WO2010104167A1 - Multi-functional compound, heteroatom polymer achieved using the same, and method for manufacturing both - Google Patents

Multi-functional compound, heteroatom polymer achieved using the same, and method for manufacturing both Download PDF

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WO2010104167A1
WO2010104167A1 PCT/JP2010/054176 JP2010054176W WO2010104167A1 WO 2010104167 A1 WO2010104167 A1 WO 2010104167A1 JP 2010054176 W JP2010054176 W JP 2010054176W WO 2010104167 A1 WO2010104167 A1 WO 2010104167A1
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group
compound
polyfunctional compound
functional
represented
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PCT/JP2010/054176
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Japanese (ja)
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一彦 石原
公彰 高見
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国立大学法人東京大学
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
    • C08G18/76—Polyisocyanates or polyisothiocyanates cyclic aromatic
    • C08G18/7657—Polyisocyanates or polyisothiocyanates cyclic aromatic containing two or more aromatic rings
    • C08G18/7664—Polyisocyanates or polyisothiocyanates cyclic aromatic containing two or more aromatic rings containing alkylene polyphenyl groups
    • C08G18/7671—Polyisocyanates or polyisothiocyanates cyclic aromatic containing two or more aromatic rings containing alkylene polyphenyl groups containing only one alkylene bisphenyl group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/38—Low-molecular-weight compounds having heteroatoms other than oxygen
    • C08G18/3878—Low-molecular-weight compounds having heteroatoms other than oxygen having phosphorus
    • C08G18/3891—Low-molecular-weight compounds having heteroatoms other than oxygen having phosphorus having sulfur in addition to phosphorus
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/62—Polymers of compounds having carbon-to-carbon double bonds
    • C08G18/6216—Polymers of alpha-beta ethylenically unsaturated carboxylic acids or of derivatives thereof
    • C08G18/622—Polymers of esters of alpha-beta ethylenically unsaturated carboxylic acids
    • C08G18/6225—Polymers of esters of acrylic or methacrylic acid
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
    • C08G18/76—Polyisocyanates or polyisothiocyanates cyclic aromatic
    • C08G18/7614—Polyisocyanates or polyisothiocyanates cyclic aromatic containing only one aromatic ring
    • C08G18/7621—Polyisocyanates or polyisothiocyanates cyclic aromatic containing only one aromatic ring being toluene diisocyanate including isomer mixtures

