Method for producing a random copolymer

Abstract

To provide, in anion polymerization, a method of efficiently manufacturing a random copolymer that has uniformly distributed different kinds of monomers and can exhibit novel physical characteristics.SOLUTION: A method of manufacturing random copolymers that a manufacturing method of a random copolymer due to a ribbing anion polymerization using a micro-reactor characterized in that by ribbing anionic polymerization using a microreactor, in which a first monomer having a monomer reactivity ratio r1 derived from a straight line obtained from Fineman-Ross plot (where, a correlation coefficient is R≥0.9) and a second monomer having monomer reactivity ratio r2 larger than the monomer reactivity ratio r1 are reacted at predetermined concentrations derived from Mayo-Lewis formula to obtain a random copolymer.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for manufacturing a random copolymer. - one

Background Art

[0002] In industrially widely used random copolymers, it is technically difficult to evenly distribute different monomer units in the polymer molecule. However, it has recently been reported that a random copolymer in which different monomer units are evenly distributed in the polymer molecule can exhibit physical properties different from known physical properties (see, for example, Non-Patent Documents 1 and 2).

[0003] As a method for evenly distributing different monomers, in radical polymerization, methods using the Fineman-Ross plot and the Mayo-Lewis equation have been established (see, for example, Non-Patent Documents 3 to 6). On the other hand, in anionic polymerization, since the polymerization rate is very high, it has been difficult to realize the method using the Fineman-Ross plot and the Mayo-Lewis equation.

[0004] Therefore, in the above anionic polymerization, a method for efficiently producing a random copolymer in which different monomers are evenly distributed and which can exhibit new physical properties has not yet been provided, and there is a strong demand for its prompt provision.

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention aims to solve the above-mentioned conventional problems and achieve the following objectives. That is, the present invention aims to provide a method for efficiently producing a random copolymer that exhibits new physical properties with heterogeneous monomers evenly distributed in anionic polymerization.

Means for Solving the Problems

[0007] As a result of intensive research by the present inventors to achieve the above object, in the production of a random copolymer by living anionic polymerization, a microreactor comprising a flow path capable of mixing a plurality of liquids and an introduction path communicating with the flow path for introducing a liquid into the flow path, wherein the plurality of liquids supplied through the introduction path are mixed by merging in the flow path and a reaction occurs (see, for example, Chimia 2002 56:636, Tetrahedron 2002 58:4735-4757), and further under the following conditions, that is, a first monomer having a monomer reactivity ratio r1 derived from a straight line obtained by Fineman-Ross Plot (where the correlation coefficient R ≧ 0.9) and a second monomer having a monomer reactivity ratio r2 larger than the monomer reactivity ratio r1 are reacted at a predetermined concentration derived from the Mayo-Lewis equation to obtain a random copolymer, it has been found that in the above anionic polymerization, a random copolymer that exhibits new physical properties with heterogeneous monomers evenly distributed can be efficiently produced.

[0008] The present invention is based on the above findings by the present inventors, and the means for solving the above problems are as follows. That is, <1> A method for producing a random copolymer by living anionic polymerization using a microreactor, comprising reacting a first monomer having a monomer reactivity ratio r1 derived from a straight line (where the correlation coefficient R ≧ 0.9) obtained from a Fineman-Ross Plot and a second monomer having a monomer reactivity ratio r2 larger than the monomer reactivity ratio r1 at a predetermined concentration derived from the Mayo-Lewis equation to obtain a random copolymer. A method for producing a random copolymer, characterized by comprising: <2> A method for producing a random copolymer by living anionic polymerization using a microreactor, comprising adding and reacting the second monomer to a random copolymer obtained by reacting at least a first monomer and a second monomer having a larger monomer reactivity ratio than the first monomer to extend the random copolymer. A method for producing a random copolymer, characterized by comprising: <3> A random copolymer comprising a first monomer and a second monomer, wherein the ratio of the abundance of the first monomer in the range within 20% of the whole polymer from the end at the polymerization initiation end of the random copolymer to the abundance of the first monomer in the whole polymer of the random copolymer is 0.6 or more and 1.4 or less. A random copolymer, characterized by:

Advantages of the Invention

[0009] According to the present invention, in anionic polymerization, a method for efficiently producing a random copolymer capable of exhibiting new physical properties in which different monomers are evenly distributed can be provided.

Brief Description of the Drawings

[0010]

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Figure 18

Embodiments for Carrying Out the Invention

[0011] (Method for Producing Random Copolymer) The method for producing the random copolymer is a method for producing a random copolymer by living anionic polymerization using a microreactor, which includes a step of reacting a first monomer having a monomer reactivity ratio r1 and a second monomer having a monomer reactivity ratio r2 greater than the monomer reactivity ratio r1 at a predetermined concentration to obtain a random copolymer, and may further include other steps.

[0012] -Microreactor- The microreactor is not particularly limited and can be appropriately selected according to the purpose. For example, a microreactor (hereinafter sometimes referred to as a "flow microreactor") having a mixing means and a flow path, and further having other means as required can be mentioned. The mixing means and the flow path may be integrated or separate.

[0013] The mixing means is a means capable of mixing two or more kinds of liquids. The flow path is a tube through which a liquid can flow. The flow path is connected to at least one of the mixing means.

[0014] By using the flow microreactor, for a compound with low stability, the residence time from generation to the next reaction can be shortened, and side reactions can be suppressed. In addition, since the flow microreactor has excellent cooling efficiency, side reactions due to heat generation in an exothermic reaction can be suppressed.

[0015] --Integrated Flow Microreactor-- Examples of the mixing means and the flow path of the integrated flow microreactor include a substrate-type micromixer.

[0016] The substrate-type micromixer is composed of a substrate with a passage formed inside or on the surface, and may be referred to as a microchannel. The substrate-type micromixer is not particularly limited and can be appropriately selected according to the purpose. For example, a mixer having a fine flow path for mixing described in WO 96 / 30113 pamphlet; a mixer described in the literature "Chapter 3 of 'Microreactors', by W. Ehrfeld, V. Hessel, and H. Lowe, published by Wiley-VCH" and the like can be mentioned.

[0017] In the substrate-type micromixer, the mixing means and the flow path are constituted by minute flow paths capable of mixing a plurality of liquids.

[0018] Preferably, in addition to the flow path, an introduction path that communicates with the flow path and introduces a plurality of liquids into the flow path is formed in the substrate-type micromixer. That is, a configuration in which the upstream side of the flow path branches according to the number of the introduction paths is preferable.

[0019] The number of the introduction paths is not particularly limited and can be appropriately selected according to the purpose. However, it is preferable to introduce a plurality of liquids desired to be mixed from separate introduction paths, and to merge and mix them in the flow path. In addition, a configuration may be adopted in which one liquid is charged into the flow path in advance, and the other liquids are introduced through the introduction paths. Further, it is preferable that an introduction path capable of adding a monomer is formed so as to connect to the middle of the reaction flow path where anionic copolymerization is carried out.

[0020] --Separate-type flow microreactor-- The separate-type flow microreactor is formed by connecting a mixing means and a flow path.

[0021] As the mixing means, there is no particular limitation as long as two or more liquids can be mixed, and it can be appropriately selected according to the purpose. For example, a pipe joint type micromixer can be mentioned.

[0022] The pipe joint type micromixer includes a flow path formed inside, and a connecting member for connecting the flow path formed inside and the flow passage as needed. There is no particular limitation on the connection method in the connecting member, and it can be appropriately selected according to the purpose from known connection methods. For example, a screw-in type, a union type, a butt welding type, an insertion welding type, a socket welding type, a flange type, a biting type, a flare type, a mechanical type, etc. can be mentioned.

[0023] Inside the pipe joint type micromixer, preferably, in addition to the flow path, an introduction path that communicates with the flow path and introduces a plurality of liquids into the flow path is formed. That is, a configuration in which the upstream side of the flow path is branched according to the number of the introduction paths is preferable. When the number of the introduction paths is two, for example, a T-shaped or Y-shaped pipe joint type micromixer can be used. When the number of the introduction paths is three, for example, a cross-shaped one can be used. In addition, a configuration may be adopted in which one liquid is previously charged into the flow path and the other liquids are introduced through the introduction paths. Further, it is preferable that an introduction path through which a monomer can be added is formed so as to connect to the middle of the reaction flow path where anionic copolymerization is carried out.

