Compounds that can be used as RAFT agents and methods for producing polymers using the same

Abstract

To provide a novel compound which can be used as a RAFT agent of a RAFT polymerization in a highly polar solvent such as water, and which can be applied to surface modification of various base materials such as a metal oxide.SOLUTION: A compound represented by formula (1) (In formula (1), R1 is selected from a group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group, R2 is a monovalent organic group comprising a phosphorus-containing group selected from a group consisting of a phosphate group, a phosphonic acid group, a phosphoric ester group, and a phosphonic acid ester group, X is selected from a group consisting of a single bond, S, O, and NR3, R3 is selected from a group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group, and may form a heterocyclic structure by bonding to R1).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to compounds that can be used as RAFT agents and methods for making polymers using the same. [Background technology]

[0002] Living radical polymerization (also known as "controlled radical polymerization") is a well-known method for obtaining polymers and copolymers with controlled molecular weights. One example of living radical polymerization is reversible addition / fragmentation chain transfer (RAFT) polymerization. RAFT polymerization utilizes a reversible chain transfer reaction mediated by a chain transfer agent (also known as a "RAFT agent") to control the propagation reaction during polymerization. This allows the production of polymers and block copolymers with narrow molecular weight distributions. RAFT polymerization can be applied to many radically polymerizable monomers. Because of its high tolerance to functional groups in the monomers and solvents, a wide variety of polymers and block copolymers can be synthesized in water or protic solvents. Furthermore, RAFT polymerization produces polymers with RAFT agent fragments attached to the ends of the polymer chains, allowing the functional groups of the RAFT agent to impart functionality to the polymer.

[0003] Patent Document 1 (WO 2011 / 093401) describes a compound represented by the following general formula (1) as a RAFT agent having both surface activity and polymerization control ability, in which R 1 is an organic group having a hydrophobic-hydrophilic balance (HLB) value of 3 or more as determined by the Griffin method. [ka]

[0004] Non-Patent Document 1 (Macromolecules 2001, 34, 7269-7275) describes the RAFT polymerization of styrene using benzyl(diethoxyphosphoryl)dithioformate and benzyl(diethoxythiophosphoryl)dithioformate as RAFT agents.

[0005] Non-Patent Document 2 (Polymer 48 (2007) 5850-5858) describes the formation of TiO2 / polyacrylic acid (PAA) nanocomposites by RAFT polymerization. The RAFT agents used were 2-(((butylsulfanyl)carbonothioyl)sulfanyl)propanoic acid and 2-(ethoxythiocarbonyl)-2-methylmalonate.

[0006] Non-Patent Document 3 (Polymer 51 (2010) 5345-5351) describes the formation of an n-TiO2 / polymethyl methacrylate (PMMA) nanocomposite by RAFT polymerization of methyl methacrylate using 4-cyano-4-(dodecylsulfanylthiocarbonylsulfanyl)pentanoic acid coordinated to the surface of nanotitania (n-TiO2) as a RAFT agent.

[0007] Non-Patent Document 4 (J. Mater. Chem. C, 2013, 1, 484-492) describes the formation of a rutile TiO-polystyrene composite by RAFT polymerization of styrene using 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoic acid coordinated to rutile TiO nanoparticles as a RAFT agent. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2011 / 093401 [Non-patent literature]

[0009] [Non-Patent Document 1] Macromolecules 2001, 34, 7269-7275 [Non-patent document 2] Polymer 48 (2007) 5850-5858 [Non-patent document 3] Polymer 51 (2010) 5345-5351 [Non-patent document 4] J. Mater. Chem. C, 2013, 1, 484-492 Summary of the Invention [Problem to be solved by the invention]

[0010] The present disclosure aims to provide novel compounds that can be used as RAFT agents for RAFT polymerization in highly polar solvents such as water, and that can be applied to the surface modification of various substrates such as metal oxides. [Means for solving the problem]

[0011] The present inventors have found that a thiocarbonylthio group-containing compound having a specific phosphorus-containing group can effectively undergo RAFT polymerization in a highly polar solvent such as water, and that the surface of a substrate such as a metal oxide can be modified with the compound via the phosphorus-containing group, or with a polymer obtained by RAFT polymerization using the compound.

[0012] The present invention includes the following aspects.

[0013] [Aspect 1] Formula (1) [ka] (In formula (1), R 1 is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups; R 2is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphate group, a phosphonate group, a phosphate ester group, and a phosphonate ester group; X is a single bond, S, O, or NR 3 selected from the group consisting of R 3 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; R 1 may be bonded to form a heterocyclic structure. A compound represented by the formula: [Aspect 2] The compound according to embodiment 1, wherein X in formula (1) is a single bond or S. [Aspect 3] In formula (1), R 2 However, equation (2) [ka] (In formula (2), R 4 is selected from the group consisting of a hydrogen atom, a cyano group, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, a carboxy group, a substituted or unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms, and a substituted or unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms; R 5 is selected from the group consisting of a hydrogen atom and a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms; R 6 is a divalent organic group having 1 to 30 carbon atoms, R 7 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, and a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; Y is selected from the group consisting of a single bond and O; * indicates the bonding site with the sulfur atom.) 3. The compound according to any one of aspects 1 or 2, wherein [Aspect 4] In formula (2), Y is O and R 7is a hydrogen atom. [Aspect 5] In formula (2), R 6 Aspect 5. The compound of any of aspects 3 or 4, wherein comprises an amide bond or an ether bond. [Aspect 6] The compound is represented by formula (3) [ka] 2. The compound according to embodiment 1, represented by: [Aspect 7] A method for producing a polymer, comprising carrying out RAFT polymerization using the compound according to any one of aspects 1 to 6. [Aspect 8]

