JP2009067999A - METHOD FOR PRODUCING POLYMER HAVING Mw/Mn OF 1.25 OR LOWER - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a polymer having an M<SB>w</SB>/M<SB>n</SB>of 1.25 or lower by which the polymer of a narrow molecular weight distribution can be efficiently produced even at a reaction temperature of -28°C or higher, and to provide a method for producing a block polymer which has an M<SB>w</SB>/M<SB>n</SB>of 1.25 or lower and can be produced by a continuous process. <P>SOLUTION: Disclosed is a method for producing a polymer of an M<SB>w</SB>/M<SB>n</SB>of 1.25 or lower which comprises effecting a living polymerization of a monomer in the presence of an initiator by using a microreactor provided with a channel capable of mixing a plurality of liquids with each other. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to a method for producing a polymer having M _w / M _n of 1.25 or less, and in particular, M _w / M capable of efficiently producing a polymer having a narrow molecular weight distribution even when the reaction temperature is −28 ° C. or higher. _{The present} invention relates to a method for producing a polymer in which _n is 1.25 or less.

  Living polymerization consists of only an initiation reaction and a growth reaction, and is a polymerization reaction in which the transfer reaction and termination reaction can be almost ignored. Compared with general polymer polymerization reactions, living polymerization can (1) accurately control the molecular weight of the resulting polymer by the molar ratio of monomer to initiator; (2) a polymer with a very narrow molecular weight distribution can be synthesized. (3) The molecular design of various polymers (block copolymer, graft copolymer, terminal functionalized polymer, star polymer, etc.) can be made by utilizing the stability and reactivity of the polymer terminal; Has advantages such as.

  Living polymerization began with a report on living anionic polymerization of styrene by Szwarc in 1956, and was mostly found in living anionic polymerization until the 1970s. In recent years, not only living anionic polymerization but also various living polymerizations such as living cationic polymerization and living radical polymerization have been developed.

Among the living polymerizations, the living anionic polymerization is still the most excellent method for living polymerization of styrene and 1,3-dienes, and has a narrow molecular weight distribution (M _w / M _n ) and a molecular weight of several hundreds. It has the feature that tens of thousands of polymers can be synthesized. Furthermore, the living anionic polymerization is the best method for considering precise molecular design because knowledge on the reactivity and structure of the growth carbaion of the polymer has been accumulated over the past several decades. It is thought that there is.

Conventionally, the living polymerization is performed in a batch mode. In the batch system, in order to prepare the initiation reaction of living polymerization, the monomer and the initiator must be mixed while being cooled to −78 ° C. or lower, so that there is a problem that an ultra-low temperature cooling facility is required. In addition, in order to align the initiation reaction of living polymerization, the monomer has to be added in a mist form or at a low concentration (for example, less than 1.5M), which is not suitable for mass production.
In addition, when an electrophile having two reactive sites such as dichlorosilane is used as a building block to produce a block polymer by connecting different living polymers, first, an excessive amount of the above-mentioned living polymer is used. After adding the electrophile and isolating the polymer to which the electrophile has been added once, it has to be reacted with another living polymer, which is troublesome.

On the other hand, recently, in the field of chemical synthesis, a chemical reaction using a micro container called a microreactor has been studied (for example, see Non-Patent Documents 1 and 2). The microreactor is a micro container provided with a flow channel capable of mixing a plurality of liquids, and an introduction channel that communicates with the flow channel and introduces the liquid into the flow channel. The one of 100 μm is typical. The plurality of liquids supplied through the introduction path of the microreactor are mixed together by the flow path to cause a reaction.
In reactions using microreactors, it is thought that precise flow control of reaction solutions, temperature control, and rapid mixing are possible. Compared with conventional batch-type reactions, the conversion rate and selectivity are controlled. Improvement is expected, and it is attracting attention as a highly efficient production method. The German IMM and FZK laboratories are developing microreactors for mixing, heat exchange, catalytic reactions, and electrochemical reactions, and are proposing the construction of mini-plants using these reactor components.

As described above, the batch method has a problem that a cooling device is necessary to realize a low temperature environment during the reaction, and further, it takes time and effort because it needs to be atomized or diluted. Furthermore, when a block polymer is produced using an electrophile having two reactive sites as a building block, there is a problem that it takes time since a process for isolating the polymer is required.
Therefore, a novel technique for synthesizing a polymer having a narrow molecular weight distribution, for example, a method capable of producing a polymer efficiently and at a high conversion without using a special cooling device, etc., by a method of producing using the microreactor, In addition, there is a demand for a method capable of producing a block polymer in a continuous process, but at present, no satisfactory method has been provided.

“Chimia”, 2002, volume 56, p. 636 “Tetrahedron”, vol. 58, p. 4735-4757

An object of the present invention is to solve the conventional problems and achieve the following objects. That is, an object of the present invention is to provide a method for producing a polymer having an M _w / M _n of 1.25 or less, which can efficiently produce a polymer having a narrow molecular weight distribution even when the reaction temperature is −28 ° C. or higher. And Moreover, this invention aims at providing the manufacturing method of the block polymer which can be manufactured by a continuous process and whose _Mw / _Mn is 1.25 or less.

  In order to solve the above-mentioned problems, the present inventors have made extensive studies and as a result, obtained the following findings. That is, by using a microreactor to react a monomer and an initiator, a polymer having a narrow molecular weight distribution can be efficiently produced even at a reaction temperature of −28 ° C. or higher. It was found that a polymer having a functional group at the terminal or a block polymer can be produced by reacting the growth terminal carbanion with an electrophile.

The present invention is based on the above findings by the present inventors, and means for solving the above problems are as follows. That is,
<1> A polymer having M _w / M _n of 1.25 or less, wherein a monomer is living-polymerized in the presence of an initiator using a microreactor having a flow path capable of mixing a plurality of liquids. It is a manufacturing method.
<2> The production method according to <1>, wherein M _w / M _n is 1.20 or less.
<3> The production method according to any one of <1> to <2>, wherein the living polymerization is a living anion polymerization.
<4> The production method according to any one of <1> to <3>, wherein a reaction temperature in the living polymerization is −28 ° C. or higher.
<5> The production method according to <4>, wherein the reaction temperature in the living polymerization is 24 ° C. or higher.
<6> The production method according to any one of <1> to <5>, wherein the initiator is an organolithium reagent.
<7> Any one of <1> to <6>, wherein an inner diameter of each of the first introduction path for introducing the monomer into the flow path and the second introduction path for introducing the initiator into the flow path is 500 μm or less. It is a manufacturing method as described in above.
<8> The production method according to any one of <1> to <7>, wherein the monomer is introduced into the flow path at a flow rate of 3 ml / min or more and the initiator is introduced at a flow rate of 1 ml / min or more.
<9> The production method according to <8>, wherein the molecular weight of the polymer is controlled by changing a ratio between a flow rate at which the monomer is introduced and a flow rate at which the initiator is introduced.
<10> The production method according to any one of <1> to <9>, wherein the concentration of the monomer in the first introduction path for introducing the monomer into the flow path is 1.5 M or more.
<11> The production method according to any one of <1> to <10>, wherein the monomer is styrene.
<12> The production method according to any one of <1> to <10>, wherein the monomer has a functional group.
<13> The production method according to <12>, wherein the monomer is a styrene derivative.
<14> The production method according to any one of <1> to <13>, wherein the initiator is alkyllithium.
<15> The method according to <14>, wherein the alkyl lithium is sec-butyl lithium.
<16> The production method according to any one of <1> to <10>, wherein the monomer is methyl methacrylate.
<17> The production method according to <16>, wherein the initiator is one of a molecule bulkier than sec-butyllithium and a molecule having a large steric hindrance.
<18> The production method according to <17>, wherein the bulky molecule or the molecule having a large steric hindrance is any one of methylstyryl lithium, diphenylmethylphenyl lithium, and diphenylhexyl lithium.
<19> The production method according to any one of <1> to <18>, wherein the polymer is a linear polymer.
<20> including a step of reacting a growth terminal of a polymer after living polymerization with an electrophile having two or more reaction points using a microreactor including a flow path capable of mixing a plurality of liquids <1 > To <19>.
<21> The production method according to any one of <1> to <20>, wherein the polymer is a block polymer.
<22> The production method according to <21>, wherein living polymerization is performed in multiple stages.
<23> A step of reacting a polymer growth terminal after at least one stage of living polymerization with an electrophile having two or more reaction points, using a microreactor including a flow path capable of mixing a plurality of liquids. It is a manufacturing method as described in <22> containing.
<24> The production method according to <23>, wherein the electrophile is dichlorodimethylsilane.
<25> The method according to any one of <23> to <24>, wherein the amount of the electrophile added is 1 to 10 equivalents relative to the initiator.
<26> Using a microreactor equipped with a flow path capable of mixing a plurality of liquids, and produced by living polymerizing monomers in the presence of an initiator, containing Si in the polymer skeleton, It is a block polymer whose _Mw / _Mn is 1.25 or less.

According to the present invention, conventional problems can be solved, and a polymer having a narrow molecular weight distribution can be efficiently produced even at a reaction temperature of −28 ° C. or higher. M _w / M _n is 1.25 or lower. A method for producing a polymer can be provided. Moreover, according to this invention, it can manufacture with a continuous process and can provide the manufacturing method of the block polymer whose _Mw / _Mn is 1.25 or less.

