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WO2015064674A1 - Procédé de fabrication d'un colorant absorbant les uv polymérisable - Google Patents

Procédé de fabrication d'un colorant absorbant les uv polymérisable Download PDF

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WO2015064674A1
WO2015064674A1 PCT/JP2014/078851 JP2014078851W WO2015064674A1 WO 2015064674 A1 WO2015064674 A1 WO 2015064674A1 JP 2014078851 W JP2014078851 W JP 2014078851W WO 2015064674 A1 WO2015064674 A1 WO 2015064674A1
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meth
acrylate
group
acrylic acid
polymerizable
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Japanese (ja)
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正宏 田村
隆英 尾下
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Kowa Co Ltd
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Kowa Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
    • C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
    • C07C245/06—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings
    • C07C245/08—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
    • C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
    • C08F220/365—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate containing further carboxylic moieties
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B29/00—Monoazo dyes prepared by diazotising and coupling
    • C09B29/10—Monoazo dyes prepared by diazotising and coupling from coupling components containing hydroxy as the only directing group
    • C09B29/12—Monoazo dyes prepared by diazotising and coupling from coupling components containing hydroxy as the only directing group of the benzene series
    • C09B29/14—Hydroxy carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B69/00—Dyes not provided for by a single group of this subclass
    • C09B69/10—Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds
    • C09B69/106—Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds containing an azo dye
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
    • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
    • G02B1/041—Lenses
    • G02B1/043—Contact lenses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/442—Colorants, dyes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

Definitions

  • the present invention mainly relates to a method for producing a polymerizable ultraviolet absorbing dye for coloring an ophthalmic lens material.
  • the entire field of view becomes foggy.
  • a treatment method thereof an operation is performed in which the clouded lens is removed and an intraocular lens is inserted and placed in the lens capsule.
  • an acrylic or silicon polymer is used as the intraocular lens material used for treatment.
  • the crystalline lens In addition to having the property of hardly transmitting ultraviolet rays, the crystalline lens is slightly colored yellow, and has the property of suppressing the transmission of part of the blue light (wavelength of about 380 to 500 nm) of visible light. ing. Therefore, the material for the intraocular lens is required to have a property of absorbing ultraviolet rays and suppressing transmission of part of light in the blue region.
  • a polymerizable ultraviolet absorbing dye having a benzophenone skeleton having ultraviolet absorption performance in one molecule, an azobenzene skeleton having blue region light absorption performance, and a polymerizable group is disclosed (see Patent Document 1). ).
  • an aminoaryl compound having no polymerizable group is diazotized, and the obtained diazonium salt and dihydroxybenzophenone compound having an ultraviolet absorption action are subjected to diazo coupling in a strong base (1N aqueous sodium hydroxide solution).
  • a method of obtaining a polymerizable ultraviolet absorbing dye by subjecting the obtained coupling reaction product to ester condensation with a compound having a polymerizable group is disclosed.
  • Patent Document 2 in addition to the benzophenone skeleton, the azobenzene skeleton, the vinyl skeleton or the (meth) acryloyl skeleton, the azobenzene skeleton and the vinyl skeleton or (meta ) A polymerizable ultraviolet absorbing dye having a urethane bond (—OCONH—) between the acryloyl skeleton and the acryloyl skeleton is disclosed.
  • Patent Document 2 has a certain improvement in terms of yield, it has a urethane bond between the azobenzene skeleton and the vinyl skeleton or the (meth) acryloyl skeleton, so the solubility in the solvent is low, and the product There was a problem that the degree of freedom of deployment was low.
  • the present invention solves the above problems, and provides a production method capable of obtaining a polymerizable ultraviolet-absorbing dye in a high yield, without having a urethane bond with reduced solubility in a solvent.
  • the present inventor has repeatedly studied to solve the above-mentioned problems, and paid attention to the manufacturing process.
  • the conventional method employs a method in which a polymerizable group is introduced into the terminal after the diazo coupling reaction by an esterification reaction or the like.
  • the side reaction is dominant and the target compound is hardly obtained. Therefore, a method of diazotizing a compound into which a polymerizable group has been introduced in advance to form a diazonium salt, and then diazo coupling the diazonium salt and the benzophenone compound was studied.