[0023] A method for producing a polymer according to embodiment 7, wherein the RAFT polymerization is carried out in an aqueous solvent. [Aspect 9] Formula (4) [ka] (In formula (4), R 1 is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups; R 2 is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphate group, a phosphonate group, a phosphate ester group, and a phosphonate ester group; X is a single bond, S, O, or NR 3 selected from the group consisting of R 3 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; R 1 may be bonded to form a heterocyclic structure, Poly represents a polymer chain. A polymer represented by the formula: [Aspect 10] The polymer of embodiment 9, wherein, in formula (4), Poly includes at least one structural unit having a zwitterionic structure. [Aspect 11] 11. A composite material comprising an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite, and the polymer according to either of aspects 9 or 10, wherein a surface of the inorganic substrate is modified with the polymer via the phosphorus-containing group of the polymer. [Aspect 12] A method for producing a composite material whose surface is modified with a polymer, the method comprising contacting an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite with the polymer according to either of Aspects 9 or 10 in an aqueous solvent having a pH of 7 or higher. [Aspect 13] A solid-phase RAFT agent comprising an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite, and a compound according to any one of Aspects 1 to 6, wherein a surface of the inorganic substrate is modified with the compound via the phosphorus-containing group of the compound. [Aspect 14] 14. A method for producing a polymer, comprising conducting a RAFT polymerization using a solid-state RAFT agent according to embodiment 13. [Aspect 15]

[0033] A method for producing a polymer according to embodiment 14, wherein the RAFT polymerization is carried out in an aqueous solvent. [Effects of the Invention]

[0014] The compounds of the present invention can be used as RAFT agents for RAFT polymerization in highly polar solvents such as water, and can also be applied to the surface modification of various substrates such as metal oxides.

[0015] The above description should not be considered as a disclosure of all embodiments of the present invention and all advantages associated with the present invention. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a H-NMR (400 MHz, DO) chart of the RAFT agent of Example 1. [Figure 2A] 1 is a UV-Vis spectrum of the RAFT agent of Example 1. [Figure 2B] 1 shows the UV-Vis spectrum of RAFT-NHS used as a raw material. [Figure 3] 1 is a H-NMR (400 MHz, DO) chart of poly(2-methacryloyloxyethyl phosphorylcholine) of Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0017] Representative embodiments of the present invention will be described in more detail below for the purpose of illustrating them, but the present invention is not limited to these embodiments.

[0018] In this disclosure, "(meth)acrylic" means acrylic or methacrylic, and "(meth)acrylate" means acrylate or methacrylate.

[0019] [Compound] In one embodiment, the compound has the formula (1) [ka] It is expressed as:

[0020] In formula (1), R 1 is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups; R 2 is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphate group, a phosphonate group, a phosphate ester group, and a phosphonate ester group, and X is a single bond, S, O, or NR 3 R 3 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; R 1 may be bonded to form a heterocyclic structure.

[0021] The compound of this embodiment has a specific phosphorus-containing group, which makes it highly soluble in highly polar solvents such as water. The compound also functions as a RAFT agent due to its thiocarbonylthio group (-(C=S)-S-). Therefore, RAFT polymerization can be advantageously carried out using this compound in an aqueous solvent. Furthermore, via the phosphorus-containing group of this compound, the surface of a substrate such as a metal oxide can be modified with this compound or with a polymer obtained by RAFT polymerization using this compound.

[0022] R 1 is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups.

[0023] R 1 The unsubstituted alkyl group is preferably an alkyl group having 1 to 20 carbon atoms, and more preferably an alkyl group having 1 to 16 carbon atoms. Examples of the alkyl group having 1 to 20 carbon atoms 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, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, a 2-ethylhexyl group, an n-decyl group, an n-dodecyl group, an n-tetradecyl group, and an n-hexadecyl group.

[0024] R 1 The unsubstituted aryl group is preferably an aryl group having 6 to 20 carbon atoms, and more preferably an aryl group having 6 to 14 carbon atoms. Examples of the aryl group having 6 to 20 carbon atoms include a phenyl group, a naphthyl group, a fluorenyl group, an anthryl group, and a phenanthrenyl group.

[0025] R 1The unsubstituted heteroaryl group is preferably a heteroaryl group having 3 to 20 carbon atoms, and more preferably a heteroaryl group having 4 to 14 carbon atoms. Examples of heteroaryl groups having 3 to 20 carbon atoms include a furanyl group, a pyridyl group, a thienyl group, a quinolinyl group, a pyrazinyl group, a triazinyl group, a benzofuranyl group, a benzothienyl group, and an indolyl group.

[0026] R 1 The substituted alkyl group, substituted aryl group, and substituted heteroaryl group are the unsubstituted alkyl group, unsubstituted aryl group, and unsubstituted heteroaryl group, respectively, in which one or more hydrogen atoms of the unsubstituted alkyl group, unsubstituted aryl group, and unsubstituted heteroaryl group have been substituted with a substituent. Examples of the substituent include an alkyl group (excluding substituted alkyl groups), a hydroxyl group, an alkoxy group, an aryloxy group, a hydroxyalkyl group (excluding substituted alkyl groups), an alkoxyalkyl group (excluding substituted alkyl groups), a halogen group, a cyano group, a nitro group, an isocyanato group, an acyl group, a carboxy group, an alkoxycarbonyl group, an epoxy group, and a silyl group. The total number of carbon atoms of the substituent is preferably 1 to 30, and more preferably 1 to 18.