(Method for producing polymer having _Mw / _Mn of 1.25 or less)
In the production method of the present invention, a monomer and an initiator for initiating polymerization are introduced into a microreactor having a flow channel capable of mixing a plurality of liquids, and the monomer is present in the microreactor. It includes a step of living polymerizing below, and other steps as necessary.

Herein, the "M _{w /} M _n" means a molecular weight distribution of the polymer, the a weight average molecular weight of the "M _w" in the "M _{w /} M _n", the "M _n" is Number average molecular weight.
Here, the “M _w / M _n ” can be determined by, for example, a GPC (gel permeation chromatography) method.

According to the production method of the present invention, precise flow control of the reaction solution, precise temperature control, and rapid mixing can be realized by the microreactor, so that the “M _w / M _n ” has a value close to 1. A polymer having a narrow molecular weight distribution can be produced.
The “M _w / M _n ” of the polymer produced by the production method of the present invention is not particularly limited as long as it is 1.25 or less, but is preferably 1.20 or less, more preferably 1.15 or less, 1.10 or less is more preferable.

<Living polymerization>
The living polymerization consists of only an initiation reaction and a growth reaction, and is a polymerization reaction in which a transfer reaction and a termination reaction can be almost ignored.
The polymerization method of the living polymerization is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include living anion polymerization, living cation polymerization, living radical polymerization, living coordination polymerization, and living ring-opening polymerization. Can be mentioned. Among them, living anionic polymerization is preferable because it is particularly excellent for living polymerization of styrene and 1,3-dienes, has a narrow molecular weight distribution, and can synthesize a polymer having a molecular weight of several hundred to several tens of thousands. Living anionic polymerization is also preferred because knowledge about the reactivity and structure of the growth terminal carbanion of the polymer has been abundantly accumulated over the past several decades.

The living polymerization initiation reaction and growth reaction are usually carried out by mixing a monomer as a raw material and an initiator selected according to the desired polymerization method. The initial monomer and initiator are introduced into the microreactor in the form of a liquid solubilized in a solvent.
Here, in the production method of the present invention, the monomer and the initiator are mixed using a microreactor. By using the microreactor, the monomer and the initiator can be efficiently mixed, so that the initiation reaction can be made uniform, and the molecular weight distribution of the produced polymer can be narrowed. In addition, since the reaction heat can be efficiently removed by using the microreactor, temperature unevenness in the reaction solution is eliminated, and even if the monomer has a functional group, the functional group starts with the functional group. Side reaction with the agent can be suppressed.

-Microreactor-
The microreactor includes a minute flow path capable of mixing a plurality of liquids, and if necessary, includes an introduction path that communicates with the flow path and introduces the liquid into the flow path. Includes configurations other than the flow path and the introduction path.

  The microreactor used in the present invention is not particularly limited as long as it has a minute flow path capable of mixing a plurality of liquids, and can be appropriately selected according to the purpose. For example, a micromixer (substrate type A micromixer, a pipe joint type micromixer, etc.) and a branched tube.

The substrate-type micromixer includes a substrate having a flow path formed inside or on the surface, and is sometimes referred to as a microchannel.
The substrate-type micromixer is not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. For example, the mixing type described in International Publication No. 96/30113 pamphlet And a mixer described in the document “Microreactors”, Chapter 3, W. Ehrfeld, V. Hessel, H. Lowe, published by Wiley-VCH, and the like.

In addition to the flow path, the substrate-type micromixer is preferably provided with an introduction path that communicates with the flow path and introduces a plurality of liquids into the flow path. That is, a configuration in which the upstream side of the flow path branches according to the number of the introduction paths is preferable.
The number of the introduction paths is not particularly limited and may be appropriately selected depending on the purpose. However, a plurality of liquids desired to be mixed are introduced from different introduction paths, and are mixed and mixed in the flow paths. Is preferred. In addition, it is good also as a structure which prepares one liquid previously in a flow path, and introduces other liquids by an introduction path.

  The pipe joint type micromixer includes a flow path formed inside, and a connection unit that connects the flow path formed inside and the tube as necessary. The connection method in the connection means is not particularly limited, and can be appropriately selected from known tube connection methods according to the purpose. For example, a screw type, a union type, a butt welding type, a plug welding type, Examples include a socket welding type, a flange type, a biting type, a flare type, and a mechanical type.

  In addition to the flow path, it is preferable that an introduction path that communicates with the flow path and introduces a plurality of liquids into the flow path is formed inside the pipe joint type micromixer. 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 can be used as the pipe joint type micromixer, and when the number of the introduction paths is three, For example, a cross shape can be used. In addition, it is good also as a structure which prepares one liquid previously in a flow path, and introduces other liquids by an introduction path.

  The material of the micromixer is not particularly limited and can be appropriately selected according to requirements such as heat resistance, pressure resistance, solvent resistance, and processability. For example, stainless steel, titanium, copper, Examples thereof include nickel, aluminum, silicon, fluorine resin such as Teflon (registered trademark) and PFA (perfluoroalkoxy resin), TFAA (trifluoroacetamide), and the like.

Since the micromixer accurately controls the flow of the reaction solution by its fine structure, it is preferable that the micromixer is manufactured by a fine processing technique.
The microfabrication technology is not particularly limited and can be appropriately selected according to the purpose. For example, (a) LIGA technology combining X-ray lithography and electroplating, (b) high aspect ratio using EPON SU8 Specific photolithography, (c) mechanical micro-cutting (such as micro-drilling that rotates a drill with a micro-order drill diameter at high speed), (d) high-aspect-ratio silicon processing by Deep RIE, (e) Hot Emboss Examples of the processing method include (f) stereolithography, (g) laser processing, and (h) ion beam method.

  Commercially available products can be used as the micromixer, for example, a microreactor having an interdigital channel structure, a single mixer and a caterpillar mixer manufactured by Institute Hugh Microtechnique Mainz (IMM); manufactured by Microglass Micrograss Reactor; CPC Systems Cytos; Yamatake YM-1 mixer, YM-2 mixer; Shimadzu GLC mixing tee and tee (T-connector); Micro Chemical Giken IMT chip reactor; Toray Engineering-developed micro-high mixer; Swagelok union tee.

  As the microreactor, the micromixer may be used alone, or a tube reactor may be connected downstream thereof to extend the flow path. The length of the flow path can be adjusted by connecting the tube reactor downstream of the micromixer. The residence time (reaction time) of the mixed liquid is proportional to the length of the flow path.

The tube reactor is a reactor for precisely controlling (retention time control) a time required for a solution rapidly mixed by a micromixer to perform a subsequent reaction.
There is no restriction | limiting in particular as said tube reactor, For example, structures, such as an inner diameter of a tube, an outer diameter, length, and a material, can be suitably selected according to desired reaction.
As the tube reactor, 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 diameter 250 μm, 500 μm, and 1,000 μm can be selected. Tube length can be adjusted by the user).
There is no restriction | limiting in particular as a material of the said tube reactor, What was illustrated as a material of the said micro mixer can be utilized suitably.

--- Flow path--
The flow path has a function of mixing a plurality of liquids by diffusion and a function of removing reaction heat.
There is no restriction | limiting in particular as a mixing method of the liquid in the said flow path, According to the objective, it can select suitably, For example, mixing by a laminar flow and mixing by a turbulent flow are mentioned. Among these, laminar mixing (static mixing) is preferable because reaction control and heat removal can be performed more efficiently. In addition, since the flow path of the microreactor is very small, a plurality of liquids introduced from the introduction path tend to become a laminar flow dominant flow and are diffused and mixed in a direction perpendicular to the flow. In the mixing by the laminar flow, the laminar flow cross section of the flowing liquid may be divided by providing a branch point and a confluence in the flow path, and the mixing speed may be increased.
When mixing by turbulent flow (dynamic mixing) in the microreactor flow path, the flow velocity, the shape of the flow path (the three-dimensional shape of the wetted part, the shape of the flow path, etc., the rough surface of the wall) And so on) can be changed from laminar flow to turbulent flow. The mixing by the turbulent flow has an advantage that the mixing efficiency is high and the mixing speed is high as compared with the mixing by the laminar flow.

Here, the smaller the inner diameter of the channel, the shorter the diffusion distance of molecules, so that 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, and the temperature control of the liquid such as heat removal from the reaction heat can be easily performed.
On the other hand, if the inner diameter of the flow path is too small, the pressure loss when the liquid flows is increased, and a special high pressure-resistant pump is required as a pump used for liquid feeding, which increases the manufacturing cost. There is. In addition, the structure of the micromixer may be limited by limiting the flow rate of the liquid.

The inner diameter of the flow path is not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. Is more preferable, and 500 μm to 1 mm is particularly preferable.
If the inner diameter is less than 50 μm, pressure loss may increase. When the inner diameter exceeds 4 mm, the surface area per unit volume decreases, and as a result, rapid mixing and heat removal from the reaction heat may be difficult. On the other hand, when the inner diameter is in the particularly preferable range, it is advantageous in that mixing can be performed more rapidly and reaction heat can be removed more efficiently.
More specifically, the inner diameter of the flow path formed inside the micromixer is preferably 50 to 1000 μm, more preferably 100 to 800 μm, and still more preferably 250 to 500 μm. The inner diameter of the tube reactor connected downstream of the micromixer is preferably 50 μm to 4 mm, more preferably 100 μm to 2 mm, and even more preferably 500 μm to 1 mm.

