Method for producing polyrotaxane

Abstract

To provide a method for producing polyrotaxane that enables sufficient hydroxyalkylation in a short time.SOLUTION: A method for producing polyrotaxane comprising a cyclic molecule having a hydroxyalkyl group, the method including: preparation of a solution that contains polyrotaxane with a cyclic molecule having a hydroxy group, a cyclic ether, and water; and addition of the cyclic ether to the hydroxy group under pressurization.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to a method for producing polyrotaxanes. [Background technology]

[0002] Polyrotaxanes, which are complexes with a structure in which linear molecules thread through cyclic molecules, have properties different from conventional polymer materials and are therefore being investigated for various applications.

[0003] Patent Document 1 discloses a polyrotaxane in which the hydroxy groups of cyclodextrin, a cyclic molecule, are modified with hydrophobic modifying groups. Patent Document 1 describes a method for producing the polyrotaxane, in which the hydroxy groups of cyclodextrin are hydroxypropylated and then modified with ε-caprolactone. Patent Document 1 also describes the reaction conditions for the hydroxypropylation as being stirred overnight at room temperature in a 1 mol / L aqueous NaOH solution.

[0004] Patent Document 2 discloses a method for producing a hydroxyalkylated polyrotaxane by reacting a polyrotaxane having cyclic molecules with a hydroxy group with a specific cyclic ether. Patent Document 2 describes that the reaction conditions for the hydroxyalkylation are 40°C for 6 hours in the presence of a base such as triethylamine. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-091938 [Patent Document 2] International Publication No. 2013 / 147300 Summary of the Invention [Problem to be solved by the invention]

[0006] From the viewpoint of improving the productivity of polyrotaxanes, there is a demand for shortening the reaction time of the hydroxyalkylation.

[0007] In view of the above circumstances, an object of the present disclosure is to provide a method for producing polyrotaxanes that allows for sufficient hydroxyalkylation in a short period of time. [Means for solving the problem]

[0008] The present disclosure includes the following aspects. [1] A method for producing a polyrotaxane having cyclic molecules having a hydroxyalkyl group, comprising: preparing a solution containing a polyrotaxane having cyclic molecules having hydroxy groups, a cyclic ether, and water; adding a cyclic ether to the hydroxy group under pressure; Method for producing polyrotaxane. [2] The method for producing a polyrotaxane according to [1], wherein the temperature condition for the addition reaction of the cyclic ether is 42 to 58°C. [3] The method for producing a polyrotaxane according to [1] or [2], wherein the pressure condition in the addition reaction of the cyclic ether is 0.11 to 0.22 MPa. [4] The method for producing a polyrotaxane according to any one of [1] to [3], wherein the reaction time in the addition reaction of the cyclic ether is 2 to 8 hours. [5] The method for producing a polyrotaxane according to any one of [1] to [4], wherein the addition rate of hydroxyalkyl groups after the addition reaction of a cyclic ether is 50 to 60% of the total number of hydroxy groups possessed by the cyclic molecule before the reaction. [6] The method for producing a polyrotaxane according to any one of [1] to [5], wherein the cyclic molecule contains a cyclodextrin. [7] The method for producing a polyrotaxane according to any one of [1] to [6], wherein the cyclic ether is propylene oxide. [Effects of the Invention]

[0009] The present disclosure provides a method for producing polyrotaxanes that allows for sufficient hydroxyalkylation in a short period of time. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a flowchart illustrating an example of a manufacturing method according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0011] The method for producing the polyrotaxane according to this embodiment will be described below. In this specification, numerical ranges indicated using "to" include the numerical values ​​before and after "to" as the minimum and maximum values, respectively. For convenience, in this specification, the "polyrotaxane having cyclic molecules having hydroxy groups" prepared in the preparation step (S10) will be referred to as the "polyrotaxane (A)," and the "polyrotaxane having cyclic molecules having hydroxyalkyl groups (hydroxyalkyloxy groups)" obtained in the addition step (S20) will be referred to as the "polyrotaxane (B)." Each step will be described later.

[0012] [Method of producing polyrotaxane] A method for producing a polyrotaxane according to an embodiment will be outlined with reference to FIG. 1. FIG. 1 is a flowchart showing an example of the production method according to an embodiment. This production method includes at least a step (S10) of preparing a solution containing a polyrotaxane having cyclic molecules with hydroxy groups, a cyclic ether, and water, and a step (S20) of adding the cyclic ether to the hydroxy groups. The method may further include various post-processing steps (S30) as necessary. Note that the division of each step is for convenience of explanation, and the steps are not necessarily clearly distinguished as shown in FIG. 1.