  • a strong base such as sodium hydroxide used as a catalyst in diazo coupling breaks the ester bond formed during the esterification reaction.
  • the present inventors have solved the above-mentioned new problem by using a weak base as a catalyst, and found a production method capable of obtaining a polymerizable ultraviolet-absorbing dye in a high yield. It came to be completed.
  • the present invention A method for producing a compound represented by the following general formula (1), A diazotization step of obtaining a diazonium salt by diazotizing a polymerizable group-containing aminoaryl compound, and diazo coupling of the diazonium salt obtained in the diazotization step with a benzophenone compound, and represented by the following general formula (1)
  • the diazo coupling step is a method for producing a compound represented by the following general formula (1), wherein a weak base is used as a catalyst.
  • R 1 is a hydrogen atom, a hydroxy group, a carboxy group, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a sulfonic acid group or a benzyloxy group
  • 2 is a hydrogen atom, a hydroxy group, or an alkoxy group having 1 to 4 carbon atoms
  • R 3 is a group selected from the groups represented by the following general formulas (2) to (7).
  • R 4 is a hydrogen atom or a methyl group
  • m is an integer of 0 to 4
  • n is an integer of 1 to 8.
  • the weak base used in the diazo coupling step preferably contains one or more selected from sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium acetate and potassium acetate.
  • the benzophenone compound is represented by the following general formula (8), and is preferably a 2-hydroxybenzophenone compound or a 2-hydroxy-4-substituted-benzophenone compound.
  • R 1 and R 2 are the same groups as described above.
  • the polymerizable group-containing aminoaryl compound is represented by the following general formula (9):
  • R 3 is the same group as described above, and R is a hydrogen atom or a protecting group.
  • Another embodiment of the present invention is a compound produced by the above production method.
  • Another aspect of the present invention is a polymer obtained by copolymerizing one or more of the above compounds with another polymerizable monomer, and the polymer is preferably for an intraocular lens.
  • the compound represented by the general formula (1) can be obtained in high yield.
  • the compound represented by the general formula (1) has, in its molecule, a benzophenone skeleton having ultraviolet absorption performance, an azobenzene skeleton having blue light absorption performance, and a polymerizable group, so that it is copolymerized with other polymerizable monomers.
  • the polymer thus obtained is useful as a material for an intraocular lens.
  • 6 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: NBZ-EMA) in which the dye compound obtained in Example 17 is blended in Polymer Synthesis Example 1.
  • 10 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: HBZ-EMA) in which the dye compound obtained in Example 18 is blended in Polymer Synthesis Example 1.
  • 6 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: MBZ-EAC) in which the dye compound obtained in Example 23 is blended in Polymer Synthesis Example 1.
  • Example 10 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: EBZ-PEM) in which the dye compound obtained in Example 12 is blended in Polymer Synthesis Example 1.
  • 6 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: HBZ-PHM) in which the dye compound obtained in Example 34 is blended in Polymer Synthesis Example 1.
  • Polymer Synthesis Example 2 it is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: NBZ-EMA) in which the dye compound obtained in Example 17 is blended.
  • polymer synthesis example 2 it is a chart showing the ultraviolet visible absorption spectrum of the polymer sheet (polymerizable ultraviolet absorption dye: HBZ-EMA) which mix
  • 14 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: MBZ-EAC) in which the dye compound obtained in Example 23 is blended in Polymer Synthesis Example 2.
  • 10 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet (polymerizable ultraviolet absorbing dye: EBZ-PEM) in which the dye compound obtained in Example 12 is blended in Polymer Synthesis Example 2.
  • polymer synthesis example 2 it is a chart showing the ultraviolet visible absorption spectrum of the polymer sheet (polymerizable ultraviolet absorption pigment
  • the present invention relates to a diazotization step in which a polymerizable group-containing aminoaryl compound is diazotized to obtain a diazonium salt, a diazonium salt obtained in the diazotization step and a benzophenone compound are diazocoupled, and represented by the general formula (1). And a diazo coupling step for obtaining a compound to be produced.
  • a weak base is used as a catalyst.
  • the compound produced by the production method of the present invention is represented by the following general formula (1).