[0027] R 1 is preferably an alkyl group having 1 to 16 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, or a heteroaryl group having 4 to 14 carbon atoms which may have a substituent, and more preferably an alkyl group having 1 to 16 carbon atoms which may have a substituent, or an aryl group having 6 to 14 carbon atoms which may have a substituent.

[0028] R 1 In an embodiment in which has a substituent, the substituent is preferably an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a cyano group, or a silyl group.

[0029] R 2is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphoric acid group, a phosphonic acid group, a phosphoric ester group, and a phosphonic acid ester group. When the compound represented by formula (1) is used as a RAFT agent for RAFT polymerization or after RAFT polymerization, the phosphorus-containing group, that is, the phosphoric ester group or the phosphonic acid ester group, may be hydrolyzed to convert it to a phosphoric acid group or a phosphonic acid group.

[0030] R 2 The phosphorus-containing group is preferably a phosphate group or a phosphonate group, more preferably a phosphate group. The phosphate group and the phosphonate group can further increase the solubility of the compound represented by formula (1) in highly polar solvents such as water.

[0031] R 2 The number of carbon atoms in R is preferably 1 to 60, more preferably 1 to 40, and even more preferably 1 to 30. 2 By adjusting the number of carbon atoms to 1 to 60, the solubility of the compound represented by formula (1) in highly polar solvents such as water can be increased.

[0032] In one embodiment, R 2 is expressed as equation (2) [ka] It is expressed as:

[0033] In equation (2), R 4 is selected from the group consisting of a hydrogen atom, a cyano group, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, a carboxy group, a substituted or unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms, and a substituted or unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms; R 5 is selected from the group consisting of a hydrogen atom and a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, and R 6 is a divalent organic group having 1 to 30 carbon atoms, and R 7is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, and a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; Y is selected from the group consisting of a single bond and O; and * represents the bonding site to the sulfur atom.

[0034] R 4 is selected from the group consisting of a hydrogen atom, a cyano group, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, a carboxy group, a substituted or unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms, and a substituted or unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms.

[0035] R 4 unsubstituted alkyl groups having 1 to 20 carbon atoms, and R 4 The unsubstituted aryl group having 6 to 20 carbon atoms is R 1 This is the same as that described above.

[0036] R 4 Examples of the unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, an n-butoxycarbonyl group, an isobutoxycarbonyl group, a sec-butoxycarbonyl group, and a tert-butoxycarbonyl group. The number of carbon atoms in the unsubstituted alkoxycarbonyl group is preferably 2 to 13.

[0037] R 4 Examples of the unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms include a phenyloxycarbonyl group, a naphthyloxycarbonyl group, an anthryloxycarbonyl group, and a fluorenyloxycarbonyl group.

[0038] R 4The substituted alkyl group, substituted aryl group, substituted alkoxycarbonyl group, and substituted aryloxycarbonyl group are unsubstituted alkyl groups, unsubstituted aryl groups, unsubstituted alkoxycarbonyl groups, and unsubstituted aryloxycarbonyl groups, respectively, in which one or more hydrogen atoms have been substituted with a substituent. Examples of the substituent include alkyl groups (excluding substituted alkyl groups and substituted alkoxycarbonyl groups), hydroxyl groups, alkoxy groups, aryloxy groups, hydroxyalkyl groups (excluding substituted alkyl groups and substituted alkoxycarbonyl groups), alkoxyalkyl groups (excluding substituted alkyl groups and substituted alkoxycarbonyl groups), halogen groups, cyano groups, nitro groups, isocyanato groups, acyl groups, carboxy groups, alkoxycarbonyl groups, epoxy groups, and silyl groups. The total number of carbon atoms in the substituents is preferably 1 to 30, and more preferably 1 to 18.

[0039] R 5 is selected from the group consisting of a hydrogen atom and a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms. 5 The substituted or unsubstituted alkyl group having 1 to 20 carbon atoms is R 4 This is the same as that described above.

[0040] R 2 and the sulfur atom (S) that constitutes the thiocarbonylthio group (SR 2 ) is homolytically cleaved during RAFT polymerization, and R is released as a free radical. 2 · becomes a polymerization initiation species and restarts polymerization. Therefore, in formula (2), R, which is a substituent on the bonded carbon atom of the sulfur atom (S) constituting the thiocarbonylthio group, 4 and R 5 is appropriately selected depending on the type of monomer to be polymerized, specifically, the polymerization activity of the monomer.

[0041] For example, in the RAFT polymerization of highly active monomers such as methyl (meth)acrylate, (meth)acrylic acid, (meth)acrylamide, acrylonitrile, and styrene, R 4is preferably a cyano group, a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, a carboxy group, a substituted or unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms, or a substituted or unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms, and more preferably a cyano group or a substituted or unsubstituted aryl group having 6 to 20 carbon atoms. 5 is preferably a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms.

[0042] On the other hand, in the RAFT polymerization of low activity monomers such as vinyl acetate, N-vinylpyrrolidone, and N-vinylcarbazole, R 4 and R 5 At least one of is a hydrogen atom, or R 4 and R 5 is preferably a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms.