Definitions

  • the present invention relates to a heteroatom polymer used for industrial materials and biomaterials, and a polyfunctional compound used for the production thereof.
  • Heteroatom polymers such as polyester and polyurethane are used in various fields because of their excellent mechanical properties and durability.
  • the heteroatom polymer can be obtained by continuously reacting compounds having two or more functional groups A and B that react with each other.
  • Heteroatomic polymers are expected as biomaterials in the field of medical devices because of their mechanical properties and durability.
  • the isocyanate group also reacts with an amino group (—NH 2 ) or a mercapto group (—SH), when other functional groups are present in the diisocyanate or diol, the intermolecular molecules are cross-linked to form a network-like macromolecule. Is synthesized. Since this macromolecule is difficult to dissolve in various solvents and has a very high melting point, there is a problem in the molding process when applied to industrial applications. This event can occur in other heteroatom polymers as well as polyurethane.
  • Vinyl monomer is a general term for compounds containing one or more unsaturated carbon bonds in the molecule, and is a molecule that can obtain a vinyl polymer by various polymerization methods.
  • Vinyl polymers have been put into practical use as many industrial materials typified by polyvinyl chloride, polyethylene and polypropylene.
  • the functions of polyvinyl vary widely, because it is possible to synthesize polymers having the functions of these monomers by polymerizing various vinyl monomers at an arbitrary ratio. Therefore, a great number of vinyl monomers have been developed and manufactured at present. That is, if a vinyl monomer can be freely introduced into a heteroatom polymer, it can be said that heteroatom polymers having various functions can be obtained.
  • the present invention provides a polyfunctional compound as shown below, a heteroatom polymer obtained using the same, a production method thereof, and the like.
  • the compound having an ethylenically unsaturated carbon bond is 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate, N-vinyl.
  • the polyfunctional compound according to [4] which is selected from the group consisting of pyrrolidone, allyl alcohol, N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate, and vinyl cinnamate.
  • Z has the formula -COOZ '[wherein, Z' represents a hydroxyl group, an amino group, a nitro group, a sulfonyl group, an optionally C 1 ⁇ optionally having a substituent selected from phenyl groups and active ester groups 20 alkyl group; ethyl phosphorylcholine group (—CH 2 CH 2 OP ( ⁇ O) (O ⁇ ) OCH 2 CH 2 N + (CH 3 ) 3 ); or polyethylene glycol group (— (CH 2 CH 2 0) n OH ).
  • Z is —COOCH 2 CH 2 OP ( ⁇ O) (O ⁇ ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3
  • Z is —COOCH 2 CH 2 OP ( ⁇ O) (O ⁇ ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3
  • the manufacturing method of a polyfunctional compound including the process mixed in a solvent. [11] The production method according to [10], wherein the compound represented by the formula (II) and the compound represented by the formula (III) are mixed in the presence of an amine. [12] The production method according to [11], wherein the amine is at least one selected from the group consisting of triethylamine and diisopropylamine.
  • the compound represented by the formula (III) is 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate, N-vinylpyrrolidone
  • the heteroatom polymer according to [15], wherein the compound causing a polycondensation or polyaddition reaction with the polyfunctional compound is a polyisocyanate compound.
  • the polyisocyanate compound include those selected from the group consisting of methylene diphenyl diisocyanate, tolylene diisocyanate, and derivatives thereof.
  • R is a hydrogen atom or a methyl group
  • X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation
  • Y is a sulfur atom or a group represented by —NH—
  • Z is a functional functional group
  • n is an integer of 1 to 4.
  • a method for producing a heteroatom polymer comprising a step of polycondensation or cationic polymerization of the polyfunctional compound according to any one of [1] to [9].
  • a heteroatom polymer comprising the step of reacting the polyfunctional compound according to any one of [1] to [9] with the polyfunctional compound and a compound causing a polycondensation or polyaddition reaction.
  • a heteroatom polymer having various functions can be obtained by a very simple method.
  • the heteroatom polymer of the present invention can be used in various applications such as industrial materials and biomaterials.
  • FIG. 2 is a graph showing the reaction rate of MPC addition diol obtained in Example 1.
  • FIG. 1 is a diagram showing 1 H-NMR measurement data of an MPC addition type diol obtained in Example 1.
  • FIG. 3 is a diagram showing 1 H-NMR measurement data of a BMA addition diol.
  • FIG. 3 is a diagram showing 1 H-NMR measurement data of a HEMA addition type diol.
  • FIG. 3 is a diagram showing 1 H-NMR measurement data of an MPTS-added diol.
  • FIG. 3 is a diagram showing 1 H-NMR measurement data of an MTF addition diol. It is the figure which showed the reaction rate of the methacrylate addition type diol.
  • the polyfunctional compound of the present invention is a compound represented by the following formula (I). [Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
  • the polyfunctional compound of the present invention has a functional group X which causes ring-opening polymerization, polyaddition or polycondensation via a linking group (—Y—CH 2 CHR—).
  • the functional group Z is bonded.
  • the polyfunctional compound of the present invention can be a monomer by having the atomic group X, and the functional group Z can be introduced into the polymer by a very simple method by polymerizing with the atomic group X. It is what makes it possible.
  • the atomic group X is not particularly limited as long as it causes ring-opening polymerization, polyaddition or polycondensation.
  • the atomic group X include an organic group having two or more reactive functional groups; an organic group that causes polycondensation by a dehalogenated atom; an organic group that causes ring-opening polymerization; and the like.
  • the “organic group” may be saturated or unsaturated acyclic, or may be saturated or unsaturated cyclic. In the case of acyclic, it may be linear or branched. In the case of cyclic, it may be a heterocyclic ring.
  • Examples of the organic group having two or more reactive functional groups include a saturated or unsaturated acyclic hydrocarbon group or a cyclic hydrocarbon group.
  • the hydrocarbon group is interrupted by an oxygen atom, a sulfur atom, a silicon atom or a group represented by the formula —N (R ′) — (wherein R ′ is a hydrogen atom or a C 1 -C 20 hydrocarbon group). May be.
  • Preferred examples of the reactive functional group include a hydroxyl group, an amino group, an isocyanate group, a carboxyl group, and an imide group. Among these, a hydroxyl group is preferable.
  • the reactive functional group may be one kind or a combination of two or more kinds.
  • organic group which has two or more reactive functional groups the organic group shown by a following formula is mentioned, for example.
  • X 1 and X 2 are each independently a reactive functional group
  • ring A is a benzene ring or an aromatic heterocycle
  • * indicates a bonding position with Y.
  • aromatic heterocycle of ring A examples include pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, isoxazole, isothiazole, pyridine, pyridazine, pyrimidine, pyrazine, 2H-pyran, 4H-pyran, and triazine. .
  • Examples of the organic group that causes polycondensation by dehalogenation include the following organic groups. [Wherein, X 3 and X 4 are each independently a halogen atom, ring B is a benzene ring or an aromatic heterocycle, and * represents a bonding position with Y. ]
  • Examples of the aromatic heterocycle of ring B are the same as those exemplified for ring A.
  • Examples of the organic group that causes ring-opening polymerization include cyclic carbonyl compounds such as lactones and lactams, cyclic ether compounds such as epoxides, cyclic olefin compounds, cyclic amides, ⁇ -amino acid-N-carboxylic acid anhydrides, and the like.
  • Y is a sulfur atom or a group represented by —NH—.
  • a sulfur atom is preferable because it is easy to obtain raw materials and the reaction is easily controlled.
  • R is a hydrogen atom or a methyl group. Of these, a methyl group is preferable.
  • the functional functional group Z is not particularly limited as long as it can impart a desired function to the polymer when the polymer is obtained using the polyfunctional compound of the present invention.
  • the functional functional group Z is preferably a functional group derived from a compound containing an ethylenically unsaturated carbon bond, and preferably a compound containing an ethylenically unsaturated carbon bond having an electron-withdrawing group at the ⁇ -position. Further preferred.
  • Examples of the compound containing an ethylenically unsaturated carbon bond that gives such a functional group include 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, methacrylic acid
  • Examples thereof include compounds selected from the group consisting of fluoroalkyl (C 1-20 ), N-vinyl pyrrolidone, allyl alcohol, N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate (C 1-20 ), and vinyl cinnamate.
  • Z represents a hydroxyl group, a fluorine atom, an amino group, a nitro group, a sulfonyl group, an optionally C 1 ⁇ optionally having a substituent selected from phenyl groups and active ester groups 20 alkyl group; ethyl phosphorylcholine group (—CH 2 CH 2 OP ( ⁇ O) (O ⁇ ) OCH 2 CH 2 N + (CH 3 ) 3 ); or a polyethylene glycol group (— (CH 2 CH 2 0) n OH). ] Is preferred.
  • the functional functional group Z —COOCH 2 CH 2 OP ( ⁇ O) (O ⁇ ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3 is preferred.
  • the functional functional group Z may be a C 1-20 fluoroalkyl group or the like.
  • the fluoroalkyl group By introducing the fluoroalkyl group into the heteroatom polymer, the bioaffinity, oxygen permeability, heat resistance, combustion resistance and chemical resistance of the heteroatom polymer can be improved.
  • n is an integer of 1 to 4. n is preferably 1 or 2, more preferably 1. When n is 2 or more, the combination of Y, Z and R may be the same or different.
  • the polyfunctional compound of the present invention is represented by the following formula (Ia) or (Ib). [Wherein, R is a hydrogen atom or a methyl group, X 1 and X 2 are each independently a reactive functional group, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group. ]
  • X 1 and X 2 are preferably hydroxyl groups.
  • Preferred examples of Y, R and Z are the same as those described in the description of the formula (I).
  • X 1 and X 2 are hydroxyl groups
  • Y is a sulfur atom
  • R is a hydrogen atom or a methyl group.
  • Z is —COOCH 2 CH 2 OP ( ⁇ O) (O ⁇ ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3 Compounds are preferred.
  • the polyfunctional compound of the present invention having such a structure includes a compound represented by the following formula (II): [Wherein, X is an atomic group causing ring-opening polymerization, polyaddition or polycondensation, Y ′ is a mercapto group or an amino group, and n is an integer of 1 to 4. ]
  • the production method of the present invention utilizes the fact that the vinyl monomer represented by the formula (III) undergoes Michael addition reaction or radical addition reaction with the functional group Y ′ of the compound represented by the formula (II). It is possible to introduce a functional functional group while suppressing ring-opening polymerization, polycondensation or polyaddition reaction by the atomic group X of the compound represented by II).
  • the atomic group X is the same as the atomic group X in the above formula (I), and preferred examples thereof are also the same.
  • Y ′ is a mercapto group or an amino group. Among these, a mercapto group is preferable.
  • n is an integer of 1 to 4. n is preferably 1 or 2, more preferably 1. When n is 2 or more, Y ′ may be the same or different.
  • Preferred examples of the compound represented by the formula (II) include the following compounds.
  • the functional functional group Z is the same as the functional functional group Z in the formula (I), and preferred examples are also the same.
  • R is a hydrogen atom or a methyl group, preferably a methyl group.
  • Examples of the compound represented by the above formula (III) include 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate (C 1-20 ), Preferred are vinylpyrrolidone, allyl alcohol, isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate (C 1-20 ) and vinyl cinnamate.
  • the compound represented by the formula (III) is preferably used in an equimolar amount with respect to Y ′ in the compound represented by the formula (II).
  • the solvent used in the above reaction is not particularly limited as long as it is inert with respect to the compounds represented by formulas (II) and (III), and water or an aliphatic or aromatic solvent is used.
  • the solvent include water, ethanol, alcohols such as methanol, ether solvents such as tetrahydrofuran and diethyl ether; halogenated hydrocarbons such as methylene chloride; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene; Halogenated aromatic hydrocarbons such as dichlorobenzene; Amides such as N, N-dimethylformamide; Sulfoxides such as dimethyl sulfoxide.
  • the reaction time is not particularly limited, but is preferably about 2 to 72 hours.
  • the reaction is preferably performed in the presence of an amine.
  • the amine is not particularly limited as long as it is usually used as a catalyst, but a secondary amine or a tertiary amine is preferable. Among these, triethylamine, diisopropylamine or a combination thereof is preferable.
  • the amount of amine added is not particularly limited, but is preferably 4 to 40 mol%, more preferably 4 to 20 mol%, still more preferably 4 to 10 mol% of the amount of the compound represented by the above formula (II). Use in range.
  • the heteroatom polymer of the present invention and the production method thereof The heteroatom polymer of the present invention is obtained by ring-opening polymerization, polyaddition or polycondensation of the polyfunctional compound described above, and is represented by the following formula (IV).
  • a partial structure is included as a repeating unit.
  • R is a hydrogen atom or a methyl group
  • X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation
  • Y is a sulfur atom or a group represented by —NH—
  • Z is a functional functional group
  • n is an integer of 1 to 4.
  • R, X, Y, Z and n are the same as R, X, Y, Z and n in the formula (I), and preferred examples are also the same.
  • a hetero atom is included in atomic group X in Formula (IV).
  • a hetero atom polymer can be comprised only with the structural unit shown by Formula (IV).
  • the functional functional group Z is a bioaffinity functional group in Formula (IV).
  • the heteroatom polymer can be used as a biomaterial used in the field of medical devices and the like.
  • the repeating unit represented by the formula (IV) contained in the heteroatom polymer of the present invention may be one type, or two or more types having different partial structures (for example, at least one of X, Y, Z, R and n). It may be a combination.
  • the heteroatom polymer of the present invention is obtained by reacting a polyfunctional compound with a compound that causes polycondensation or polyaddition reaction with the polyfunctional compound.
  • polyfunctional compound one or a combination of two or more different partial structures is used according to the purpose or application from those described in “1. Polyfunctional compound and production method thereof”.
  • the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound can be arbitrarily selected depending on the structure of the atomic group X of the polyfunctional compound.
  • the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound may be one kind or a combination of two or more kinds.
  • a polyisocyanate compound, a polycarboxylic acid compound, or the like is preferably used.
  • the atomic group X contains an amino group
  • polyisocyanate compounds, polycarboxylic acids, and the like are preferably used.
  • the atomic group X contains an isocyanate group
  • a polyamine compound, a polyol compound, or the like is preferably used.
  • the atomic group X contains a carboxyl group, a polyamine compound, a polyol compound, or the like is preferably used.
  • the atomic group X contains an imide group, a polyamine etc. are used preferably.
  • the heteroatom polymer of the present invention is preferably a compound obtained by reacting a polyfunctional compound containing a hydroxyl group as the atomic group X with a polyisocyanate compound having two or more isocyanate groups.
  • the polyisocyanate compound is not particularly limited and can be appropriately selected according to the purpose or use. For example, aliphatic polyisocyanate, aromatic polyisocyanate, alicyclic polyisocyanate and the like can be mentioned.
  • Examples of the aliphatic polyisocyanate include trimethylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, pentamethylene diisocyanate, 1,2-propylene diisocyanate, 2,3-butylene diisocyanate, 1,3-butylene diisocyanate, dodecamethylene diisocyanate, Examples include 2,4,4-trimethylhexamethylene diisocyanate.
  • aromatic polyisocyanate examples include 1,3-phenylene diisocyanate, 4,4′-diphenyl diisocyanate, 1,4-phenylene diisocyanate, 4,4′-diphenylmethane diisocyanate, 1,4-tolylene diisocyanate, 2,4 -Tolylene diisocyanate, 2,6-tolylene diisocyanate, 4,4'-toluidine diisocyanate, 2,4,6-triisocyanate toluene, 1,3,5-triisocyanate benzene, dianisidine diisocyanate, 4,4'- Diphenyl ether diisocyanate, 4,4 ', 4 "-triphenylmethane triisocyanate, 2,2'-methylene diphenyl diisocyanate, 2,4'-methylene diphenyl diisocyanate, 4,4'-methylene diphenyl diisocyanate Doo and the like.
  • methylene diphenyl diisocyanate, tolylene diisocyanate and their derivatives are preferred.
  • the derivatives include 1,4-butanediol, 1,4-butanediamine, ethylene glycol, 1,2-diaminoethane, propylene oxide, other adducts with polyols and polyamines.
  • Examples of the alicyclic polyisocyanate include 3-isocyanate methyl-3,5,5-trimethylcyclohexyl isocyanate, 1,3-cyclopentane diisocyanate, 1,3-cyclohexane diisocyanate, 1,4-cyclohexane diisocyanate, and methyl-2. , 4-cyclohexane diisocyanate, methyl-2,6-cyclohexane diisocyanate, 4,4′-methylenebis (cyclohexyl isocyanate), 1,4-bis (isocyanatomethyl) cyclohexane and the like.
  • the amount of the polyfunctional compound and the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound is not particularly limited. What is necessary is just to determine suitably according to the objective or a use.
  • the reaction between the polyfunctional compound and the compound causing polycondensation or polyaddition reaction with the polyfunctional compound is preferably carried out in the presence of a catalyst.
  • a catalyst a catalyst generally used for producing a heteroatom polymer can be used.
  • an amine catalyst or a metal catalyst is used.
  • amine catalysts examples include trialkylamines such as triethylamine, tetraalkyldiamines such as N, N, N ′, N′-tetramethyl-1,3-butanediamine, aminoalcohols such as dimethylethanolamine, triethylenediamine, and piperazine series. , Triazine type, quaternary amine organic acid salt or phenol salt. Of these, tertiary amines are preferred.
  • the metal catalyst examples include dibutyltin dilaurate. These may be used alone or in combination of two or more. The usage-amount of a catalyst can be suitably determined according to the objective or a use.
  • the reaction between the polyfunctional compound and the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound is preferably carried out in the presence of a chain extender.
  • the chain extender is not particularly limited as long as it is usually used for polycondensation or polyaddition reaction.
  • the chain extender short chain polyols, polyamines and the like are preferably used.
  • ethylene glycol, 1,4-butanediol, propylene glycol, neopentyl glycol, 1,4-cyclohexanediol and the like can be used. Of these, 1,4-butanediol, 1,5-hexamethylenediamine, and ethylenediamine are preferable.
  • the amount of chain extender used can be appropriately determined according to the purpose or application.
  • the reaction is preferably performed in the presence of a solvent.
  • the solvent is not particularly limited as long as it is inert to the polyfunctional compound and the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound. Water, an aliphatic solvent or an aromatic solvent Is used.
  • the solvent examples include water, ethanol, alcohols such as methanol, ether solvents such as tetrahydrofuran and diethyl ether; halogenated hydrocarbons such as methylene chloride; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene; Halogenated aromatic hydrocarbons such as dichlorobenzene; Amides such as N, N-dimethylformamide; Sulfoxides such as dimethyl sulfoxide.
  • the polymer of the present invention is obtained by subjecting a polyfunctional compound alone to a polycondensation or cationic polymerization reaction.
  • a polyfunctional compound described above in “1. Multifunctional compound and method for producing the same”, one or a combination of two or more different partial structures can be used depending on the purpose or application.
  • the reaction conditions for polycondensation or cationic polymerization may be in a range usually used, and can be appropriately selected depending on the structure of the polyfunctional compound.
  • Example 1 Synthesis of MPC-added diol 5 mmol each of 2-methacryloyloxyethyl phosphorylcholine (MPC) and ⁇ -thioglycerol was dissolved in dimethyl sulfoxide (DMSO).
  • DMSO dimethyl sulfoxide
  • TAA triethylamine
  • DIPA diisopropylamine
  • FIG. 2 shows 1 H-NMR measurement data of the MPC addition type diol finally obtained.
  • x represents DIPA 4 mol%
  • ⁇ represents TEA 40 mol%
  • ⁇ represents TEA 4 mol%
  • ⁇ represents no catalyst.
  • Example 4 Synthesis of polyurethane using methacrylate addition type diol MPC addition type diol (MPC-diol), MTF addition type diol (MTF-diol), 1,4-butanediol (BD) and Methylene diphenyl diisocyanate (MDI) are shown in Table 1.
  • MPC-diol methacrylate addition type diol MPC addition type diol
  • MTF addition type diol MTF addition type diol
  • BD 1,4-butanediol
  • MDI Methylene diphenyl diisocyanate
  • the heteroatom polymer obtained by the present invention can be applied in all fields of industry as an industrial material or a biomaterial.
  • a heteroatom polymer into which a biocompatible functional group is introduced can be applied as a biomaterial and is highly useful.

Abstract

Provided are a method for imparting a variety of functions to a heteroatom polymer by a simple method without compromising processability caused by crosslinking, and a heteroatom polymer having a variety of functions imparted thereto. A variety of functions can be imparted to the heteroatom polymer by using a multi-functional compound represented by formula (I) as a monomer. [In the formula, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition, or polycondensation, Y is a sulfur atom or an -NH- group, Z is a functional group, and n is an integer from 1-4.]