[0013] The production method of this embodiment uses water as a reaction solvent and performs an addition reaction under pressure, which allows cyclic ethers (hydroxyalkyl groups) to be added to 50% or more of the hydroxy groups in the cyclic molecules in a relatively short time (-O-ROH, where ROH is a hydroxyalkyl group derived from a cyclic ether). When the addition rate of hydroxyalkyl groups reaches 50% or more, aggregation of the cyclic molecules is suppressed, improving the solubility in water and the handleability of the polyrotaxane in subsequent processes. Furthermore, according to the production method of this embodiment, the addition reaction is performed under pressurized conditions, but addition polymerization of the cyclic ether is suppressed. The manufacturing method of this embodiment will be described in detail below.

[0014] First, a solution containing a polyrotaxane (A) having cyclic molecules with hydroxy groups, a cyclic ether, and water is prepared. Although the term "solution" is used, for example, at least a portion of the polyrotaxane (A) may not dissolve and may be in a dispersed state. Furthermore, the solution may further contain other components as necessary. Each component constituting the solution will be described below.

[0015] <Polyrotaxane (A)> Polyrotaxane is a complex in which linear molecules penetrate multiple cyclic molecules and the linear molecules have blocking groups on both sides of the cyclic molecules. The blocking groups prevent the cyclic molecules from detaching from the linear molecules. The cyclic molecules can move in the linear direction of the linear molecules, using the space between the blocking groups as a range of motion. The cyclic molecules remain movable relative to the linear molecules even after crosslinking. In polyrotaxane (A), the cyclic molecules have hydroxy groups.

[0016] (cyclic molecule) The cyclic molecule has a ring structure through which a linear molecule can penetrate and a hydroxy group. The ring structure constituting the cyclic molecule may be appropriately selected from those capable of encapsulating a linear molecule. Specific examples of ring structures include cyclodextrin, crown ether, cyclophane, calixarene, benzocrown, dibenzocrown, dicyclohexanocrown, and derivatives thereof. Of these, cyclodextrin and calixarene usually have a hydroxy group. Crown ether, cyclophane, benzocrown, dibenzocrown, and dicyclohexanocrown are used by introducing a hydroxy group.

[0017] The cyclic molecule is preferably cyclodextrin or a cyclodextrin derivative, more preferably cyclodextrin. Examples of cyclodextrin include α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, δ-cyclodextrin, and ε-cyclodextrin. Examples of cyclodextrin derivatives include derivatives in which some of the hydroxy groups in cyclodextrin are esterified, etherified, or amidated.

[0018] Among these, the cyclic molecule is preferably α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin, and more preferably α-cyclodextrin.

[0019] The number of hydroxy groups per cyclic molecule may be one or more, and is preferably 1 to 30, more preferably 6 to 24, and even more preferably 18 to 24.

[0020] Furthermore, the cyclic molecule may have a substituent that has little effect on hydroxyalkylation depending on the intended use of the cyclodextrin, etc. Examples of such a substituent include a nitro group, a cyano group, and an alkoxy group.

[0021] The multiple cyclic molecules constituting the cyclodextrin may be of only one type, or may be a combination of two or more types selected from the above.

[0022] (linear molecule) The linear molecule has a linear structure that penetrates the ring structure of the cyclic molecule and a blocking group that prevents the cyclic molecule from being released. The linear structure may be a linear polymer, etc. The linear structure may have a branched structure as long as it does not hinder the movement of the cyclic molecules. Specific examples of the linear polymer include vinyl polymers such as polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, polyvinyl chloride, polyvinyl acetate, polyvinyl butyral, and vinyl chloride-vinyl acetate copolymers; acrylic polymers such as poly(meth)acrylic acid, poly(meth)acrylamide, polymethyl(meth)acrylate, and acrylonitrile-methyl acrylate copolymers; cellulose polymers such as carboxymethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose; polyethers such as polyethylene oxide, polyethylene glycol, polypropylene glycol, and polyacetal; Examples of suitable polymers include polyolefins such as polyethylene and polypropylene; polyamides such as nylon; polystyrene, acrylonitrile-styrene copolymer, acrylonitrile-butadiene-styrene copolymer, and other polystyrenes; polysiloxanes such as polydimethylsiloxane; polydienes such as polyisoprene and polybutadiene; polyesters, polyamines, polyimides, polyanilines, polyurethanes, polycarbonates, polyethyleneimines, casein, gelatin, and starch; polysulfones, polyimines, polyacetic anhydrides, polyureas, polysulfides, polyphosphazenes, polyketones, polyphenylenes, polyhaloolefins, and derivatives thereof. From the viewpoints of the stability of the linear molecule and the toughness of the cured product, the linear structure is preferably polyethylene glycol, polyisoprene, polyisobutylene, polybutadiene, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, polypropylene, polyvinyl alcohol, or polyvinyl methyl ether, more preferably polyethylene glycol, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, or polypropylene, and among these, polyethylene glycol is even more preferable.

