and a water-insoluble segment. The block copolymer described in Patent Document 1 can achieve both temperature responsiveness and coating properties. When cell culture is performed using a device coated with the block copolymer, the cultured cells can be detached and recovered by the sol-gel transition of the temperature-responsive segment due to the temperature drop in the surrounding environment.

[0004] Since there are two or more types of segments in a block copolymer, the molar ratio (composition ratio) of each segment does not become uniform, resulting in a composition distribution. If the composition distribution is broad, the physical properties of the block copolymer cannot be expressed as expected, so conditions for narrowing the composition distribution are required, but are not known at present.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Document

[0006]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of the present invention is to provide a block copolymer with a narrow composition distribution.

Means for Solving the Problems

[0008] In view of the above points, the present inventors have conducted intensive research and as a result, completed the present invention.

[0009] That is, one aspect of the present invention is a block copolymer in which the standard deviation of the repeating unit having the highest composition ratio (hereinafter sometimes referred to as the maximum repeating unit) among the repeating units constituting the block copolymer is 3.0 mol% or less.

Effects of the Invention

[0010] According to the present invention, a block copolymer in which the physical properties of each segment are easily exhibited can be produced.

Modes for Carrying Out the Invention

[0011] Hereinafter, modes for carrying out the present invention (hereinafter simply referred to as "the present embodiment") will be described in detail. The present embodiment is an exemplification for explaining the present invention and is not intended to limit the present invention to the following content. The present invention can be appropriately modified and implemented within the scope of its gist.

[0012] In the present invention, "segment" refers to a structural unit of a block copolymer, and "repeating unit" refers to a structural unit of a segment. Each segment is composed of one or more repeating units.

[0013] The block copolymer of the present invention is characterized in that the standard deviation of the maximum repeating unit among the repeating units constituting the block copolymer is 3.0 mol% or less.

[0014] Among the repeating units constituting the block copolymer of the present invention, the standard deviation of the maximum repeating unit (hereinafter sometimes referred to as the composition distribution) is 3.0 mol% or less, preferably 2.0 mol% or less, and more preferably 1.5 mol% or less. The method for measuring the standard deviation is not particularly limited, but the block copolymer can be divided by items such as molecular weight, hydrophobicity, and density, and the standard deviation σ can be calculated from the following formula (1) by obtaining the composition ratio for each divided sample.

[0015]

Equation

[0016] In formula (1), i is the sample number of the divided sample. Xi is the composition ratio (mol%) of the i-th sample, x is the average composition ratio (mol%), and Pi is the ratio of the i-th sample to all samples. The number of samples (number of divided samples) for obtaining the composition distribution is preferably 10 to 1000, and more preferably 50 to 200. The method for dividing the block copolymer is not particularly limited, but it is preferably divided by molecular weight because the measurement is easy. As an example of the measurement method, gel permeation chromatography (GPC)-FTIR can be mentioned. Frequency measurement and eluent fractionation are performed for each molecular weight with a GPC equipped with a differential refractometer, and the samples fractionated for each molecular weight are measured by FTIR. Pi can be analyzed from the frequency measurement for each molecular weight, and Xi can be analyzed from the specific peak intensity derived from the repeating unit of FTIR. Also, the method for measuring the average composition ratio x is not particularly limited, and as an example, 1 It can be analyzed by 1H-NMR.

[0017] The maximum repeating unit refers to the repeating unit with the highest molar ratio (hereinafter referred to as the composition ratio) among the repeating units constituting the block copolymer. The value of the composition ratio is not particularly limited, and the lower limit value and the upper limit value differ depending on the number of types of repeating units constituting the copolymer.

[0018] The block copolymer consists of two or more segments and may consist of three or more segments. The segments constituting the copolymer are not particularly limited, but from the viewpoint of ease of polymerization, a segment containing any repeating unit of vinyl-based, styrene-based, acrylate-based, methacrylate-based, acrylamide-based, or methacrylamide-based is preferable, and a segment containing a repeating unit showing a lower critical solution temperature (LCST; Lower Critical Solution Temperature) (hereinafter referred to as an LCST repeating unit) is more preferable. LCST is a temperature at which the polymer dissolves in water at a low temperature, but phase separation occurs with water and turbidity occurs when the temperature is raised. This phenomenon can vary depending on the concentration of the polymer, but LCST is generally confirmed at the temperature obtained in a high-concentration aqueous solution.