[0024] There is no particular limitation on the material of the pipe joint type micromixer, and it can be appropriately selected according to requirements such as heat resistance, pressure resistance, solvent resistance, and ease of processing. For example, stainless steel, titanium, copper, nickel, aluminum, silicon, and fluororesins such as Teflon (registered trademark) and PFA (perfluoroalkoxy resin), TFAA (trifluoroacetamide), etc. can be mentioned.

[0025] As the pipe joint type micromixer, commercially available products can be used. For example, the YM-1 type mixer and YM-2 type mixer manufactured by Azbil Corporation; the mixing tee and tee (T-shaped connector) manufactured by Shimadzu GLC; the micro high mixer developed by Toray Engineering; the union tee manufactured by Swagelok, and the T-shaped micromixer manufactured by Sanko Seiki Kogyo Co., Ltd. etc. can be mentioned.

[0026] As the mixing method of two or more raw material substances in the mixing means, there is no particular limitation, and it can be appropriately selected according to the purpose. For example, mixing by laminar flow, mixing by turbulent flow, etc. can be mentioned. Among them, mixing by laminar flow (static mixing) is preferable in terms of being able to control the reaction and remove heat more efficiently.

[0027] In addition, since the flow path in the mixing means is minute, the plurality of liquids introduced into the mixing means naturally tend to be in a laminar flow-dominated flow, and diffuse and mix in a direction orthogonal to the flow. In mixing by laminar flow, further, by providing branch points and confluence points in the flow path, a configuration can be adopted to divide the laminar cross-section of the flowing liquid, and a configuration to increase the mixing speed may also be adopted. Also, in the flow path of the mixing means, when performing mixing by turbulent flow (dynamic mixing), it can be changed from laminar flow to turbulent flow by adjusting the flow rate and the shape of the flow path (such as the three-dimensional shape of the liquid contact part, the shape of the flow path bend, the roughness of the wall surface, etc.). The mixing by turbulent flow has the advantages of better mixing efficiency and faster mixing speed compared with the mixing by laminar flow.

[0028] Here, the smaller the inner diameter of the flow path in the mixing means, the shorter the diffusion distance of the molecules can be, so the time required for mixing can be shortened and the mixing efficiency can be improved. Furthermore, the smaller the inner diameter of the flow path, the larger the ratio of the surface area to the volume becomes, and for example, temperature control of the liquid such as removal of reaction heat can be easily performed. On the other hand, if the inner diameter of the flow path is too small, the pressure loss during liquid flow increases, and a special high-pressure-resistant pump is required for liquid delivery, which may increase the manufacturing cost. In addition, due to the limitation of the liquid delivery flow rate, the structure of the micromixer may also be limited.

[0029] The inner diameter of the flow path in the mixing means is not particularly limited and can be appropriately selected according to the purpose. However, 50 μm to 4 mm is preferable, 50 μm to 1 mm is more preferable, 100 μm to 800 μm is more preferable, and 250 μm to 500 μm is even more preferable. If the inner diameter is less than 50 μm, the pressure loss may increase. If the inner diameter exceeds 4 mm, the surface area per unit volume becomes small, and as a result, rapid mixing and heat removal of the reaction heat may become difficult. On the other hand, when the inner diameter is within the particularly preferable range, it is advantageous in that mixing can be performed more rapidly and the reaction heat can be removed more efficiently.

[0030] The cross-sectional area of the flow path is not particularly limited and can be appropriately selected according to the purpose, and is preferably 100 μm 2 ~16 mm 2 more preferably 1,000 μm 2 ~4.0 mm 2 even more preferably 10,000 μm 2 ~2.1 mm 2 particularly preferably 190,000 μm 2 ~1 mm 2 is particularly preferable.

[0031] The cross-sectional shape of the flow path is not particularly limited and can be appropriately selected according to the purpose. Examples include a circular shape, a rectangular shape, a semi-circular shape, a triangular shape, and the like.

[0032] The flow passage is connected to at least one of the mixing means and is not particularly limited as long as it is a tube through which liquid can flow, and can be appropriately selected according to the purpose. The configuration such as its inner diameter, outer diameter, length, and material can be appropriately selected according to the desired reaction.

[0033] The flow path is used, for example, when supplying a raw material substance to the mixing means. Further, the flow path is used, for example, when supplying the reaction product of two or more substances mixed by the mixing means to the next mixing means. At this time, a reaction may continue to occur in the flow path.

[0034] As the flow path, commercially available products can be used. For example, a stainless steel tube manufactured by GL Sciences Inc. (outer diameter 1 / 16 inch (1.58 mm), inner diameters selectable from 250 μm, 500 μm, and 1,000 μm, tube length adjustable by the user), etc. can be mentioned.

[0035] There is no particular limitation on the material of the flow path, and those exemplified as the material of the mixing means can be preferably used.

[0036] There is no particular limitation on the inner diameter of the flow path, and it can be appropriately selected according to the purpose. However, 50 μm to 4 mm is preferable, 100 μm to 3 mm is more preferable, 250 μm to 2 mm is still more preferable, and 500 μm to 1 mm is particularly preferable.

[0037] There is no particular limitation on the flow rate of the liquid in the flow path for supplying the raw material, and it can be appropriately selected according to the purpose. For example, it may be 1.0 ml / min to 20 ml / min, or 2.0 ml / min to 15 ml / min, or 3.0 ml / min to 10 ml / min.

[0038] There is no particular limitation on the residence time of the reaction liquid in the flow path through which the reaction liquid flows, and it can be appropriately selected according to the purpose. For example, 0.001 sec to 10 sec, etc. can be mentioned.

[0039] --Other means-- There is no particular limitation on the other means, and it can be appropriately selected according to the purpose. For example, liquid feeding means, temperature adjusting means, etc. can be mentioned.

[0040] As the liquid feeding means, there is no particular limitation as long as various raw material substances can be supplied to the flow path of the flow microreactor, and it can be appropriately selected according to the purpose. For example, a pump or the like can be mentioned.

[0041] There is no particular limitation on the pump, and it can be appropriately selected from those that can be industrially used. However, those that do not generate pulsation during liquid feeding are preferable. For example, a plunger pump, a gear pump, a rotary pump, a diaphragm pump, etc. can be mentioned.

[0042] As the temperature adjusting means, there is no particular limitation as long as the temperature of the mixing means and the flow path of the flow microreactor can be adjusted, and it can be appropriately selected according to the purpose.

[0043] <Step of obtaining a random copolymer> The step of obtaining the random copolymer is a step of reacting a first monomer having a monomer reactivity ratio r1 derived from a straight line (where the correlation coefficient R ≥ 0.9) obtained by Fineman-Ross Plot and a second monomer having a monomer reactivity ratio r2 larger than the monomer reactivity ratio r1 at a predetermined concentration derived from the Mayo-Lewis equation to obtain a random copolymer.

[0044] - First monomer and second monomer - As the first monomer and the second monomer, there is no particular limitation as long as the conditions of the monomer reactivity ratio described later are satisfied, and each can be appropriately selected according to the purpose. For example, methacrylic acid esters, acrylic acid esters, etc. can be mentioned. Among these, methacrylic acid esters are preferable.

[0045] The methacrylic acid ester is not particularly limited and can be appropriately selected according to the purpose. For example, methyl methacrylate, tert-butyl methacrylate, benzyl methacrylate, di(ethylene glycol) methyl ether methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, dodecyl methacrylate, lauryl methacrylate, methoxyethyl methacrylate, dimethylaminoethyl methacrylate, diethylaminoethyl methacrylate, glycidyl methacrylate, trimethoxysilylpropyl methacrylate, trifluoromethyl methacrylate, trifluoroethyl methacrylate, nonafluorhexyl methacrylate, tridecafluoro-n-octyl methacrylate, isopropyl methacrylate, cyclohexyl methacrylate, isobornyl methacrylate, etc. can be mentioned. Among them, methyl methacrylate, tert-butyl methacrylate, benzyl methacrylate, and di(ethylene glycol) methyl ether methacrylate are preferred.