The cross-sectional area of the flow path is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 100μm ² ~16mm ^2, more preferably 1,000μm ² ~4.0mm ^2, 10,000μm ² ˜2.1 mm ² is more preferable, and 190,000 μm ² −1 mm ² is particularly preferable.

There is no restriction | limiting in particular as the length of the said flow path, Although it can adjust suitably according to optimal reaction time, 0.1-3 m is preferable and 0.5-2 m is more preferable.
The cross-sectional shape of the channel is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a circle, a rectangle, a semicircle, and a triangle.

--Introduction path--
The introduction path communicates with the flow path and has a function of introducing the plurality of liquids into the flow path. In the introduction path, one end different from the side communicating with the flow path is usually connected to a container containing a liquid desired to be mixed.

There is no restriction | limiting in particular as long as the internal diameter of the said introduction path does not impair the effect of this invention, Although it can select suitably according to the objective, 500 micrometers or less are preferable and 250 micrometers or less are more preferable. If the inner diameter exceeds 500 μm, the M _w / M _n of the polymer may not be 1.25 or less.
When the microreactor has a plurality of introduction paths, the inner diameters of the introduction paths may be different from each other or the same.

-Configuration other than flow path and introduction path-
The configuration other than the flow path and the introduction path is not particularly limited and can be appropriately selected according to the purpose. For example, a pump used for liquid feeding, a temperature adjusting means, a reaction promoting means, a sensor, and the like are manufactured. And a tank for storing the polymer.

  The pump is not particularly limited and can be appropriately selected from those that can be used industrially. However, pumps that do not cause pulsation during liquid feeding are preferable. For example, a plunger pump, a gear pump, a rotary pump, and a diaphragm pump Etc.

There is no restriction | limiting in particular as said temperature adjustment means, According to reaction temperature, it can select suitably, For example, a thermostat, a circulation circulator, a heat exchanger etc. are mentioned.
For example, when the reaction temperature is −28 ° C., it is preferable to use a constant temperature layer of −28 ° C. obtained by adding dry ice to methanol, and when it is 0 ° C., a constant temperature layer of ice water is preferable, For example, when it is 24 ° C., a water bath is preferable. For example, when it is −78 ° C., a constant temperature layer in which dry ice is added to acetone is preferable.

The reaction promoting means can be appropriately selected according to the liquid to be mixed and the desired reaction. Examples thereof include vibration energy applying means, heating means, light irradiation means, and voltage applying means. Examples of the microreactor provided with the voltage applying means include a microflow electrochemical reactor disclosed in JP-A-2006-104538.
There is no restriction | limiting in particular as said sensor, For example, a temperature sensor, a flow sensor, a pressure sensor for measuring the pressure in a flow path, etc. are mentioned.

-Reaction temperature-
There is no restriction | limiting in particular as reaction temperature in the said living polymerization, According to the objective, it can select suitably, It can apply suitably also at -78 degrees C or less applied with the conventional batch system, However, -28 degreeC or more is preferable. 0 ° C. or higher is more preferable, and 24 ° C. or higher is particularly preferable. When the temperature is −28 ° C. or higher, a polymer having M _w / M _n of 1.25 or lower can be manufactured using a cooling device with a simple configuration, which is preferable in that the manufacturing cost can be reduced. When the temperature is 24 ° C. or higher, a polymer having a M _w / M _n of 1.25 or lower can be manufactured using a cooling device having a simpler configuration, which is preferable in that the manufacturing cost can be greatly reduced. .

-Monomer-
There is no restriction | limiting in particular as said monomer, According to the objective, it can select suitably, For example, a vinyl aromatic hydrocarbon, a (meth) acrylic-type monomer, a conjugated diene etc. are mentioned.

  Examples of the vinyl aromatic hydrocarbon include styrene, styrene derivatives (p-dimethylsilylstyrene, (p-vinylphenyl) methyl sulfide, p-hexynylstyrene, p-methoxystyrene, p-tert-butyldimethylsiloxystyrene. , O-methylstyrene, p-methylstyrene, p-tert-butylstyrene, α-methylstyrene, etc.), vinylnaphthalene, vinylanthracene, 1,1-diphenylethylene, and the like.

Examples of the acrylic monomer include methyl acrylate, ethyl acrylate, isopropyl acrylate, isobutyl acrylate, epoxy acrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, trimethylol propane triacrylate, tetramethylene glycol tetraacrylate, 2-hydroxy-1 , 3-Diacryloxypropane, 2,2-bis [4- (acryloxymethoxy) phenyl] propane, 2,2-bis [4- (acryloxyethoxy) phenyl] propane, dicyclopentenyl acrylate tricyclodecanyl Examples include acrylate, tris (acryloxyethyl) isocyanurate, urethane acrylate and the like.
Moreover, what made said acrylate into methacrylate, such as methyl methacrylate (MMA), is mentioned, for example.

Examples of the conjugated diene include 1,3-butadiene, 2-methyl-1,3-butadiene, 2,3-dimethyl-1,3-butadiene, 1,3-pentadiene, 1,3-hexadiene, 1, Examples include 3-cyclohexadiene.
The said monomer may be used individually by 1 type, and may use 2 or more types together.

  There is no restriction | limiting in particular as a density | concentration of the said monomer, Although it can select suitably according to the objective, 0.01-4.0M (mol / l, the following is same) is preferable, 0.1-3.0M is preferable. More preferred is 0.5 to 2.0M. When the concentration is less than 0.01M, the amount of polymer produced per unit time may decrease. If the concentration exceeds 4.0M, it may be difficult to remove the heat of polymerization reaction. On the other hand, when the concentration is within the particularly preferable range, it is advantageous in that the heat of polymerization reaction can be removed more efficiently.

  The flow rate at which the monomer is introduced from the first introduction path of the microreactor is not particularly limited and can be appropriately selected according to the purpose, and is preferably 0.1 to 50 ml / min, preferably 0.5 to 25 ml. / Min is more preferable, and 1 to 10 ml / min is still more preferable. If the flow rate is less than 0.1 ml / min, it may be difficult to achieve rapid mixing. When the flow rate exceeds 50 ml / min, the pressure loss may increase. On the other hand, when the flow rate is in the particularly preferable range, it is advantageous in that mixing can be performed more rapidly within a range where pressure loss does not become a problem.

-Initiator-
There is no restriction | limiting in particular as said initiator, According to the kind of monomer and the polymerization system of living polymerization, it can select suitably.
Examples of the initiator in the case where the living polymerization is living anionic polymerization include an organic lithium reagent.
The organolithium reagent is not particularly limited and can be appropriately selected from conventionally known organolithium reagents. For example, methyllithium, ethyllithium, propyllithium, butyllithium (n-butyllithium, sec-butyllithium, iso-butyllithium, tert-butyllithium, etc.), alkyllithium such as pentyllithium, hexyllithium, methoxymethyllithium, ethoxymethyllithium; α-methylstyryllithium, 1,1-diphenyl-3-methylpentryllithium, 3- Benzyl lithium such as methyl-1,1-diphenylpentyl lithium; alkenyl lithium such as vinyl lithium, allyl lithium, propenyl lithium, butenyl lithium; ethynyl lithium, butynyl lithium, pentynyl lithium Alkynyl lithium such as hexynyl lithium; aralkyl lithium such as benzyl lithium and phenylethyl lithium; aryl lithium such as phenyl lithium and naphthyl lithium; heterocyclic lithium such as 2-thienyl lithium, 4-pyridyl lithium and 2-quinolyl lithium An alkyl lithium magnesium complex such as tri (n-butyl) magnesium lithium and trimethyl magnesium lithium; Of these, alkyllithium is preferred and sec-butyllithium is more preferred because it has high reactivity and can perform a fast initiation reaction. The said organic lithium reagent may be used individually by 1 type, and may use 2 or more types together.

  In addition, when the monomer is methyl methacrylate, it is preferable to use either a molecule bulky than sec-butyl lithium or a molecule having a large steric hindrance as the initiator. Examples of the bulky molecule and the highly sterically hindered molecule include, for example, α-methylstyryl lithium, 1,1-diphenyl 3-methylpentyl lithium, 1,1-diphenylhexyl lithium, 3-methyl-1, Examples include 1-diphenylpentyl lithium.

  There is no restriction | limiting in particular as a density | concentration of the said initiator, Although it selects suitably according to the kind and density | concentration of the said monomer, 0.001-1.0M is preferable, 0.002-0.75M is more preferable, 0 0.01 to 0.5M is more preferable, and 0.02 to 0.2M is particularly preferable. When the concentration is less than 0.001M, the initiator may be decomposed by a small amount of water contained in the solvent. When the concentration exceeds 1.0 M, insoluble substances may precipitate during polymerization, and the microreactor flow path may be blocked. On the other hand, when the concentration is within the particularly preferable range, it is advantageous in that the reaction can be performed more practically without causing the microreactor flow path to be blocked.