  • R 1 represents a hydrogen atom, a hydroxy group, a carboxy group, an alkyl group, an alkoxy group having 1 to 8 carbon atoms, a sulfonic acid group or a benzyl group having 1 to 8 carbon atoms
  • R 2 Is a hydrogen atom, a hydroxy group or an alkoxy group having 1 to 4 carbon atoms
  • R 3 is a group selected from the groups represented by the following general formulas (2) to (7).
  • R 4 is a hydrogen atom or a methyl group
  • m is an integer of 0 to 4
  • n is an integer of 1 to 8. Since the compound represented by the general formula (1) obtained by the production method of the present invention has, in its molecule, a benzophenone skeleton having an ultraviolet absorption capability, an azobenzene skeleton having a blue region light absorption capability, and a polymerizable group, Polymers obtained by copolymerization with other polymerizable monomers are useful as materials for intraocular lenses.
  • the ultraviolet absorption performance refers to the performance of suppressing the transmission of ultraviolet rays (wavelength of about 380 nm or less), and the blue region light absorption performance refers to light in the blue region (wavelength of about 380 to 500 nm).
  • the polymerizable group is a group having an unsaturated double bond at the end, and examples thereof include an acryloyloxy group, a methacryloyloxy group, an acryloylamino group, a methacryloylamino group, and a vinyl group.
  • the substituent R 1 is preferably a hydrogen atom, a methyl group or an ethyl group from the viewpoint of reaction efficiency in the production method.
  • the substituent R 2 is preferably a hydrogen atom, a hydroxy group, a methoxy group or an ethoxy group, and more preferably a hydroxy group.
  • the substituent R 3 is preferably a group represented by the general formula (2) or (3).
  • the substituent R 4 is a hydrogen atom or a methyl group, and m is preferably an integer of 0 to 2 from the viewpoint of the stability of the dye compound, and n is 1 to An integer of 4 is preferable.
  • the substituent R 3 is preferably bonded to the 3rd or 4th position of the azophenyl group.
  • the substituent R 3 is optionally a spacer on a polymerizable group such as a (meth) acryloyloxy group or a (meth) acryloylamino group, as represented by the general formulas (2) to (7). Is a bonded group and participates in copolymerization.
  • Examples thereof include an alkylene group, an alkylene group having 1 to 8 aminocarbonyl carbon atoms, and an alkylene group having 1 to 8 carbon atoms and an amino group having 1 to 8 carbon atoms.
  • the alkylene having 1 to 4 carbon atoms specifically means methylene, ethylene, propylene, or butylene, and the alkylene having 1 to 8 carbon atoms further includes pentylene in addition to the aforementioned alkylene having 1 to 4 carbon atoms.
  • Hexylene, heptylene and octylene are added to the candidates. By introducing these spacers, the dye compound of the present invention has a high reaction rate with other polymerizable monomers and a high solubility.
  • the diazotization step in the production method of the present invention is a step of diazotizing the polymerizable group-containing aminoaryl compound to obtain a diazonium salt.
  • the polymerizable group-containing aminoaryl compound used in the present invention is represented by the following general formula (9),
  • R 3 is the same group as described above, and R is a hydrogen atom or a protecting group.
  • amino-substituted aromatic compound those in which the amino group is substituted with a protecting group such as a t-butoxycarbonyl group can be used.
  • amino-substituted aromatic alkenes such as 4-aminostyrene and 4-allylaniline can also be used as the polymerizable group-containing aminoaryl compound.
  • (meth) acrylic acid means acrylic acid or methacrylic acid. Thereafter, the same display is used.
  • (meth) acryloyl is used in the meaning of acryloyl or methacryloyl
  • (meth) acrylate is used in the meaning of acrylate or methacrylate.
  • Examples of the polymerizable group-containing aminoaryl compound or amino-substituted aromatic alkene obtained by the esterification reaction or amidation reaction of a-1) to h-2) include the following.
  • N- (4-aminophenyl) (meth) acrylamide N-[(4-aminophenyl) methyl] (meth) acrylamide, N- [2- (4-aminophenyl) ethyl] (meth) acrylamide, N- [ 3- (4-aminophenyl) propyl] (meth) acrylamide, N- [4- (4-aminophenyl) butyl] (meth) acrylamide, N-[(3-aminophenyl) methyl] (meth) acrylamide, N -[2- (3-aminophenyl) ethyl] (meth) acrylamide, N- [3- (3-aminophenyl) propyl] (meth) acrylamide, or N- [4- (3-aminophenyl) butyl] ( (Meth) acrylamide.