[0043] In one embodiment, R 4 is a cyano group, and R 5 is an unsubstituted alkyl group having 1 to 20 carbon atoms.

[0044] R 6 is a divalent organic group having 1 to 30 carbon atoms.

[0045] R 6Examples of R include linear alkanediyl groups having 1 to 20 carbon atoms, such as methylene, ethylene, propane-1,3-diyl, butane-1,4-diyl, hexane-1,6-diyl, octane-1,8-diyl, decane-1,10-diyl, and dodecane-1,12-diyl; saturated cyclic hydrocarbon groups having 5 to 20 carbon atoms, such as cyclopentanediyl, cyclohexanediyl, norbornanediyl, and adamantanediyl; and unsaturated cyclic hydrocarbon groups having 6 to 30 carbon atoms, such as phenylene and naphthylene. Some or all of the hydrogen atoms in these groups may be substituted with alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl, or groups containing heteroatoms, such as oxygen, sulfur, nitrogen, and halogen atoms. 6 A heteroatom such as an oxygen atom, a nitrogen atom or a sulfur atom may be present between the carbon atoms constituting the formula (I).

[0046] R 6 Preferably, R contains an amide bond or an ether bond, more preferably an amide bond. The amide bond and the ether bond can increase the solubility of the compound represented by formula (1) in highly polar solvents such as water. R containing an ether bond 6 Examples of the alkylene group include groups containing a polyalkylene oxide moiety such as polyethylene oxide (PEO) and polypropylene oxide (PPO).

[0047] R 7 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, and a substituted or unsubstituted aryl group having 6 to 20 carbon atoms. 7 The substituted or unsubstituted alkyl group having 1 to 20 carbon atoms and the substituted or unsubstituted aryl group having 6 to 20 carbon atoms are represented by R 4 This is the same as that described above.

[0048] R 7is preferably a hydrogen atom, an alkyl group having 1 to 16 carbon atoms which may have a substituent, or an aryl group having 6 to 14 carbon atoms which may have a substituent, and more preferably a hydrogen atom.

[0049] Y is selected from the group consisting of a single bond and O. When Y is a single bond, the phosphorus-containing group is a phosphonic acid group or a phosphonic acid ester group. When Y is O, the phosphorus-containing group is a phosphoric acid group or a phosphate ester group.

[0050] In one embodiment, Y is O and R 7 is a hydrogen atom.

[0051] X is a single bond, S, O, or NR 3 X is selected from the group consisting of R 1 Together, these influence the rate of addition-fragmentation reactions during RAFT polymerization.

[0052] For example, in RAFT polymerization of highly active monomers such as methyl (meth)acrylate, (meth)acrylic acid, (meth)acrylamide, acrylonitrile, styrene, etc., X is preferably a single bond or S. In embodiments where X is a single bond, R 1 is preferably an aryl group having 6 to 14 carbon atoms which may have a substituent. In an embodiment where X is S, R 1 is preferably an alkyl group having 1 to 16 carbon atoms which may have a substituent.

[0053] On the other hand, in the RAFT polymerization of less reactive monomers such as vinyl acetate, N-vinylpyrrolidone, and N-vinylcarbazole, X is O or NR 3 In embodiments where X is O, R 1 is preferably an alkyl group having 1 to 16 carbon atoms which may have a substituent. 3 In embodiments where R 1 is preferably an alkyl group having 1 to 16 carbon atoms which may have a substituent.

[0054] R3 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. 3 The substituted or unsubstituted alkyl group, the substituted or unsubstituted aryl group, and the substituted or unsubstituted heteroaryl group are R 1 This is the same as that described above.

[0055] R 3 is preferably an alkyl group having 1 to 16 carbon atoms which may have a substituent, or an aryl group having 6 to 14 carbon atoms which may have a substituent.

[0056] R 3 is R 1 and may bond to form a heterocyclic structure. Examples of the heterocyclic structure include saturated heterocyclic rings such as a pyrrolidine ring, an imidazolidine ring, a pyrazolidine ring, and a piperidine ring, and unsaturated heterocyclic rings such as a pyrrole ring, an imidazole ring, a pyrazole ring, and a pyridine ring. Some or all of the hydrogen atoms on the carbon atoms or heteroatoms constituting the heterocyclic structure may be substituted with an alkyl group such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group; or a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

[0057] In one embodiment, X is a single bond or S.

[0058] In one embodiment, the compound has formula (3): [ka] It is expressed as:

[0059] [Method of manufacturing the compound] The compound represented by formula (1) can be synthesized by a known method, for example, by forming an ester bond or an amide bond between a compound having a thiocarbonylthio group and a carboxy group or a derivative thereof and a compound having a phosphorus-containing group and a hydroxyl group or an amino group.

[0060] For the formation of ester or amide bonds, the carboxyl group can be activated using known activating reagents. Examples of activating reagents include N-hydroxysuccinimide (NHS), thionyl chloride (SOCl), and phosphorus tribromide (PBr). N-hydroxysuccinimide forms an N-succinimidyl ester as an activated intermediate. Thionyl chloride and phosphorus tribromide form an acid halide as an activated intermediate.

[0061] For example, the compound represented by formula (3) can be obtained as follows: 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid, a compound having a thiocarbonylthio group and a carboxy group, is reacted with N-hydroxysuccinimide to synthesize the activated ester N-succinimidyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate (RAFT-NHS). Next, RAFT-NHS is reacted with O-phosphorylethanolamine to form an amide bond, synthesizing the compound represented by formula (3).