  The flow rate at which the initiator is introduced from the second introduction path of the microreactor is not particularly limited and may be appropriately selected depending on the purpose, preferably 0.1 to 10 ml / min, 0.5 to 5 ml / min is more preferable, and 1 to 3 ml / min is particularly preferable. If the flow rate is less than 0.1 ml / min, it may be difficult to achieve rapid mixing. When the flow rate exceeds 10 ml / min, pressure loss may increase. On the other hand, when the flow rate is in the particularly preferable range, it is advantageous in that mixing can be performed more rapidly within a range where pressure loss does not become a problem.

Here, in the living polymerization using a microreactor, the present inventors clearly show that the equivalent ratio of the monomer and the initiator matches the ratio of the product of the respective concentration and the flow rate, as shown in the examples described later. It became.
The equivalent ratio of the monomer to the initiator is not particularly limited and may be appropriately selected depending on the purpose. The initiator is preferably 1 to 1,000 equivalents, and preferably 5 to 500 equivalents with respect to the monomers. More preferred is 10 to 200 equivalents. When the equivalent ratio is less than 1 equivalent, the molecular weight of the obtained polymer may increase from the theoretical value. When the equivalent ratio exceeds 1,000 equivalents, the molecular weight of the obtained polymer may increase from the theoretical value. On the other hand, when the equivalent ratio is in the particularly preferable range, it is advantageous in that a polymer having a molecular weight equal to the theoretical value can be obtained.

-Solvent-
The monomer and initiator are introduced into the microreactor in a liquid state solubilized in a solvent.
There is no restriction | limiting in particular as said solvent, According to the kind of said monomer and initiator, and the polymerization system of living polymerization, it can select suitably.
Examples of the solvent in the case where the living polymerization is a living anion polymerization include linear, branched, and cyclic hydrocarbon solvents, and more specifically, for example, butane, butene, pentane, octane, cyclohexane. , Benzene, toluene, xylene, decalin, tetralin, and derivatives thereof.

As described above, according to the method for producing a polymer of the present invention, a polymer having M _w / M _n of 1.25 or less can be produced even when the reaction temperature is −28 ° C. or higher. In particular, according to the method for producing a polymer of the present invention, even when a monomer having a functional group is used as well as a monomer having no functional group, the reaction of the side chain is restricted at −28 ° C. or higher while limiting the reaction of the side chain. A chain polymer can be suitably produced.

Furthermore, according to the method for producing a polymer of the present invention, a polymer having a functional group at its terminal can be produced by introducing a functional group at the growth terminal of the polymer. Moreover, a block polymer can be produced by connecting a plurality of blocks made of the polymer.
Hereinafter, the polymer having a functional group at the terminal and the method for producing the block polymer will be specifically described.

<Method for producing polymer having functional group at terminal>
The method for producing a polymer having a functional group at the terminal includes the following steps (A1) and (A2), and includes other steps as necessary.
(A1) A monomer and an initiator for initiating polymerization are introduced into a microreactor having a channel capable of mixing a plurality of liquids, and the monomer is living polymerized in the presence of the initiator in the microreactor. Process.
(A2) The polymer polymerized in the step (A1) and an electrophile having two or more reaction points are introduced into a microreactor having a flow channel capable of mixing a plurality of liquids, and the inside of the microreactor And adding the electrophile to the growth terminal of the polymer.

Since the step (A1) is the same as the method for producing a polymer having M _w / M _n of 1.25 or less, description thereof is omitted.

  The electrophile in the step (A2) is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include chlorotrimethylsilane, benzaldehyde, acetophenone and benzophenone.

As the microreactor in the step (A2), the same microreactor as described in the method for producing a polymer having _Mw / _Mn of 1.25 or less can be used.
There is no restriction | limiting in particular as addition amount of the said electrophile, Although it can select suitably according to the objective, 1-100 equivalent is preferable with respect to the initiator added at the said (A1) process, 10 equivalents are more preferable, and 1-2 equivalents are particularly preferable. When the addition amount is less than 1 equivalent to the initiator, the theoretically required equivalent of the electrophile may be insufficient with respect to the polymer growth terminal. When the addition amount exceeds 100 equivalents with respect to the initiator, the electrophilic agent becomes a large excess with respect to the growth terminal of the polymer. Therefore, it is necessary to remove the electrophilic agent after the reaction. On the other hand, when the addition amount is within the particularly preferable range, it is advantageous in that the electrophile is close to the theoretical amount with respect to the polymer growth terminal.

In addition, the equivalent ratio of an initiator and an electrophile can be calculated | required by ratio of the product of each density | concentration and flow rate similarly to the equivalent ratio of the said monomer and an initiator.
The polymer having a functional group at the terminal thus produced can be used, for example, for production of a block polymer by bonding another polymer to the functional group or by reacting a nucleophile with the functional group. It can be used as a biofunctional substance or a functional material.

<Method for producing block polymer>
The method for producing the block polymer includes the following steps (B1) and (B2), optionally includes the step (B3), and further includes other steps as necessary.
(B1) A monomer and an initiator for initiating polymerization are introduced into a microreactor having a channel capable of mixing a plurality of liquids, and the monomer is living polymerized in the presence of the initiator in the microreactor. Process.
(B2) introducing the first polymer polymerized in the step (B1) and an electrophile having two or more reaction points into a microreactor having a flow path capable of mixing a plurality of liquids; Adding the electrophile to the growth end of the polymer in a microreactor;
(B3) A micro provided with a channel capable of mixing a plurality of liquids, the first polymer to which the electrophile is added and the second polymer that is polymerized in the step (B1) and different from the polymer. Introducing into the reactor and adding the growth end of the second polymer to the electrophile addition end of the first polymer in the microreactor;

Since the step (B1) is the same as the method for producing a polymer having M _w / M _n of 1.25 or less, the description thereof is omitted.

  There is no restriction | limiting in particular as an electrophile in the said (B2) process, According to the objective, it can select suitably, For example, dichlorodimethylsilane, trichloromethylsilane, tetrachlorosilane etc. are mentioned.

As the microreactor in the step (B2), the same microreactor as described in the method for producing a polymer having _Mw / _Mn of 1.25 or less can be used.
There is no restriction | limiting in particular as addition amount of the said electrophile, Although it can select suitably according to the objective, 1-100 equivalent is preferable with respect to the initiator added at the said (B1) process, 10 equivalents are more preferable, and 1-2 equivalents are particularly preferable. When the addition amount is less than 1 equivalent to the initiator, the theoretically required equivalent of the electrophile may be insufficient with respect to the polymer growth terminal. When the addition amount exceeds 100 equivalents with respect to the initiator, the electrophilic agent becomes a large excess with respect to the polymer growth end, and therefore it is necessary to remove the electrophilic agent after the reaction, while the addition amount is A particularly preferred range is advantageous in that the electrophile is close to the theoretical amount with respect to the polymer growth terminal.
In addition, the equivalent ratio of an initiator and an electrophile can be calculated | required by ratio of the product of each density | concentration and flow rate similarly to the equivalent ratio of the said monomer and an initiator.

There is no restriction | limiting in particular as a 2nd polymer in the said (B3) process, According to the objective, it can select suitably, For example, it manufactures with the manufacturing method of the polymer whose said _Mw / _Mn is 1.25 or less. The polymer made can be used preferably. Further, the second polymer may be manufactured using the same monomer as the first polymer, or may be manufactured using a different monomer.
As the microreactor in the step (B3), the same microreactor as described in the method for producing a polymer having _Mw / _Mn of 1.25 or less can be used.
There is no restriction | limiting in particular as the addition amount of the 2nd polymer in the said (B3) process, Although it can select suitably according to the objective, With respect to the 1st polymer manufactured at the said (B1) process, 1-1000 equivalent is preferable, 5-500 equivalent is more preferable, and 10-200 equivalent is especially preferable. When the addition amount is less than 1 equivalent with respect to the first polymer, the molecular weight of the obtained polymer may increase from the theoretical value. When the addition amount exceeds 1,000 equivalents relative to the first polymer, the molecular weight of the obtained polymer may increase from the theoretical value. On the other hand, when the addition amount is within the particularly preferable range, it is advantageous in that a polymer having a molecular weight equal to the theoretical value can be obtained.
The equivalent ratio of the first polymer to the second polymer can be determined by the ratio of the product of the respective concentrations and flow rates, similarly to the equivalent ratio of the monomer and the initiator. That is, from the concentration and flow rate of the monomer and initiator used in the production of the first polymer and the concentration and flow rate of the monomer and initiator used in the production of the second polymer, the first polymer and the second The equivalent ratio with the polymer can be determined.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

Example 1
-Production of polystyrene-
Using a microreactor, styrene was subjected to living anion polymerization in the presence of sec-butyllithium (sec-BuLi).
--Microreactor--
The microreactor used in this example is configured to include a micromixer made of a T-shaped pipe joint and a tube reactor connected downstream of the micromixer.
As the micromixer, a special order product manufactured by Sanko Seiki Kogyo Co., Ltd. was used (it is possible to request the manufacture based on the description of this example and obtain an equivalent product). Note that the micromixer used in this example has a part of the first introduction path, the second introduction path, and the flow path in which these are merged, and any of them is included in the micromixer. The inner diameter is the same. Therefore, hereinafter, these inner diameters are collectively referred to as “the inner diameter of the micromixer”.
A stainless steel tube manufactured by GL Sciences Inc. was used as the tube reactor (in the drawing, described as “micro tube reactor”). As a pump for liquid feeding, a syringe pump Model 11 Plus manufactured by Harvard was used. The reaction temperature was adjusted by burying the entire microreactor in a constant temperature layer.