[0046] The acrylic acid ester is not particularly limited and can be appropriately selected according to the purpose. For example, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, isobutyl acrylate, hexyl acrylate, 2-ethylhexyl acrylate, dodecyl acrylate, lauryl acrylate, methoxyethyl acrylate, dimethylaminoethyl acrylate, diethylaminoethyl acrylate, glycidyl acrylate, trimethoxysilylpropyl acrylate, trifluoromethyl acrylate, trifluoroethyl acrylate, isopropyl acrylate, cyclohexyl acrylate, isobornyl acrylate, tert-butyl acrylate, etc. can be mentioned.

[0047] -Monomer reactivity ratio- The monomer reactivity ratios of the first monomer and the second monomer are derived from the straight line (however, the correlation coefficient R≧0.9) obtained by the Fineman-Ross Plot as described in Non-Patent Documents 3 and 5, etc.

[0048] Using a flow microreactor system, an initiator and a monomer mixed solution (the first monomer and the second monomer) are introduced into a micromixer, and the mixture is passed through microtube reactors with various inner diameters and lengths. After the reaction stops, the product solution is collected, and monomer conversion is measured by gas chromatography analysis. The monomer charge ratio (F = [M 第1のモノマー / [M 第2のモノマー ) is calculated from the initial concentrations and flow rates of the respective monomers, and the monomer ratio in the copolymer (f = d[M 第1のモノマー / d[M 第2のモノマー ) is calculated from the conversion rates of the respective monomers. Using the obtained monomer charge ratio F and the monomer ratio f in the copolymer, a Fineman-Ross Plot is created, and the monomer reactivity ratios of the first monomer and the second monomer are obtained from the slope and intercept of the resulting straight line.

[0049] Here, in order for the correlation coefficient of the straight line obtained in the Fineman-Ross Plot to be 0.9 or more, it is important to use the microreactor to increase the mixing efficiency of the monomers and perform high-speed mixing. Also, it is possible to use the measured values of the points in the range where the ratio of the total consumption amount of the first monomer and the second monomer to the total charged amount of the first monomer and the second monomer is 10% or less. The ratio can be adjusted by setting the inner diameter and length of the microtube reactor so that the residence time is short. The ratio can also be adjusted within the range of 10% or less corresponding to the combination of the first monomer and the second monomer.

[0050] - Predetermined concentration - The predetermined concentration is a concentration based on a predetermined monomer ratio and is derived from the Mayo-Lewis equation as described in Non-Patent Document 3 and the like. For example, when the predetermined monomer ratio (monomer ratio in the copolymer) is 1, d[M 第1のモノマー / d[M 第2のモノマー =1, and it is calculated using the Mayo-Lewis equation (Equation 1) shown below. Similarly, the concentration based on a desired monomer ratio such as 0.5, 2, etc. of the predetermined monomer ratio (monomer ratio in the copolymer) can be calculated.

[0051]

Number

[0052] When reacting a first monomer, which is the monomer reactivity ratio r1 derived from the straight line obtained by the Fineman-Ross Plot (where the correlation coefficient R ≥ 0.9), and a second monomer, which is a monomer reactivity ratio r2 greater than the monomer reactivity ratio r1, at a predetermined concentration derived from the Mayo-Lewis equation, the time of the reaction is not particularly limited and can be appropriately selected according to the purpose, and also depends on the combination of the first monomer and the second monomer. However, the time when the ratio of the total consumption amount of the first monomer and the second monomer to the total charged amount of the first monomer and the second monomer is 80% or less is preferable, the time when it is 50% or less is more preferable, the time when it is 30% or less is further preferable, the time when it is 20% or less is particularly preferable, and the time when it is 10% or less is most preferable. The temperature of the reaction is not particularly limited and can be appropriately selected according to the purpose, but 25°C or lower is preferable, 20°C or lower is more preferable, 4°C or lower is further preferable, 0°C or lower is particularly preferable, and -10°C or lower is most preferable.

[0053] The reaction between the first monomer and the second monomer can be carried out in the presence of an initiator. The initiator is not particularly limited and can be appropriately selected according to the purpose, but an initiator represented by the following general formula (1) is preferable.

Chemistry

[0054] In the general formula (1), "Li" represents a lithium group.

[0055] In the general formula (1), R 1 and R 2 one of them is an aryl group, the other is an aryl group or an alkyl group having 1 to 10 carbon atoms, and R 3 is n-Bu (n-butyl group) or s-Bu (sec-butyl group).

[0056] The alkyl group having 1 to 10 carbon atoms is not particularly limited and can be appropriately selected according to the purpose. However, from the viewpoint of obtaining a polymer with high conversion efficiency and narrow dispersion, an alkyl group having 1 to 8 carbon atoms is preferable, an alkyl group having 1 to 6 carbon atoms is more preferable, an alkyl group having 1 to 4 carbon atoms is further preferable, an alkyl group having 1 to 2 carbon atoms is particularly preferable, and a methyl group is most preferable.

[0057] The aryl is not particularly limited and can be appropriately selected according to the purpose. Examples thereof include a phenyl group, a tolyl group, and an o-xylyl group. Among these, a phenyl group is preferable from the viewpoint of obtaining a polymer with high conversion efficiency and narrow dispersion.

[0058] Examples of the compound represented by the general formula (1) include a compound (DPHLi) represented by the following structural formula (1) or the following structural formula (4), a compound (2PHLi) represented by the following structural formula (2) or the following structural formula (5), and a compound (3POLi) represented by the following structural formula (3) or the following structural formula (6).

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chem.

[0059] <Other processes> The above-mentioned other processes are not particularly limited and can be appropriately selected according to the purpose. For example, an elongation process, a stop process, etc. can be mentioned.

[0060] -Elongation process- The above-mentioned elongation process is a process of elongating the random copolymer obtained in the process of obtaining the above-mentioned random copolymer. By reacting at the above-mentioned predetermined concentration, a random copolymer in which the consumption ratio of the first monomer and the second monomer is substantially constant can be obtained. However, over time, the relationship in which the consumption ratio of the first monomer and the second monomer is substantially constant breaks down. Therefore, by adding and reacting the second monomer to the random copolymer to elongate the random copolymer, the consumption ratio of the first monomer and the second monomer can be made substantially constant.

[0061] The above-mentioned substantially constant means that when the ratio of the abundance ratio of the first monomer up to a predetermined time point to the abundance ratio of the first monomer based on the predetermined monomer ratio of the random copolymer is 0.8 or more and 1.2 or less, the consumption ratio at the predetermined time point is substantially constant. The abundance ratio of the first monomer is calculated from the cumulative composition (Fcum, first monomer) of the first monomer. The cumulative composition of the first monomer is determined from the monomer consumption ratio. That is, it is determined from the value obtained by dividing (the monomer consumption amount of the first monomer) by (the monomer consumption amount of the first monomer + the second monomer). The abundance of the first monomer based on the predetermined monomer ratio is, for example, 0.5 (1 / 2) when the predetermined monomer ratio (monomer ratio in the copolymer) is set to 1 (1 / 1), 0.667 (2 / 3) when the predetermined monomer ratio (monomer ratio in the copolymer) is set to 2 (2 / 1), and 0.333 (1 / 3) when the predetermined monomer ratio (monomer ratio in the copolymer) is set to 0.5 (1 / 2). The ratio of the abundance of the first monomer to the abundance of the first monomer based on the predetermined monomer ratio of the random copolymer is calculated by dividing (the cumulative composition of the first monomer) by (the abundance of the first monomer based on the predetermined monomer ratio).

[0062] The timing of adding and reacting the second monomer is not particularly limited as long as the relationship in which the consumption ratio of the first monomer and the second monomer is substantially constant breaks down. However, it may be when the ratio of the total consumption amount of the first monomer and the second monomer to the total charged amount of the first monomer and the second monomer exceeds 10% in the reaction between the first monomer and the second monomer. The ratio can be adjusted within the range of 10% or less corresponding to the combination of the first monomer and the second monomer.