[0023] The blocking group may be appropriately selected from substituents bulkier than the opening of the cyclic molecule. Specific examples of the blocking group include aryl groups such as phenyl, naphthyl, and pyrenyl; alkyl groups having an aryl group as a substituent, such as trityl; and cyclic alkyl groups such as adamantyl. These blocking groups may also have a substituent. Examples of the substituent include alkyl groups, oxyalkyl groups, hydroxy groups, cyano groups, sulfonyl groups, carboxy groups, amino groups, aryl groups, and halogen atoms. As the blocking group, from the viewpoint of chemical stability of the molecule, a dinitrophenyl group, an adamantyl group, a trityl group, a pyrenyl group, fluoresceins, or cyclodextrins is preferred, and an adamantyl group or a trityl group is more preferred. The blocking groups present in the linear molecule may be the same or different, but from the viewpoint of ease of synthesis, it is preferable that the blocking groups are the same substituents.

[0024] The molecular weight of the linear molecule may be adjusted appropriately depending on the number of cyclic molecules contained in the polyrotaxane, the range of motion required for the cyclic molecules, etc. The weight-average molecular weight of the linear molecule can be adjusted, for example, in the range of 1,000 to 1,000,000, preferably 2,000 to 500,000, and more preferably 3,000 to 200,000. The number-average molecular weight of the linear molecule is a value measured, for example, by gel permeation chromatography (GPC; standard substance: polystyrene, pullulan, or polyethylene oxide).

[0025] The ratio of cyclic molecules introduced into the linear molecules (inclusion ratio) is not particularly limited and may be adjusted appropriately taking into consideration the desired physical properties of the polyrotaxane to be produced, etc. In order to ensure the movement of the cyclic molecules, the inclusion ratio, which is the ratio of cyclic molecules introduced into the linear molecules, is preferably 0.05 to 0.80, more preferably 0.10 to 0.70, and even more preferably 0.15 to 0.60, where 1.0 is the closest inclusion ratio of cyclic molecules in the linear molecules (filling ratio: 100%).

[0026] The polyrotaxane (A) may be synthesized by referring to, for example, Patent Documents 1 and 2 above, or a commercially available product may be used.

[0027] <Cyclic ether> The cyclic ether is a compound that reacts with the hydroxy group of the cyclic molecule to form a hydroxyalkyl group. Examples of cyclic ethers include compounds represented by the following formula (1). [ka] In the formula, R 1 ~R 4 each independently represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, or an optionally substituted aralkyl group, R 1 and R 2 and / or R 3 and R 4 may be bonded to form a 3- to 12-membered carbocyclic ring (for example, oxaspiroalkylenes, etc.), L is a single bond or an alkylene group having 1 to 12 carbon atoms which may have a substituent, and the substituent is a fluorine atom, a nitro group, a cyano group, an alkoxy group, or a hydroxy group, provided that the number of carbon atoms in formula (1) is 50 or less.

[0028] Among them, the cyclic ether is preferably a compound represented by the following formula (2) or (3). [ka] In the formula, R 1 ~R 4 is the same as the above formula (1), R 5 ~R 6 are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a substituent, and the substituent is a fluorine atom, a nitro group, a cyano group, an alkoxy group, or a hydroxy group, provided that the number of carbon atoms in formula (2) and formula (3) is 50 or less.

[0029] The alkyl group is preferably a linear or branched alkyl group having 1 to 12 carbon atoms, and more preferably a linear or branched alkyl group having 1 to 8 carbon atoms. Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, and an octyl group. Furthermore, one or more hydrogen atoms of the alkyl group may be substituted with the above-mentioned substituents. R 5 and R 6 Examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group.

[0030] The cycloalkyl group is preferably a cycloalkyl group having 3 to 12 carbon atoms. Specific examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclododecyl group. In addition, one or more hydrogen atoms of the cycloalkyl group may be substituted with the above-mentioned substituents. The aryl group is preferably an aryl group having 6 to 18 carbon atoms. Specific examples of the aryl group include a phenyl group, a naphthyl group, a biphenyl group, etc. In addition, one or more hydrogen atoms of the aryl group may be substituted with the above-mentioned substituents. The aralkyl group is preferably an aralkyl group having 7 to 18 carbon atoms. Specific examples of the aralkyl group include a benzyl group, a phenethyl group, etc. In addition, one or more hydrogen atoms of the aralkyl group may be substituted with the above-mentioned substituents.