[0062] Formation of ester or amide bonds can also be promoted using known condensation agents, such as carbodiimide-based condensation agents such as N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, imidazole-based condensation agents such as N,N'-carbonyldiimidazole, and triazine-based condensation agents such as 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n-hydrate (DMT-MM).

[0063] In another embodiment, the compound represented by formula (1) can be synthesized by phosphorylating the hydroxyl group of a compound having a thiocarbonylthio group and a hydroxyl group using a phosphorylating agent such as morpholinophosphorodichloridate. The compound having a thiocarbonylthio group and a hydroxyl group may contain a polyalkylene oxide moiety such as polyethylene oxide (PEO) or polypropylene oxide (PPO). The compound having a thiocarbonylthio group and a hydroxyl group can also be obtained by forming an amide bond between a compound having a thiocarbonylthio group and a carboxyl group and an alkanolamine such as ethanolamine. The above-mentioned activating reagents or condensing agents can also be used to form this amide bond.

[0064] [Polymer manufacturing method using RAFT polymerization] The compound of formula (1) can be used to produce a polymer by RAFT polymerization. The RAFT polymerization can be solution polymerization, emulsion polymerization, suspension polymerization, or bulk polymerization. The RAFT polymerization can be batch or continuous.

[0065] <monomer> The monomer to be applied to the RAFT polymerization using the compound represented by formula (1) is not particularly limited as long as it is capable of RAFT polymerization, and examples thereof include vinyl compounds such as styrene, vinyltoluene, α-methylstyrene, chlorostyrene, p-methoxystyrene, p-butoxystyrene, styrenesulfonic acid and its salts, vinyl acetate, vinyl chloride, N-vinylpyrrolidone, and N-vinylcarbazole; alkyl(meth)acrylates such as methyl(meth)acrylate, ethyl(meth)acrylate, n-butyl(meth)acrylate, isobutyl(meth)acrylate, n-hexyl(meth)acrylate, n-octyl(meth)acrylate, isooctyl(meth)acrylate, 2-ethylhexyl(meth)acrylate, cyclohexyl(meth)acrylate, and isobornyl(meth)acrylate; Examples of suitable monomers include (meth)acrylamides such as (meth)acrylamide, N,N-dimethyl(meth)acrylamide, and N-isopropyl(meth)acrylamide; (meth)acrylic acid; unsaturated nitriles such as acrylonitrile and methacrylonitrile; silicon-containing unsaturated monomers such as vinyltrimethoxysilane and vinyltriethoxysilane; unsaturated carboxylic acids and their anhydrides and esters such as maleic acid, maleic anhydride, maleic acid esters, fumaric acid, and fumaric acid esters; and maleimides such as maleimide, N-methylmaleimide, N-ethylmaleimide, N-propylmaleimide, N-butylmaleimide, N-hexylmaleimide, N-octylmaleimide, N-dodecylmaleimide, N-stearylmaleimide, N-phenylmaleimide, and N-cyclohexylmaleimide. These monomers may be substituted with halogen atoms such as fluorine, chlorine, bromine, and iodine. These monomers may further have functional groups such as hydroxyl groups, carboxyl groups, epoxy groups, amino groups, phosphate groups, phosphonic acid groups, phosphate ester groups, phosphonate ester groups, sulfonyl groups, sulfo groups, ammonium groups, etc. The monomers may have zwitterionic structures containing both acidic and basic groups.

[0066] A polyfunctional monomer can also be used as the monomer. Examples of the polyfunctional monomer include bifunctional (meth)acrylates such as allyl (meth)acrylate, 1,4-butanediol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, ethylene glycol di(meth)acrylate, cyclohexanedimethanol di(meth)acrylate, diethylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, and polyethylene glycol di(meth)acrylate; trifunctional (meth)acrylates such as glycerol tri(meth)acrylate, trimethylolpropane tri(meth)acrylate, and pentaerythritol tri(meth)acrylate; and (meth)acrylates having four or more functional groups such as ditrimethylolpropane tetra(meth)acrylate, dipentaerythritol penta(meth)acrylate, and pentaerythritol tetra(meth)acrylate.

[0067] The above monomers may be used alone or in combination of two or more.

[0068] The amount of monomer used can be determined so that the product of the molar ratio of the monomer to the compound represented by formula (1) used as a RAFT agent (molar number of monomer / molar number of compound represented by formula (1)) and the molecular weight of the monomer will be the target molecular weight of the polymer.

[0069] <Radical Polymerization Initiator> RAFT polymerization can be carried out using a known radical polymerization initiator in the presence of a compound represented by formula (1).

[0070] Examples of radical polymerization initiators include organic peroxides such as benzoyl peroxide, cumene peroxide, and di-t-butyl peroxide; azo compounds such as 1,1'-azobis(cyclohexanecarbononitrile), 2,2'-azobis(2-methylpropionamidine) dihydrochloride, 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobisisobutyronitrile, 2,2'-azobis(2,4-dimethylvaleronitrile), and 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile); and redox initiators. The radical polymerization initiators may be used alone or in combination of two or more.

[0071] The amount of radical polymerization initiator used is determined so that the molar ratio of the compound represented by formula (1) used as a RAFT agent to the radical initiator (number of moles of the compound represented by formula (1) / number of moles of the radical polymerization initiator) is generally 1 or more, or 10 or more, and 10,000 or less, or 5,000 or less.