Description

多官能性化合物及びそれを用いて得られるヘテロ原子ポリマーならびにそれらの製造方法Polyfunctional compound, heteroatom polymer obtained using the same, and production method thereof
　本発明は、工業材料及び生体材料などに用いられるヘテロ原子ポリマー及びその製造に用いられる多官能性化合物に関する。 The present invention relates to a heteroatom polymer used for industrial materials and biomaterials, and a polyfunctional compound used for the production thereof.
　ポリエステル及びポリウレタンなどに代表されるヘテロ原子ポリマーはその優れた力学特性及び耐久性から様々な分野で利用されている。ヘテロ原子ポリマーは、互いに反応する官能基Ａ及びＢを２つ以上持つ化合物同士を連続的に反応させることで得られる。例えば、ポリウレタンはヒドロキシル基（-OH）を１分子中に２つ持つジオール化合物、及びイソシアネート基（-N=C=O）を２つ持つジイソシアネート化合物を触媒存在下で等量反応させることで合成される。
　ヘテロ原子ポリマーは生体材料として医療機器の分野でもその力学特性及び耐久性から期待されている。しかし、工業用に開発されたヘテロ原子ポリマーは生体内で異物として認識されるため、炎症反応を惹起し、生体機能を損なうことが指摘されている。したがって、ポリウレタンなどのヘテロ原子ポリマーを生体材料として応用する場合、何らかの修飾を施す必要がある。
　ポリマーに機能を付与するために化学的な修飾を施そうとした場合、一般的にポリマー中に何らかの反応を引き起こす官能基を導入する手法がとられている（例えば、第５版実験化学講座２６巻、高分子化学、日本化学会編（２００５）、１９４－２０２（非特許文献１）参照）。しかし、イソシアネート基はアミノ基（－ＮＨ2）又はメルカプト基（－ＳＨ）などとも反応するため、ジイソシアネート又はジオール中に他の官能基が存在する場合、分子間が架橋され、網目状の巨大分子が合成される。この巨大分子は各種溶媒に溶解させることが困難であり、また、融点もきわめて高くなることが多いため、産業用に応用する場合、成形加工に問題が生じる。この事象はポリウレタンのみならず、その他のヘテロ原子ポリマーにおいても同様に起こり得る。 Heteroatom polymers such as polyester and polyurethane are used in various fields because of their excellent mechanical properties and durability. The heteroatom polymer can be obtained by continuously reacting compounds having two or more functional groups A and B that react with each other. For example, polyurethane is synthesized by reacting diol compounds with two hydroxyl groups (-OH) in one molecule and diisocyanate compounds with two isocyanate groups (-N = C = O) in the presence of a catalyst in equal amounts. Is done.
Heteroatomic polymers are expected as biomaterials in the field of medical devices because of their mechanical properties and durability. However, it has been pointed out that a heteroatom polymer developed for industrial use is recognized as a foreign substance in a living body, thereby causing an inflammatory reaction and impairing a biological function. Therefore, when a heteroatom polymer such as polyurethane is applied as a biomaterial, some modification is required.
When a chemical modification is attempted to impart a function to a polymer, a technique is generally adopted in which a functional group that causes some reaction is introduced into the polymer (for example, the 5th edition Experimental Chemistry Course 26). Volume, Polymer Chemistry, The Chemical Society of Japan (2005), 194-202 (Non-Patent Document 1)). However, since the isocyanate group also reacts with an amino group (—NH 2 ) or a mercapto group (—SH), when other functional groups are present in the diisocyanate or diol, the intermolecular molecules are cross-linked to form a network-like macromolecule. Is synthesized. Since this macromolecule is difficult to dissolve in various solvents and has a very high melting point, there is a problem in the molding process when applied to industrial applications. This event can occur in other heteroatom polymers as well as polyurethane.
　上記のような状況の中で、架橋のために加工性を損なうことなく、簡便な方法でヘテロ原子ポリマーに様々な機能を修飾する方法および種々の機能を付与されたヘテロ原子ポリマーの提供が望まれている。 Under such circumstances, it is desired to provide a method for modifying various functions of a heteroatom polymer by a simple method without impairing processability due to crosslinking and to provide a heteroatom polymer provided with various functions. It is rare.
　本発明者らはビニルモノマーに着目した。ビニルモノマーは不飽和炭素結合を１つ以上分子内に含む化合物の総称であり、種々の重合方法によりビニルポリマーを得ることが可能な分子である。ビニルポリマーはポリ塩化ビニル、ポリエチレン及びポリプロピレンなどに代表される多くの工業材料として実用化されている。ポリビニルの機能は多種多様に及ぶが、これは種々のビニルモノマーを任意の割合で重合することで、それらモノマーの機能を併せ持つポリマーを合成することが可能であるためである。そのために、現時点で非常に多くのビニルモノマーが開発、製造されている。つまり、ビニルモノマーをヘテロ原子ポリマーに自由に導入することができれば、多種多様な機能を持つヘテロ原子ポリマーを得ることが可能であると言える。 The inventors focused on vinyl monomers. Vinyl monomer is a general term for compounds containing one or more unsaturated carbon bonds in the molecule, and is a molecule that can obtain a vinyl polymer by various polymerization methods. Vinyl polymers have been put into practical use as many industrial materials typified by polyvinyl chloride, polyethylene and polypropylene. The functions of polyvinyl vary widely, because it is possible to synthesize polymers having the functions of these monomers by polymerizing various vinyl monomers at an arbitrary ratio. Therefore, a great number of vinyl monomers have been developed and manufactured at present. That is, if a vinyl monomer can be freely introduced into a heteroatom polymer, it can be said that heteroatom polymers having various functions can be obtained.
　しかし、ビニルモノマーとジオール又はジイソシアネート等を自由に重合する方法は確立されていない。類似の技術としてビニルポリマーとヘテロ原子ポリマーの混合物（ポリマーブレンド）又はビニルポリマーをヘテロ原子ポリマーの側鎖にグラフトしたグラフトポリマーおよびその逆が考案され、研究が進められている（例えば、ポリマーアロイの開発と応用、秋山三郎監修、伊沢槇一監修、シーエムシー出版（２００３）、１－３０（非特許文献２）参照）。しかし、ポリマーブレンドはヘテロ原子ポリマーの本来の力学特性を損なう可能性が高く、また長期の使用により片方のポリマーが溶出する可能性も否定できない。グラフトポリマーの場合も同様に力学特性を損なう可能性があり、さらに、ポリマー中に枝分かれが存在するために溶媒への溶解性やポリマーの結晶性を低下させる、ビニルポリマーの導入量が比較的多い必要があるといった問題点がある。 However, a method for freely polymerizing vinyl monomers and diols or diisocyanates has not been established. Similar techniques have been devised and studied as a mixture of vinyl polymers and heteroatom polymers (polymer blends) or graft polymers grafted onto side chains of heteroatom polymers and vice versa (eg, polymer alloys Development and application, supervised by Saburo Akiyama, supervised by Junichi Izawa, CMC Publishing (2003), 1-30 (non-patent document 2)). However, the polymer blend is highly likely to impair the original mechanical properties of the heteroatom polymer, and the possibility that one polymer will elute due to long-term use cannot be denied. In the case of graft polymers as well, there is a possibility that the mechanical properties are similarly impaired, and furthermore, the presence of branching in the polymer causes a relatively large amount of vinyl polymer to be introduced, which reduces the solubility in the solvent and the crystallinity of the polymer. There is a problem that it is necessary.
　これらの問題点を解決するためには直鎖状であり、かつビニルモノマーを主鎖に導入したポリマーを発明する必要があった。そこで発明者らは、ビニルモノマーをジオールなどの多官能性化合物にあらかじめ修飾することを考案した。 In order to solve these problems, it was necessary to invent a polymer that is linear and has a vinyl monomer introduced into the main chain. Therefore, the inventors have devised that the vinyl monomer is modified in advance to a polyfunctional compound such as diol.
　すなわち、本発明は、以下に示したとおりの多官能性化合物及びそれを用いて得られるヘテロ原子ポリマーならびにそれらの製造方法等を提供するものである。 That is, the present invention provides a polyfunctional compound as shown below, a heteroatom polymer obtained using the same, a production method thereof, and the like.
［１］下記式（Ｉ）で示される多官能性化合物。
Figure JPOXMLDOC01-appb-C000007
［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］
［２］下記式（Ｉａ）又は（Ｉｂ）で示されるものである、［１］記載の多官能性化合物。
Figure JPOXMLDOC01-appb-C000008
［式中、Ｒは、水素原子又はメチル基であり、Ｘ1及びＸ2は、それぞれ独立して、反応性官能基であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基である。］
［３］前記反応性官能基が、水酸基、アミノ基、イソシアネート基、カルボキシル基及びイミド基からなる群から選ばれる少なくとも１種である、［２］記載の多官能性化合物。［４］前記機能性官能基が、エチレン性不飽和炭素結合を含む化合物に由来する官能基である、［１］～［３］のいずれか１項に記載の多官能性化合物。
 前記エチレン性不飽和炭素結合を含む化合物としては、例えばβ位に電子吸引性基を持つものが挙げられる。
［５］前記エチレン性不飽和炭素結合を有する化合物が、２－メタクリロイルオキシエチルホスホリルコリン、メタクリル酸メチル、メタクリル酸ブチル、メタクリル酸２－ヒドロキシエチル、メタクリル酸ポリエチレングリコール、メタクリル酸フルオロアルキル、Ｎ－ビニルピロリドン、アリルアルコール、Ｎ－イソプロピルアクリルアミド、アクリルアミド、メタクリル酸メトキシシランアルキル及び桂皮酸ビニルからなる群から選ばれるものである、［４］記載の多官能性化合物。
［６］Ｘ1及びＸ2が水酸基である、［２］～［５］のいずれか１項に記載の多官能性化合物。
［７］Ｙが硫黄原子である、［１］～［６］のいずれか１項に記載の多官能性化合物。
［８］Ｚが、式－ＣＯＯＺ’［式中、Ｚ’は、水酸基、アミノ基、ニトロ基、スルホニル基、フェニル基及び活性エステル基から選ばれる置換基を有していてもよいＣ1～20アルキル基；エチルホスホリルコリン基（－ＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3）；又はポリエチレングリコール基（－（ＣＨ2ＣＨ2０）nＯＨ）である。］
で示される官能基である、［１］～［７］のいずれか１項に記載の多官能性化合物。
［９］Ｚが、－ＣＯＯＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3；－ＣＯＯＣＨ2ＣＨ2ＯＨ；又は－ＣＯＯＣＨ2ＣＨ2ＣＨ2ＣＨ3である、［１］～［８］のいずれか１項に記載の多官能性化合物。
［１０］下記式（Ｉ）で示される多官能性化合物の製造方法であって、
Figure JPOXMLDOC01-appb-C000009
［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］
　下記式（ＩＩ）で示される化合物と、
Figure JPOXMLDOC01-appb-C000010
［式中、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙ’は、メルカプト基又はアミノ基であり、ｎは１～4の整数である。］
　下記式（ＩＩＩ）で示される化合物とを、
Figure JPOXMLDOC01-appb-C000011
［式中、Ｒは、水素原子又はメチル基であり、Ｚは、機能性官能基である。］
溶媒中で混合する工程を含む、多官能性化合物の製造方法。
［１１］アミンの存在下、前記式（ＩＩ）で示される化合物と前記式（ＩＩＩ）で示される化合物とを混合する、［１０］記載の製造方法。
［１２］前記アミンが、トリエチルアミン及びジイソプロピルアミンからなる群から選ばれる少なくとも１種である、［１１］記載の製造方法。
［１３］前記アミンの添加量が、前記式（ＩＩ）で示される化合物の使用量の４～４０モル％である、［１１］又は［１２］のいずれか１項に記載の製造方法。
［１４］前記式（ＩＩＩ）で示される化合物が、２－メタクリロイルオキシエチルホスホリルコリン、メタクリル酸メチル、メタクリル酸ブチル、メタクリル酸２－ヒドロキシエチル、メタクリル酸ポリエチレングリコール、メタクリル酸フルオロアルキル、Ｎ－ビニルピロリドン、アリルアルコール、Ｎ－イソプロピルアクリルアミド、アクリルアミド、メタクリル酸メトキシシランアルキル及び桂皮酸ビニルからなる群から選ばれるものである、［１０］～［１３］のいずれか１項に記載の製造方法。
［１５］［１］～［９］のいずれか１項に記載の多官能性化合物と、前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させて得られる、ヘテロ原子ポリマー。
［１６］前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物が、ポリイソシアネート化合物である、［１５］記載のヘテロ原子ポリマー。
 前記ポリイソシアネート化合物としては、例えばメチレンジフェニルジイソシアネート、トリレンジイソシアネート及びそれらの誘導体からなる群から選ばれるものが挙げられる。
［１７］下記式（ＩＶ）で示される構造を繰り返し単位として含む、ヘテロ原子ポリマー。
Figure JPOXMLDOC01-appb-C000012
［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］
［１８］［１］～［９］のいずれか１項に記載の多官能性化合物を重縮合又はカチオン重合させる工程を含む、ヘテロ原子ポリマーの製造方法。
［１９］［１］～［９］のいずれか１項に記載の多官能性化合物と、前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させる工程を含む、ヘテロ原子ポリマーの製造方法。
［２０］鎖延長剤の存在下、前記多官能性化合物と、前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させる、［１９］記載の製造方法。
［２１］前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物が、ポリイソシアネート化合物である、［１９］又は［２０］記載の製造方法。
 前記ポリイソシアネート化合物としては、例えばメチレンジフェニルジイソシアネート、トリレンジイソシアネート及びそれらの誘導体からなる群から選ばれるものが挙げられる。 [1] A polyfunctional compound represented by the following formula (I).
Figure JPOXMLDOC01-appb-C000007
[Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
[2] The polyfunctional compound according to [1], which is represented by the following formula (Ia) or (Ib).
Figure JPOXMLDOC01-appb-C000008
[Wherein, R is a hydrogen atom or a methyl group, X 1 and X 2 are each independently a reactive functional group, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group. ]
[3] The polyfunctional compound according to [2], wherein the reactive functional group is at least one selected from the group consisting of a hydroxyl group, an amino group, an isocyanate group, a carboxyl group, and an imide group. [4] The polyfunctional compound according to any one of [1] to [3], wherein the functional functional group is a functional group derived from a compound containing an ethylenically unsaturated carbon bond.
Examples of the compound containing an ethylenically unsaturated carbon bond include those having an electron-withdrawing group at the β-position.
[5] The compound having an ethylenically unsaturated carbon bond is 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate, N-vinyl. [4] The polyfunctional compound according to [4], which is selected from the group consisting of pyrrolidone, allyl alcohol, N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate, and vinyl cinnamate.
[6] The polyfunctional compound according to any one of [2] to [5], wherein X 1 and X 2 are hydroxyl groups.
[7] The polyfunctional compound according to any one of [1] to [6], wherein Y is a sulfur atom.
[8] Z has the formula -COOZ '[wherein, Z' represents a hydroxyl group, an amino group, a nitro group, a sulfonyl group, an optionally C 1 ~ optionally having a substituent selected from phenyl groups and active ester groups 20 alkyl group; ethyl phosphorylcholine group (—CH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ); or polyethylene glycol group (— (CH 2 CH 2 0) n OH ). ]
The multifunctional compound according to any one of [1] to [7], which is a functional group represented by:
[9] Z is —COOCH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3 The multifunctional compound according to any one of [1] to [8].
[10] A method for producing a polyfunctional compound represented by the following formula (I):
Figure JPOXMLDOC01-appb-C000009
[Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
A compound represented by the following formula (II):
Figure JPOXMLDOC01-appb-C000010
[Wherein, X is an atomic group causing ring-opening polymerization, polyaddition or polycondensation, Y ′ is a mercapto group or an amino group, and n is an integer of 1 to 4. ]
A compound represented by the following formula (III):
Figure JPOXMLDOC01-appb-C000011
[Wherein, R is a hydrogen atom or a methyl group, and Z is a functional functional group. ]
The manufacturing method of a polyfunctional compound including the process mixed in a solvent.
[11] The production method according to [10], wherein the compound represented by the formula (II) and the compound represented by the formula (III) are mixed in the presence of an amine.
[12] The production method according to [11], wherein the amine is at least one selected from the group consisting of triethylamine and diisopropylamine.
[13] The production method according to any one of [11] or [12], wherein the addition amount of the amine is 4 to 40 mol% of the amount of the compound represented by the formula (II) used.
[14] The compound represented by the formula (III) is 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate, N-vinylpyrrolidone The method according to any one of [10] to [13], which is selected from the group consisting of allyl alcohol, N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate, and vinyl cinnamate.
[15] A heteroatom polymer obtained by reacting the polyfunctional compound according to any one of [1] to [9] with a compound that causes polycondensation or polyaddition reaction with the polyfunctional compound. .
[16] The heteroatom polymer according to [15], wherein the compound causing a polycondensation or polyaddition reaction with the polyfunctional compound is a polyisocyanate compound.
Examples of the polyisocyanate compound include those selected from the group consisting of methylene diphenyl diisocyanate, tolylene diisocyanate, and derivatives thereof.
[17] A heteroatom polymer containing a structure represented by the following formula (IV) as a repeating unit.
Figure JPOXMLDOC01-appb-C000012
[Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
[18] A method for producing a heteroatom polymer, comprising a step of polycondensation or cationic polymerization of the polyfunctional compound according to any one of [1] to [9].
[19] A heteroatom polymer comprising the step of reacting the polyfunctional compound according to any one of [1] to [9] with the polyfunctional compound and a compound causing a polycondensation or polyaddition reaction. Manufacturing method.
[20] The production method according to [19], wherein the polyfunctional compound is reacted with a compound causing a polycondensation or polyaddition reaction with the polyfunctional compound in the presence of a chain extender.
[21] The production method of [19] or [20], wherein the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound is a polyisocyanate compound.
Examples of the polyisocyanate compound include those selected from the group consisting of methylene diphenyl diisocyanate, tolylene diisocyanate, and derivatives thereof.
　本発明の好ましい態様によれば、きわめて簡便な方法で種々の機能が付与されたヘテロ原子ポリマーを得ることができる。本発明のヘテロ原子ポリマーは、工業材料及び生体材料などの様々な用途に用いることができる。 According to a preferred embodiment of the present invention, a heteroatom polymer having various functions can be obtained by a very simple method. The heteroatom polymer of the present invention can be used in various applications such as industrial materials and biomaterials.
実施例１で得られたＭＰＣ付加型ジオールの反応速度を示すグラフである。2 is a graph showing the reaction rate of MPC addition diol obtained in Example 1. FIG. 実施例１で得られたＭＰＣ付加型ジオールの１Ｈ－ＮＭＲ測定データを示した図である。1 is a diagram showing 1 H-NMR measurement data of an MPC addition type diol obtained in Example 1. FIG. ＢＭＡ付加型ジオールの１Ｈ－ＮＭＲ測定データを示した図である。FIG. 3 is a diagram showing 1 H-NMR measurement data of a BMA addition diol. ＨＥＭＡ付加型ジオールの１Ｈ－ＮＭＲ測定データを示した図である。FIG. 3 is a diagram showing 1 H-NMR measurement data of a HEMA addition type diol. ＭＰＴＳ付加型ジオールの１Ｈ－ＮＭＲ測定データを示した図である。FIG. 3 is a diagram showing 1 H-NMR measurement data of an MPTS-added diol. ＭＴＦ付加型ジオールの１Ｈ－ＮＭＲ測定データを示した図である。FIG. 3 is a diagram showing 1 H-NMR measurement data of an MTF addition diol. メタクリレート付加型ジオールの反応速度を示した図である。It is the figure which showed the reaction rate of the methacrylate addition type diol.
　以下、本発明の多官能性化合物、ヘテロ原子ポリマー及びそれらの製造方法等について詳細に説明する。 Hereinafter, the polyfunctional compound, heteroatom polymer, production method thereof and the like of the present invention will be described in detail.
　１．多官能性化合物及びその製造方法
　本発明の多官能性化合物は、下記式（Ｉ）で示される化合物である。
Figure JPOXMLDOC01-appb-C000013
［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～4の整数である。］ 1. Multifunctional compound and production method thereof The polyfunctional compound of the present invention is a compound represented by the following formula (I).
Figure JPOXMLDOC01-appb-C000013
[Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
　式（Ｉ）で示されるとおり、本発明の多官能性化合物は、開環重合、重付加又は重縮合を引き起こす原子団Ｘに、結合基（－Ｙ－ＣＨ2ＣＨＲ－）を介して、機能性官能基Ｚが結合している。本発明の多官能性化合物は、原子団Xをもつことでモノマーとなることができ、原子団Ｘで重合することにより、ポリマー中にきわめて簡便な方法で機能性官能基Ｚを導入することを可能にするものである。 As represented by the formula (I), the polyfunctional compound of the present invention has a functional group X which causes ring-opening polymerization, polyaddition or polycondensation via a linking group (—Y—CH 2 CHR—). The functional group Z is bonded. The polyfunctional compound of the present invention can be a monomer by having the atomic group X, and the functional group Z can be introduced into the polymer by a very simple method by polymerizing with the atomic group X. It is what makes it possible.
　式（Ｉ）中、原子団Ｘは、開環重合、重付加又は重縮合を引き起こすものであれば特に制限されない。原子団Ｘとしては、例えば、反応性官能基を２つ以上有する有機基；脱ハロゲン原子による重縮合を引き起こす有機基；開環重合を引き起こす有機基；などが挙げられる。ここで「有機基」は、飽和若しくは不飽和の非環式であってもよく、又は飽和若しくは不飽和の環式であってもよい。非環式の場合には、線状でもよいし、枝分かれでもよい。環式の場合は、ヘテロ環であってもよい。 In the formula (I), the atomic group X is not particularly limited as long as it causes ring-opening polymerization, polyaddition or polycondensation. Examples of the atomic group X include an organic group having two or more reactive functional groups; an organic group that causes polycondensation by a dehalogenated atom; an organic group that causes ring-opening polymerization; and the like. Here, the “organic group” may be saturated or unsaturated acyclic, or may be saturated or unsaturated cyclic. In the case of acyclic, it may be linear or branched. In the case of cyclic, it may be a heterocyclic ring.
　反応性官能基を２つ以上有する有機基としては、飽和又は不飽和の非環式炭化水素基又は環式炭化水素基が挙げられる。炭化水素基は、酸素原子、硫黄原子、珪素原子又は式－Ｎ（Ｒ’）－で示される基（式中、Ｒ’は水素原子又はＣ1～Ｃ20炭化水素基である。）で中断されていてもよい。
　反応性官能基は、例えば、水酸基、アミノ基、イソシアネート基、カルボキシル基及びイミド基などが好ましく挙げられる。これらの中でも水酸基が好ましい。反応性官能基は、１種でもよく、２種以上の組み合せでもよい。 Examples of the organic group having two or more reactive functional groups include a saturated or unsaturated acyclic hydrocarbon group or a cyclic hydrocarbon group. The hydrocarbon group is interrupted by an oxygen atom, a sulfur atom, a silicon atom or a group represented by the formula —N (R ′) — (wherein R ′ is a hydrogen atom or a C 1 -C 20 hydrocarbon group). May be.
Preferred examples of the reactive functional group include a hydroxyl group, an amino group, an isocyanate group, a carboxyl group, and an imide group. Among these, a hydroxyl group is preferable. The reactive functional group may be one kind or a combination of two or more kinds.
　反応性官能基を２つ以上有する有機基としては、例えば、下記式で示される有機基が挙げられる。
Figure JPOXMLDOC01-appb-C000014
［式中、Ｘ1及びＸ2は、それぞれ独立して、反応性官能基であり、環Ａは、ベンゼン環又は芳香族複素環であり、＊は、Ｙとの結合位置を示している。］ As an organic group which has two or more reactive functional groups, the organic group shown by a following formula is mentioned, for example.
Figure JPOXMLDOC01-appb-C000014
[Wherein, X 1 and X 2 are each independently a reactive functional group, ring A is a benzene ring or an aromatic heterocycle, and * indicates a bonding position with Y. ]
　環Ａの芳香族複素環は、ピロール、フラン、チオフェン、イミダゾール、オキサゾール、チアゾール、ピラゾール、イソオキサゾール、イソチアゾール、ピリジン、ピリダジン、ピリミジン、ピラジン、２Ｈ－ピラン、４Ｈ－ピラン、トリアジンなどが挙げられる。 Examples of the aromatic heterocycle of ring A include pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, isoxazole, isothiazole, pyridine, pyridazine, pyrimidine, pyrazine, 2H-pyran, 4H-pyran, and triazine. .
　脱ハロゲンによる重縮合を引き起こす有機基としては、例えば下記の有機基が挙げられる。
Figure JPOXMLDOC01-appb-C000015
［式中、Ｘ3及びＸ4は、それぞれ独立して、ハロゲン原子であり、環Ｂは、ベンゼン環又は芳香族複素環であり、＊は、Ｙとの結合位置を示している。］ Examples of the organic group that causes polycondensation by dehalogenation include the following organic groups.
Figure JPOXMLDOC01-appb-C000015
[Wherein, X 3 and X 4 are each independently a halogen atom, ring B is a benzene ring or an aromatic heterocycle, and * represents a bonding position with Y. ]
　環Ｂの芳香族複素環は、環Ａで例示したものと同じものが挙げられる。 Examples of the aromatic heterocycle of ring B are the same as those exemplified for ring A.
　開環重合を引き起こす有機基としては、ラクトン、ラクタムなどの環状カルボニル化合物、エポキシドなどの環状エーテル化合物、環状オレフィン化合物、環状アミド、α－アミノ酸－N－カルボン酸無水物などが挙げられる。 Examples of the organic group that causes ring-opening polymerization include cyclic carbonyl compounds such as lactones and lactams, cyclic ether compounds such as epoxides, cyclic olefin compounds, cyclic amides, α-amino acid-N-carboxylic acid anhydrides, and the like.
　これらの中でも、原子団Ｘとしては、下記の基が好ましく挙げられる。
Figure JPOXMLDOC01-appb-C000016
［式中、＊は、Ｙとの結合位置を示している。］ Among these, as the atomic group X, the following groups are preferably exemplified.
Figure JPOXMLDOC01-appb-C000016
[In the formula, * represents a bonding position with Y. ]
　式（Ｉ）中、Ｙは、硫黄原子又は－ＮＨ－で示される基である。中でも、原料入手が容易であること、反応が制御しやすいことから、硫黄原子が好ましい。 In formula (I), Y is a sulfur atom or a group represented by —NH—. Among these, a sulfur atom is preferable because it is easy to obtain raw materials and the reaction is easily controlled.
　式（Ｉ）中、Ｒは、水素原子又はメチル基である。中でも、メチル基が好ましい。 In the formula (I), R is a hydrogen atom or a methyl group. Of these, a methyl group is preferable.
　式（Ｉ）中、機能性官能基Ｚは、本発明の多官能性化合物を用いてポリマーを得る際に、ポリマーに所望の機能を付与できるものであれば特に制限されない。
　機能性官能基Ｚとしては、エチレン性不飽和炭素結合を含む化合物に由来する官能基であることが好ましく、β位に電子吸引性基を持つエチレン性不飽和炭素結合を含む化合物であることがさらに好ましい。そのような官能基を与えるエチレン性不飽和炭素結合を含む化合物としては、例えば、２－メタクリロイルオキシエチルホスホリルコリン、メタクリル酸メチル、メタクリル酸ブチル、メタクリル酸２－ヒドロキシエチル、メタクリル酸ポリエチレングリコール、メタクリル酸フルオロアルキル（C1～20)、Ｎ－ビニルピロリドン、アリルアルコール、Ｎ－イソプロピルアクリルアミド、アクリルアミド、メタクリル酸メトキシシランアルキル（C1～20)及び桂皮酸ビニルからなる群から選ばれる化合物が挙げられる。 In the formula (I), the functional functional group Z is not particularly limited as long as it can impart a desired function to the polymer when the polymer is obtained using the polyfunctional compound of the present invention.
The functional functional group Z is preferably a functional group derived from a compound containing an ethylenically unsaturated carbon bond, and preferably a compound containing an ethylenically unsaturated carbon bond having an electron-withdrawing group at the β-position. Further preferred. Examples of the compound containing an ethylenically unsaturated carbon bond that gives such a functional group include 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, methacrylic acid Examples thereof include compounds selected from the group consisting of fluoroalkyl (C 1-20 ), N-vinyl pyrrolidone, allyl alcohol, N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate (C 1-20 ), and vinyl cinnamate.
　例えば、機能性官能基Ｚとしては、式
 