[0031] The alkylene group having 1 to 12 carbon atoms in L is preferably a methylene group, an ethylene group, a propylene group, or a butylene group, and more preferably a methylene group or an ethylene group. In addition, one or more hydrogen atoms of the alkylene group may be substituted with the above-mentioned substituents.

[0032] Specific examples of the cyclic ether represented by formula (2) include (alkoxymethyl)oxiranes having 1 to 8 carbon atoms, such as methyloxirane (propylene oxide), ethyloxirane (1,2-butylene oxide), propyloxirane (1,2-pentylene oxide), butyloxirane (1,2-hexylene oxide), phenyloxirane, and methoxymethyloxirane, and glycidol (2,3-epoxymethanol); 2,2-bis(alkoxymethyl)oxiranes having 1 to 8 carbon atoms, such as 2,3-dimethyloxirane, 2,2-dimethyloxirane, 2,3-diethyloxirane, 2,2-diethyloxirane, 2,3-dipropyloxirane, 2,2-dipropyloxirane, 2,3-dibutyloxirane, 2,2-dibutyloxirane, 2,3-diphenyloxirane, 2,2-diphenyloxirane, 2,3-bis(alkoxymethyl)oxirane having 1 to 8 carbon atoms, and 2,2-bis(methoxymethyl)oxirane; 2,2,3-tris(alkoxymethyl)oxiranes having 1 to 8 carbon atoms, such as 2,2,3-trimethyloxirane, 2,2,3-triethyloxirane, 2,2,3-tripropyloxirane, 2,2,3-tributyloxirane, 2,2,3-triphenyloxirane, and 2,2,3-tris(methoxymethyl)oxirane; Examples thereof include 2,2,3,3-tetramethyloxirane, 2,2,3,3-tetraethyloxirane, 2,2,3,3-tetrapropyloxirane, 2,2,3,3-tetrabutyloxirane, 2,2,3,3-tetraphenyloxirane, and 2,2,3,3-tetrakis(alkoxymethyl having 1 to 8 carbon atoms). The cyclic ethers can be used alone or in combination of two or more.

[0033] Specific examples of the cyclic ether represented by formula (3) include oxetane, 3-methyloxetane, 3-ethyloxetane, and 3-ethyl-3-hydroxyethyloxetane. In addition, in formula (1), R 1 and R 2 and / or R 3 and R 4 Examples of cyclic ethers in which the carbon atoms bond to form a 3- to 12-membered carbon ring include 1-oxaspiro[2.4]heptane and 1-oxaspiro[2.5]octane.

[0034] From the viewpoints of reactivity, the structure of the resulting polyrotaxane, and the like, the cyclic ether is preferably oxirane (ethylene oxide), methyloxirane (propylene oxide), ethyloxirane (1,2-butylene oxide), propyloxirane (1,2-pentylene oxide), butyloxirane (1,2-hexylene oxide), phenyloxirane, or glycidol (2,3-epoxymethanol), and more preferably oxirane (ethylene oxide), methyloxirane (propylene oxide), or ethyloxirane (1,2-butylene oxide).

[0035] The amount of cyclic ether used may be 0.5 mol or more per mol of hydroxy groups in polyrotaxane (A), and may be, for example, in the range of 0.5 to 150 mol, preferably 0.8 to 20 mol, more preferably 1.0 to 15 mol, and even more preferably 1.25 to 7.5 mol. By adjusting the amount of cyclic ether to be equal to or greater than the above lower limit, polyrotaxane (B) having a hydroxyalkyl group addition rate [= total number of hydroxyalkyl groups derived from cyclic ethers in polyrotaxane (B) / total number of hydroxy groups in polyrotaxane (A)] of 50 to 60% can be produced.

[0036] <base> The solution may further contain a base to promote the addition reaction, and from the viewpoint of separation and purification after the reaction, the base is preferably an organic base having a boiling point of 200° C. or less.

[0037] Examples of the organic base include amines, pyridines, imidazoles, triazoles, etc. The organic base is preferably a tertiary amine represented by the following formula (4). [ka] In the formula, R a , R b and R c each independently represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, or an optionally substituted trialkylsilyl group, and R a and R b may be bonded to form a 3- to 12-membered ring structure, The substituent is a fluorine atom, a nitro group, a cyano group, an alkoxy group, or a hydroxy group.