[0063] The concentration of the second monomer when adding and reacting the second monomer is not particularly limited and can be appropriately selected according to the purpose. However, it is preferably 0.01 M or more and 10 M or less, more preferably 0.05 M or more and 5 M or less, and even more preferably 0.1 M or more and 1 M or less.

[0064] The number of times of performing the addition reaction of the second monomer is not particularly limited and can be appropriately selected according to the purpose. However, it is preferably performed 2 times or more.

[0065] - Stopping step - The stopping step is not particularly limited and can be appropriately selected according to the purpose. For example, it includes a step of mixing the obtained random copolymer and a methanol solution. The concentration of the methanol solution is not particularly limited and can be appropriately selected according to the purpose, but is preferably 0.01 M or more and 10 M or less, and more preferably 0.1 M or more and 1 M or less.

[0066] (Random copolymer) The random copolymer is a random copolymer containing a first monomer and a second monomer, and the ratio of the abundance ratio of the first monomer in the range within 20% of the whole polymer from the end at the polymerization initiation end of the random copolymer to the abundance ratio of the first monomer in the whole polymer of the random copolymer is 0.6 or more and 1.4 or less.

[0067] The range within 20% of the whole polymer from the end at the polymerization initiation end of the random copolymer means within 20% from the end at the polymerization initiation end of the random copolymer (the normalized polymer chain length at the initial stage of polymerization is within 20%) when the whole random copolymer is regarded as 100%.

[0068] The normalized polymer chain length is calculated from the value obtained by dividing the monomer consumption amount of (the first monomer + the second monomer) at each residence time by the monomer consumption amount of (the first monomer + the second monomer) at the longest residence time. The abundance ratio of the first monomer is calculated from the cumulative composition of the first monomer (Fcum, the first monomer). The cumulative composition of the first monomer is determined from the monomer consumption ratio. That is, it is determined from the value obtained by dividing (the monomer consumption amount of the first monomer) by (the monomer consumption amount of the first monomer + the second monomer). The ratio is calculated by dividing (the cumulative composition of the first monomer with a normalized polymer chain length within 20% at the initial stage of polymerization) by (the cumulative composition of the first monomer in the whole polymer).

[0069] As long as the ratio of the abundance ratio of the first monomer within 20% of the entire polymer from the end at the polymerization initiation end of the random copolymer to the abundance ratio of the first monomer in the entire polymer of the random copolymer is 0.6 or more and 1.4 or less, there is no particular limitation, and it can be appropriately selected according to the purpose. As long as the lower limit value of the ratio of the abundance ratio of the first monomer within 20% of the entire polymer from the end at the polymerization initiation end of the random copolymer to the abundance ratio of the first monomer in the entire polymer of the random copolymer is 0.6 or more, there is no particular limitation, and it can be appropriately selected according to the purpose. However, from the viewpoint of evenly distributing different monomers in the entire polymer, 0.65 or more is preferable, 0.7 or more is more preferable, 0.8 or more is particularly preferable, and 0.9 or more is most preferable. As long as the upper limit value of the ratio of the abundance ratio of the first monomer within 20% of the entire polymer from the end at the polymerization initiation end of the random copolymer to the abundance ratio of the first monomer in the entire polymer of the random copolymer is 1.4 or less, there is no particular limitation, and it can be appropriately selected according to the purpose. However, from the viewpoint of evenly distributing different monomers in the entire polymer, 1.35 or less is preferable, 1.3 or less is more preferable, and 1.25 or less is particularly preferable.

[0070] The number average molecular weight (Mn) of the random copolymer is not particularly limited and can be appropriately selected according to the purpose. However, 200 to 100,000 is preferable, 500 to 10,000 is more preferable, and 1,000 to 5,000 is even more preferable.

[0071] The molecular weight distribution (Mw / Mn) obtained by dividing the weight average molecular weight (Mw) of the random copolymer by the number average molecular weight (Mn) is not particularly limited and can be appropriately selected according to the purpose. However, 1.50 or less is preferable, and 1.40 or less is more preferable.

[0072] The random copolymer can be obtained by the method for producing the random copolymer.

Example

[0073] Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples at all.

[0074] <1. Copolymerization of alkyl methacrylate> (Reference Example 1) A flow microreactor composed of two T-shaped micromixers (M1 and M2: manufactured by Mitsuyuki Seiki Kogyo Co., Ltd.) and two microtube reactors (R1 and R2: manufactured by GL Sciences) shown in FIG. 1 was used. Three pre-cooling units (P1, P2, and P3: φ = 1000 μm, length = 100 cm: manufactured by GL Sciences) were connected to each inlet of the micromixers M1 and M2.

[0075] The flow microreactor system was placed in a cooling bath at -20°C, and a diphenylhexyl lithium (DPHLi) solution (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: methyl methacrylate (MMA: Tokyo Chemical Industry Co., Ltd.): 0.25 M THF solution, monomer 2: di(ethylene glycol) methyl ether methacrylate (MEO 2 MA: Sigma-Aldrich Co.): 0.25 M THF solution, undecane as an internal standard: 0.06 M THF solution) (flow rate: 6.0 mL / min) manufactured by the following method were introduced into M1 (φ = 250 μm) by a syringe pump (Harvard PHD 2000: SGE), and the mixture was passed through R1 having the inner diameter and length described in Table 1, and at M2 (φ = 250 μm), it was mixed with a methanol solution (0.33 M THF solution) (flow rate: 3.0 mL / min) supplied by a syringe pump. The resulting solution was passed through R2 (φ2 = 1000 μm, L2 = 50 cm), and after reaching a steady state, the product solution was collected (for 30 seconds).

[0076] The monomers were distilled using CaH 2 before use. The monomer conversion was measured by gas chromatography analysis (using a fused silica capillary column: SHIMADZU GC-2014 gas chromatograph equipped with a flame ionization detector with CBP1 0.22 mm × 25 m), and the results are shown in Table 1 and Figure 2(a). The black triangles in Figure 2(a) indicate the monomer consumption of MMA, and the black squares indicate the monomer consumption of MEO 2 MA.

[0077] -Preparation of -DPHLi- A hexane solution of n-BuLi (Kanto Chemical Co., Inc.) was added to a slightly excess THF solution (1.1 molar equivalents) of 1,1-diphenylethylene (Sigma-Aldrich Co.) at 0 °C and warmed to room temperature. 1,1-Diphenylethylene was distilled using CaH 2 before use. Tetrahydrofuran (THF) was purchased from Fujifilm Wako Pure Chemical Corporation as a dry solvent and used without purification.

[0078] [Table 1]

[0079] (Comparative Example 1) As monomer 2, tert-butyl methacrylate (tBuMA: Tokyo Chemical Industry Co., Ltd.) was used, and the procedure was the same as in Reference Example 1 except that R1 with the inner diameter and length described in Table 2 was used. The results are shown in Table 2 and Figure 2(b). The black triangles in Figure 2(b) indicate the monomer consumption of MMA, and the black circles indicate the monomer consumption of tBuMA.

[0080] [Table 2]

[0081] (Comparative Example 2) As monomer 1, tert-butyl methacrylate (tBuMA: Tokyo Chemical Industry Co., Ltd.) was used, and the procedure was the same as in Reference Example 1 except that R1 with the inner diameter and length described in Table 3 was used. The results are shown in Table 3 and Figure 2(c). The black circles in Figure 2(c) indicate the monomer consumption of tBuMA, and the black squares indicate the monomer consumption of MEO 2 MA.

[0082]

Table 3

[0083] From the results of Tables 1 to 3 and Figure 2, unlike the case where the consumption rates of monomer 1 and monomer 2 do not deviate (Reference Example 1), when the consumption rates of monomer 1 and monomer 2 deviate (Comparative Examples 1 and 2), it was found that a random copolymer could not be obtained and a gradient copolymer could be obtained (Figures 2(b) and (c)).

[0084] <2. Measurement of Monomer Reactivity Ratio by Quench Flow Method> (Example 1) A flow microreactor composed of two T-type micromixers (M1 and M2: manufactured by Sanko Seiki Kogyo Co., Ltd.) and two microtube reactors (R1 and R2: manufactured by GL Sciences) shown in Figure 3 was used. Three pre-cooling units (P1, P2, and P3: φ = 1000 μm, length = 100 cm: manufactured by GL Sciences) were connected to the inlets of the micromixers M1 and M2.