　－ＣＯＯＺ’
 
［式中、Ｚ’は、水酸基、フッ素原子、アミノ基、ニトロ基、スルホニル基、フェニル基及び活性エステル基から選ばれる置換基を有していてもよいＣ1～20アルキル基；エチルホスホリルコリン基（－ＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3）；又はポリエチレングリコール基（－（ＣＨ2ＣＨ2０）nＯＨ）である。］
で示される官能基が好ましい。 For example, as the functional functional group Z, the formula
-COOZ '

Wherein, Z 'represents a hydroxyl group, a fluorine atom, an amino group, a nitro group, a sulfonyl group, an optionally C 1 ~ optionally having a substituent selected from phenyl groups and active ester groups 20 alkyl group; ethyl phosphorylcholine group (—CH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ); or a polyethylene glycol group (— (CH 2 CH 2 0) n OH). ]
Is preferred.
　中でも、機能性官能基Ｚとしては、－ＣＯＯＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3；－ＣＯＯＣＨ2ＣＨ2ＯＨ；又は－ＣＯＯＣＨ2ＣＨ2ＣＨ2ＣＨ3が好ましい。これらの機能性官能基がヘテロ原子ポリマー中に導入されることで、ポリマーの生体親和性が高められ、ヘテロ原子ポリマーを生体材料として利用することが可能になる。 Among them, as the functional functional group Z, —COOCH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3 is preferred. By introducing these functional functional groups into the heteroatom polymer, the biocompatibility of the polymer is enhanced, and the heteroatom polymer can be used as a biomaterial.
　あるいは、機能性官能基Ｚは、Ｃ1～20のフルオロアルキル基などであってもよい。フルオロアルキル基がヘテロ原子ポリマー中に導入されることで、ヘテロ原子ポリマーの生体親和性、酸素透過性、耐熱性、耐燃焼性及び耐薬品性を高めることができる。 Alternatively, the functional functional group Z may be a C 1-20 fluoroalkyl group or the like. By introducing the fluoroalkyl group into the heteroatom polymer, the bioaffinity, oxygen permeability, heat resistance, combustion resistance and chemical resistance of the heteroatom polymer can be improved.
　式（Ｉ）中、ｎは１～４の整数である。ｎは好ましくは１又は２であり、より好ましくは１である。ｎが２以上の場合、Ｙ、Ｚ及びＲの組み合わせは、同一であってもよく、異なってもよい。 In the formula (I), n is an integer of 1 to 4. n is preferably 1 or 2, more preferably 1. When n is 2 or more, the combination of Y, Z and R may be the same or different.
　本発明の好ましい実施形態では、本発明の多官能性化合物は、下記式（Ｉａ）又は（Ｉｂ）で示される。
Figure JPOXMLDOC01-appb-C000017
［式中、Ｒは、水素原子又はメチル基であり、Ｘ1及びＸ2は、それぞれ独立して、反応性官能基であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基である。］ In a preferred embodiment of the present invention, the polyfunctional compound of the present invention is represented by the following formula (Ia) or (Ib).
Figure JPOXMLDOC01-appb-C000017
[Wherein, R is a hydrogen atom or a methyl group, X 1 and X 2 are each independently a reactive functional group, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group. ]
　上記式（Ｉａ）又は（Ｉｂ）において、Ｘ1及びＸ2は水酸基であることが好ましい。好ましいＹ、Ｒ、Ｚについては、前記式（Ｉ）の説明において述べたものと同じものが例示される。 In the above formula (Ia) or (Ib), X 1 and X 2 are preferably hydroxyl groups. Preferred examples of Y, R and Z are the same as those described in the description of the formula (I).
　これらの中でも、本発明の多官能性化合物としては、式（Ｉａ）又は（Ｉｂ）において、Ｘ1及びＸ2が水酸基であり、Ｙが硫黄原子であり、Ｒが水素原子又はメチル基であり、且つ、Ｚが－ＣＯＯＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3；－ＣＯＯＣＨ2ＣＨ2ＯＨ；又は－ＣＯＯＣＨ2ＣＨ2ＣＨ2ＣＨ3である化合物が好ましい。 Among these, as the polyfunctional compound of the present invention, in the formula (Ia) or (Ib), X 1 and X 2 are hydroxyl groups, Y is a sulfur atom, and R is a hydrogen atom or a methyl group. And Z is —COOCH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3 Compounds are preferred.
　このような構造を有する本発明の多官能性化合物は、下記式（ＩＩ）で示される化合物と、
Figure JPOXMLDOC01-appb-C000018
［式中、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙ’は、メルカプト基又はアミノ基であり、ｎは１～４の整数である。］
　下記式（ＩＩＩ）で示される化合物とを、
Figure JPOXMLDOC01-appb-C000019
［式中、Ｒは、水素原子又はメチル基であり、Ｚは、機能性官能基である。］
溶媒中で混合することによって製造することができる。 The polyfunctional compound of the present invention having such a structure includes a compound represented by the following formula (II):
Figure JPOXMLDOC01-appb-C000018
[Wherein, X is an atomic group causing ring-opening polymerization, polyaddition or polycondensation, Y ′ is a mercapto group or an amino group, and n is an integer of 1 to 4. ]
A compound represented by the following formula (III):
Figure JPOXMLDOC01-appb-C000019
[Wherein, R is a hydrogen atom or a methyl group, and Z is a functional functional group. ]
It can manufacture by mixing in a solvent.
　本発明の製造方法は、式（ＩＩＩ）で示されるビニルモノマーが、式（ＩＩ）で示される化合物の官能基Ｙ’とMichael付加反応又はラジカル付加反応することを利用するものであり、式（ＩＩ）で示される化合物の原子団Ｘによる開環重合、重縮合又は重付加反応を抑制しながら、機能性官能基を導入することを可能にする。 The production method of the present invention utilizes the fact that the vinyl monomer represented by the formula (III) undergoes Michael addition reaction or radical addition reaction with the functional group Y ′ of the compound represented by the formula (II). It is possible to introduce a functional functional group while suppressing ring-opening polymerization, polycondensation or polyaddition reaction by the atomic group X of the compound represented by II).
　式（ＩＩ）中、原子団Ｘは、上記式（Ｉ）中の原子団Ｘと同じであり、好ましい例も同じである。 In the formula (II), the atomic group X is the same as the atomic group X in the above formula (I), and preferred examples thereof are also the same.
　式（ＩＩ）中、Ｙ’は、メルカプト基又はアミノ基である。中でも、メルカプト基が好ましい。 In formula (II), Y ′ is a mercapto group or an amino group. Among these, a mercapto group is preferable.
　式（ＩＩ）中、ｎは１～４の整数である。ｎは好ましくは１又は２であり、より好ましくは１である。なお、ｎが２以上の場合、Ｙ’は、同一であってもよく、異なってもよい。 In the formula (II), n is an integer of 1 to 4. n is preferably 1 or 2, more preferably 1. When n is 2 or more, Y ′ may be the same or different.
　式（ＩＩ）で示される化合物としては、例えば、下記の化合物が好ましく挙げられる。
Figure JPOXMLDOC01-appb-C000020
 Preferred examples of the compound represented by the formula (II) include the following compounds.
Figure JPOXMLDOC01-appb-C000020
　式（ＩＩＩ）中、機能性官能基Ｚは、上記式（Ｉ）中の機能性官能基Ｚと同じであり、好ましい例も同じである。 In the formula (III), the functional functional group Z is the same as the functional functional group Z in the formula (I), and preferred examples are also the same.
　式（ＩＩＩ）中、Ｒは、水素原子又はメチル基であり、好ましくはメチル基である。 In the formula (III), R is a hydrogen atom or a methyl group, preferably a methyl group.
　上記式（ＩＩＩ）で示される化合物としては、例えば、２－メタクリロイルオキシエチルホスホリルコリン、メタクリル酸メチル、メタクリル酸ブチル、メタクリル酸ヒドロキシエチル、メタクリル酸ポリエチレングリコール、メタクリル酸フルオロアルキル（C1～20）、ビニルピロリドン、アリルアルコール、イソプロピルアクリルアミド、アクリルアミド、メタクリル酸メトキシシランアルキル（C1～20）及び桂皮酸ビニルが好ましく挙げられる。 Examples of the compound represented by the above formula (III) include 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate (C 1-20 ), Preferred are vinylpyrrolidone, allyl alcohol, isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate (C 1-20 ) and vinyl cinnamate.
　式（ＩＩＩ）で示される化合物は、好ましくは、式（ＩＩ）で示される化合物におけるＹ’と等モル量で用いられる。 The compound represented by the formula (III) is preferably used in an equimolar amount with respect to Y ′ in the compound represented by the formula (II).
　上記反応に用いる溶媒は、式（ＩＩ）及び（ＩＩＩ）で示される化合物に対して不活性なものであれば特に制限されなく、水、あるいは、脂肪族系又は芳香族系の溶媒が用いられる。溶媒としては、例えば、水、エタノール、メタノールなどのアルコール、テトラヒドロフラン、ジエチルエーテルなどのエーテル系溶媒；塩化メチレンなどのハロゲン化炭化水素；ベンゼン、トルエン、キシレン、メシチレンなどの芳香族炭化水素；ｏ－ジクロロベンゼンなどのハロゲン化芳香族炭化水素；Ｎ，Ｎ－ジメチルホルムアミド等のアミド、ジメチルスルホキシドなどのスルホキシドなどが挙げられる。
　溶媒の使用量は、ビニルモノマー／溶媒＝１／１００～１０／１（ｍｏｌ／ｖｏｌ）が好ましい。 The solvent used in the above reaction is not particularly limited as long as it is inert with respect to the compounds represented by formulas (II) and (III), and water or an aliphatic or aromatic solvent is used. . Examples of the solvent include water, ethanol, alcohols such as methanol, ether solvents such as tetrahydrofuran and diethyl ether; halogenated hydrocarbons such as methylene chloride; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene; Halogenated aromatic hydrocarbons such as dichlorobenzene; Amides such as N, N-dimethylformamide; Sulfoxides such as dimethyl sulfoxide.
The amount of the solvent used is preferably vinyl monomer / solvent = 1/100 to 10/1 (mol / vol).
　反応時間は、特に制限されないが、２～７２時間程度が好ましい。 The reaction time is not particularly limited, but is preferably about 2 to 72 hours.
　反応は、アミンの存在下で行うことが好ましい。アミンは、通常触媒として用いられるものであれば特に制限されないが、２級アミン又は３級アミンが好ましい。中でも、トリエチルアミン、ジイソプロピルアミン又はその組み合わせが好ましい。アミンの添加量は、特に制限されないが、上記式（ＩＩ）で示される化合物の使用量の４～４０モル％が好ましく、より好ましくは４～２０モル％、さらに好ましくは４～１０モル％の範囲で用いる。 The reaction is preferably performed in the presence of an amine. The amine is not particularly limited as long as it is usually used as a catalyst, but a secondary amine or a tertiary amine is preferable. Among these, triethylamine, diisopropylamine or a combination thereof is preferable. The amount of amine added is not particularly limited, but is preferably 4 to 40 mol%, more preferably 4 to 20 mol%, still more preferably 4 to 10 mol% of the amount of the compound represented by the above formula (II). Use in range.
　２．本発明のヘテロ原子ポリマー及びその製造方法
　本発明のヘテロ原子ポリマーは、上述した多官能性化合物を開環重合、重付加又は重縮合して得られるものであり、下記式（ＩＶ）で示される部分構造を繰り返し単位として含む。
Figure JPOXMLDOC01-appb-C000021
［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］ 2. The heteroatom polymer of the present invention and the production method thereof The heteroatom polymer of the present invention is obtained by ring-opening polymerization, polyaddition or polycondensation of the polyfunctional compound described above, and is represented by the following formula (IV). A partial structure is included as a repeating unit.
Figure JPOXMLDOC01-appb-C000021
[Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
　式（ＩＶ）中、Ｒ、Ｘ、Ｙ、Ｚ及びｎは、式（Ｉ）中のＲ、Ｘ、Ｙ、Ｚ及びｎと同じであり、好ましい例も同じである。 In the formula (IV), R, X, Y, Z and n are the same as R, X, Y, Z and n in the formula (I), and preferred examples are also the same.
　本発明の一実施形態では、式（ＩＶ）中、原子団Ｘにヘテロ原子を含むことが好ましい。原子団Ｘにヘテロ原子を含むことで、式（ＩＶ）で示される構成単位のみでヘテロ原子ポリマーを構成することができる。
　また、本発明の一実施形態では、式（ＩＶ）中、機能性官能基Ｚが生体親和性官能基であることが好ましい。機能性官能基Ｚとして生体親和性官能基を有することで、ヘテロ原子ポリマーを医療機器等の分野で用いられる生体材料として利用することができる。 In one Embodiment of this invention, it is preferable that a hetero atom is included in atomic group X in Formula (IV). By containing a hetero atom in the atomic group X, a hetero atom polymer can be comprised only with the structural unit shown by Formula (IV).
Moreover, in one Embodiment of this invention, it is preferable that the functional functional group Z is a bioaffinity functional group in Formula (IV). By having a biocompatible functional group as the functional functional group Z, the heteroatom polymer can be used as a biomaterial used in the field of medical devices and the like.
　本発明のヘテロ原子ポリマーに含まれる式（ＩＶ）で示される繰り返し単位は、１種でもよく、部分構造（例えば、Ｘ、Ｙ、Ｚ、Ｒ及びｎの少なくともいずれか）が異なる２種以上の組み合わせであってもよい。 The repeating unit represented by the formula (IV) contained in the heteroatom polymer of the present invention may be one type, or two or more types having different partial structures (for example, at least one of X, Y, Z, R and n). It may be a combination.
　本発明の一実施形態では、本発明のヘテロ原子ポリマーは、多官能性化合物と、この多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させて得られる。 In one embodiment of the present invention, the heteroatom polymer of the present invention is obtained by reacting a polyfunctional compound with a compound that causes polycondensation or polyaddition reaction with the polyfunctional compound.
　多官能性化合物は、前記「１．多官能性化合物及びその製造方法」において説明したものの中から、目的又は用途に応じて１種又は部分構造の異なる２種以上を組み合わせて用いる。 As the polyfunctional compound, one or a combination of two or more different partial structures is used according to the purpose or application from those described in “1. Polyfunctional compound and production method thereof”.