[0038] R a ~R c The alkyl group, cycloalkyl group, aryl group, and aralkyl group in 1 It is similar to that in In the trialkylsilyl group, each alkyl group is preferably a linear or branched alkyl group having 1 to 12 carbon atoms, and more preferably a linear or branched alkyl group having 1 to 8 carbon atoms. Specific examples of the trialkylsilyl group include a trimethylsilyl group, a triethylsilyl group, and a tert-butyldimethylsilyl group.

[0039] Specific examples of the base include trimethylamine, triethylamine, tri-n-propylamine, diisopropylmethylamine, tri-n-butylamine; N-trimethylsilyldimethylamine, N-triethylsilyldimethylamine, N-tert-butyldimethylsilyldimethylamine, N-trimethylsilyldiethylamine, N-triethylsilyldiethylamine, N-tert-butyldimethylsilyldiethylamine, N-trimethylsilyldi-n-propylamine, N-triethylsilyldi-n-propylamine, N-tert-butyldimethylsilyldi-n-propylamine, N-trimethylsilyldiisopropylamine, N-triethylsilyldiisopropylamine, N-tert-butyldimethylsilyl dimethylphenylamine, ethylmethylphenylamine, diethylphenylamine, dipropylphenylamine, diphenylmethylamine, diphenylethylamine, n-propyldiphenylamine, isopropyldiphenylamine, triphenylamine; N-trimethylsilyldiphenylamine, N-triethylsilyldiphenylamine, N-tert-butyldimethylsilyldiphenylamine; alicyclic tertiary amines such as diazabicycloundecene (DBU), diazabicyclononene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), quinuclidine, N-substituted pyrrolidines, N-substituted piperidines, and N,N'-disubstituted piperazines; and heteroalicyclic tertiary amines such as N-substituted morpholines. Among them, the base is preferably triethylamine, tri-n-propylamine, diisopropylmethylamine, tri-n-butylamine or pyridine. The base may be used alone or in combination of two or more.

[0040] When a base is used, the amount used can be 0.01 to 500 mol, preferably 0.05 mol to 50 mol, more preferably 0.10 mol to 10 mol, and even more preferably 0.10 mol to 5 mol, per mol of hydroxy groups in the polyrotaxane (A). By using the base in this amount within the above range, a polyrotaxane (B) having a hydroxyalkyl group addition rate of 50 to 60% can be produced in a short period of time.

[0041] [water] In this production method, the addition reaction of the cyclic ether is carried out in the presence of water, which suppresses the production of polyalkylene oxide. The amount of water used in the present invention can be 0.01 to 200 g, preferably 0.1 g to 150 g, more preferably 1.0 g to 100 g, still more preferably 3.0 g to 50 g, and particularly preferably 4.0 g to 30 g, per 1 g of polyrotaxane (A).

[0042] [Solution preparation] The method for preparing the solution is not particularly limited, and examples thereof include a method in which the polyrotaxane (A), a cyclic ether, and an optional base are added to water and mixed. In consideration of subsequent steps, the mixture may be mixed in a pressure-resistant container, or the prepared solution may be transferred to a pressure-resistant container. A sealed reaction vessel may also be used as the container.

[0043] [Additional process] The hydroxyl groups of the cyclic molecules of the polyrotaxane (A) are reacted with the cyclic ether under pressure. The pressurization method is not particularly limited, but for example, a gas may be supplied into a container to pressurize it and then the container may be sealed. The gas is preferably an inert gas such as nitrogen or argon.

[0044] The pressure condition during the reaction is preferably 0.11 MPa or higher. By carrying out the reaction under pressure, the addition rate of hydroxyalkyl groups can be increased to 50% or higher in a short period of time. The pressure is preferably 0.11 to 0.23 MPa, more preferably 0.11 to 0.22 MPa, and even more preferably 0.11 to 0.21 MPa.

[0045] The temperature condition during the reaction is preferably 40 to 60°C, more preferably 42 to 58°C, and more preferably 45 to 55°C. By setting the temperature at or above the lower limit, the reaction rate is improved. On the other hand, by setting the temperature at or below the upper limit, the addition rate of the hydroxyalkyl group is easily improved.

[0046] The reaction time may be terminated when the addition rate of hydroxyalkyl groups reaches 50% or more, and may be, for example, 2 hours or more, preferably 2.5 hours or more, and more preferably 3 hours or more. On the other hand, the upper limit is not particularly limited, but 12 hours or less is sufficient, preferably 10 hours or less, more preferably 8 hours or less, and even more preferably 6 hours or less.