[0085] The entire flow microreactor system was placed in a cooling bath at -20°C, and a solution of diphenylhexyl lithium (DPHLi) (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: tert-butyl methacrylate (tBuMA: Tokyo Chemical Industry Co., Ltd.): C described in Table 4 1 M THF solution, monomer 2: di(ethylene glycol) methyl ether methacrylate (MEO2 MA: Sigma - Aldrich Co.): C described in Table 4 2 M THF solution, undecane as internal standard: 0.06 M THF solution) (flow rate: 6.0 mL / min) and were introduced into M1 (φ = 250 μm) by a syringe pump (Harvard PHD 2000: SGE), and the mixture was passed through R1 with the inner diameter (φ 1 ), and length (L 1 ) described in Table 4, and mixed with the methanol solution (0.33 M THF solution) (flow rate: 3.0 mL / min) supplied by the syringe pump at M2 (φ = 250 μm). The resulting solution was passed through R2 (φ 2 = 1000 μm, L 2 = 50 cm), and after reaching a steady state, the product solution was collected (for 30 seconds).

[0086] The monomer was distilled using CaH 2 before use. Monomer conversion was measured by gas chromatography analysis (a SHIMADZU GC - 2014 gas chromatograph equipped with a flame ionization detector using a fused silica capillary column: CBP1 0.22 mm × 25 m), and the results are shown in Table 4.

[0087]

Table 4

[0088] The feed ratio of monomers (F = [M tBuMA / [M MEO2MA ) was calculated from the initial concentrations and flow rates of each monomer. [M tBuMA = ([tBuMA] 0 × 6.0 mL / min) / ([tBuMA] 0 × 6.0 mL / min + [MEO 2 MA] 0 × 6.0 mL / min) Next, the monomer ratio in the copolymer (f = d[M tBuMA / d[M MEO2MA ) was calculated from the conversion rates of each monomer. d[M 1 =([tBuMA] 0 ×6.0 mL / min×Conv.(tBuMA)) / ([tBuMA] 0 ×6.0 mL / min×Conv.(tBuMA)+[MEO 2 MA] 0 ×6.0 mL / min×Conv.(MEO 2 MA))

[0089] Table 5 shows the values of the feed ratio F of the monomers and the monomer ratio f in the copolymer, calculated from the results of Entries 3, 6, and 7 in Table 4. Note that for all of Entries 3, 6, and 7, the ratio of the total monomer consumption to the total monomer charge amount is 10% or less.

[0090]

Table 5

[0091] The monomer reactivity ratios were determined from the Fineman-Ross Plot created using the above F and f. Figure 4 shows the Fineman-Ross Plot created using the results of Entries 3, 6, and 7 in Table 4. From the slope and intercept of the straight line obtained in the Fineman-Ross Plot of Figure 4, the monomer reactivity ratios r1 and r2 were derived as follows. r1(tBuMA)=0.98 r2(MEO 2 MA)=40 The correlation coefficient at this time was 0.93.

[0092] <3. Determination of Initial Concentration> The total initial concentration was set to 1.0 M, and when the monomer ratio in the copolymer was 1 (d[M tBuMA / d[M MEO2MA =1), the initial concentrations of each monomer were calculated using the Mayo-Lewis equation (Equation 1) shown below, and [tBuMA] 0 =0.86 M, [MEO 2 MA]0 It was 0.14 M.

[0093]

Number

[0094] Similarly, when the monomer ratio in the copolymer was 2, the initial concentration of each monomer was calculated. For [tBuMA] 0 = 0.91 M, [MEO 2 MA] 0 = 0.09 M. When the initial concentration of each monomer was calculated when the monomer ratio in the copolymer was 0.5, for [tBuMA] 0 = 0.81 M, [MEO 2 MA] 0 = 0.19 M (Table 6).

[0095]

Table 6

[0096] <4. Copolymerization of alkyl methacrylate with a predetermined initial concentration> (Example 2) A flow microreactor composed of two T-type micromixers (M1 and M2: manufactured by Mitsuyuki Seiki Kogyo Co., Ltd.) and two microtube reactors (R1 and R2: manufactured by GL Sciences) shown in Fig. 5 was used. Three pre-cooling units (P1, P2, and P3: φ = 1000 μm, length = 100 cm: manufactured by GL Sciences) were connected to each inlet of the micromixers M1 and M2.

[0097] The entire flow microreactor system was placed in a cooling bath at -20°C, and a diphenylhexyl lithium (DPHLi) solution (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: tert-butyl methacrylate (tBuMA: Tokyo Chemical Industry Co., Ltd.): C 1M (0.86M) THF solution, monomer 2: di(ethylene glycol) methyl ether methacrylate (MEO 2 MA: Sigma-Aldrich Co.): C 2 M (0.14M) THF solution, undecane as the internal standard: 0.06M THF solution) (flow rate: 6.0 mL / min) and were introduced into M1 (φ = 250 μm) by a syringe pump (Harvard PHD 2000: SGE), and the mixture was passed through R1 with the inner diameter (φ 1 ), and length (L 1 ) described in Table 7, and at M2 (φ = 250 μm), it was mixed with a methanol solution (0.33M THF solution) (flow rate: 3.0 mL / min) supplied by a syringe pump. The resulting solution was passed through R2 (φ 2 = 1000 μm, L 2 = 50 cm), and after reaching a steady state, the product solution was collected (for 30 seconds).

[0098] The monomer was distilled using CaH 2 before use. Monomer conversion was measured by gas chromatography analysis (a fused silica capillary column: SHIMADZU GC-2014 gas chromatograph equipped with a flame ionization detector using CBP1 0.22 mm × 25 m). The cumulative composition of tBuMA (Fcum, tBuMA) was determined from the monomer consumption ratio. That is, it was determined from the value obtained by dividing the monomer consumption amount of tBuMA by the monomer consumption amount of (tBuMA + MEO 2 MA). The results are shown in Table 7. The monomer consumption amount is shown in Fig. 6(a), and the cumulative composition of tBuMA is shown in Fig. 6(b). The black circles in Fig. 6(a) indicate the monomer consumption amount of tBuMA, and the black squares indicate the monomer consumption amount of MEO 2 MA.

[0099]

Table 7

[0100] (Example 3) The initial concentration of monomer 1: tBuMA was changed from 0.86 M to 0.91 M, and the initial concentration of monomer 2: MEO 2 MA was changed from 0.14 M to 0.09 M. The procedure was the same as in Example 2 except that R1 with the inner diameter and length described in Table 8 was used. The results are shown in Table 8 and Figure 7. The black circles in Figure 7(a) indicate the monomer consumption of tBuMA, and the black squares indicate MEO 2 indicate the monomer consumption of MA.

[0101]

Table 8

[0102] (Example 4) The initial concentration of monomer 1: tBuMA was changed from 0.86 M to 0.81 M, and the initial concentration of monomer 2: MEO 2 MA was changed from 0.14 M to 0.19 M. The procedure was the same as in Example 2 except that R1 with the inner diameter and length described in Table 9 was used. The results are shown in Table 9 and Figure 8. The black circles in Figure 8(a) indicate the monomer consumption of tBuMA, and the black squares indicate MEO 2 indicate the monomer consumption of MA.

[0103]

Table 9

[0104] From the results of Tables 7 to 9 and Figures 6 to 8, when a first monomer with a monomer reactivity ratio r1 derived from the straight line obtained by the Fineman-Ross Plot (where the correlation coefficient R ≥ 0.9) and a second monomer with a monomer reactivity ratio r2 greater than the monomer reactivity ratio r1 are reacted at a predetermined concentration derived from the Mayo-Lewis equation, it was found that a random copolymer in which different monomer units are evenly distributed in the polymer molecules can be produced.