　多官能性化合物と重縮合又は重付加反応を引き起こす化合物は、多官能性化合物の原子団Ｘの構造によって任意に選択することができる。多官能性化合物と重縮合又は重付加反応を引き起こす化合物は、１種でもよく、２種以上の組み合わせであってもよい。 The compound that causes polycondensation or polyaddition reaction with the polyfunctional compound can be arbitrarily selected depending on the structure of the atomic group X of the polyfunctional compound. The compound that causes polycondensation or polyaddition reaction with the polyfunctional compound may be one kind or a combination of two or more kinds.
　例えば、原子団Ｘが水酸基を含む場合は、ポリイソシアネート化合物、ポリカルボン酸化合物などが好ましく用いられる。また、例えば、原子団Ｘがアミノ基を含む場合は、ポリイソシアネート化合物、ポリカルボン酸などが好ましく用いられる。また、例えば、原子団Ｘがイソシアネート基を含む場合は、ポリアミン化合物、ポリオール化合物などが好ましく用いられる。また、例えば、原子団Ｘがカルボキシル基を含む場合は、ポリアミン化合物、ポリオール化合物などが好ましく用いられる。また、原子団Ｘがイミド基を含む場合は、ポリアミンなどが好ましく用いられる。 For example, when the atomic group X contains a hydroxyl group, a polyisocyanate compound, a polycarboxylic acid compound, or the like is preferably used. For example, when the atomic group X contains an amino group, polyisocyanate compounds, polycarboxylic acids, and the like are preferably used. For example, when the atomic group X contains an isocyanate group, a polyamine compound, a polyol compound, or the like is preferably used. For example, when the atomic group X contains a carboxyl group, a polyamine compound, a polyol compound, or the like is preferably used. Moreover, when the atomic group X contains an imide group, a polyamine etc. are used preferably.
　これらの中でも、本発明のヘテロ原子ポリマーとしては、原子団Ｘとして水酸基を含む多官能性化合物と、イソシアネート基を２つ以上もつポリイソシアネート化合物とを反応させて得られる化合物が好ましい。ポリイソシアネート化合物は特に制限されなく、目的又は用途等に応じて適宜選択することができる。例えば、脂肪族ポリイソシアネート、芳香族ポリイソシアネート、脂環式ポリイソシアネート等が挙げられる。 Among these, the heteroatom polymer of the present invention is preferably a compound obtained by reacting a polyfunctional compound containing a hydroxyl group as the atomic group X with a polyisocyanate compound having two or more isocyanate groups. The polyisocyanate compound is not particularly limited and can be appropriately selected according to the purpose or use. For example, aliphatic polyisocyanate, aromatic polyisocyanate, alicyclic polyisocyanate and the like can be mentioned.
　脂肪族ポリイソシアネートとしては、例えば、トリメチレンジイソシアネート、テトラメチレンジイソシアネート、ヘキサメチレンジイソシアネート、ペンタメチレンジイソシアネート、１，２－プロピレンジイソシアネート、２，３－ブチレンジイソシアネート、１，３－ブチレンジイソシアネート、ドデカメチレンジイソシアネート、２，４，４－トリメチルヘキサメチレンジイソシアネート等が挙げられる。 Examples of the aliphatic polyisocyanate include trimethylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, pentamethylene diisocyanate, 1,2-propylene diisocyanate, 2,3-butylene diisocyanate, 1,3-butylene diisocyanate, dodecamethylene diisocyanate, Examples include 2,4,4-trimethylhexamethylene diisocyanate.
　芳香族ポリイソシアネートとしては、例えば、１，３－フェニレンジイソシアネート、４，４'－ジフェニルジイソシアネート、１，４－フェニレンジイソシアネート、４，４'－ジフェニルメタンジイソシアネート、１，４－トリレンジイソシアネート、２，４－トリレンジイソシアネート、２，６－トリレンジイソシアネート、４，４'－トルイジンジイソシアネート、２，４，６－トリイソシアネートトルエン、１，３，５－トリイソシアネートベンゼン、ジアニシジンジイソシアネート、４，４'－ジフェニルエーテルジイソシアネート、４，４'，４"－トリフェニルメタントリイソシアネート、２，２’－メチレンジフェニルジイソシアネート、２，４’－メチレンジフェニルジイソシアネート、４，４’－メチレンジフェニルジイソシアネート等が挙げられる。中でも、メチレンジフェニルジイソシアネート、トリレンジイソシアネート及びそれらの誘導体が好ましい。
  誘導体としては、例えば1,4-ブタンジオール、1,4-ブタンジアミン、エチレングリコール、1,2-ジアミノエタン、プロピレンオキシド、その他ポリオールおよびポリアミンとの付加体が挙げられる。 Examples of the aromatic polyisocyanate include 1,3-phenylene diisocyanate, 4,4′-diphenyl diisocyanate, 1,4-phenylene diisocyanate, 4,4′-diphenylmethane diisocyanate, 1,4-tolylene diisocyanate, 2,4 -Tolylene diisocyanate, 2,6-tolylene diisocyanate, 4,4'-toluidine diisocyanate, 2,4,6-triisocyanate toluene, 1,3,5-triisocyanate benzene, dianisidine diisocyanate, 4,4'- Diphenyl ether diisocyanate, 4,4 ', 4 "-triphenylmethane triisocyanate, 2,2'-methylene diphenyl diisocyanate, 2,4'-methylene diphenyl diisocyanate, 4,4'-methylene diphenyl diisocyanate Doo and the like. Among these, methylene diphenyl diisocyanate, tolylene diisocyanate and their derivatives are preferred.
Examples of the derivatives include 1,4-butanediol, 1,4-butanediamine, ethylene glycol, 1,2-diaminoethane, propylene oxide, other adducts with polyols and polyamines.
　脂環式ポリイソシアネートとしては、例えば、３－イソシアネートメチル－３，５，５－トリメチルシクロヘキシルイソシアネート、１，３－シクロペンタンジイソシアネート、１，３－シクロヘキサンジイソシアネート、１，４－シクロヘキサンジイソシアネート、メチル－２，４－シクロヘキサンジイソシアネート、メチル－２，６－シクロヘキサンジイソシアネート、４，４'－メチレンビス（シクロヘキシルイソシアネート）、１，４－ビス（イソシアネートメチル）シクロヘキサン等が挙げられる。 Examples of the alicyclic polyisocyanate include 3-isocyanate methyl-3,5,5-trimethylcyclohexyl isocyanate, 1,3-cyclopentane diisocyanate, 1,3-cyclohexane diisocyanate, 1,4-cyclohexane diisocyanate, and methyl-2. , 4-cyclohexane diisocyanate, methyl-2,6-cyclohexane diisocyanate, 4,4′-methylenebis (cyclohexyl isocyanate), 1,4-bis (isocyanatomethyl) cyclohexane and the like.
　多官能性化合物と、この多官能性化合物と重縮合又は重付加反応を引き起こす化合物との使用量は特に制限されない。目的又は用途等に応じて適宜決定すればよい。 The amount of the polyfunctional compound and the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound is not particularly limited. What is necessary is just to determine suitably according to the objective or a use.
　多官能性化合物と、この多官能性化合物と重縮合又は重付加反応を引き起こす化合物との反応は、好ましくは触媒の存在下で行う。
　触媒は、一般にヘテロ原子ポリマーの製造に用いられる触媒を使用することができる。
　例えば、原子団Ｘとして水酸基を含む多官能性化合物と、イソシアネート基を２つ以上もつポリイソシアネート化合物とを反応させる場合は、アミン触媒又は金属触媒が用いられる。
　アミン触媒としては、トリエチルアミン等のトリアルキルアミン、Ｎ，Ｎ，Ｎ'，Ｎ'－テトラメチル－１，３－ブタンジアミン等のテトラアルキルジアミン、ジメチルエタノールアミン等のアミノアルコール、トリエチレンジアミン、ピペラジン系、トリアジン系、４級アミンの有機酸塩又はフェノール塩等が挙げられる。中でも、三級アミンが好ましい。
　金属触媒としては、ジブチル錫ジラウレート等を例示することができる。これらは１種類で用いてもよく、２種類以上を組み合わせて用いてもよい。
　触媒の使用量は、目的又は用途等に応じて適宜決定することができる。 The reaction between the polyfunctional compound and the compound causing polycondensation or polyaddition reaction with the polyfunctional compound is preferably carried out in the presence of a catalyst.
As the catalyst, a catalyst generally used for producing a heteroatom polymer can be used.
For example, when a polyfunctional compound containing a hydroxyl group as the atomic group X is reacted with a polyisocyanate compound having two or more isocyanate groups, an amine catalyst or a metal catalyst is used.
Examples of amine catalysts include trialkylamines such as triethylamine, tetraalkyldiamines such as N, N, N ′, N′-tetramethyl-1,3-butanediamine, aminoalcohols such as dimethylethanolamine, triethylenediamine, and piperazine series. , Triazine type, quaternary amine organic acid salt or phenol salt. Of these, tertiary amines are preferred.
Examples of the metal catalyst include dibutyltin dilaurate. These may be used alone or in combination of two or more.
The usage-amount of a catalyst can be suitably determined according to the objective or a use.
　多官能性化合物と、この多官能性化合物と重縮合又は重付加反応を引き起こす化合物との反応は、好ましくは鎖延長剤の存在下で行う。
　鎖延長剤としては、重縮合又は重付加反応に通常用いられるものであれば特に制限されない。鎖延長剤としては、短鎖ポリオール、ポリアミンなどが好ましく用いられる。例えば、エチレングリコール、１、４－ブタンジオール、プロピレングリコール、ネオペンチルグリコール、１、４－シクロヘキサンジオールなどを使用できる。中でも、１、４－ブタンジオール、１，５－ヘキサメチレンジアミン、エチレンジアミンが好ましい。
　鎖延長剤の使用量は、目的又は用途等に応じて適宜決定することができる。 The reaction between the polyfunctional compound and the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound is preferably carried out in the presence of a chain extender.
The chain extender is not particularly limited as long as it is usually used for polycondensation or polyaddition reaction. As the chain extender, short chain polyols, polyamines and the like are preferably used. For example, ethylene glycol, 1,4-butanediol, propylene glycol, neopentyl glycol, 1,4-cyclohexanediol and the like can be used. Of these, 1,4-butanediol, 1,5-hexamethylenediamine, and ethylenediamine are preferable.
The amount of chain extender used can be appropriately determined according to the purpose or application.
　また、反応は、好ましくは溶媒の存在下で行う。溶媒は、多官能性化合物及び多官能性化合物と重縮合又は重付加反応を引き起こす化合物に対して不活性なものであれば特に制限されなく、水、あるいは、脂肪族系又は芳香族系の溶媒が用いられる。溶媒としては、例えば、水、エタノール、メタノールなどのアルコール、テトラヒドロフラン、ジエチルエーテルなどのエーテル系溶媒；塩化メチレンなどのハロゲン化炭化水素；ベンゼン、トルエン、キシレン、メシチレンなどの芳香族炭化水素；ｏ－ジクロロベンゼンなどのハロゲン化芳香族炭化水素；Ｎ，Ｎ－ジメチルホルムアミド等のアミド、ジメチルスルホキシドなどのスルホキシドなどが挙げられる。 The reaction is preferably performed in the presence of a solvent. The solvent is not particularly limited as long as it is inert to the polyfunctional compound and the compound that causes polycondensation or polyaddition reaction with the polyfunctional compound. Water, an aliphatic solvent or an aromatic solvent Is used. Examples of the solvent include water, ethanol, alcohols such as methanol, ether solvents such as tetrahydrofuran and diethyl ether; halogenated hydrocarbons such as methylene chloride; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene; Halogenated aromatic hydrocarbons such as dichlorobenzene; Amides such as N, N-dimethylformamide; Sulfoxides such as dimethyl sulfoxide.
　また、本発明の別の実施形態では、本発明のポリマーは、多官能性化合物を単独で重縮合又はカチオン重合反応させて得られる。
　多官能性化合物は、前記「１．多官能性化合物及びその製造方法」において説明したものの中から、目的又は用途に応じて１種又は部分構造の異なる２種以上を組み合わせて用いることができる。
　重縮合又はカチオン重合の反応条件は、通常用いられる範囲であればよく、多官能性化合物の構造等によって適宜選択することができる。 In another embodiment of the present invention, the polymer of the present invention is obtained by subjecting a polyfunctional compound alone to a polycondensation or cationic polymerization reaction.
Among the polyfunctional compounds described above in “1. Multifunctional compound and method for producing the same”, one or a combination of two or more different partial structures can be used depending on the purpose or application.
The reaction conditions for polycondensation or cationic polymerization may be in a range usually used, and can be appropriately selected depending on the structure of the polyfunctional compound.
　以下、実施例を挙げて本発明をさらに詳細に説明するが、本発明は何らこれらに制限されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
［実施例１］
　ＭＰＣ付加型ジオールの合成
　２－メタクリロイルオキシエチルホスホリルコリン（ＭＰＣ）、α－チオグリセロールそれぞれ５ｍｍｏｌをジメチルスルホキシド（ＤＭＳＯ）に溶解させた。触媒としてトリエチルアミン（ＴＥＡ）２０ｍｇ、トリエチルアミン２００ｍｇ、ジイソプロピルアミン（ＤＩＰＡ）２０ｍｇをそれぞれ加え、２，２４，４８，１２０時間後に１Ｈ－ＮＭＲにより反応物の構造を調べた。その結果、下記の反応式によりＭＰＣの付加したジオール（ＭＰＣ付加型ジオール）を得ることができた。ＭＰＣ付加型ジオールの反応速度を図１に示す。また、最終的に得られたＭＰＣ付加型ジオールの１Ｈ－ＮＭＲ測定データを図２に示す。図１において、「×」はＤＩＰＡ ４ｍｏｌ％、「▲」はＴＥＡ ４０ｍｏｌ％、「◆」はＴＥＡ ４ｍｏｌ％、「■」は触媒なしを表す。
Figure JPOXMLDOC01-appb-C000022
 [Example 1]
Synthesis of MPC-added diol 5 mmol each of 2-methacryloyloxyethyl phosphorylcholine (MPC) and α-thioglycerol was dissolved in dimethyl sulfoxide (DMSO). As a catalyst, 20 mg of triethylamine (TEA), 200 mg of triethylamine and 20 mg of diisopropylamine (DIPA) were added, respectively, and the structure of the reaction product was examined by 1 H-NMR after 2, 24, 48 and 120 hours. As a result, a diol to which MPC was added (MPC addition type diol) could be obtained by the following reaction formula. The reaction rate of MPC addition type diol is shown in FIG. Further, FIG. 2 shows 1 H-NMR measurement data of the MPC addition type diol finally obtained. In FIG. 1, “x” represents DIPA 4 mol%, “▲” represents TEA 40 mol%, “♦” represents TEA 4 mol%, and “■” represents no catalyst.
Figure JPOXMLDOC01-appb-C000022
［実施例２］
　ＭＰＣ付加型ポリウレタンの合成
　実施例１に基づいて合成したＭＰＣ付加型ジオール（ＭＰＣ－ｄｉｏｌ）及びトリレン１，４－ジイソシアネート（ＴＤＩ）を等モル量ＤＭＳＯに溶解し、室温で２４時間混合した。得られた溶液をアセトンに滴下することで、ポリウレタンの再沈殿を行った。減圧乾燥し、得られたポリウレタンを蒸留水に溶解させ、ＧＰＣによる分子量測定を行ったところ、分子量はＭｗ＝４００００，Ｍｎ＝２５０００であった。
 