[0072] <solvent> As the solvent for RAFT polymerization, an organic solvent or an aqueous solvent can be used.

[0073] Examples of organic solvents include ketones such as acetone and methyl ethyl ketone (MEK); alcohols such as methanol, ethanol, and isopropanol (IPA); ethers such as diethyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, and propylene glycol monomethyl ether; esters such as ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, and 2-ethoxyethyl acetate; aromatic hydrocarbons such as toluene and xylene; sulfoxides such as dimethyl sulfoxide; and amides such as dimethylformamide and dimethylacetamide. The organic solvents may be used alone or in combination of two or more.

[0074] Examples of aqueous solvents include water and mixtures of water and water-soluble organic solvents. Examples of water-soluble organic solvents include alcohols such as methanol, ethanol, and isopropanol (IPA); ethers such as diethyl ether and tetrahydrofuran; sulfoxides such as dimethyl sulfoxide; and amides such as dimethylformamide and dimethylacetamide. The water-soluble organic solvents may be used alone or in combination of two or more. The water content in the aqueous solvent may be 1% by mass or more, 2% by mass or more, or 5% by mass or more, and 100% by mass or less, 90% by mass or less, or 80% by mass or less.

[0075] In one embodiment, the RAFT polymerization is carried out in an aqueous solvent.

[0076] <Polymerization temperature> The polymerization temperature is generally −20 to 200° C., and preferably 40 to 160° C. The polymerization time can be appropriately determined depending on the polymerization activity of the monomer and the type of the compound represented by formula (1) used as the RAFT agent, and can be, for example, 10 minutes to 120 hours.

[0077] <Copolymer> The compound represented by formula (1) can also be used to synthesize block copolymers, a feature of RAFT polymerization. For example, a diblock copolymer can be synthesized by polymerizing a first monomer followed by the addition and polymerization of a second monomer. A multiblock copolymer can then be synthesized by sequentially polymerizing a third monomer, a fourth monomer, and so on. In another embodiment, the copolymer is a gradient copolymer, a random copolymer, or a statistical copolymer. For example, a gradient copolymer, a random copolymer, or a statistical copolymer can be synthesized by adding each monomer to the reaction solution in a predetermined ratio, or by adding the monomers to the reaction solution in a ratio that varies as the polymerization progresses, or by both.

[0078] [polymer] In one embodiment the polymer is Formula (4) [ka] It is expressed as:

[0079] In formula (4), R 1 is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups; R 2 is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphate group, a phosphonate group, a phosphate ester group, and a phosphonate ester group, and X is a single bond, S, O, or NR 3 R 3 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; R 1 may be bonded to form a heterocyclic structure, and Poly represents a polymer chain.

[0080] R in equation (4) 1 , R 2 , and X are the same as those described for the compound represented by formula (1). That is, the polymer represented by formula (4) can be obtained by the SR 2 The fragments generated by bond cleavage are each added to the end of a polymer chain.

[0081] Poly in formula (4) is a polymer chain derived from the above-mentioned monomers. Examples of such polymer chains include homopolymers of polystyrene, polyvinyl acetate, polyvinyl chloride, poly(N-vinylpyrrolidone), poly(meth)acrylate, poly(meth)acrylic acid, polyacrylonitrile, polymaleimide, etc., as well as block copolymers thereof.

[0082] In one embodiment, in formula (4), Poly contains at least one structural unit having a zwitterionic structure. Examples of the monomer that forms the structural unit having a zwitterionic structure include phosphorylcholines having a radical polymerizable group, such as 2-methacryloyloxyethyl phosphorylcholine.

[0083] The number average molecular weight (Mn) and weight average molecular weight (Mw) of a polymer can be controlled by the molar ratio of the monomer to the compound represented by formula (1) used as a RAFT agent (moles of monomer / moles of compound represented by formula (1)). The polydispersity index (Mw / Mn) of the polymer is generally 1 or more and 1.5 or less, 1.3 or less, or 1.1 or less. In this disclosure, the terms "number average molecular weight" and "weight average molecular weight" respectively refer to the molecular weight measured by gel permeation chromatography (GPC) using a standard substance commonly used for the polymer being measured.

[0084] [Composite materials] In one embodiment, the composite material comprises an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite, and the above-described polymer, and the surface of the inorganic substrate is modified with the polymer via the phosphorus-containing group of the polymer.

[0085] In one embodiment, the inorganic substrate comprises titanium oxide.

[0086] The shape and size of the inorganic substrate are not particularly limited, and examples of the inorganic substrate include particles, plates, discs, spheres, rods, and other irregular shapes.

[0087] The inorganic substrate may be nanoparticles. The average primary particle diameter of nanoparticles is generally 1 to 150 nm. The average primary particle diameter of nanoparticles is determined by the following procedure. 100 nanoparticles are randomly selected from an electron micrograph obtained by photographing nanoparticles using a transmission electron microscope (TEM) or a scanning electron microscope (SEM). The maximum cross-sectional length of each nanoparticle is defined as the diameter of the nanoparticle. The volume of this diameter converted into a sphere is calculated, and the 50% diameter (median diameter, D) in the cumulative volume distribution of 100 nanoparticles is determined. 50 ) is the average primary particle size of the nanoparticles. In one embodiment, the nanoparticles are titanium oxide nanoparticles.