[0019] The LCST repeating unit is not particularly limited. As an example of the LCST repeating unit and its LCST, N-ethylacrylamide (LCST = 72 °C), N-cyclopropylacrylamide (LCST = 46 °C), N-isopropylacrylamide (LCST = 32 °C), N-n-propylacrylamide (LCST = 22 °C), N-tetrahydrofurfurylacrylamide (LCST = 28 °C), N-ethoxyethylacrylamide (LCST = 35 °C), N-methyl-N-ethylacrylamide (LCST = 56 °C), N-methyl-N-isopropylacrylamide (LCST = 23 °C), N-methyl-N-n-propylacrylamide (LCST = 20 °C), N,N-diethylacrylamide (LCST = 32 °C), N-cyclopropylmethacrylamide (LCST = 59 °C), N-isopropylmethacrylamide (LCST = 44 °C), N-n-propylmethacrylamide (LCST = 28 °C), or N-tetrahydrofurfurylmethacrylamide (LCST = 35 °C) can be exemplified. The LCST segment may use only one type of the repeating unit or may use a combination of two or more types. Further, as long as it has temperature responsiveness, in addition to the LCST repeating unit, the segment may contain different repeating units.

[0020] As the block copolymer of the present invention containing an LCST segment, specifically, a block copolymer as disclosed in JP-A-2018-087316 containing a hydrophobic segment and a hydrophilic segment is preferable, and a block copolymer composed of segments of 2-methoxyethyl acrylate (hydrophilic segment), n-butyl acrylate (hydrophobic segment), and N-isopropylacrylamide (LCST segment) is particularly preferable.

[0021] When the block copolymer of the present invention contains an LCST repeating unit, the maximum repeating unit is preferably the LCST repeating unit, and its composition ratio is preferably 30 to 90 mol%.

[0022] The number average molecular weight (Mn) of the block copolymer of the present invention is not particularly limited, but is preferably from 1,000 to 1,000,000, more preferably from 10,000 to 300,000.

[0023] The method for producing the block copolymer of the present invention will be described below.

[0024] The synthesis method of the block copolymer is not particularly limited as long as it is living polymerization, but is preferably reversible addition fragmentation chain transfer polymerization or atom transfer radical polymerization. For example, referring to the methods described in "Radical Polymerization Handbook", pp. 161-225 (2010), published by N.T.S. Co., Ltd., a block copolymer can be synthesized.

[0025] Regarding the purification method, it can be purified using general purification methods such as precipitation method and ultrafiltration method.

[0026] The reaction solvent used in the synthesis is not particularly limited, but is preferably a solvent having a chain transfer constant (Cs) of 2,000 or less when radical polymerization is carried out with methyl methacrylate. As solvents having Cs of 2,000 or less, for example, as described in "Polymer Data Handbook - Basic Edition -", pp. 436-441 (1986), published by Baifukan Co., Ltd., acetone (Cs: 1,950), anisole (Cs: 0), triphenyl phosphite (Cs: 650), isobutyl alcohol (Cs: 1,000), chlorobenzene (Cs: 740), 1,2-dichloroethane (Cs: 350), diphenylamine (Cs: 0), dimethyl sulfoxide (Cs: 710), toluene (Cs; 1,700), tert-butyl alcohol (Cs: 850), benzene (Cs: 40), water (Cs: 20), etc. can be mentioned, and tert-butyl alcohol is preferred.

[0027] The reaction solution concentration is not particularly limited, but is preferably 5 to 20 wt%.

[0028] The shape of the reactor is not particularly limited, and it may be a flask-type or a cylinder-type reactor, and baffles may also be provided. The shape of the stirring blades is also not particularly limited, and it may be paddle blades, or may be a propeller type, an anchor blade, a full-zone blade, or a combination thereof. The stirring condition is preferably such that the Reynolds (Re) number during reaction stirring is 1000 or more. The Re number is calculated by the following formula (2).