[0047] The addition rate of hydroxyalkyl groups after the addition reaction of the cyclic ether needs to be 50% or more. Furthermore, an addition rate of 60% or less is sufficient. When the addition rate of hydroxyalkyl groups is 50% or more, aggregation of cyclic molecules is suppressed, improving the solubility of the polyrotaxane in water. In the production method of this embodiment, the reaction is carried out under pressure in the presence of water, and therefore the addition rate of hydroxyalkyl groups is unlikely to exceed 60% due to side reactions with water, etc.

[0048] <Polyrotaxane (B)> In the polyrotaxane (B) obtained by the above reaction, 50-60% of the hydroxy groups (-OH) in the cyclic molecules are replaced with hydroxyalkyl groups, forming -O-ROH. Here, ROH is a hydroxyalkyl group derived from a cyclic ether. Except for this point, polyrotaxane (B) has the same structure as polyrotaxane (A), so a detailed explanation will be omitted here.

[0049] [Post-process] The obtained polyrotaxane (B) may be separated and purified as necessary. Specifically, the reaction product containing the polyrotaxane (B) is subjected to a reprecipitation operation either directly or by adding an additional solvent (e.g., a reprecipitation solvent) described below, and then subjected to a separation operation such as decantation and / or filtration, thereby obtaining a hydroxyalkylated polyrotaxane as a solid. Alternatively, the reaction product containing the polyrotaxane (B) can be purified using a dialysis membrane and then freeze-dried to obtain a hydroxyalkylated polyrotaxane as a solid.

[0050] (Reprecipitation operation) In order to obtain the target polyrotaxane (B) as a solid substance with high purity from the reaction solution, a reprecipitation procedure may be performed. Here, the reprecipitation procedure includes not only phase separation of the polyrotaxane (B) as a solid substance from the reaction solution, but also phase separation of a liquid substance containing the polyrotaxane (B) from the reaction solution. The reprecipitation solvent used in the reprecipitation operation may be selected from those that are poor solvents for the target polyrotaxane (B). Specific examples of the reprecipitation solvent include ketones such as acetonitrile, acetone, butanone, methyl isobutyl ketone, and cyclohexanone; alcohols such as methanol, ethanol, isopropanol, and ethylene glycol; ethers such as tetrahydrofuran, tetrahydropyran, 1,2-dimethoxyethane, and dioxane; and mixed solvents thereof. The amount of the reprecipitation solvent used can be, for example, 0.1 g to 1000 g, preferably 0.5 g to 100 g, and more preferably 1 g to 50 g, per 1 g of the reaction solution after the reaction is completed. The obtained solid polyrotaxane (B) or the phase containing polyrotaxane (B) may be further separated by a known separation method such as filtration or decantation, or may be subjected to repeated reprecipitation, filtration, decantation, etc. The obtained polyrotaxane (B) may further be washed with the poor solvent.

[0051] Depending on the intended use, the obtained polyrotaxane (B) may further contain a substituent, a graft chain which may have a substituent, etc. For the method of introducing each substituent, etc., reference can be made to, for example, Patent Documents 1 and 2 and WO 2021 / 149779. [Example]

[0052] The present invention will be explained in more detail below using examples, but the present invention is not limited to these examples.

[0053] <Analytical equipment for each compound> 1 H-NMR measurements were performed using a 400 MHz JEOL JNM-AL400 (manufactured by JEOL Ltd.). Molecular weight and molecular weight distribution were measured using a TOSOH HLC-8220 GPC system. Columns were TSK guard columns Super AW-H and TSKgel Super AWM-H (two columns connected), eluent was dimethyl sulfoxide (DMSO) / 0.01M LiBr, column oven temperature was 50°C, flow rate was 0.5 ml / min, sample concentration was approximately 0.2 wt / vol%, injection volume was 20 μl, pretreatment was filtration through a 0.2 μm filter, and standard molecular weight was PEO.

[0054] <Synthesis Example 1: Preparation of Polyrotaxane (A) (APR11)> Polyrotaxane (A) (hereinafter sometimes abbreviated as "APR11") (weight-average molecular weight Mw = 76,000) consisting of a linear molecule: polyethylene glycol (Mw: 11,000), a cyclic molecule: α-cyclodextrin (hereinafter sometimes abbreviated as "α-CD"), and a blocking group: adamantane group was prepared by the method described in WO2005 / 052026 or WO2013 / 147301. In addition, 1The inclusion rate of APR11 calculated by H-NMR measurement was 33%, where the inclusion rate was calculated by setting the maximum amount of α-CD included when α-CD was skewered by polyethylene glycol as 1 (see Macromolecules 1993, 26, 5698-5703, the contents of which are incorporated herein in their entirety).