--Reaction conditions--
FIG. 1 is a diagram showing an outline of the reaction system of Examples 1-8. As shown in FIG. 1, the inner diameter of the micromixer M1 of Example 1 is 250 μm, the inner diameter of the tube reactor is 1.0 mm, and the length of the tube reactor is 50 cm.
Then, in Example 1, by introducing a styrene solution of concentration _{C a} is 2M from the first inlet channel at a flow rate of 6 ml / min, the concentration _{C b} is 0.2 M sec-butyl lithium solution a second introduction passage Was introduced at a flow rate _Vb of 2 ml / min and mixed in the channel by laminar flow. The reaction temperature T is 24 ° C.
The styrene solution was prepared by adding 53.2 ml of tetrahydrofuran and 14.37 g (15.8 ml) of styrene in a 100 ml flask substituted with argon gas, and the sec-butyllithium solution was replaced with argon gas. The prepared 100 ml flask was prepared by adding 10 ml of 1.0 M sec-butyllithium and 40 ml of hexane.

-Evaluation method-
--Measurement of conversion rate--
The reaction was terminated by collecting the polymerization reaction solution coming out of the microreactor in a container containing a large excess of methanol. The obtained solution was evaporated after the solvent was distilled off under reduced pressure, and the conversion rate was measured by the change in weight of the monomer used to the polymer.

--Measurement of number average molecular weight and molecular weight distribution--
The number average molecular weight ( _Mn ) and molecular weight distribution ( _Mw / _Mn ) were determined by gel permeation chromatography (GPC) measurement. Specifically, two Shodex LF-804 columns (manufactured by Showa Denko KK) and two Shodex KF-800RL columns (manufactured by Showa Denko KK), a total of four columns, are arranged in series at 40 ° C. Then, tetrahydrofuran was used as a developing solvent, and measurement was performed with a RI (Refractive Index, differential refractive index) detector. Calibration was performed using a commercially available styrene polymer (manufactured by TSK, standard polystyrene TOSOH A-500 (TS-505) M _w = 500, A1000 (TS-501) M _w = 1,050, A-2500 (TS- 502) _Mw = 2,500, A-5000 (TS-503) _Mw = 5,870, F-1 (TS-203) _Mw = 9,830, F-2 (TS-504) _Mw = 17, 100, F-4 (TS-202) _Mw = 37,200, F-10 (TS-144) _Mw = 98,900, F-20 (TS-140) _Mw = 189,000, F _{-40 (TS-85) M w} = 354,000, F-80 (TS-201) M w = 707,000, F128 and _{(TS-206) M w =} 1,110,000) mark It was carried out using as a sample.

(Examples 2 to 4)
In Example 1, the concentration C _a of the styrene solution, the concentration C _b of the sec-butyl lithium solution, and the flow velocity V _b of the sec-butyl lithium solution were changed to the values shown in Table 1, and were the same as in Example 1. By the method, the polymer of Examples 2-4 was manufactured, and the conversion rate, the number average molecular weight, and the molecular weight distribution were evaluated about the polymer of Examples 2-4 by the method similar to Example 1. FIG. The results are shown in Table 1.

(Example 5)
In Example 1, the polymer of Example 5 was produced in the same manner as in Example 1 except that the reaction temperature T was changed to 0 ° C. instead of 24 ° C. The conversion rate, number average molecular weight and molecular weight distribution were evaluated for 5 polymers. The results are shown in Table 1.

(Examples 6 to 8)
In Example 5, the concentration C _a of the styrene solution, the concentration C _b of the sec-butyl lithium solution, and the flow velocity V _b of the sec-butyl lithium solution were changed to the values shown in Table 1, and were the same as in Example 5. By the method, the polymer of Examples 6-8 was manufactured, By the method similar to Example 5, the conversion rate, the number average molecular weight, and molecular weight distribution were evaluated about the polymer of Examples 6-8. The results are shown in Table 1.

(Comparative Example 1)
Using a batch reactor, styrene was subjected to living anion polymerization in the presence of sec-butyllithium. Specifically, the following procedure was used.
A 100 ml two-necked flask replaced with argon gas was charged with 1 ml of a 0.2 M sec-butyllithium solution, and the batch reactor was immersed in a thermostatic layer and cooled to 0 ° C. While stirring using a magnetic stirrer, 6 ml of 1.0 M styrene solution was added dropwise over 10 seconds (sec) and stirred at 0 ° C. for 5 minutes.
Then, the conversion rate, number average molecular weight, and molecular weight distribution of the polymer of Comparative Example 1 were evaluated by the same method as in Example 1. The results are shown in Table 1.

From the results shown in Table 1, the following became clear.
When living anion polymerization was performed using a microreactor, a polymer having a molecular weight distribution of 1.25 or less could be produced not only at 0 ° C. but also at 24 ° C. On the other hand, when living anion polymerization was carried out in a batch mode, a polymer having a wide M _w / M _n was produced even when the reaction temperature was 0 ° C.

Example 9
The polymer of Example 9 was produced in the same manner as in Example 5, and the conversion rate, number average molecular weight and molecular weight distribution of the polymer in Example 9 were evaluated in the same manner as in Example 5. The results are shown in Table 2.

(Comparative Example 2)
In Example 9, the polymer of Comparative Example 2 was produced in the same manner as in Example 9 except that the inner diameter of the micromixer M1 (shown as “d” in Table 2) was changed to 500 μm instead of 250 μm. The conversion, the number average molecular weight, and the molecular weight distribution of the polymer of Comparative Example 2 were evaluated in the same manner as in Example 9. The results are shown in Table 2.

(Comparative Example 3)
In Example 9, the polymer of Comparative Example 3 was produced in the same manner as in Example 9 except that the inner diameter d of the micromixer M1 was changed to 800 μm instead of 250 μm, and in the same manner as in Example 9, The polymer of Comparative Example 3 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 2.

From the results shown in Table 2, the following became clear.
When the inner diameter d of the micromixer M1 is 250 μm, a polymer having M _w / M _n of 1.25 or less can be produced, but when the inner diameter d of the micromixer M1 is 500 μm or more, the molecular weight distribution A wide polymer was produced.

(Examples 10 to 12 and Comparative Examples 4 and 5)
FIG. 2 is a diagram schematically showing reaction systems of Examples 10 to 12 and Comparative Examples 4 and 5, and Example 13 and Comparative Examples 6 to 9.
In Example 9, the flow velocity _{V b} of the flow velocity _{V a} and sec- butyllithium solution styrene solution, except for changing the values shown in Table 3, in the same manner as in Example 9, Examples 10 to 12 and Comparative The polymers of Examples 4 and 5 were produced, and the conversion rate, number average molecular weight and molecular weight distribution of the polymers of Examples 10 to 12 and Comparative Examples 4 and 5 were evaluated in the same manner as in Example 9. The results are shown in Table 3.

(Example 13 and Comparative Examples 6-9)
In Comparative Example 2, the flow velocity V _b of the flow velocity V _a and sec- butyllithium solution styrene solution, except for changing the values shown in Table 3, in the same manner as in Comparative Example 2, Example 13, Comparative Example 6 The polymer of -9 was manufactured and the conversion rate, number average molecular weight, and molecular weight distribution were evaluated about the polymer of Example 13 and Comparative Examples 6-9 by the method similar to the comparative example 2. The results are shown in Table 3.

From the results shown in Table 3, the following became clear.
And velocity _{V a} of introducing styrene solution, sec- butyl lithium solution the ratio between the flow velocity _{V b} of introducing 3: fixed with 1, when a 250μm internal diameter d of the micro mixer M1 is, _{V a} is 3ml / at least _min, M w / _{M n} is able to produce polymers is 1.25 or less, when a 500μm internal diameter d of the micro mixer M1, when _{V a} is equal to or more than 9 ml / min In addition, a polymer having M _w / M _n of 1.25 or less could be produced.

(Examples 14 to 24)
FIG. 3 is a diagram showing an outline of the reaction system of Examples 14-24.
In Example 5, sec-concentration C _b and flow rate V _b of butyl lithium solution, except for changing the values shown in Table 4, in the same manner as in Example 5, to produce a polymer of Example 14 to 24 In the same manner as in Example 5, the conversion rate, number average molecular weight and molecular weight distribution of the polymers of Examples 14 to 24 were evaluated. The results are shown in Table 4.

In Table 4, “[M] / [I]” means the equivalent ratio of styrene to sec-butyllithium, [M] is the monomer concentration, and [I] is the sec-butyllithium concentration. is there.

FIG. 4 is a correlation diagram showing the relationship between the number average molecular weight M _{n of} Examples 14 to 24 and “[M] / [I]”. As shown in FIG. 4, it was revealed that the molecular weight of the polymer can be controlled by changing the flow rate of the monomer and the initiator and changing the equivalent ratio of the monomer to the initiator.

(Examples 25, 29, 31, 33 and Comparative Examples 10, 11)
-Production of styrene derivative polymer-
In Example 1, the polymers of Examples 25, 29, 31, 33 and Comparative Examples 10 and 11 were produced in the same manner as in Example 1 except that the monomers shown in Table 5 were used instead of styrene. Then, the conversion rate, number average molecular weight and molecular weight distribution of the polymers of Examples 25, 29, 31, 33 and Comparative Examples 10 and 11 were evaluated in the same manner as in Example 1. The results are shown in Table 5.