[0029]

Number

[0030] In formula (2), ρ represents density [kg / m 3 , n represents the rotation speed [ / s], d represents the stirring blade diameter [m], and μ represents the viscosity of the solution at the reaction temperature [Pa·s]. To make the Re number 1000 or more, the density may be increased, or the rotation speed may be increased or the stirring blade diameter may be adjusted.

Examples

[0031] Examples of the present invention will be described below, but the present invention is not limited by these examples. Unless otherwise specified, commercially available reagents were used. <Average composition ratio of block copolymer> The average composition ratio x of the block copolymer was determined by 1 1H-NMR measurement using a Fourier transform nuclear magnetic resonance (NMR) method. An NMR apparatus JNM-ECZ400S / L1 manufactured by JEOL Ltd. was used, and 10 mg of the block copolymer was dissolved in 0.75 mL of deuterated chloroform for measurement. <Molecular weight and molecular weight distribution of block copolymer> The weight-average molecular weight (Mw), number-average molecular weight (Mn), and molecular weight distribution (Mw / Mn) of the block copolymer were measured by GPC. The GPC apparatus used was the HLC-8320GPC manufactured by Tosoh Corporation. Two TSKgel Super AWM-H columns manufactured by Tosoh Corporation were used, the column temperature was set at 40°C, the concentration detector was a differential refractometer, and the eluent used was a 10 mM sodium trifluoroacetate / 2,2,2-trifluoroethanol solution. Measurements were carried out under the conditions of a sample concentration of 1 mg / mL, a sample injection volume of 0.1 mL, and an eluent flow rate of 0.6 mL / min. Also, the calibration curve for molecular weight calculation was prepared by measuring polymethyl methacrylate manufactured by PSS Polymer Standards Service GmbH with a known molecular weight under the same conditions. <Composition distribution> The composition distribution was obtained by gel permeation chromatography-Fourier transform infrared spectroscopy (GPC-FTIR) in which the copolymer was fractionated by molecular weight using GPC and the composition for each molecular weight was measured by analyzing their FTIR spectra.

[0032] The GPC apparatus used was the Prominence HPLC system (DGU-20A3, LC-20AD, SIL-20AHT, CTO-20A, SPD-20A, RID-20A, CBM-20A) manufactured by Shimadzu Corporation. Two TSKgel α-M columns manufactured by Tosoh Corporation were used, the column temperature was 40°C, the concentration detector was a differential refractive index meter, and the eluent used was 2,2,2-trifluoroethanol. Measurements were carried out under the conditions of a sample concentration of 2 mg / mL, a sample injection volume of 0.2 mL, and an eluent flow rate of 0.6 mL / min. Also, the calibration curve for molecular weight calculation was prepared by measuring polymethyl methacrylate manufactured by Agilent Technologies, Inc. with a known molecular weight under the same conditions. The eluent emerging from the column in the GPC measurement was sprayed onto a germanium disc using the LC-Transform series 600 manufactured by Lab Connections, fractionated into 72 sections for each elution time, and dried. The ratio (Pi) occupied by the i-th section in the whole was obtained from the peak ratio of the differential refractive index meter for each section.

[0033] Subsequently, ATR-FTIR measurements were performed on each section. ATR-FTIR was measured in the region of 4000 - 650 cm -1 using Nicolet iS10 manufactured by Thermo Fisher Scientific, Inc. The peak intensity A -1 of the main-chain methylene peak (2967 cm 2967 ) in the block copolymer and the ratio A X / A 2967 of the peak intensity AX of the highest repeating unit were obtained for each molecular weight.