[0055] <Example 1-1: Preparation of polyrotaxane (B) (HAPR11) at 40°C under pressure> APR11 (2 g), ion-exchanged water (10 g), triethylamine (0.55 g), and propylene oxide (5.25 g) were placed in a pressure-resistant glass tube, sealed, and stirred in a 40°C oil bath for 3 hours. The internal pressure was estimated to be approximately 0.13 MPa based on the vapor pressure curve. After the reaction, the product was purified using a dialysis tube with a fractionation of 6,000 and then lyophilized to obtain 1.66 g of polyrotaxane (B) (hereinafter sometimes simply referred to as "HAPR11"). GPC showed a Mw of 114,200. The modification rate of the hydroxy groups of the cyclic molecules by hydroxyalkylation (hydroxypropyl group modification rate, hereinafter sometimes abbreviated as "H rate") was: 1 1H-NMR revealed that the purity was 36.5% (see WO2013 / 147300, the contents of which are incorporated herein in their entirety).

[0056] <Example 1-2: Preparation of HAPR11 at 40°C under pressure> The same experiment as in Example 1-1 was carried out except that the reaction time was changed to 6 hours. As a result, 1.81 g of HAPR11 was obtained. Mw=121,300 by GPC. 1 H-NMR revealed that the hydrogenation rate was 50.6%.

[0057] <Example 1-3: Preparation of HAPR11 at 40°C under pressure> The same experiment as in Example 1-1 was carried out except that the reaction time was changed to 8 hours. As a result, 1.93 g of HAPR11 was obtained. Mw=116,000 by GPC. 1 H-NMR revealed that the hydrogenation rate was 56.6%.

[0058] Example 2-1: Preparation of HAPR11 at 50°C under pressure A pressure-resistant glass tube was charged with 2 g of APR11, 10 g of ion-exchanged water, 0.55 g of triethylamine, and 5.25 g of propylene oxide, and the tube was sealed and stirred in a 50°C oil bath for 3 hours. The internal pressure was estimated to be approximately 0.17 MPa based on the vapor pressure curve. After the reaction, the product was purified using a dialysis tube with a fractionation of 6,000 and then lyophilized to obtain 1.88 g of HAPR11. Mw was determined by GPC to be 118,400. 1 H-NMR revealed that the hydrogenation rate was 53.6%.

[0059] <Example 2-2: Preparation of HAPR11 at 50°C under pressure> The same experiment as in Example 2-1 was carried out except that the reaction time was changed to 6 hours. As a result, 1.89 g of HAPR11 was obtained. Mw=121,400 by GPC. 1 H-NMR revealed that the hydrogenation rate was 54.6%.

[0060] <Example 2-3: Preparation of HAPR11 at 50°C under pressure> The same experiment as in Example 2-1 was carried out except that the reaction time was 8 hours. As a result, 1.90 g of HAPR11 was obtained. Mw=122,600 by GPC. 1 H-NMR revealed that the hydrogenation rate was 54.6%.

[0061] Example 3-1: Preparation of HAPR11 at 60°C under pressure A pressure-resistant glass tube was charged with 2 g of APR11, 10 g of ion-exchanged water, 0.55 g of triethylamine, and 5.25 g of propylene oxide, and the tube was sealed and stirred in a 60°C oil bath for 3 hours. The internal pressure was estimated to be approximately 0.25 MPa based on the vapor pressure curve. After the reaction, the product was purified using a dialysis tube with a fractionation of 6,000 and then lyophilized to obtain 1.76 g of HAPR11. Mw was determined by GPC to be 115,600. 1 H-NMR revealed that the hydrogenation rate was 49.0%.

[0062] <Example 3-2: Preparation of HAPR11 at 60°C under pressure> The same experiment as in Example 3-1 was carried out except that the reaction time was changed to 6 hours. As a result, 1.73 g of HAPR11 was obtained. Mw=115,300 by GPC. 1 H-NMR revealed that the hydrogenation rate was 49.5%.

[0063] <Example 3-3: Preparation of HAPR11 at 60°C under pressure> The same experiment as in Example 3-1 was carried out except that the reaction time was changed to 8 hours. As a result, 1.77 g of HAPR11 was obtained. Mw=118,400 by GPC. 1 H-NMR revealed that the hydrogen modification rate was 47.7%.