[0105] <5. Random copolymer synthesis by monomer addition> (Example 5) A flow microreactor composed of three T-shaped micromixers (M1, M2, and M3; manufactured by Mitsuyuki Seiki Kogyo Co., Ltd.) and three microtube reactors (R1, R2, and M3; manufactured by GL Sciences) shown in Fig. 9 was used. Four precooling units (P1, P2, P3, and P4; φ = 1000 μm, length = 100 cm; manufactured by GL Sciences) were connected to the inlets of the micromixers M1, M2, and M3.

[0106] The entire flow microreactor system was placed in a cooling bath at -20°C, and a diphenylhexyl lithium (DPHLi) solution (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: tert-butyl methacrylate (tBuMA; manufactured by Tokyo Chemical Industry Co., Ltd.): C 1 M (0.86 M) THF solution, monomer 2: methyl ether methacrylate di(ethylene glycol) methyl ether methacrylate (MEO 2 MA; manufactured by Sigma-Aldrich Co.): C 2 M (0.14 M) THF solution, undecane as an internal standard: 0.06 M THF solution) (flow rate: 6.0 mL / min) were introduced into M1 (φ = 250 μm) by a syringe pump (Harvard PHD 2000; SGE), and the mixture was passed through R1 (φ 1 = 1000 μm, L 1 = 6.5 cm) and mixed with the MEO 2 MA solution (C 3 M (0.2 M) THF solution) (flow rate: 2.0 mL / min) in M2 (φ = 250 μm).

[0107] The resulting mixture was passed through R2 with the inner diameter (φ2) and length (L2) described in Table 10 and mixed with a methanol solution (0.33 M THF solution) (flow rate: 3.0 mL / min) supplied by a syringe pump in M3 (φ = 250 μm). The resulting solution was passed through R3 (φ 3 = 1000 μm, L 3It was passed through (length = 50 cm), and after reaching a steady state, the product solution was collected (for 30 seconds).

[0108] The monomer was distilled using CaH 2 before use. Monomer conversion was measured by gas chromatography analysis (a fused silica capillary column: SHIMADZU GC - 2014 gas chromatograph equipped with a flame ionization detector using CBP1 0.22 mm×25 m). The cumulative composition of tBuMA (Fcum,tBuMA) was determined from the monomer consumption ratio. That is, it was determined from the value obtained by dividing the monomer consumption amount of tBuMA by the monomer consumption amount of (tBuMA + MEO 2 MA). The results are shown in Table 10. The monomer consumption amount is shown in Fig. 10(a), and the cumulative composition of tBuMA is shown in Fig. 10(b). The black circles in Fig. 10(a) indicate the monomer consumption amount of tBuMA before adding and reacting MEO 2 MA in M2, the white circles indicate the monomer consumption amount of tBuMA after adding and reacting MEO 2 MA in M2, the black squares indicate the monomer consumption amount of MEO 2 MA before adding and reacting MEO 2 MA in M2, and the white squares indicate the monomer consumption amount of MEO 2 MA after adding and reacting MEO 2 MA in M2.

[0109]

Table 10

[0110] (Example 6) The initial concentration of monomer 1: tBuMA was changed from 0.86 M to 0.91 M, and the initial concentration of monomer 2: MEO 2 MA was changed from 0.14 M to 0.09 M. It was carried out in the same manner as in Example 5 except that R2 with the inner diameter and length described in Table 11 was used. The results are shown in Table 11 and Fig. 11. The black circles in Fig. 11(a) are for MEO in M2 2 show the monomer consumption of tBuMA before the addition reaction of MA, and the white circles are for MEO in M2 2 show the monomer consumption of tBuMA after the addition reaction of MA, and the black squares are for MEO in M2 2 show the monomer consumption of MEO before the addition reaction of MA 2 and the white squares are for MEO in M2 2 show the monomer consumption of MEO after the addition reaction of MA 2 .

[0111]

Table 11

[0112] (Example 7) The initial concentration of monomer 1: tBuMA was changed from 0.86 M to 0.81 M, and the initial concentration of monomer 2: MEO 2 MA was changed from 0.14 M to 0.19 M, and it was carried out in the same manner as in Example 5 except that R2 with the inner diameter and length described in Table 12 was used. The results are shown in Table 12 and Fig. 12. The black circles in Fig. 12(a) are for MEO in M2 2 show the monomer consumption of tBuMA before the addition reaction of MA, and the white circles are for MEO in M2 2 show the monomer consumption of tBuMA after the addition reaction of MA, and the black squares are for MEO in M2 2 show the monomer consumption of MEO before the addition reaction of MA 2 and the white squares are for MEO in M2 2 show the monomer consumption of MEO after the addition reaction of MA 2 .

[0113]

Table 12

[0114] From the results of Tables 10 to 12 and Figures 10 to 12, a first monomer with a monomer reactivity ratio r1 derived from the straight line obtained by the Fineman-Ross Plot (where the correlation coefficient R ≥ 0.9) and a second monomer with a monomer reactivity ratio r2 greater than the monomer reactivity ratio r1 are reacted at a predetermined concentration derived from the Mayo-Lewis equation. It was found that a random copolymer in which different monomer units are evenly distributed in the polymer molecules can be produced. Furthermore, by adding and reacting the second monomer to the random copolymer, the random copolymer in which the different monomer units are evenly distributed in the polymer molecules can be extended in a state where the different monomer units are evenly distributed.

[0115] <6. Random copolymer synthesis by sequential monomer addition> (Example 8) A flow microreactor composed of four T-type micromixers (M1, M2, M3, and M4: manufactured by Mitsuyuki Seiki Kogyo Co., Ltd.) and four microtube reactors (R1, R2, M3, and M4: manufactured by GL Sciences) shown in Fig. 13 was used. Five pre-cooling units (P1, P2, P3, P4, and P5: φ = 1000 μm, length = 100 cm: manufactured by GL Sciences) were connected to the inlets of the micromixers M1, M2, M3, and M4.

[0116] The entire flow microreactor system was placed in a cooling bath at -20°C, and a diphenylhexyl lithium (DPHLi) solution (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: tert-butyl methacrylate (tBuMA: Tokyo Chemical Industry Co., Ltd.): C 1 M (0.86 M) THF solution, monomer 2: di(ethylene glycol) methyl ether methacrylate (MEO 2 MA: Sigma-Aldrich Co.): C 2M (0.14 M) THF solution and undecane as an internal standard: 0.06 M THF solution) (flow rate: 6.0 mL / min) were introduced into M1 (φ = 250 μm) by a syringe pump (Harvard PHD 2000: SGE), and the mixture was passed through R1 (φ 1 = 1000 μm, L 1 = 6.5 cm), and at M2 (φ = 250 μm), it was mixed with the MEO 2 MA solution (C 3 M (0.2 M) THF solution) (flow rate: 2.0 mL / min).

[0117] The resulting mixture was passed through R2 (φ 2 = 1000 μm, L 2 = 25 cm), and at M3 (φ = 250 μm), it was further mixed with the MEO 2 MA solution (C 4 M (0.2 M) THF solution) (flow rate: 2.5 mL / min).

[0118] The resulting mixture was passed through R3 with the inner diameter (φ3) and length (L3) described in Table 13, and at M4 (φ = 250 μm), it was mixed with the methanol solution (0.33 M THF solution) (flow rate: 3.0 mL / min) supplied by a syringe pump. The resulting solution was passed through R4 (φ 4 = 1000 μm, L 4 = 50 cm), and after reaching a steady state, the product solution was collected (for 30 seconds).

[0119] The monomer was distilled using CaH 2 before use. Monomer conversion was measured by gas chromatography analysis (a SHIMADZU GC - 2014 gas chromatograph equipped with a flame ionization detector using a fused silica capillary column: CBP1 0.22 mm × 25 m). The cumulative composition of tBuMA (Fcum, tBuMA) was determined from the monomer consumption ratio. That is, it was determined from the value obtained by dividing the monomer consumption amount of tBuMA by the monomer consumption amount of (tBuMA + MEO 2 MA). The results are shown in Table 13.