[0034] The peak intensity ratio A X / A 2967 was converted to the composition ratio Xi so that the material balance could be achieved from the ratio Pi and the average composition ratio x. Based on this, the composition distribution was obtained by formula (1). <Measurement of density> The density of the reaction solution was measured using a pycnometer. <Viscosity measurement> The viscosity of the reaction solution was measured using a rotational rheometer MCR-300 manufactured by Anton-Paar. The shear rate was measured in the range of 10 - 100 / s. (Example 1) 1.952 g (15 mmol) of 2-methoxyethyl acrylate (MEA) was added to a 500 mL cylindrical flask (inner diameter 80 mm), and further 95.1 mg (300 μmol) of cyanomethyl dodecyl trithiocarbonate, 4.8 mg (30 μmol) of azobisisobutyronitrile, and 30 mL of tert-butyl alcohol (Cs: 850) were added. After purging with argon gas, the reaction was carried out at 62 °C for 24 hours with a rotation speed of 5 revolutions per second using two paddle blades with a stirring blade diameter of 0.07 m.

[0035] After the first heating and stirring, 11.535 g (90 mmol) of n-butyl acrylate (BA) was added to the above reaction solution, and further 4.8 mg (30 μmol) of azobisisobutyronitrile and 10 mL of tert-butyl alcohol were added. After purging with argon gas, the reaction was carried out at 62 °C for 24 hours with a rotation speed of 5 revolutions per second using two paddle blades with a stirring blade diameter of 0.07 m.

[0036] After the second heating and stirring, 22.066 g (195 mmol) of N-isopropylacrylamide (IPAAm: LCST = 32 °C) was added to the above reaction solution, and further 4.8 mg (30 μmol) of azobisisobutyronitrile and 255 mL of tert-butyl alcohol were added. After purging with argon gas, the reaction was carried out at 62 °C for 24 hours with a rotation speed of 5 revolutions per second using two paddle blades with a stirring blade diameter of 0.07 m.

[0037] The concentration of the obtained reaction solution was 13.2 wt%, the density of the reaction solution was 0.81 g / cm 3 (62 °C), the viscosity of the reaction solution was 0.02 Pa·s (62 °C), and the Re number was 1100.

[0038] 300 mL of the reaction solution was dropped into a 3 L beaker containing 2 L of pure water, and the precipitated yellow viscous substance was collected. This viscous substance was immersed in 2 L of pure water for 12 hours, then heated to 40 °C to collect the solid, and vacuum dried at 100 °C for 12 hours. After dissolving this solid in 300 mL of chloroform, 5 g of magnesium sulfate was added and stirred at room temperature for 1 hour, and the filtrate was collected by filtration. The filtrate was dropped into a 3 L beaker containing 2 L of heptane, and the precipitated white solid was collected, and block copolymer 1 (17.8 g) was obtained by drying under reduced pressure at 100 °C for 12 hours. (Example 2) 0.831 g (6 mmol) of 2-methoxyethyl acrylate (MEA) was added to a 500 mL cylindrical flask (inner diameter 80 mm), and further 40.5 mg (128 μmol) of cyanomethyl dodecyl trithiocarbonate, 4.2 mg (26 μmol) of azobisisobutyronitrile, and 30 mL of tert-butyl alcohol (Cs: 850) were added. After purging with argon gas, the reaction was carried out at 62 °C for 24 hours with a rotation speed of 5 revolutions per second using two paddle blades with a stirring blade diameter of 0.07 m.

[0039] After the first heating and stirring, 4.909 g (38 mmol) of n-butyl acrylate (BA) was added to the above reaction solution, and further 4.2 mg (26 μmol) of azobisisobutyronitrile and 10 mL of tert-butyl alcohol were added. After purging with argon gas, the reaction was carried out at 62 °C for 24 hours with a rotation speed of 5 revolutions per second using two paddle blades with a stirring blade diameter of 0.07 m.

[0040] After the second heating and stirring, 28.892 g (255 mmol) of N-isopropylacrylamide (IPAAm: LCST = 32 °C) was added to the above reaction solution, and further 4.2 mg (26 μmol) of azobisisobutyronitrile and 370 mL of tert-butyl alcohol were added. After purging with argon gas, the reaction was carried out at 62 °C for 48 hours with a rotation speed of 5 revolutions per second using two paddle blades with a stirring blade diameter of 0.07 m.

[0041] The concentration of the obtained reaction solution was 10.1 wt%, the density of the reaction solution was 0.80 g / cm 3 (62 °C), the viscosity of the reaction solution was 0.014 Pa·s (62 °C), and the Re number was 1380.