(Examples 26 to 28, 30, 32, 34)
In Example 5, the polymers of Examples 26 to 28, 30, 32, and 34 were produced in the same manner as in Example 5 except that the monomers shown in Table 5 were used instead of styrene. In the same manner as in Example 5, the conversion rate, number average molecular weight and molecular weight distribution of the polymers of Examples 26 to 28, 30, 32, and 34 were evaluated. The results are shown in Table 5.

In Table 5, p-dimethylsilylstyrene, (p-vinylphenyl) methylsulfide, p-hexynylstyrene, p-methoxystyrene, and p-tert-butyldimethylsiloxystyrene are each represented by the following structural formula (1 ) To (5).
However, in the structural formulas (1), (2) and (4), “Me” represents a methyl group, and in the structural formula (5), “TBS” represents a tert-butyldimethylsilyl group.

From the results shown in Table 5, the following became clear.
At least at 0 ° C., a polymer having M _w / M _n of 1.25 or less could be produced in any styrene derivative. Further, even at 24 ° C., it was possible to produce a polymer having M _w / M _n of 1.25 or less depending on the type of styrene derivative.

(Example 35)
-Production of polymer having functional group at terminal-
Using a microreactor, styrene was subjected to living anion polymerization in the presence of sec-butyllithium as the first-stage reaction, and the growth terminal of polystyrene synthesized as the second-stage reaction was supplemented with an electrophile.

--Microreactor--
As the microreactor used in the first and second stage reactions, the same microreactor used in Example 1 was used. The first-stage micromixer M1 and the first introduction path in the second-stage micromixer M2 are connected via the first-stage tube reactor to connect the first-stage micromixer M1. The reactor and the second-stage microreactor were connected in series (see FIG. 5). Other configurations such as a pump for feeding liquid and adjustment of the reaction temperature are the same as those in the first embodiment.

--Reaction conditions--
FIG. 5 is a diagram showing an outline of the reaction system of Examples 35-38. As shown in FIG. 5, the inner diameters of the first-stage micromixer M1 and the second-stage micromixer M2 of Example 35 are 250 μm, and the inner diameters of the first-stage tube reactor and the second-stage tube reactor are 1.0 mm, the length of both tube reactors is 50 cm.
In Example 35, the 2M styrene solution was introduced at a flow rate of 3 ml / min from the first introduction path of the first stage micromixer M1, and the 0.2M sec-butyllithium solution was introduced into the first stage micromixer. The mixture was introduced from the second introduction path of the mixer M1 at a flow rate of 3 ml / min and mixed in the flow path by laminar flow. The reaction temperature T is 24 ° C.
Then, the mixed solution (polystyrene solution) is introduced from the first introduction path of the second stage micromixer M2, and the 2M chlorotrimethylsilane (TMSCl) solution is introduced to the second stage of the second stage micromixer M2. The solution was introduced from the channel at a flow rate of 3 ml / min and mixed in the channel by laminar flow. The reaction temperature T is 24 ° C.
The styrene solution and the sec-butyllithium solution prepared by the same method as in Example 1 were used. The chlorotrimethylsilane solution was prepared by adding 14.9 ml of tetrahydrofuran and 4.35 g (5.08 ml) of chlorotrimethylsilane to a 50 ml flask substituted with argon gas.
And as a result of analyzing the terminal structure of the polymer of Example 35 by NMR (Nuclear Magnetic Resonance), it was confirmed that chlorotrimethylsilane was added to the polymer terminal.
Further, the conversion rate, number average molecular weight and molecular weight distribution of the polymer of Example 35 were evaluated in the same manner as in Example 1. The results are shown in Table 6.

(Example 36)
In Example 35, the polymer of Example 36 was produced in the same manner as in Example 35 except that the reaction temperature T was changed to 0 ° C. instead of 24 ° C. The terminal structure of the polymer of Example 36 was confirmed, and the conversion and molecular weight distribution were evaluated. The results are shown in Table 6.

(Example 37)
In Example 35, the polymer of Example 37 was produced in the same manner as in Example 35 except that benzaldehyde (PhCHO) was used instead of chlorotrimethylsilane. The benzaldehyde solution introduced into the micromixer M2 was prepared by adding 20.0 ml of tetrahydrofuran and 5.31 g (5.08 ml) of benzaldehyde to a 50 ml flask substituted with argon gas.
And by the method similar to Example 35, the terminal structure was confirmed about the polymer of Example 37, and the conversion rate, the number average molecular weight, and molecular weight distribution were evaluated. The results are shown in Table 6.

(Example 38)
In Example 37, the polymer of Example 38 was produced in the same manner as in Example 37 except that the reaction temperature T was changed to 0 ° C. instead of 24 ° C. The terminal structure of the polymer of Example 38 was confirmed, and the conversion rate, number average molecular weight, and molecular weight distribution were evaluated. The results are shown in Table 6.

In Table 6, c (equivalent) represents the equivalent of the electrophile to the initiator introduced into the first-stage micromixer M1.

From the results shown in Table 6, the following became clear.
Regardless of the type of electrophile, by adding 10 equivalents of electrophile to the initiator, a polymer having a functional group at the terminal and having M _w / M _n of 1.25 or less is produced. I was able to. Moreover, it was the same result in both 0 degreeC and 24 degreeC.

(Example 39)
-Production of block polymer-
Using a microreactor, styrene was living anion-polymerized in the presence of sec-butyllithium as the first-stage reaction, and the growth end of polystyrene synthesized as the second-stage reaction was supplemented with dichlorosilane. As a reaction, the dichlorosilane addition terminal of polystyrene and the second polymer were bonded. The second polymer is produced in parallel with the first stage reaction by subjecting the second monomer to living anion polymerization, and is referred to as the 1 'stage in the following description. .

--Microreactor--
The same microreactor used in the first to third stage and 1 ′ stage reactions was used in Example 1. The first-stage micromixer M1 and the first introduction path in the second-stage micromixer M2 are connected via the first-stage tube reactor to connect the first-stage micromixer M1. The reactor and the second-stage microreactor are connected in series, and similarly, the second-stage and 1'-stage microreactors and the third-stage microreactor are connected in series (see FIG. 6). . Other configurations such as a pump for feeding liquid and adjustment of the reaction temperature are the same as those in the first embodiment.

--Reaction conditions--
FIG. 6 is a diagram showing an outline of the reaction system of Examples 39 to 42. As shown in FIG. 6, the inner diameter of the first-stage micromixer M1, the second-stage micromixer M2 and the 1′-stage micromixer M1 ′ of Example 39 is 250 μm, and the third-stage micromixer The inner diameter of M3 is 500 μm. In addition, the inner diameters of the first to third and first 'tube reactors are 1.0 mm, the length L ₁ of the first tube reactor and the length L ₂ of the _second tube reactor are 50 cm. Yes, the length L ₃ of the third-stage tube reactor is 200 cm, and the length L _{1 ′} of the 1′-stage tube reactor is 50 cm.
In Example 39, a 1.0M styrene solution was introduced at a flow rate of 3 ml / min from the first introduction path of the first-stage micromixer M1, and a 0.025M sec-butyllithium solution was introduced at the first-stage. Were introduced at a flow rate of 2 ml / min from the second introduction path of the micromixer M1 and mixed by laminar flow in the flow path. The reaction temperature T is 24 ° C.
Then, the mixed solution (polystyrene solution) is introduced from the first introduction path of the second-stage micromixer M2, and the 0.05M dichlorosilane solution is introduced from the second introduction path of the second-stage micromixer M2. The solution was introduced at a flow rate of 3 ml / min and mixed by a laminar flow in the channel. The reaction temperature T is 24 ° C.

  On the other hand, a 1.0 M styrene solution as the second monomer is introduced at a flow rate of 3 ml / min from the first introduction path of the 1′-stage micromixer M1 ′, and a 0.10 M sec-butyllithium solution is obtained. It was introduced at a flow rate of 3 ml / min from the second introduction path of the 1'-stage micromixer M1 ', and was mixed by laminar flow in the flow path. The reaction temperature T is 24 ° C.

Then, the solution mixed by the second stage microreactor is introduced from the first introduction path of the third stage micromixer M3, and the solution mixed by the first stage microreactor is added to the third stage microreactor. It was introduced from the second introduction path of the micromixer M3 and mixed by a laminar flow in the flow path. The reaction temperature T is 24 ° C.
The styrene solution and the sec-butyllithium solution prepared by the same method as in Example 1 were used. The dichlorosilane solution was prepared by adding 82.3 ml of dichlorodimethylsilane and 177.3 mg (160.7 μl) of dichlorosilane to a 100 ml flask substituted with argon gas.
And as a result of analyzing the molecular structure of the polymer of Example 39 by NMR, the existence of Si atoms was confirmed in the polymer main chain, and it was confirmed that two polymers were bonded via the Si atoms. Further, the conversion rate and molecular weight distribution of the polymer of Example 39 were evaluated in the same manner as in Example 1. The results are shown in Table 7.