[0120] The cumulative composition of tBuMA when the normalized polymer chain length at the initial stage of polymerization in Table 7 is within 20% (Entry 7: normalized polymer chain length is 0.2) is 0.586. The cumulative composition of tBuMA in the entire polymer in Table 13 (Entry 8: normalized polymer chain length is 1) is 0.477, and the ratio is 1.229. The monomer consumption is shown in Fig. 14(a), and the cumulative composition of tBuMA is shown in Fig. 14(b). The black circles in Fig. 14(a) are the monomer consumption of tBuMA before the addition reaction of MEO 2 MA in M2, and the monomer consumption of tBuMA after the addition reaction of MEO 2 MA in M3. The white circles are the monomer consumption of tBuMA after the addition reaction of MEO 2 MA in M2 until the addition reaction of MEO 2 MA in M3. The black squares are the monomer consumption of tBuMA before the addition reaction of MEO 2 MA in M2, and the monomer consumption of MEO 2 MA before and after the addition reaction of MEO 2 MA in M3. The white squares are the monomer consumption of MEO 2 MA after the addition reaction of MEO in M2 until the addition reaction of MEO 2 MA in M3. The monomer consumption of MEO 2 MA before the addition reaction is shown. The number average molecular weight (Mn) and the molecular weight distribution (Mw / Mn) were determined using a Shodex GPC - 101 equipped with two LF - 804L columns (Shodex) in THF at 40°C. The number average molecular weight (Mn) was 2800, and the molecular weight distribution (Mw / Mn) was 1.38.

[0121] [Table 13]

[0122] (Example 9) The initial concentration of monomer 1: tBuMA was changed from 0.86 M to 0.91 M, and monomer 2: MEO 2The initial concentration of MA was changed from 0.14 M to 0.09 M, and the procedure was the same as in Example 8 except that R3 with the inner diameter and length described in Table 14 was used. The results are shown in Table 14 and Figure 15.

[0123] The cumulative composition of tBuMA when the normalized polymer chain length at the initial stage of polymerization in Table 8 was within 20% (Entry 5: normalized polymer chain length was 0.173) was 0.692, and the cumulative composition of tBuMA in the entire polymer in Table 14 (Entry 9: normalized polymer chain length was 1) was 0.697, and the ratio was 0.993. The black circles in Figure 15(a) are the monomer consumption of tBuMA before adding and reacting MEO 2 MA in M2, and the monomer consumption of tBuMA after adding and reacting MEO 2 MA in M3. The white circles are the monomer consumption of tBuMA after adding and reacting MEO 2 MA in M2 until adding and reacting MEO 2 MA in M3, and the black squares are the monomer consumption of tBuMA before adding and reacting MEO 2 MA in M2 before and after adding and reacting MEO 2 MA in M3, and the monomer consumption of MEO 2 MA. The white squares are the monomer consumption of MEO 2 MA after adding and reacting MEO in M2 until adding and reacting MEO 2 MA in M3, and the monomer consumption of MEO 2 MA before adding and reacting MEO is shown.

[0124]

Table 14

[0125] (Example 10) Monomer 1: The initial concentration of tBuMA was changed from 0.86 M to 0.81 M, Monomer 2: The initial concentration of MEO 2 MA was changed from 0.14 M to 0.19 M, and the procedure was the same as in Example 8 except that R3 with the inner diameter and length described in Table 15 was used. The results are shown in Table 15 and Figure 16.

[0126] The cumulative composition of tBuMA when the normalized polymer chain length at the initial stage of polymerization in Table 9 is within 20% (Entry 3: normalized polymer chain length is 0.182) is 0.455, and the cumulative composition of tBuMA in the entire polymer in Table 15 (Entry 12: normalized polymer chain length is 1) is 0.369, and the ratio is 1.233. The black circles in Fig. 16(a) are for MEO in M2 2 The monomer consumption of tBuMA before the addition reaction of MEO MA in M2, and MEO in M3 2 The monomer consumption of tBuMA after the addition reaction of MEO MA is shown. The white circles are for MEO in M2 2 After the addition reaction of MEO MA in M2 to MEO in M3 2 The monomer consumption of tBuMA before the addition reaction of MEO MA is shown. The black squares are for MEO in M2 2 Before the addition reaction of MEO MA, and MEO in M3 2 The monomer consumption of MEO MA after the addition reaction of MEO MA is shown. The white squares are for MEO in M2 2 After the addition reaction of MEO MA in M2 to MEO in M3 2 The monomer consumption of MEO MA before the addition reaction of MEO MA is shown. 2 The monomer consumption of MEO MA before the addition reaction of MEO MA is shown. 2 The monomer consumption of MEO MA is shown.

[0127]

Table 15

[0128] From the results in Tables 10 to 12 and Figures 10 to 12, a first monomer with a monomer reactivity ratio r1 derived from the straight line obtained by the Fineman-Ross Plot (where the correlation coefficient R ≥ 0.9) and a second monomer with a monomer reactivity ratio r2 greater than the monomer reactivity ratio r1 were reacted at a predetermined concentration derived from the Mayo-Lewis equation. It was found that a random copolymer in which different monomer units are evenly distributed in the polymer molecules can be produced. Furthermore, by adding and reacting the second monomer to the random copolymer multiple times, the random copolymer in which the different monomer units are evenly distributed in the polymer molecules can be extended in a state where the different monomer units are evenly distributed.

[0129] <7. Comparison of Polymer Solubilities> (Example 11) From the product solution obtained in Example 8 (tBuMA-MEO 2 MA random copolymer solution: Mn = 2800, Mw / Mn = 1.38), after removing low molecular weight components using preparative HPLC, trifluoroacetic acid (TFA) (3.0 mL, 39 mmol) was added to the random copolymer solution (15 mL, 0.10 M CH 2 Cl 2 solution). After stirring at room temperature for 12 hours under an argon atmosphere, the product solution was concentrated under reduced pressure. The obtained product was washed with chloroform while suction filtering and then dried in vacuo to obtain a methacrylic acid (MAA)-MEO 2 MA random copolymer.

Chemical formula

[0130] The obtained MAA-MEO 2 MA random copolymer and a buffer (phosphate buffer: pH 7, or borate buffer: pH 9) were added to a vial and placed in a refrigerator (about 4°C) overnight. Then, the temperature was raised to 20°C and the solubility was examined. The results are shown in the upper part of Figure 17.

[0131] (Comparative Example 3) A flow microreactor composed of two T-type micromixers (M1 and M2: manufactured by Mitsuyuki Seiki Kogyo Co., Ltd.) and two microtube reactors (R1 and R2: manufactured by GL Sciences) shown in Fig. 18 was used. Three pre-cooling units (P1, P2, and P3: φ = 1000 μm, length = 100 cm: manufactured by GL Sciences) were connected to each inlet of the micromixers M1 and M2.

[0132] The flow microreactor system was placed in a cooling bath at -20°C, and a solution of diphenylhexyl lithium (DPHLi) (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: tert-butyl methacrylate (tBuMA: Tokyo Chemical Industry Co., Ltd.): 0.12 M THF solution, monomer 2: di(ethylene glycol) methyl ether methacrylate (MEO 2 MA: Sigma-Aldrich Co.): 0.12 M THF solution, undecane as an internal standard: 0.06 M THF solution) (flow rate: 6.0 mL / min) were introduced into M1 (φ = 250 μm) by a syringe pump (Harvard PHD 2000: SGE), and the mixture was passed through R1 (φ 1 = 1000 μm, L 1 = 450 cm), and in M2 (φ = 250 μm), it was mixed with a methanol solution (0.33 M THF solution) (flow rate: 3.0 mL / min) supplied by a syringe pump. The resulting solution was passed through R2 (φ 2 = 1000 μm, L 2 = 50 cm), and after reaching a steady state, the product solution was collected (for 6 minutes). The monomers were distilled using CaH 2 before use.

[0133] The resulting product solution (tBuMA-MEO 2MA gradient copolymer solution: Mn = 3100, Mw / Mn = 1.44, using polystyrene (polySt) standard sample for calibration. After removing low molecular weight components using preparative HPLC, trifluoroacetic acid (TFA) (3.0 mL, 39 mmol) was added to the gradient copolymer solution (15 mL, 0.10 M CH 2 Cl 2 solution). After stirring at room temperature for 12 hours under an argon atmosphere, the product solution was concentrated under reduced pressure. The obtained product was washed with chloroform while suction filtering, and then dried in vacuo to obtain a methacrylic acid (MAA)-MEO 2 MA gradient copolymer.