[実施例3]
メタクリレート付加型ジオールの合成
Methacryroyl 2,2,2-trifuluoroethane(MTF)、2-Methacryroyloxypropyl TetramethoxySilane(MPTS)、n-Butyl methacrylates(BMA)、 2-Hydroxyethyl methacrylates(HEMA)及びVinyl cynnamate(VC) を5mmol はかりとり、それぞれなすフラスコに投入した。これにαチオグリセロール5mmol を加え、10 mL のDMSO に溶解させた。さらにトリエチルアミン２０ｍｇを加え、フラスコ内をアルゴンガスで置換した。常温で24 時間攪拌した後、水（MTF, MPTS, BMA, VC）又はジエチルエーテル（HEMA）を用いて反応生成物を再沈殿させた。洗浄、減圧乾燥の後、粘調な液体を得た。得られたジオールを、１H-NMR を用いて構造解析したところ、目的の構造を持つ化合物であることが確認された。NMRの結果を図３～６に示す。また、メタクリレート付加型ジオールの反応速度を図７に示す。図７において、「▲」はHEMA、「◆」はMPC、「■」はBMA、「＋」はMPTS、「×」はVCを表す。
 
[実施例４]
メタクリレート付加型ジオールを用いたポリウレタンの合成
 MPC 付加型ジオール（MPC-diol）、MTF 付加型ジオール（MTF-diol）、 1,4-ブタンジオール(BD)及びMethylene diphenyl diisocyanate(MDI)を、表１に示す組成に従ってなすフラスコに仕込んだ。DMSO 10mL を溶媒とし、ジラウリン酸ジブチルスズ20μL を加えた後に、フラスコ中をアルゴンガスで置換した。常温で24 時間攪拌し、得られた溶液を十分量のジエチルエーテルに滴下することでポリマーを再沈殿させた。沈殿を洗浄、減圧乾燥後に得られた粉末を1H-NMR を用いて構造解析したところ、表１に示すモノマー組成が確認された。
 
Figure JPOXMLDOC01-appb-T000023
  
 
  [Example 2]
Synthesis of MPC addition type polyurethane MPC addition type diol (MPC-diol) synthesized based on Example 1 and tolylene 1,4-diisocyanate (TDI) were dissolved in an equimolar amount of DMSO and mixed at room temperature for 24 hours. The resulting solution was added dropwise to acetone to reprecipitate the polyurethane. After drying under reduced pressure, the obtained polyurethane was dissolved in distilled water and measured for molecular weight by GPC. The molecular weight was Mw = 40000 and Mn = 25000.

[Example 3]
Synthesis of methacrylate-added diol
Weigh 5 mmol of Methacryroyl 2,2,2-trifuluoroethane (MTF), 2-Methacryroyloxypropyl TetramethoxySilane (MPTS), n-Butyl methacrylates (BMA), 2-Hydroxyethyl methacrylates (HEMA), and Vinyl cynnamate (VC) into each flask. I put it in. To this, 5 mmol of α-thioglycerol was added and dissolved in 10 mL of DMSO. Further, 20 mg of triethylamine was added, and the inside of the flask was replaced with argon gas. After stirring at room temperature for 24 hours, the reaction product was reprecipitated using water (MTF, MPTS, BMA, VC) or diethyl ether (HEMA). After washing and drying under reduced pressure, a viscous liquid was obtained. When the obtained diol was subjected to structural analysis using 1H-NMR, it was confirmed to be a compound having the target structure. The NMR results are shown in FIGS. The reaction rate of the methacrylate addition diol is shown in FIG. In FIG. 7, “▲” represents HEMA, “♦” represents MPC, “■” represents BMA, “+” represents MPTS, and “×” represents VC.

[Example 4]
Synthesis of polyurethane using methacrylate addition type diol MPC addition type diol (MPC-diol), MTF addition type diol (MTF-diol), 1,4-butanediol (BD) and Methylene diphenyl diisocyanate (MDI) are shown in Table 1. The flask made according to the composition shown in FIG. 10 mL of DMSO was used as a solvent, 20 μL of dibutyltin dilaurate was added, and the flask was replaced with argon gas. The mixture was stirred at room temperature for 24 hours, and the resulting solution was added dropwise to a sufficient amount of diethyl ether to reprecipitate the polymer. The structure of the powder obtained after washing the precipitate and drying under reduced pressure was analyzed using 1H-NMR, and the monomer composition shown in Table 1 was confirmed.

Figure JPOXMLDOC01-appb-T000023

　本発明により得られたヘテロ原子ポリマーは工業材料、生体材料として産業のあらゆる分野において応用されうる。特に生体親和性官能基を導入したヘテロ原子ポリマーは、生体材料として応用することができ有用性が高い。
  The heteroatom polymer obtained by the present invention can be applied in all fields of industry as an industrial material or a biomaterial. In particular, a heteroatom polymer into which a biocompatible functional group is introduced can be applied as a biomaterial and is highly useful.