  • the diazotizing agent sodium nitrite or sodium nitrite aqueous solution, potassium nitrite or potassium nitrite aqueous solution, isoamyl nitrite, and / or nitrosyl sulfuric acid (sulfuric acid solution) can be used.
  • the amount of the diazotizing agent is not particularly limited, but is preferably 1.00 to 1.20 mol, more preferably 1.02 to 1.10 mol, per mol of the polymerizable group-containing aminoaryl compound. preferable.
  • the reaction temperature in the diazotization step is in the range of ⁇ 78 ° C.
  • the diazotization step is preferably carried out under neutral to acidic conditions, and an acid such as hydrochloric acid can be appropriately added to the reaction solvent.
  • an acid such as hydrochloric acid
  • the diazonium salt of the polymerizable aryl group-containing aminoaryl compound that has undergone the above diazotization step is subsequently bonded to a benzophenone compound described later in the diazo coupling step, and becomes a polymerizable ultraviolet absorbing dye that is the target product.
  • the diazo coupling step in the production method of the present invention is a step in which the diazonium salt obtained in the diazotization step and a benzophenone compound are subjected to a diazo coupling reaction.
  • the diazo coupling step needs to be performed under weak base conditions.
  • a strong base such as sodium hydroxide, triethylamine, dimethylaminopyridine or the like usually employed as a catalyst
  • a polymerizable group-containing aminoaryl compound is used.
  • the present inventor has found a new problem that the ester or amide structure contained in the diazonium salt is decomposed and the target product is hardly obtained.
  • the weak base used in the present invention is a salt composed of a strong alkali and a weak acid, and means that its aqueous solution does not hydrolyze the ester bond at 1 atm, 0 ° C. to 25 ° C., and includes sodium carbonate, sodium hydrogen carbonate, Examples thereof include potassium carbonate, sodium acetate and potassium acetate.
  • the amount of weak base used is preferably 4.0 to 10.0 moles, more preferably 6.0 to 8.0 moles per mole of diazonium salt in terms of sodium equivalent. .
  • the reaction temperature of the diazo coupling reaction is in the range of ⁇ 10 ° C. to 10 ° C., and more preferably in the range of ⁇ 5 ° C. to 5 ° C.
  • reaction solvent in the diazo coupling reaction examples include organic solvents (alcohol solvents such as methanol, ethanol and isopropyl alcohol, amides such as N, N-dimethylacetamide, N, N-dimethylformamide and 1-methyl-2-pyrrolidone).
  • organic solvents such as methanol, ethanol and isopropyl alcohol
  • amides such as N, N-dimethylacetamide, N, N-dimethylformamide and 1-methyl-2-pyrrolidone.
  • Solvents such as sulfolane, sulfoxide solvents such as dimethyl sulfoxide, ureido solvents such as tetramethylurea, halogen solvents such as dichloromethane, chloroform, 1,2-dichloroethane, ester solvents such as ethyl acetate and butyl acetate, diethyl Ether solvents such as ether and tetrahydrofuran, pyridine solvents such as pyridine, ⁇ -picoline and 2,6-lutidine, etc.) alone or as a mixed system of a plurality of types, or in addition, a mixed system of an organic solvent and water and a single water system Can be used But is preferably an alcoholic solvent in these, It is also preferred to use a mixture of water thereto. Furthermore, depending on the reaction, in addition to the alcohol solvent and water, an amide solvent, ester solvent and ether solvent may be added and used.
  • the benzophenone compound used in the diazo coupling step of the present invention is represented by the following general formula (8):
  • R 1 and R 2 are the same groups as described above.
  • Examples thereof include 2-hydroxybenzophenone and 2-hydroxy-4-substituted benzophenone, wherein the substituent at the 4-position is a hydroxy group or an alkoxy group having 1 to 4 carbon atoms.
  • Specific examples include 2-hydroxybenzophenone, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-ethoxybenzophenone, 2-hydroxy-4-propoxybenzophenone, 2-hydroxy-4- Butoxybenzophenone, 2,2'-dihydroxybenzophenone, 2,2 ', 4-trihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4-ethoxybenzophenone, 2,2' -Dihydroxy-4-propoxybenzophenone or 2,2'-dihydroxy-4-butoxybenzophenone can be mentioned.