(Example 40)
In Example 39, the polymer of Example 40 was produced in the same manner as in Example 39 except that the reaction temperature T was changed to 0 ° C. instead of 24 ° C. The molecular structure of the polymer of Example 40 was confirmed, and the conversion, number average molecular weight, and molecular weight distribution were evaluated. The results are shown in Table 7.

(Example 41)
In Example 39, the polymer of Example 41 was produced in the same manner as in Example 39 except that the second monomer was changed to the second monomer shown in Table 7. The same method as in Example 39 Thus, the molecular structure of the polymer of Example 41 was confirmed, and the conversion rate, number average molecular weight and molecular weight distribution were evaluated. The results are shown in Table 7.

(Example 42)
In Example 39, the second monomer was replaced with styrene as the second monomer shown in Table 7, and the length L _{1 ′} of the 1′-th stage tube reactor was changed to 50 cm instead of 200 cm. Except that, the polymer of Example 42 was produced in the same manner as in Example 39, the molecular structure of the polymer in Example 42 was confirmed by the same method as in Example 39, and the conversion rate, number average molecular weight and molecular weight were confirmed. Distribution was evaluated. The results are shown in Table 7.

From the results shown in Table 7, the following became clear.
Using a microreactor, one equivalent of dichloromethylsilane is added to the initiator used in the first-stage reaction, so that a polymer with one polymer growth end added to one molecule of dichlorosilane is selected. I was able to get it. Furthermore, the block polymer whose _Mw / _Mn was 1.25 or less was able to be manufactured by adding a 2nd polymer with respect to the polymer to which this dichlorosilane was added. Moreover, it was the same result in both 0 degreeC and 24 degreeC.

(Example 43)
-Production of polymethyl methacrylate-
Using a microreactor, methyl methacrylate was subjected to living anionic polymerization in the presence of 1,1-diphenyl-3-methylpentyllithium.

--Microreactor--
The same microreactor as that used in Example 1 was used. Other configurations such as a pump for feeding liquid and adjustment of the reaction temperature are the same as those in the first embodiment.

--Reaction conditions--
FIG. 7 is a diagram schematically showing the reaction systems of Examples 43 and 44 and Comparative Examples 12 and 13. As shown in FIG. 7, in Example 43, the inner diameter of the micromixer M1 is 250 μm, and the inner diameter of the tube reactor is 1.0 mm. In Example 43, the length x of the tube reactor and 50 cm, retention time _{R t} was set to be 3.4 seconds.
In Example 43, a 1.0 M methyl methacrylate solution was introduced at a flow rate of 6.0 ml / min from the first introduction path of the micromixer M1, and 0.20 M 1,1-diphenyl-3-methyl pen was introduced. The tolyl lithium solution was introduced from the second introduction path of the micromixer M1 at a flow rate of 1.0 ml / min and mixed in the flow path by laminar flow. The reaction temperature T is 24 ° C.
The methyl methacrylate solution was prepared by adding 88.2 ml of tetrahydrofuran and 9.896 g (10.6 ml) of methyl methacrylate into a 100 ml flask substituted with argon gas, and the 1,1-diphenyl-3 -The methylpentryl lithium solution was prepared by adding 16 ml of tetrahydrofuran, 721.9 mg (704 μl) of 1,1-diphenylethene and 4 ml of 1.0 M sec-butyllithium in a 100 ml flask substituted with argon gas. Then, the conversion rate, number average molecular weight and molecular weight distribution of the polymer of Example 43 were evaluated in the same manner as in Example 1. The results are shown in Table 8.

(Example 44)
In Example 43, the polymer of Example 44 was produced in the same manner as in Example 43 except that the reaction temperature was changed to 0 ° C instead of 24 ° C. The 44 polymers were evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 8.

(Comparative Example 12)
In Example 43, by a 400cm instead the length x of the tube reactor in 50 cm, the dwell time _{R t,} except that the 27 seconds instead of 3.4 seconds, the same method as in Example 43 Thus, the polymer of Comparative Example 12 was produced, and the conversion rate, number average molecular weight and molecular weight distribution of the polymer of Comparative Example 12 were evaluated in the same manner as in Example 43. The results are shown in Table 8.

(Comparative Example 13)
In Comparative Example 12, a polymer of Comparative Example 13 was produced in the same manner as in Comparative Example 12, except that the reaction temperature was changed to 0 ° C. instead of 24 ° C., and Comparative Example 13 was produced in the same manner as in Comparative Example 12. The polymers were evaluated for conversion, number average molecular weight and molecular weight distribution. The results are shown in Table 8.

(Comparative Example 14)
-Production of polymethyl methacrylate by batch method-
Using a batch reactor, methyl methacrylate was subjected to living anion polymerization in the presence of 1,1-diphenyl-3-methylpentyllithium. Specifically, the following procedure was used.
A 100 ml two-necked flask replaced with argon gas was charged with 1 ml of 1.0M 1,1-diphenyl-3-methylpentryl lithium solution, and the batch reactor was immersed in a thermostatic layer and cooled to -78 ° C. While stirring using a magnetic stirrer, 6 ml of 1.0 M methyl methacrylate solution was added dropwise over 10 seconds and stirred at -78 ° C for 5 minutes.
Then, the conversion rate, number average molecular weight, and molecular weight distribution of the polymer of Comparative Example 14 were evaluated by the same method as in Example 1. The results are shown in Table 8.

(Comparative Example 15)
In Comparative Example 14, the polymer of Comparative Example 15 was produced in the same manner as in Comparative Example 15 except that the reaction temperature T was changed to 0 ° C. instead of −78 ° C. The polymer of Comparative Example 15 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 8.

From the results shown in Table 8, the following became clear.
When methylmethacrylate was subjected to living anion polymerization using a microreactor, a polymer having a molecular weight distribution of 1.25 or less could be produced when the residence time _Rt was 3.4 seconds. On the other hand, a polymer having a broad molecular weight distribution was produced when the residence time was long even when a microreactor was used, or when methyl methacrylate was subjected to living anion polymerization by a batch method. That is, in the case of living anion polymerization of a monomer having a functional group such as methyl methacrylate, by controlling the residence time (reaction time) to be short, the side reaction can be prevented from progressing, and M _w / M _n is 1 It has been shown that polymers up to .25 can be produced.

(Example 45)
-Preparation of initiator-Production of polymethyl methacrylate-
Using a microreactor, 1,1-diphenylethene and sec-butyllithium were reacted as a first-stage reaction to prepare 1,1-diphenyl-3-methylpentyllithium, and as a second-stage reaction, Methyl methacrylate was subjected to living anionic polymerization in the presence of 1,1-diphenyl-3-methylpentyllithium.

--Microreactor--
As the microreactor used in the first and second stage reactions, the same microreactor used in Example 1 was used. The first-stage micromixer M1 and the first introduction path in the second-stage micromixer M2 are connected via the first-stage tube reactor to connect the first-stage micromixer M1. The reactor and the second-stage microreactor were connected in series (see FIG. 8). Other configurations such as a pump for feeding liquid and adjustment of the reaction temperature are the same as those in the first embodiment.

--Reaction conditions--
FIG. 8 is a diagram showing an outline of the reaction system of Examples 45-48. As shown in FIG. 8, the inner diameter of the first-stage micromixer M1 of Example 45 is 500 μm, and the inner diameter of the second-stage micromixer M2 is 250 μm. The inner diameter of the first-stage tube reactor and the second-stage tube reactor is 1.0 mm, and the length is 50 cm.
In Example 45, a 0.25M 1,1-diphenylethene solution was introduced at a flow rate of 1.6 ml / min from the first introduction path of the first-stage micromixer M1, and 1.0 M sec-butyl was introduced. The lithium solution was introduced from the second introduction path of the first-stage micromixer M1 at a flow rate of 0.4 ml / min and mixed in the flow path by laminar flow. The reaction temperature T is 24 ° C.
Then, the mixed solution (1,1-diphenyl-3-methylpentyllithium) is introduced from the first introduction path of the second stage micromixer M2, and the 1.0M methyl methacrylate solution is introduced into the second stage. of was introduced at 6 ml / min from the second inlet channel of the micromixer M2 as the flow velocity V _c, it was mixed by a laminar flow in the flow path. The reaction temperature T is 24 ° C.
Then, the conversion rate, number average molecular weight, and molecular weight distribution of the polymer of Example 45 were evaluated in the same manner as in Example 1. The results are shown in Table 9.

(Example 46)
In Example 45, the polymer of Example 46 was produced in the same manner as in Example 45 except that the reaction temperature T was changed to 0 ° C. instead of 24 ° C. The polymer of Example 46 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 9.

(Example 47)
In Example 45, the flow velocity _{V c} of methyl methacrylate, except that the 9 ml / min in place of 6 ml / min is in the same manner as in Example 45, to produce a polymer of Example 47, Example 45 By the same method, the conversion rate, number average molecular weight and molecular weight distribution of the polymer of Example 47 were evaluated. The results are shown in Table 9.

(Example 48)
In Example 47, except that the reaction temperature T was changed to 0 ° C. instead of 24 ° C., the polymer of Example 48 was produced in the same manner as in Example 47, and the same procedure as in Example 47 was carried out. The polymer of Example 48 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 9.

From the results shown in Table 9, the following became clear.
Even when an initiator was prepared using a microreactor and a polymerization reaction was continuously carried out using this initiator, a block polymer having M _w / M _n of 1.25 or less could be produced. .