Claims (24)

  1. 　下記式（Ｉ）で示される多官能性化合物。
    Figure JPOXMLDOC01-appb-C000001
    ［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］     The polyfunctional compound shown by following formula (I).
    Figure JPOXMLDOC01-appb-C000001
    [Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
  2. 　下記式（Ｉａ）又は（Ｉｂ）で示されるものである、請求項１記載の多官能性化合物。
    Figure JPOXMLDOC01-appb-C000002
    ［式中、Ｒは、水素原子又はメチル基であり、Ｘ1及びＸ2は、それぞれ独立して、反応性官能基であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基である。］     The polyfunctional compound according to claim 1, which is represented by the following formula (Ia) or (Ib).
    Figure JPOXMLDOC01-appb-C000002
    [Wherein, R is a hydrogen atom or a methyl group, X 1 and X 2 are each independently a reactive functional group, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group. ]
  3. 　前記反応性官能基が、水酸基、アミノ基、イソシアネート基、カルボキシル基及びイミド基からなる群から選ばれる少なくとも１種である、請求項２記載の多官能性化合物。 The polyfunctional compound according to claim 2, wherein the reactive functional group is at least one selected from the group consisting of a hydroxyl group, an amino group, an isocyanate group, a carboxyl group, and an imide group.
  4. 　前記機能性官能基が、エチレン性不飽和炭素結合を含む化合物に由来する官能基である、請求項１～３のいずれか１項に記載の多官能性化合物。 The multifunctional compound according to any one of claims 1 to 3, wherein the functional functional group is a functional group derived from a compound containing an ethylenically unsaturated carbon bond.
  5.  前記エチレン性不飽和炭素結合を含む化合物がβ位に電子吸引性基を持つものである、請求項４記載の多官能性化合物。 The polyfunctional compound according to claim 4, wherein the compound containing an ethylenically unsaturated carbon bond has an electron-withdrawing group at the β-position.
  6. 　前記エチレン性不飽和炭素結合を有する化合物が、２－メタクリロイルオキシエチルホスホリルコリン、メタクリル酸メチル、メタクリル酸ブチル、メタクリル酸２－ヒドロキシエチル、メタクリル酸ポリエチレングリコール、メタクリル酸フルオロアルキル、Ｎ－ビニルピロリドン、アリルアルコール、Ｎ－イソプロピルアクリルアミド、アクリルアミド、メタクリル酸メトキシシランアルキル及び桂皮酸ビニルからなる群から選ばれるものである、請求項４又は５記載の多官能性化合物。 The compound having an ethylenically unsaturated carbon bond is 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate, N-vinylpyrrolidone, allyl 6. The polyfunctional compound according to claim 4 or 5, which is selected from the group consisting of alcohol, N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate and vinyl cinnamate.
  7. 　Ｘ1及びＸ2が水酸基である、請求項２～６のいずれか１項に記載の多官能性化合物。 The polyfunctional compound according to any one of claims 2 to 6, wherein X 1 and X 2 are hydroxyl groups.
  8. 　Ｙが硫黄原子である、請求項１～７のいずれか１項に記載の多官能性化合物。 The polyfunctional compound according to any one of claims 1 to 7, wherein Y is a sulfur atom.
  9. 　Ｚが、式－ＣＯＯＺ’［式中、Ｚ’は、水酸基、アミノ基、ニトロ基、スルホニル基、フェニル基及び活性エステル基から選ばれる置換基を有していてもよいＣ1～20アルキル基；エチルホスホリルコリン基（－ＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3）；又はポリエチレングリコール基（－（ＣＨ2ＣＨ2０）nＯＨ）である。］で示される官能基である、請求項１～８のいずれか１項に記載の多官能性化合物。 Z has the formula -COOZ '[wherein, Z' represents a hydroxyl group, an amino group, a nitro group, a sulfonyl group, a phenyl group and an active ester good C 1 ~ 20 alkyl group optionally having a substituent selected from the group An ethylphosphorylcholine group (—CH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ); or a polyethylene glycol group (— (CH 2 CH 2 0) n OH); . The multifunctional compound according to any one of claims 1 to 8, which is a functional group represented by the formula:
  10. 　Ｚが、－ＣＯＯＣＨ2ＣＨ2ＯＰ（＝Ｏ）（Ｏ-）ＯＣＨ2ＣＨ2Ｎ+（ＣＨ3）3；－ＣＯＯＣＨ2ＣＨ2ＯＨ；又は－ＣＯＯＣＨ2ＣＨ2ＣＨ2ＣＨ3である、請求項１～９のいずれか１項に記載の多官能性化合物。 Z is —COOCH 2 CH 2 OP (═O) (O − ) OCH 2 CH 2 N + (CH 3 ) 3 ; —COOCH 2 CH 2 OH; or —COOCH 2 CH 2 CH 2 CH 3 Item 10. The multifunctional compound according to any one of Items 1 to 9.
  11. 　下記式（Ｉ）で示される多官能性化合物の製造方法であって、
    Figure JPOXMLDOC01-appb-C000003
    ［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］
    　下記式（ＩＩ）で示される化合物と、
    Figure JPOXMLDOC01-appb-C000004
    ［式中、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙ’は、メルカプト基又はアミノ基であり、ｎは１～４の整数である。］
    　下記式（ＩＩＩ）で示される化合物とを、
    Figure JPOXMLDOC01-appb-C000005
    ［式中、Ｒは、水素原子又はメチル基であり、Ｚは、機能性官能基である。］
    溶媒中で混合する工程を含む、多官能性化合物の製造方法。     A method for producing a polyfunctional compound represented by the following formula (I):
    Figure JPOXMLDOC01-appb-C000003
    [Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
    A compound represented by the following formula (II):
    Figure JPOXMLDOC01-appb-C000004
    [Wherein, X is an atomic group causing ring-opening polymerization, polyaddition or polycondensation, Y ′ is a mercapto group or an amino group, and n is an integer of 1 to 4. ]
    A compound represented by the following formula (III):
    Figure JPOXMLDOC01-appb-C000005
    [Wherein, R is a hydrogen atom or a methyl group, and Z is a functional functional group. ]
    The manufacturing method of a polyfunctional compound including the process mixed in a solvent.
  12. 　アミンの存在下、前記式（ＩＩ）で示される化合物と前記式（ＩＩＩ）で示される化合物とを混合する、請求項１１記載の製造方法。 The production method according to claim 11, wherein the compound represented by the formula (II) and the compound represented by the formula (III) are mixed in the presence of an amine.
  13. 　前記アミンが、トリエチルアミン及びジイソプロピルアミンからなる群から選ばれる少なくとも１種である、請求項１２記載の製造方法。 The production method according to claim 12, wherein the amine is at least one selected from the group consisting of triethylamine and diisopropylamine.
  14. 　前記アミンの添加量が、前記式（ＩＩ）で示される化合物の使用量の４～４０モル％である、請求項１２又は１３記載の製造方法。 The production method according to claim 12 or 13, wherein the addition amount of the amine is 4 to 40 mol% of the amount of the compound represented by the formula (II).
  15. 　前記式（ＩＩＩ）で示される化合物が、２－メタクリロイルオキシエチルホスホリルコリン、メタクリル酸メチル、メタクリル酸ブチル、メタクリル酸２－ヒドロキシエチル、メタクリル酸ポリエチレングリコール、メタクリル酸フルオロアルキル、Ｎ－ビニルピロリドン、アリルアルコール、Ｎ－イソプロピルアクリルアミド、アクリルアミド、メタクリル酸メトキシシランアルキル及び桂皮酸ビニルからなる群から選ばれるものである、請求項１１～１４のいずれか１項に記載の製造方法。 The compound represented by the formula (III) is 2-methacryloyloxyethyl phosphorylcholine, methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol methacrylate, fluoroalkyl methacrylate, N-vinylpyrrolidone, allyl alcohol The production method according to any one of claims 11 to 14, which is selected from the group consisting of N-isopropylacrylamide, acrylamide, methoxysilane alkyl methacrylate, and vinyl cinnamate.
  16. 　下記式（ＩＶ）で示される構造を繰り返し単位として含む、ヘテロ原子ポリマー。
    Figure JPOXMLDOC01-appb-C000006
    ［式中、Ｒは、水素原子又はメチル基であり、Ｘは、開環重合、重付加又は重縮合を引き起こす原子団であり、Ｙは、硫黄原子又は－ＮＨ－で示される基であり、Ｚは、機能性官能基であり、ｎは１～４の整数である。］     A heteroatom polymer comprising a structure represented by the following formula (IV) as a repeating unit.
    Figure JPOXMLDOC01-appb-C000006
    [Wherein, R is a hydrogen atom or a methyl group, X is an atomic group that causes ring-opening polymerization, polyaddition or polycondensation, Y is a sulfur atom or a group represented by —NH—, Z is a functional functional group, and n is an integer of 1 to 4. ]
  17. 　請求項１～１０のいずれか１項に記載の多官能性化合物と、前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させて得られる、ヘテロ原子ポリマー。 A heteroatom polymer obtained by reacting the polyfunctional compound according to any one of claims 1 to 10 with a compound that causes polycondensation or polyaddition reaction with the polyfunctional compound.
  18. 　前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物が、ポリイソシアネート化合物である、請求項１６記載のヘテロ原子ポリマー。 The heteroatom polymer according to claim 16, wherein the compound causing polycondensation or polyaddition reaction with the polyfunctional compound is a polyisocyanate compound.
  19.  前記ポリイソシアネート化合物がメチレンジフェニルジイソシアネート、トリレンジイソシアネート及びそれらの誘導体からなる群から選ばれるものである請求項１８記載のヘテロ原子ポリマー。 The heteroatom polymer according to claim 18, wherein the polyisocyanate compound is selected from the group consisting of methylene diphenyl diisocyanate, tolylene diisocyanate and derivatives thereof.
  20. 　請求項１～１０のいずれか１項に記載の多官能性化合物を重縮合又はカチオン重合させる工程を含む、ヘテロ原子ポリマーの製造方法。 A process for producing a heteroatom polymer, comprising a step of polycondensation or cationic polymerization of the polyfunctional compound according to any one of claims 1 to 10.
  21. 　請求項１～１０のいずれか１項に記載の多官能性化合物と、前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させる工程を含む、ヘテロ原子ポリマーの製造方法。 A method for producing a heteroatom polymer, comprising a step of reacting the polyfunctional compound according to any one of claims 1 to 10 with a compound that causes polycondensation or polyaddition reaction with the polyfunctional compound.
  22. 　鎖延長剤の存在下、前記多官能性化合物と、前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物とを反応させる、請求項２１記載の製造方法。 The production method according to claim 21, wherein the polyfunctional compound is reacted with a compound that causes polycondensation or polyaddition reaction with the polyfunctional compound in the presence of a chain extender.
  23. 　前記多官能性化合物と重縮合又は重付加反応を引き起こす化合物が、ポリイソシアネート化合物である、請求項２１又は２２記載の製造方法。 The production method according to claim 21 or 22, wherein the compound causing a polycondensation or polyaddition reaction with the polyfunctional compound is a polyisocyanate compound.
  24.  前記ポリイソシアネート化合物がメチレンジフェニルジイソシアネート、トリレンジイソシアネート及びそれらの誘導体である請求項２３記載の製造方法。
          The production method according to claim 23, wherein the polyisocyanate compound is methylene diphenyl diisocyanate, tolylene diisocyanate and derivatives thereof.
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WO2012086762A1 (en) * 2010-12-24 2012-06-28 日油株式会社 Amino group-containing phosphorylcholine, and method for producing same
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US20140323651A1 (en) * 2011-11-15 2014-10-30 Centre National De La Recherche Scientifique (C.N.R.S.) New Process of Preparation of Polyols and Polyamines, and Products as Obtained
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JP2013203713A (en) * 2012-03-29 2013-10-07 Sumitomo Seika Chem Co Ltd Alcohol derivative and method for preparing alcohol derivative
JP2013234160A (en) * 2012-05-10 2013-11-21 Nof Corp Carboxyl group including phosphorylcholine compound and process for production thereof
JP2013253043A (en) * 2012-06-07 2013-12-19 Nof Corp Phosphorylcholine group-containing compound and method for producing the same
WO2014057095A1 (en) * 2012-10-11 2014-04-17 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for converting reactive groups of si-c-bound groups of silanes while simultaneously increasing the physical distance between said groups

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