[0064] Example 4-1: Preparation of HAPR11 at 70°C under pressure A pressure-resistant glass tube was charged with 2 g of APR11, 10 g of ion-exchanged water, 0.55 g of triethylamine, and 5.25 g of propylene oxide, and the tube was sealed and stirred in a 70°C oil bath for 3 hours. The internal pressure was estimated to be approximately 0.33 MPa based on the vapor pressure curve. After the reaction, the product was purified using a dialysis tube with a fractionation of 6,000 and then lyophilized to obtain 1.73 g of HAPR11. Mw was determined by GPC to be 118,900. 1 H-NMR revealed that the hydrogenation rate was 40.7%.

[0065] Example 4-2: Preparation of HAPR11 at 70°C under pressure The same experiment as in Example 3-1 was carried out except that the reaction time was changed to 6 hours. As a result, 1.72 g of HAPR11 was obtained. Mw=119,600 by GPC. 1 H-NMR revealed that the hydrogenation rate was 38.9%.

[0066] Example 4-3: Preparation of HAPR11 at 70°C under pressure The same experiment as in Example 3-1 was carried out except that the reaction time was 8 hours. As a result, 1.67 g of HAPR11 was obtained. Mw=120,200 by GPC. 1 H-NMR revealed that the hydrogenation rate was 39.8%.

[0067] <Comparative Example 1-1: Preparation of HAPR11 under normal pressure> APR11 (2 g), ion-exchanged water (10 g), triethylamine (0.55 g), and propylene oxide (5.25 g) were placed in a recovery flask equipped with a condenser and refluxed in a 40°C oil bath for 3 hours with stirring. After the reaction, the mixture was purified using a 6,000 dialysis tube and then lyophilized to obtain 1.61 g of HAPR11. Mw was measured by GPC at 105,100. 1 H-NMR revealed that the hydrogenation rate was 10.1%.

[0068] <Comparative Example 1-2: Preparation of HAPR11 under normal pressure> The same experiment as in Comparative Example 1-1 was carried out except that the reaction time was changed to 5 hours. As a result, 1.72 g of HAPR11 was obtained. Mw=109,400 by GPC. 1 H-NMR revealed that the hydrogenation rate was 29.2%.

[0069] <Comparative Example 1-3: Preparation of HAPR11 under normal pressure> The same experiment as in Comparative Example 1-1 was carried out except that the reaction time was changed to 8 hours. As a result, 1.88 g of HAPR11 was obtained. Mw=112,800 by GPC. 1 H-NMR revealed that the hydrogenation rate was 51.7%.

[0070] <Comparative Example 1-4: Preparation of HAPR11 under normal pressure> The same experiment as in Comparative Example 1-1 was carried out except that the reaction time was changed to 15 hours. As a result, 1.87 g of HAPR11 was obtained. Mw=133,232 by GPC. 1 H-NMR revealed that the hydrogen content was 56.6%.

[0071] <Comparative Example 1-5: Preparation of HAPR11 under normal pressure> The same experiment as in Comparative Example 1-1 was carried out except that the reaction time was changed to 21 hours. As a result, 1.91 g of HAPR11 was obtained. Mw=114,500 by GPC. 1 H-NMR revealed that the hydrogenation rate was 54.3%.

[0072] The results of the examples and comparative examples are shown in Table 1. The pressures in the table are calculated values. [Table 1]

[0073] As shown in Table 1, it was demonstrated that the production method of this embodiment enables sufficient hydroxyalkylation in a short period of time.

Claims

1. A method for producing a polyrotaxane having cyclic molecules having a hydroxyalkyl group, comprising: preparing a solution containing a polyrotaxane having cyclic molecules having hydroxy groups, a cyclic ether, and water; adding a cyclic ether to the hydroxy group under pressure; Method for producing polyrotaxane.

2. 2. The method for producing a polyrotaxane according to claim 1, wherein the temperature condition for the addition reaction of the cyclic ether is 42 to 58°C.

3. 2. The method for producing a polyrotaxane according to claim 1, wherein the pressure condition in the addition reaction of the cyclic ether is 0.11 to 0.22 MPa.

4. 2. The method for producing a polyrotaxane according to claim 1, wherein the reaction time in the addition reaction of the cyclic ether is 2 to 8 hours.

5. 2. The method for producing a polyrotaxane according to claim 1, wherein the addition rate of hydroxyalkyl groups after the addition reaction of the cyclic ether is 50 to 60% of the total number of hydroxy groups in the cyclic molecule before the reaction.

6. The method for producing a polyrotaxane according to claim 1 , wherein the cyclic molecule comprises a cyclodextrin.

7. The method for producing a polyrotaxane according to claim 1 , wherein the cyclic ether is propylene oxide.

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