[0042] 410 mL of the reaction solution was dropped into a 3 L beaker containing 2 L of pure water, and the precipitated yellow viscous substance was collected. This viscous substance was immersed in 2.8 L of pure water for 12 hours, then heated to 40 °C to collect the solid, and vacuum dried at 100 °C for 12 hours. After dissolving this solid in 350 mL of chloroform, 5 g of magnesium sulfate was added and stirred at room temperature for 1 hour, and the filtrate was collected by filtration. The filtrate was dropped into a 5 L beaker containing 3 L of heptane, and the precipitated white solid was collected, and 20.9 g of block copolymer 5 was obtained by drying under reduced pressure at 100 °C for 12 hours. (Comparative Example 1) The reaction was carried out in the same manner as in Example 1 except that 1,4-dioxane (Cs: 2220) was added instead of tert-butyl alcohol. The amount of 1,4-dioxane added was the same as that of tert-butyl alcohol in each case.

[0043] The concentration of the obtained reaction solution was 10.3 wt%, the density of the reaction solution was 1.03 g / cm 3 (62 °C), the viscosity of the reaction solution was 0.01 Pa·s (62 °C), and the Re number was 2200.

[0044] A white solid was collected in the same procedure as in Example 1, and 18.5 g of block copolymer 2 was obtained. (Comparative Example 2) The reaction was carried out in the same manner as in Comparative Example 1, except that the amount of 1,4-dioxane added after the second heat stirring was changed to 110 mL.

[0045] The concentration of the obtained reaction solution was 22.3 wt%, the density of the reaction solution was 1.04 / cm 3 (62 °C), the viscosity of the reaction solution was 0.22 Pa·s (62 °C), and the Re number was 110.

[0046] A white solid was recovered by the same procedure as in Example 1, and 19.2 g of block copolymer 3 was obtained. (Comparative Example 3) The reaction was carried out in the same manner as in Example 1, except that the rotation speed of the two paddle blades with a stirring blade diameter of 0.07 m was changed to 1 rotation / s.

[0047] The concentration of the obtained reaction solution was 13.2 wt%, the density of the reaction solution was 0.81 g / cm 3 (62 °C), the viscosity of the reaction solution was 0.03 Pa·s (62 °C), and the Re number was 150.

[0048] A white solid was recovered by the same procedure as in Example 1, and 14.0 g of block copolymer 4 was obtained.

[0049] The number average molecular weights, average composition ratios of IPAAm, and composition distributions of block copolymers 1 to 5 are shown in Table 1.

[0050]

Table 1

Claims

1. A method for producing a block copolymer, wherein the number of segments constituting the block copolymer is 3 or more, the segments contain repeating units of any one of acrylate, methacrylate, acrylamide, and methacrylamide, the block copolymer has a segment composed of 2-methoxyethyl acrylate, a segment composed of n-butyl acrylate, and a segment composed of N-isopropylacrylamide, the reaction solvent when producing the block polymer is tert-butyl alcohol, A method for producing a block copolymer, characterized in that the composition distribution of the maximum repeating unit among the repeating units constituting the block copolymer is 3.0 mol% or less.

2. The method for producing a block copolymer according to claim 1, wherein the segment composed of N-isopropylacrylamide is a segment exhibiting a lower critical solution temperature (LCST) with respect to water.

3. The method for producing a block copolymer according to claim 1 or 2, characterized in that the composition ratio of the repeating unit exhibiting LCST is 30 to 90 mol%.

4. The method for producing a block copolymer according to any one of claims 1 to 3, characterized in that the number average molecular weight of the block copolymer is 10,000 to 300,000.

5. The method for producing a block copolymer according to any one of claims 1 to 4, characterized in that a reaction solvent having a chain transfer constant of 2,000 or less when radical polymerization is carried out with methyl methacrylate is selected, and the Reynolds number during stirring of the reaction solution is 1,000 or more.

6. The production method according to claim 5, characterized in that the reaction solution concentration is 5 to 20 wt%.

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