  • 2-hydroxybenzophenone or 2-hydroxy-4-substituted-benzophenone is preferable in terms of availability of raw materials, and 2-hydroxybenzophenone, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone or 2-hydroxybenzophenone Hydroxy-4-ethoxybenzophenone is more preferred.
  • the polymerizable ultraviolet absorbing dye obtained by the method of the present invention is copolymerized with another polymerizable monomer to give a polymer having both ultraviolet absorption performance and blue region light absorption performance.
  • Such polymers are particularly suitable as materials for intraocular lenses.
  • the polymerizable UV-absorbing dye obtained by the method of the present invention is 0.001 to 5 parts by mass with respect to 100 parts by mass of all the polymerizable monomers constituting the polymer, such as other polymerizable monomers described later.
  • the amount is preferably 0.005 to 2 parts by mass, and more preferably 0.01 to 0.06 parts by mass. If the blending ratio of the polymerizable dye is less than 0.001 part by mass, the blue region light absorption performance of the finally obtained polymer is not sufficient, and if it exceeds 5 parts by mass, the polymer is highly colored. Thus, the transparency is lowered and the physical properties (for example, strength) of the lens are lowered, and the unreacted polymerizable ultraviolet absorbing dye tends to be eluted after polymerization.
  • the “other polymerizable monomer” is not particularly limited as long as it is a known monomer used as an ophthalmic lens material.
  • Styrene pentafluorostyrene, methylstyrene, trimethylstyrene, trifluoromethylstyrene, (pentamethyl-3,3-bis (trimethylsiloxy) trisiloxanyl) styrene, (hexamethyl-3-trimethylsiloxytrisiloxanyl) styrene, dimethylaminostyrene Styrene derivatives such as;
  • Vinyl lactams such as N-vinylpyrrolidone, ⁇ -methylene-N-methylpyrrolidone, N-vinylcaprolactam, N- (meth) acryloylpyrrolidone; (Meth) acrylamide, N-methyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-hydroxyethyl (meth) acrylamide, N, N-dimethyl (meth) acrylamide, N, N-diethyl (meth) acrylamide, (Meth) acrylamides such as N-ethyl-N-aminoethyl (meth) acrylamide;
  • Aminoalkyl (meth) acrylates such as aminoethyl (meth) acrylate, N-methylaminoethyl (meth) acrylate, N, N-dimethylaminoethyl (meth) acrylate;
  • Alkoxy group-containing (meth) acrylates such as methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, and methoxydiethylene glycol (meth) acrylate;
  • Aromatic ring-containing (meth) acrylates such as benzyl (meth) acrylate and 2- (phenoxy) ethyl (meth) acrylate; Alkyl esters optionally substituted with alkyl groups such as itaconic acid, crotonic acid, maleic acid, fumaric acid, fluorine-containing alkyl groups, and siloxanyl alkyl groups; Glycidyl (meth) acrylate; And so on.
  • alkyl (meth) acrylates impart good transparency, refractive index and hardness to the polymer as an intraocular lens material.
  • Aromatic ring-containing (meth) acrylates and styrene derivatives are appropriately used to impart a high refractive index to the polymer.
  • Silicon-containing (meth) acrylates and silicon-containing styrenes impart good oxygen permeability to polymers as intraocular lens materials, and fluorine-containing (meth) acrylates impart antilipid contamination to polymers.
  • Hydroxy group-containing (meth) acrylates, (meth) acrylamides, aminoalkyl (meth) acrylates, and alkoxy group-containing (meth) acrylates impart hydrophilicity to the polymer.
  • a known polymerizable UV absorber mainly absorbing the UV portion
  • polymerization Sexual dyes hose that absorb the light mainly in the blue region without UV absorption ability
  • the combined use of these polymerizable ultraviolet absorbers and polymerizable dyes makes it possible to finely adjust the balance between the ultraviolet absorption performance and the blue region light absorption performance of the finally obtained polymer.
  • polymerizable ultraviolet absorbers that can be used in combination for this purpose include benzophenone-based polymerizable ultraviolet absorbers disclosed in JP-A No.
  • polymerizable dye polymerizable group-containing azo, anthraquinone, nitro and phthalocyanine type polymerizable dyes disclosed in JP-A-10-251537 can be used.