Chemical formula

[0134] The obtained MAA-MEO 2 MA gradient copolymer and buffer (phosphate buffer: pH 7, or borate buffer: pH 9) were added to a vial and placed in a refrigerator (about 4°C) overnight. Then, the temperature was raised to 20°C and the solubility was examined. The results are shown in the middle section of Figure 17.

[0135] (Reference Example 2) A flow microreactor composed of two T-type micromixers (M1 and M2: manufactured by Mitsuyuki Seiki Kogyo Co., Ltd.) and two microtube reactors (R1 and R2: manufactured by GL Sciences) shown in Figure 18 was used. Three pre-cooling units (P1, P2, and P3: φ = 1000 μm, length = 100 cm: manufactured by GL Sciences) were connected to each inlet of the micromixers M1 and M2.

[0136] Place the flow microreactor system in a cooling bath at -20°C and introduce a solution of diphenylhexyl lithium (DPHLi) (0.050 M THF solution) (flow rate: 2.0 mL / min) and a monomer mixed solution (monomer 1: benzyl methacrylate (BnMA: Tokyo Chemical Industry Co., Ltd.): 0.12 M THF solution, monomer 2: di(ethylene glycol) methyl ether methacrylate (MEO 2 MA: Sigma-Aldrich Co.): 0.12 M THF solution, undecane as an internal standard: 0.06 M THF solution) (flow rate: 6.0 mL / min) prepared in the same manner as in Reference Example 1 into M1 (φ = 250 μm) using a syringe pump (Harvard PHD 2000: SGE), and pass the mixture through R1 (φ 1 = 1000 μm, L 1 = 450 cm), and mix it with a methanol solution (0.33 M THF solution) (flow rate: 3.0 mL / min) supplied by a syringe pump at M2 (φ = 250 μm). Pass the resulting solution through R2 (φ 2 = 1000 μm, L 2 = 50 cm), and after reaching a steady state, collect the product solution (for 6 minutes). The monomers were distilled using CaH 2 before use.

[0137] After removing the low molecular weight components from the obtained product solution (BnMA-MEO 2 MA random copolymer solution: Mn = 3600, Mw / Mn = 1.39, using a polystyrene (polySt) standard sample for calibration), add a boron trichloride (BCl 2 Cl 2 ) solution (1.0 M, 15 mL, 15 mmol) to the random copolymer solution (30 mL, 0.10 M CH 3 ) solution. Stir the product solution at room temperature for 12 hours under an argon atmosphere, and then concentrate the product solution under reduced pressure. Wash the obtained product with chloroform while suction filtering, and then dissolve it in acetone. Add a large excess of CHCl 3was added. The resulting precipitate was filtered and dried under reduced pressure to obtain a MAA-MEO 2 MA random copolymer. [Chemical formula]

[0138] The obtained MAA-MEO 2 MA random copolymer and a buffer (phosphate buffer: pH 7, or borate buffer: pH 9) were added to a vial and placed in a refrigerator (about 4°C) overnight. Then, the temperature was raised to 20°C and the solubility was examined. The results are shown in the lower part of FIG. 17.

[0139] From the results in FIG. 17, when the consumption rates of monomer 1 and monomer 2 deviate, the random copolymer produced by controlling the reaction conditions according to the method for producing a random copolymer of the present application (Example 11, upper part of FIG. 17) has a significantly increased polymer solubility and new physical properties compared to the case where the reaction conditions are not controlled (Comparative Example 3, middle part of FIG. 17). The solubility of the random copolymer produced by controlling the reaction conditions according to the method for producing a random copolymer of the present application (Example 11, upper part of FIG. 17) was comparable to that in the case where the consumption rates of monomer 1 and monomer 2 did not deviate (Reference Example 2, lower part of FIG. 17).

[0140] Examples of the aspects of the present invention include, for example, the following. <1> A method for producing a random copolymer by living anionic polymerization using a microreactor, comprising reacting a first monomer having a monomer reactivity ratio r1 derived from a straight line obtained by a Fineman-Ross Plot (where the correlation coefficient R ≧ 0.9) and a second monomer having a monomer reactivity ratio r2 larger than the monomer reactivity ratio r1 at a predetermined concentration derived from the Mayo-Lewis equation to obtain a random copolymer. A method for producing a random copolymer characterized by the above. <2> Reacting the first monomer and the second monomer so that the ratio of the total consumption amount of the first monomer and the second monomer to the total charged amount of the first monomer and the second monomer is 10% or less to obtain a random copolymer, which is the method for producing a random copolymer according to <1> above. <3> The method for producing a random copolymer according to <2> above, which includes adding and reacting the second monomer to the random copolymer to extend the random copolymer. <4> A method for producing a random copolymer by living anionic polymerization using a microreactor, which includes reacting at least a first monomer and a second monomer having a larger monomer reactivity ratio than the first monomer, and adding and reacting the second monomer to the obtained random copolymer to extend the random copolymer. <5> The method for producing a random copolymer according to any one of <3> to <4> above, wherein the addition reaction of the second monomer is carried out so that the consumption ratio of the first monomer and the second monomer in the random copolymer to be extended is substantially constant. <6> The method for producing a random copolymer according to any one of <3> to <5> above, wherein the addition reaction of the second monomer is carried out a plurality of times. <7> The method for producing a random copolymer according to any one of <1> to <6> above, wherein the first monomer and the second monomer are selected from methacrylic acid esters. <8> The method for producing a random copolymer according to any one of <1> to <7> above, wherein the reaction between the first monomer and the second monomer is carried out in the presence of an initiator. <9> A random copolymer containing a first monomer and a second monomer, The ratio of the abundance of the first monomer in the range within 20% of the whole polymer from the end at the polymerization initiation end of the random copolymer to the abundance of the first monomer in the whole polymer of the random copolymer is 0.6 or more and 1.4 or less, and the random copolymer is characterized by this. <10> The random copolymer according to <9> above, wherein the number average molecular weight (Mn) is from 200 to 100,000. <11> The random copolymer according to any one of <9> to <10> above, wherein the molecular weight distribution (Mw / Mn) obtained by dividing the weight average molecular weight (Mw) by the number average molecular weight (Mn) is 1.50 or less.

Claims

1. A method for producing a random copolymer by living anionic polymerization using a microreactor, comprising: derived from a straight line obtained by a Fineman-Ross Plot (where the correlation coefficient R ≥ 0.9), a first monomer having a monomer reactivity ratio r1, and a second monomer having a monomer reactivity ratio r2 greater than the monomer reactivity ratio r1 of the first monomer, reacting them at a predetermined concentration derived from the Mayo-Lewis equation to obtain a random copolymer. A method for producing a random copolymer, characterized by including this.

2. Reacting to obtain a random copolymer such that the ratio of the total consumption amount of the first monomer and the second monomer to the total charged amount of the first monomer and the second monomer is 10% or less. The method for producing a random copolymer according to Claim 1.

3. The method for producing a random copolymer according to any one of Claims 1 to 2, comprising adding and reacting the second monomer to the random copolymer to extend the random copolymer.

4. A method for producing a random copolymer by living anionic polymerization using a microreactor, comprising: reacting at least a first monomer and a second monomer having a larger monomer reactivity ratio than the first monomer to obtain a random copolymer, and adding and reacting the second monomer to the random copolymer to extend the random copolymer. A method for producing a random copolymer, characterized by including this.

5. The method for producing a random copolymer according to any one of Claims 3 to 4, wherein the addition reaction of the second monomer is performed such that the consumption ratio of the first monomer and the second monomer in the random copolymer to be extended is substantially constant.

6. The method for producing a random copolymer according to any one of Claims 3 to 5, wherein the addition reaction of the second monomer is performed a plurality of times.

7. The method for producing a random copolymer according to any one of Claims 1 to 6, wherein the first monomer and the second monomer are selected from methacrylic acid esters.

8. The method for producing a random copolymer according to any one of Claims 1 to 7, wherein the reaction between the first monomer and the second monomer is performed in the presence of an initiator. ​

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