(Example 49)
-Preparation of initiator-Production of polymethyl methacrylate-
Using a batch reaction vessel, n-butyllithium was added to diphenylethylene to prepare an initiator 3-methyl-1,1-diphenylpentyllithium solution. Then, using a microreactor, methyl methacrylate was anionically polymerized in the presence of an initiator 3-methyl-1,1-diphenylpentyllithium solution as a first-stage reaction, and methanol was added in the second-stage microreactor. The reaction was terminated and the polymer of Example 49 was obtained.

--Microreactor--
The same microreactor used in Example 1 was used as the microreactor used in the first stage reaction. Further, the same microreactor used in the second stage reaction was used as in Example 45. The first-stage micromixer M1 and the first introduction path in the second-stage micromixer M2 are connected via the first-stage tube reactor to connect the first-stage micromixer M1. The reactor and the second-stage microreactor were connected in series (see FIG. 9). Other configurations such as a pump for feeding liquid and adjustment of the reaction temperature are the same as those in the first embodiment.

--Reaction conditions--
FIG. 9 is a diagram showing an outline of the reaction systems of Examples 49 to 51 and Comparative Example 16. As shown in FIG. 9, the inner diameter of the first-stage micromixer M1 of Example 49 is 250 μm, and the inner diameter of the second-stage micromixer M2 is 500 μm. The inner diameter of the first-stage tube reactor is 1.0 mm and the length is 200 cm, and the inner diameter of the second-stage tube reactor is 1.0 mm and the length is 50 cm.
In Example 49, a 0.50 M methyl methacrylate solution was introduced at a flow rate of 6.0 ml / min from the first introduction path of the first-stage micromixer M1, and 0.05 M initiator 3-methyl- The 1,1-diphenylpentyllithium solution was introduced at a flow rate of 2.0 ml / min from the second introduction path of the first-stage micromixer M1, and mixed by laminar flow in the flow path. The reaction temperature T is 0 ° C.
Then, the mixed solution is introduced from the first introduction path of the second-stage micromixer M2, and the 0.33M methanol solution is introduced from the second introduction path of the second-stage micromixer M2 at a flow rate of 3.0 ml / Introduced in min, the reaction was terminated by mixing and laminating in the flow path. The reaction temperature T is 0 ° C.
Then, the conversion rate, number average molecular weight and molecular weight distribution of the polymer of Example 49 were evaluated in the same manner as in Example 1. The results are shown in Table 10.

(Example 50)
In Example 49, the polymer of Example 50 was produced in the same manner as in Example 49 except that the reaction temperature T was changed to -28 ° C instead of 0 ° C. In the same manner as in Example 49, The polymer of Example 50 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 10.

(Example 51)
In Example 49, the polymer of Example 51 was produced in the same manner as in Example 49 except that the reaction temperature T was changed to -48 ° C instead of 0 ° C. The polymer of Example 51 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 10.

(Comparative Example 16)
In Example 49, the polymer of Comparative Example 16 was produced in the same manner as in Example 49 except that the reaction temperature T was changed to -78 ° C instead of 0 ° C. The polymer of Comparative Example 16 was evaluated for conversion, number average molecular weight, and molecular weight distribution. The results are shown in Table 10.

(Comparative Example 17)
FIG. 10 is a diagram showing an outline of the reaction system of Comparative Examples 17-20. In Comparative Example 17, a batch reactor was used to add 1 equivalent of n-butyllithium solution to 1.1 equivalent of diphenylethylene solution to prepare an initiator 3-methyl-1,1-diphenylpentyllithium solution. . In the presence of the initiator 3-methyl-1,1-diphenylpentyllithium solution, 30 equivalents of a methyl methacrylate solution was added to carry out living anion polymerization. 10 equivalent of methanol solution was added to this mixed solution to terminate the reaction, and a polymer of Comparative Example 17 was obtained. Specifically, the following procedure was used.
A batch reactor in which 1.9 ml of 0.05 M diphenylethylene solution was charged in a 100 ml two-necked flask replaced with argon gas was immersed in a constant temperature layer, cooled to 0 ° C., and 2.77 M n-butyllithium solution 36. 1 μl was added. While stirring this using a magnetic stirrer, 6 ml of a 0.50 M methyl methacrylate solution was added dropwise over 3 seconds (sec), and the reaction temperature T was set to 0 ° C., followed by stirring for 10 seconds. Thereafter, 3 ml of a 0.33 M methanol solution was added dropwise over 3 seconds, and the reaction temperature T was set to 0 ° C., followed by stirring for 10 minutes.
Then, the conversion rate, number average molecular weight, and molecular weight distribution of the polymer of Comparative Example 1 were evaluated by the same method as in Example 1. The results are shown in Table 10.

(Comparative Example 18)
In Comparative Example 18, the polymer of Comparative Example 18 was produced in the same manner as in Comparative Example 17, except that the reaction temperature T in Comparative Example 17 was changed to -28 ° C instead of 0 ° C. By the method, the conversion rate, number average molecular weight and molecular weight distribution of the polymer of Comparative Example 18 were evaluated. The results are shown in Table 10.

(Comparative Example 19)
In Comparative Example 19, the polymer of Comparative Example 19 was produced in the same manner as in Comparative Example 17, except that the reaction temperature T in Comparative Example 17 was changed to -48 ° C instead of 0 ° C. The conversion, the number average molecular weight, and the molecular weight distribution of the polymer of Comparative Example 19 were evaluated by the above method. The results are shown in Table 10.

(Comparative Example 20)
In Comparative Example 20, the polymer of Comparative Example 20 was produced in the same manner as in Comparative Example 17, except that the reaction temperature T in Comparative Example 17 was changed to -78 ° C instead of 0 ° C. The conversion, the number average molecular weight, and the molecular weight distribution of the polymer of Comparative Example 20 were evaluated by the above method. The results are shown in Table 10.

From the results in Table 10, the following became clear.
That is, in Examples 49, 50, and 51 using a microreactor, a polymer having M _w / M _n of 1.25 or less is prepared with reaction temperatures T of 0 ° C., −28 ° C., and −48 ° C. I was able to. Further, in Examples 49 and 50 in which the reaction temperature T is 0 ° C. and −28 ° C., respectively, the polymer is produced at a good conversion rate (100%) compared to Example 51 in which the reaction temperature T is −48 ° C. I was able to. On the other hand, in Comparative Example 16 in which the reaction temperature T was -78 ° C, a polymer having _Mw / _Mn of 1.25 or less could not be produced.
In Comparative Examples 17 to 20 using a batch reactor, the molecular weight distribution increases as the temperature increases, and at any reaction temperature of 0 ° C., −28 ° C., −48 ° C., and −78 ° C. A polymer having _w / _Mn of 1.25 or less could not be produced.

The method for producing a polymer having M _w / M _n of 1.25 or less according to the present invention can efficiently produce a polymer having a narrow molecular weight distribution even when the reaction temperature is −28 ° C. or more. For example, fibers, rubbers, films It can be suitably used for the production of polymers useful in fields such as adhesives and plastic products.

FIG. 1 is a diagram showing an outline of the reaction system of Examples 1-8. FIG. 2 is a diagram schematically showing reaction systems of Examples 10 to 12 and Comparative Examples 4 and 5, and Example 13 and Comparative Examples 6 to 9. FIG. 3 is a diagram showing an outline of the reaction system of Examples 14-24. FIG. 4 is a correlation diagram showing the relationship between the number average molecular weight M _{n of} Examples 14 to 24 and “[M] / [I]”. FIG. 5 is a diagram showing an outline of the reaction system of Examples 35-38. FIG. 6 is a diagram showing an outline of the reaction system of Examples 39 to 42. FIG. 7 is a diagram schematically showing the reaction systems of Examples 43 and 44 and Comparative Examples 12 and 13. FIG. 8 is a diagram showing an outline of the reaction system of Examples 45-48. FIG. 9 is a diagram showing an outline of the reaction systems of Examples 49 to 51 and Comparative Example 16. FIG. 10 is a diagram showing an outline of the reaction system of Comparative Examples 17-20.

Claims (12)

A method for producing a polymer having M _w / M _n of 1.25 or less, wherein a monomer is living polymerized in the presence of an initiator using a microreactor having a flow path capable of mixing a plurality of liquids .   The production method according to claim 1, wherein the reaction temperature in the living polymerization is -28 ° C or higher.   The manufacturing method according to any one of claims 1 to 2, wherein an inner diameter of each of the first introduction path for introducing the monomer into the flow path and the second introduction path for introducing the initiator into the flow path is 500 µm or less. .   The production method according to claim 1, wherein the initiator is an organolithium reagent.   The production method according to claim 1, wherein the monomer has a functional group.   The production method according to claim 5, wherein the monomer is a styrene derivative.   The production method according to claim 1, wherein the initiator is alkyl lithium.   The production method according to claim 7, wherein the alkyl lithium is sec-butyl lithium.   The production method according to claim 1, wherein the polymer is a linear polymer.   The production method according to claim 1, wherein the polymer is a block polymer.   The production method according to claim 10, wherein living polymerization is performed in multiple stages.   A step of reacting a growth terminal of a polymer after at least one stage of living polymerization with an electrophile having two or more reaction points using a microreactor having a flow path capable of mixing a plurality of liquids. Item 12. The manufacturing method according to Item 11.