  • a known crosslinking agent is added to make the polymer into a three-dimensional crosslinked structure. , Increase the strength and hardness of the polymer, and impart durability (chemical resistance, heat resistance, solvent resistance) as an intraocular lens material.
  • a polyfunctional monomer having two or more polymerizable groups in the molecule can be used.
  • monomers include ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, dipropylene glycol di (meth) acrylate, Allyl (meth) acrylate, vinyl (meth) acrylate, trimethylolpropane tri (meth) acrylate, methacryloyloxyethyl acrylate, divinylbenzene, diallyl phthalate, diallyl adipate, triallyl isocyanurate, ⁇ -methylene-N-vinylpyrrolidone, etc. Can be given.
  • crosslinking agents are preferably used in a proportion of 0.01 to 10 parts by mass with respect to 100 parts by mass of all monomer mixtures to be polymerized. If the blending ratio is less than 0.01 part by mass, the effect is difficult to obtain, and if it exceeds 10 parts by mass, the resulting lens tends to be brittle.
  • Polymerization may be performed by a known polymerization method such as bulk polymerization or solution polymerization, but bulk polymerization is preferred because a high-purity polymer can be obtained.
  • a radical polymerization initiator is appropriately used, and temperature rising polymerization can be employed as necessary.
  • radical polymerization initiator examples include known azobisisobutyronitrile, azobisdimethylvaleronitrile, benzoyl peroxide, t-butyl hydroperoxide, cumene hydroperoxide, and the like, one or two of these. The above is selected and used. The amount used is preferably in the range of about 0.01 to 1 part by mass with respect to 100 parts by mass of the total monomer mixture to be subjected to polymerization. In the case of polymerization using light or the like, it is preferable to further add a photopolymerization initiator or a sensitizer.
  • An intraocular lens is obtained by copolymerizing the polymerizable UV-absorbing dye obtained by the method of the present invention in a mold having a predetermined shape together with the other polymerizable monomer and performing post-processing such as cutting and polishing as necessary. Materials can be obtained.
  • the concentrated residue was purified by silica gel column chromatography using hexane-ethyl acetate (2: 1 v / v) and then hexane-ethyl acetate (1: 1 v / v) to obtain the desired product as white prism crystals.
  • Ammonium chloride (183 mg) and iron powder (573 mg) were added and refluxed at 80 ° C. for 4 hours.
  • the iron powder was collected by filtration and concentrated with a rotary evaporator. Water and ethyl acetate were added, extraction operation was performed, and washing was performed with water and saturated brine. The extract was dried over sodium sulfate, and the desiccant was collected by filtration, followed by concentration, and the target product was obtained as a pale red oil.
  • N- [2- (4-Nitrophenyl) ethyl] methacrylamide (1.20 g) was then dissolved in ethanol (15 mL) and water (5 mL).
  • Ammonium chloride (364 mg) and iron powder (933 mg) were added and refluxed at 80 ° C. for 4 hours.
  • the iron powder was collected by filtration and concentrated with a rotary evaporator. Water and ethyl acetate were added, extraction operation was performed, and washing was performed with water and saturated brine. The extract was dried over sodium sulfate, and the desiccant was collected by filtration, followed by concentration, and the target product was obtained as a pale red oil.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] methacrylamide (609 mg) was acid-treated and then diazonium salified to give 2-hydroxybenzophenone (396 mg) and diazo Coupling was performed to obtain the target product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] methacrylamide (609 mg) was acid-treated and then diazonium salified to give 2,4-dihydroxybenzophenone (428 mg). Diazo coupling was performed to obtain the target product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] methacrylamide (609 mg) was subjected to acid treatment followed by diazonium chloride to give 2-hydroxy-4-methoxybenzophenone ( 456 mg) and diazo coupling to obtain the desired product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] methacrylamide (609 mg) was subjected to acid treatment followed by diazonium chloride to give 4-ethoxy-2-hydroxybenzophenone ( 485 mg) and diazo coupling were performed to obtain the desired product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] acrylamide (581 mg) was acid-treated and then diazonium-chlorinated to give 2-hydroxybenzophenone (396 mg) and diazocup Ringing was performed to obtain the target product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] acrylamide (581 mg) was acid-treated and then diazonium salified with 2,4-dihydroxybenzophenone (428 mg). Diazo coupling was performed to obtain the target product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] acrylamide (581 mg) was acid-treated and then diazonium salified to give 2-hydroxy-4-methoxybenzophenone (456 mg). ) And diazo coupling to obtain the desired product.