[0088] [Method of manufacturing composite materials] In one embodiment, a method for producing a composite material includes contacting an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite with the polymer in an aqueous solvent having a pH of 7 or higher. The surface of the composite material is modified with the polymer via the phosphorus-containing group of the polymer.

[0089] Aqueous solvents include those described as solvents used in RAFT polymerization.

[0090] The pH of the aqueous solvent can be adjusted using an alkaline compound such as an alkali metal hydroxide, e.g., sodium hydroxide or potassium hydroxide, or an alkaline earth metal hydroxide, e.g., calcium hydroxide. The pH of the aqueous solvent may also be adjusted using a buffering agent. The pH of the aqueous solvent may be 8 or higher, or 9 or higher, and is generally 11 or lower, or 10 or lower.

[0091] The contact temperature is preferably 0 to 60°C, more preferably 10 to 40°C.

[0092] [Solid-phase RAFT agents] In one embodiment, the solid-state RAFT agent comprises an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite, and a compound represented by formula (1), wherein the surface of the inorganic substrate is modified with the compound via a phosphorus-containing group of the compound.

[0093] The inorganic substrate of the solid-phase RAFT agent is the same as that described for the composite material.

[0094] The solid-phase RAFT agent can be produced by contacting an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite with the compound represented by formula (1) in an aqueous solvent having a pH of at least 7. The aqueous medium, its pH, and the contact temperature are the same as those described for the method for producing the composite material.

[0095] [Polymer production by RAFT polymerization using solid-state RAFT agents] A polymer can be produced by RAFT polymerization using the solid-state RAFT agent. This polymer may be in the form of a composite material in which fragments of the solid-state RAFT agent are attached to the ends of the polymer chain. The monomers, radical polymerization initiator, solvent, and polymerization temperature used in the RAFT polymerization of this embodiment are the same as those described for the method for producing a polymer by RAFT polymerization using the compound represented by formula (1).

[0096] In one embodiment, RAFT polymerization using a solid-phase RAFT agent is carried out in an aqueous solvent.

[0097] The compounds, polymers, composite materials, and solid-phase RAFT agents of the present disclosure can be suitably used in the production of functional materials that can be used in aqueous systems, such as ultrasound sensitizers, photocatalysts, functional cell sheets, drug transport carriers, mechanochemical materials, temperature sensors, separation membranes, and water retention agents. [Example]

[0098] The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples.

[0099] Example 1: Synthesis of a RAFT agent O-Phosphorylethanolamine (O-PEA, 0.388 g, 2.7 mmol) was dissolved in sodium carbonate buffer (pH 9, 25 mL). N-Succinimidyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate (RAFT-NHS, 0.94 g, 2.5 mmol) was dissolved in 50 mL of DMSO. The two resulting solutions were mixed in a recovery flask and allowed to react overnight at room temperature while shielded from light. After the reaction, the reaction mixture was purified using reverse-phase chromatography. Specifically, DMSO, salts, and unreacted O-PEA were first removed from the reaction solution using 100% water. Next, the product and unreacted RAFT-NHS were separated and recovered using a 1:1 (volume) methanol:water mixture. Methanol was removed under reduced pressure from the recovered product using an evaporator, and the remaining water was removed by lyophilization to obtain the RAFT agent of Example 1 in 61% yield. The reaction scheme is shown below.

[0100] [ka]

[0101] RAFT Agent of Example 1 1 The H-NMR (400 MHz, DO) chart is shown in Figure 1. 1 H-NMR (400MHz, D2O): δ=7.90(d,2H,benzene),7.66(t,1H,benzene),7.47(t,2H,benzene),3.92(d,2H,-C H 2-O-), 3.42(t,2H,-NH-C H 2-), 2.62-2.50(m,4H,-C H 2-C H 2-C(=O)-), 1.92(s, 3H, C H 3).

[0102] Figure 2A shows the UV-Vis spectrum of the RAFT agent of Example 1. Figure 2B shows the UV-Vis spectrum of RAFT-NHS used as the starting material. These UV-Vis spectra were measured using a DMSO solution with a sample concentration of 10 mmol / L. In the RAFT agent of Example 1, the maximum absorption wavelength (λmax = 514 nm) derived from the dithiobenzoate group hardly shifted from the maximum absorption wavelength (λmax = 513 nm) derived from the dithiobenzoate group of RAFT-NHS used as the starting material, and the molar extinction coefficients were also comparable, indicating that the RAFT structure was maintained in the RAFT agent of Example 1.

[0103] Example 2 RAFT polymerization The RAFT agent of Example 1 (4.06 mg, 10 μmol), 2-methacryloyloxyethyl phosphorylcholine (MPC) (0.3 g, 1.0 mmol, molar ratio of MPC to RAFT agent (MPC / RAFT agent) = 100), and water-soluble azo polymerization initiator V-501 (4,4'-azobis(4-cyanovaleric acid), 0.56 mg, 2.0 μmol) were weighed and dissolved in 3 mL of water. The resulting solution was placed in a Schlenk flask, and the inside of the Schlenk flask was swept under a nitrogen atmosphere. A RAFT polymerization reaction was carried out in an oil bath at 70°C for 15 hours while shielded from light, yielding poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) with the following structure. The polymerization rate was 1 The conversion was determined by H-NMR (400 MHz, D2O) from the change in the integral ratio of the double bond between DMSO and MPC used as an internal standard, and was found to be 99%.