  • N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] acrylamide (581 mg) was subjected to acid treatment followed by diazonium chloride to give 4-ethoxy-2-hydroxybenzophenone (485 mg). ) And diazo coupling to obtain the desired product.
  • N- [4- (tert-butoxycarbonylamino) benzyl] methacrylamide 581 mg was acid-treated and then diazonium chloride, and 2,4-dihydroxybenzophenone (428 mg) was combined with diazo coupling.
  • the target product was obtained.
  • N- [4- (tert-butoxycarbonylamino) benzyl] methacrylamide (581 mg) was acid-treated and then diazonium-chlorinated to give 2-hydroxy-4-methoxybenzophenone (456 mg) and diazocup Ringing was performed to obtain the target product.
  • N- (4-aminobenzyl) methacrylamide (574 mg) was added 1M hydrochloric acid (9 mL), and a solution of sodium nitrite (210 mg) in water (3 mL) was added dropwise with ice cooling, followed by stirring at 4 ° C. for 1 hour.
  • a diazonium salt was prepared.
  • 2,4-dihydroxybenzophenone (637 mg) was dissolved in ethanol (25 mL), and a solution of sodium carbonate (644 mg) in water (25 mL) was added.
  • a solution containing the above diazonium salt was added dropwise to the mixture under ice cooling. The mixture was stirred at 4 ° C.
  • 2- (4-aminophenyl) ethanol (2.74 g) was dissolved in 1N hydrochloric acid (60 mL), and a solution of sodium nitrite (1.41 g) in water (20 mL) was added dropwise under ice cooling. This mixture was stirred at 4 ° C. for 1 hour to form a diazonium salt.
  • a solution of 2,4-dihydroxybenzophenone (4.28 g) in 1N sodium hydroxide (80 mL) was cooled to 4 ° C., and a previously prepared diazonium salt solution was added dropwise over 30 minutes. The mixture was stirred at 4 ° C.
  • a solution of sodium nitrite (1.41 g) in water (10 mL) was added dropwise to a solution of 2- (4-aminophenyl) ethanol (2.74 g) in 1M hydrochloric acid (60 mL) under ice cooling. This mixture was stirred at 4 ° C. for 40 minutes to form a diazonium salt. This diazonium salt was added dropwise to a solution of 2-hydroxy-4-methoxybenzophenone (4.52 g) in 1M sodium hydroxide (80 mL) under ice cooling. The mixture was stirred at 4 ° C. for 1 hour and then at room temperature for 4 hours.
  • the light transmittance at a wavelength of 220 to 800 nm was measured.
  • the results are shown in FIGS.
  • the sample lens was immersed in ethanol at 40 ° C. for 24 hours for elution treatment, and the light transmittance was measured again.
  • the spectrum did not change before and after the elution treatment.
  • the dye compound of the present invention is used in combination with other UV absorbers for polymer synthesis, It was confirmed that no elution occurred.
  • the light transmittance was measured using an ultraviolet-visible spectrophotometer (hereinafter the same).
  • the carbamoyl derivative HBZ-AMA had the same level of solubility (0.2%) as the target compound BMAC.
  • MBZ-AMA which is a carbamoyl derivative of monohydroxybenzophenone, showed 0.5% higher solubility than the former two compounds.
  • the carbonyloxy derivatives EBZ-EMA and HBZ-EMA had 10 times the solubility (2%) of BMAC, and MBZ-PEM had 50 times the solubility (10%) of BMAC.
  • HBZ-PHM (1 part by weight) and methyl methacrylate (26 parts by weight) are charged into a mixed solvent of dioxane (52 parts by weight), N, N-dimethylformamide (22 parts by weight) and water (20 parts by weight). Then, 2.4 parts by weight of 2,2′-azobis (2,4-dimethylvaleronitrile) was added and polymerized at 75 ° C. for 5 hours under an argon atmosphere to obtain an HBZ-PHM copolymer.
  • the filtrate after the alkali treatment of the HBZ-PHM copolymer transmits light of any wavelength, and even when the pH is set to 12 or more by the alkali treatment, the dye component is not liberated from the copolymer. It was confirmed that the polymer was more stable with respect to pH change than the polymer and hardly affected by pH change.
  • the polymerizable ultraviolet-absorbing dye produced by the production method of the present invention is useful for use as a material for an intraocular lens because of its properties. However, it goes without saying that it can also be used for other purposes. Specifically, it can also be used when a pigment is deposited on a contact lens, sunglasses, glasses or the like.
  • the polymerizable ultraviolet-absorbing dye produced by the production method of the present invention which is superior in solubility compared to those used in the prior art, is useful because it has a high degree of freedom to be applied to uses other than intraocular lenses. It can be said that it is a new material.

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Abstract

La présente invention concerne un nouveau procédé de fabrication pouvant obtenir un colorant absorbant les UV polymérisable à haut rendement, et une lentille intraoculaire obtenue par la copolymérisation d'un colorant absorbant les UV polymérisable, qui est obtenu à l'aide dudit procédé de fabrication, avec un autre monomère polymérisable. L'invention concerne un procédé de fabrication d'un colorant absorbant les UV polymérisable comprenant : une étape de diazotation permettant de diazoter un composé aminoaryle contenant un groupe polymérisable ; et une étape de diazocouplage permettant de diazocoupler le sel diazonium obtenu dans ladite étape de diazotisation avec un composé benzophénone spécifié à l'aide d'une base faible comme catalyseur.
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WO2018177329A1 (fr) * 2017-03-29 2018-10-04 东莞东阳光科研发有限公司 Composé colorant polymérisable et procédé pour sa préparation et polymère contenant un colorant et utilisation correspondante
CN109641855A (zh) * 2016-11-30 2019-04-16 东莞东阳光科研发有限公司 偶氮化合物、聚合物和它们的制备方法及用途
WO2022039120A1 (fr) 2020-08-21 2022-02-24 富士フイルム株式会社 Composition polymérisable, polymère, matériau de protection contre les ultraviolets, stratifié, composé, agent absorbant les ultraviolets et procédé de production d'un composé

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JPH0588120A (ja) * 1991-09-27 1993-04-09 Tokyo Keikaku:Kk ソフトコンタクトレンズ
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WO2013162042A1 (fr) * 2012-04-27 2013-10-31 興和株式会社 Colorant absorbant les uv stable et polymérisable pour lentille intraoculaire

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JPH02232056A (ja) * 1988-09-16 1990-09-14 Menikon:Kk 眼用レンズ用重合性紫外線吸収性色素並びにそれを用いた眼用レンズ材料
JPH0588120A (ja) * 1991-09-27 1993-04-09 Tokyo Keikaku:Kk ソフトコンタクトレンズ
JP2012508171A (ja) * 2008-11-04 2012-04-05 アルコン，インコーポレイテッド 眼用レンズ材料のための紫外線／可視光吸収剤
JP2013517296A (ja) * 2010-01-18 2013-05-16 ノバルティス アーゲー 眼科用レンズの材料のための可視光吸収剤
WO2012057096A1 (fr) * 2010-10-25 2012-05-03 株式会社メニコン Colorant azoïque, matériau de lentilles oculaires, procédé de production de matériau de lentilles oculaires et lentilles oculaires
WO2013162042A1 (fr) * 2012-04-27 2013-10-31 興和株式会社 Colorant absorbant les uv stable et polymérisable pour lentille intraoculaire

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109641855A (zh) * 2016-11-30 2019-04-16 东莞东阳光科研发有限公司 偶氮化合物、聚合物和它们的制备方法及用途
CN109641855B (zh) * 2016-11-30 2022-04-29 东莞东阳光医疗智能器件研发有限公司 偶氮化合物、聚合物和它们的制备方法及用途
WO2018177329A1 (fr) * 2017-03-29 2018-10-04 东莞东阳光科研发有限公司 Composé colorant polymérisable et procédé pour sa préparation et polymère contenant un colorant et utilisation correspondante
WO2022039120A1 (fr) 2020-08-21 2022-02-24 富士フイルム株式会社 Composition polymérisable, polymère, matériau de protection contre les ultraviolets, stratifié, composé, agent absorbant les ultraviolets et procédé de production d'un composé

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