[0104] [ka]

[0105] Example 2 PMPC 1 The H-NMR (400 MHz, DO) chart is shown in Figure 3. 1H-NMR (400MHz, D2O): δ=8.00(d,2H,benzene),7.73(t,1H,benzene),7.57(t,2H,benzene),4.33-4.13(br,594H,-OC H 2-C H 2-OP(=O)(-O - )-OC H 2-), 3.72(t,891H,-N + (C H 3)3),1.95(br,198H,-C H 2-C(CH3)-C(=O)-),1.13-0.96(br,277H,-CH2-C(C H 3)-C(=O)-).

[0106] The number-average molecular weight and molecular weight distribution of PMPC were measured by gel permeation chromatography using pH 7 phosphate buffer (0.2 M) as the eluent. The measurement sample was prepared by dissolving 2 mg of PMPC in 1 mL of phosphate buffer. A molecular weight calibration curve was constructed using polyethylene glycols of known molecular weight. The theoretical molecular weight of PMPC was 30,000, whereas the number-average molecular weight Mn was 32,600, the weight-average molecular weight Mw was 33,900, and the polydispersity Mw / Mn was 1.04. [Industrial Applicability]

[0107] The compounds, polymers, composite materials, and solid-phase RAFT agents of the present disclosure can be suitably used in the production of functional materials that can be used in aqueous systems, such as ultrasound sensitizers, photocatalysts, functional cell sheets, drug transport carriers, mechanochemical materials, temperature sensors, separation membranes, and water retention agents.

Claims

1. Formula (1) 【Chemical 1】 (In formula (1), R １ is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups; R ２ is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphate group, a phosphonate group, a phosphate ester group, and a phosphonate ester group; X is a single bond, S, O, or NR ３ selected from the group consisting of R ３ is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; R １ may be bonded to form a heterocyclic structure.) A compound represented by the formula: In formula (1), X is a single bond or S; In formula (1), R 2 is a group represented by formula (2): 【Chemistry 2】 (In formula (2), R 4 is selected from the group consisting of a cyano group, a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, a carboxy group, a substituted or unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms, and a substituted or unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms; R 5 is selected from the group consisting of substituted or unsubstituted alkyl groups having 1 to 20 carbon atoms; R 6 is a divalent organic group having 1 to 30 carbon atoms; R 7 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, and a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; Y is selected from the group consisting of a single bond and O; * indicates the bonding site with the sulfur atom.) A compound represented by the formula:

2. The compound according to claim 1, wherein in formula (1), X is a single bond, and R 1 is an aryl group having 6 to 14 carbon atoms which may have a substituent.

3. The compound according to claim 1, wherein in formula (2), R 4 is a cyano group and R 5 is an unsubstituted alkyl group having 1 to 20 carbon atoms.

4. In formula (2), Y is O and R ７ The compound according to any one of claims 1 to 3, wherein is a hydrogen atom.

5. In formula (2), R ６ The compound according to any one of claims 1 to 4, wherein contains an amide bond or an ether bond.

6. The compound is represented by formula (3) 【Chemistry 3】 The compound according to claim 1, represented by:

7. A method for producing a polymer, comprising carrying out RAFT polymerization using a compound according to any one of claims 1 to 6.

8. The method of claim 7, wherein the RAFT polymerization is carried out in an aqueous solvent.

9. Formula (4) 【Chemistry 4】 (In formula (4), R １ is selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups; R ２ is a monovalent organic group containing a phosphorus-containing group selected from the group consisting of a phosphate group, a phosphonate group, a phosphate ester group, and a phosphonate ester group; X is a single bond, S, O, or NR ３ selected from the group consisting of R ３ is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; R １ may be bonded to form a heterocyclic structure, Poly represents a polymer chain. A polymer represented by the formula: In formula (4), X is a single bond or S; In formula (4), R 2 is a group represented by formula (2): 【Chemistry 5】 (In formula (2), R 4 is selected from the group consisting of a cyano group, a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, a carboxy group, a substituted or unsubstituted alkoxycarbonyl group having 2 to 20 carbon atoms, and a substituted or unsubstituted aryloxycarbonyl group having 7 to 20 carbon atoms; R 5 is selected from the group consisting of substituted or unsubstituted alkyl groups having 1 to 20 carbon atoms; R 6 is a divalent organic group having 1 to 30 carbon atoms; R 7 is selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, and a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; Y is selected from the group consisting of a single bond and O; * indicates the bonding site with the sulfur atom.) A polymer represented by the formula:

10. The polymer according to claim 9 , wherein in formula (4), Poly contains at least one structural unit having a zwitterionic structure.

11. 11. A composite material comprising an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite, and the polymer according to claim 9, wherein the surface of the inorganic substrate is modified with the polymer via the phosphorus-containing group of the polymer.

12. A method for producing a composite material whose surface is modified with a polymer, comprising contacting an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite with the polymer according to claim 9 or 10 in an aqueous solvent having a pH of 7 or higher.

13. 7. A solid-phase RAFT agent comprising an inorganic substrate selected from the group consisting of titanium oxide, zirconium oxide, and hydroxyapatite, and the compound according to any one of claims 1 to 6, wherein the surface of the inorganic substrate is modified with the compound via the phosphorus-containing group of the compound.

14. 14. A method for producing a polymer, comprising carrying out RAFT polymerization using the solid-state RAFT agent of claim 13.

15. The method of claim 14, wherein the RAFT polymerization is carried out in an aqueous solvent.

Images