JPWO2015064675A1 - Method for producing polymerizable ultraviolet absorbing dye - Google Patents

Abstract

（一般式（１）中、Ｒ¹は、水素原子、ヒドロキシ基、カルボキシ基、炭素数１〜８のアルキル基、炭素数１〜８のアルコキシ基、スルホン酸基またはベンジルオキシ基であり、Ｒ²は水素原子、ヒドロキシ基、または炭素数１〜４のアルコキシ基であり、Ｒ³は、下記式（２）で表される。）

（一般式（２）中、Ｒ⁴は水素原子またはメチル基である。また、Ｒ⁵は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基である。）
出発物質又は中間体として、下記式（３）又は（４）に記載の化合物を用いる方法による。

（一般式（３）中、Ｒ⁶は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基である。）

（一般式（４）中、Ｒ⁷は水素原子またはメチル基である。また、Ｒ⁸は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基である。）A production method for synthesizing a novel compound represented by the following general formula (1) is provided.

(In the general formula (1), 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, and R ³ is represented by the following formula (2).)

(In the general formula (2), R ⁴ is a hydrogen atom or a methyl group. R ⁵ is a C 1-4 alkylene group which may have a single bond or a substituent.)
According to a method using a compound described in the following formula (3) or (4) as a starting material or an intermediate.

(In the general formula (3), R ⁶ is an alkylene group of a single bond or a substituent having 1 to 4 carbon atoms which may have a.)

(In General Formula (4), R ⁷ is a hydrogen atom or a methyl group. R ⁸ is a C 1-4 alkylene group which may have a single bond or a substituent.)

Description

  The present invention relates to a method for producing a novel polymerizable ultraviolet-absorbing dye that is suitably used for an intraocular lens.

Cataract is a disease in which the entire visual field is fogged by turbidity and pigment formation and deposition in the lens. As a treatment method thereof, an operation is generally performed in which an opaque lens is removed and an intraocular lens (IOL) is inserted and placed in the lens capsule. Many of the intraocular lens materials used for treatment are acrylic or silicon-based polymers, and in particular, polymethyl methacrylate (PMMA) has been used for some time.
However, the original crystalline lens has the property of not transmitting ultraviolet rays, whereas the conventional polymer for intraocular lenses transmits ultraviolet rays, so there is a risk of damaging the retina.

In addition, the original crystalline lens is slightly yellowish and has a property of suppressing transmission of part of light in the blue region. However, conventional transparent polymers for intraocular lenses transmit this blue region light almost completely, so there are many cases in which patients complain of glare after intraocular lens insertion. There is also a risk of causing retina-derived diseases such as macular degeneration when blue light with high energy at a short wavelength reaches the eye.
In view of this, materials for intraocular lenses have been required to be colored with ultraviolet absorptive ability or yellow pigments. In recent years, from the viewpoint of safety, many polymers for intraocular lenses include ultraviolet absorber monomers and yellow pigment monomers. Are copolymerized. Various such monomer compounds have been developed so far (Patent Documents 1 to 4), and other intraocular lens materials having a chromophore such as an azo group and an ultraviolet absorbing portion such as a benzophenone skeleton in one molecule. Monomer compounds that can be copolymerized with other monomers have also been developed (Patent Documents 5 and 6).

Japanese Patent No. 2658980 JP-A-10-251537 Japanese Patent Publication No. 7-28911 Japanese Patent No. 2604799 Japanese Unexamined Patent Publication No. Hei 2-232056 JP 2006-291006 A

The polymerizable ultraviolet-absorbing dye monomers described in Patent Documents 5 and 6 have poor stability against pH change, particularly stability under alkaline conditions, and the dye sites (chromophores and UV-absorbing parts) are easily detached from the polymer. There is a problem. In particular, in the case of an intraocular lens material having a long intraocular implantation period, the risk of detachment of the pigment site is further increased.
Therefore, an object of the present invention is to obtain a polymerizable ultraviolet-absorbing dye monomer that is stable even under alkaline conditions.

In response to such a problem, the present inventors have found that a polymerizable ultraviolet-absorbing dye monomer compound represented by the following general formula (1) can solve the above problem, and filed an international application (PCT / JP2013 / 062537). ). The present invention provides a new method for producing a polymerizable ultraviolet absorbing dye monomer compound represented by the following general formula (1).
That is, the first embodiment of the present invention is as follows.

A method for producing a compound represented by the following general formula (1),
This is a production method using a compound represented by the following general formula (3) as a starting material or an intermediate.

（一般式（１）中、Ｒ¹は、水素原子、ヒドロキシ基、カルボキシ基、炭素数１〜８のアルキル基、炭素数１〜８のアルコキシ基、スルホン酸基またはベンジルオキシ基であり、好ましくは水素原子、メチル基又はエチル基である。Ｒ²は水素原子、ヒドロキシ基、または炭素数１〜４のアルコキシ基であり、好ましくは水素原子、ヒドロキシ基、メトキシ基、またはエトキシ基である。Ｒ³は、下記式（２）で表される。）

(In general formula (1), 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, preferably Is a hydrogen atom, a methyl group or an ethyl group, and R ² is a hydrogen atom, a hydroxy group or an alkoxy group having 1 to 4 carbon atoms, preferably a hydrogen atom, a hydroxy group, a methoxy group or an ethoxy group. R ³ is represented by the following formula (2).)

（一般式（２）中、Ｒ⁴は水素原子またはメチル基である。また、Ｒ⁵は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基であり、好ましくは置換基を有さない炭素数１〜４のアルキレン基である。）

(In general formula (2), R ⁴ is a hydrogen atom or a methyl group. R ⁵ is a single bond or an alkylene group having 1 to 4 carbon atoms which may have a substituent, preferably a substituted group. (It is a C1-C4 alkylene group which does not have a group.)

（一般式（３）中、Ｒ⁶は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基である。）

(In the general formula (3), R ⁶ is an alkylene group of a single bond or a substituent having 1 to 4 carbon atoms which may have a.)

The second embodiment of the present invention is as follows.
A method for producing a compound represented by the general formula (1),
The manufacturing method using the compound represented by following General formula (4) as a starting material or an intermediate body.

（一般式（４）中、Ｒ⁷は水素原子またはメチル基である。また、Ｒ⁸は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基である。）

(In General Formula (4), R ⁷ is a hydrogen atom or a methyl group. R ⁸ is a C 1-4 alkylene group which may have a single bond or a substituent.)

Further, a diazo compound obtained by diazo coupling a diazonium salt obtained from the compound represented by the general formula (3) and / or the general formula (4) and a benzophenone compound to obtain the compound represented by the general formula (1). A coupling step.
In the diazo coupling step, a weak base is preferably used as the catalyst, and the weak base is preferably selected from sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium acetate and potassium acetate.

  According to this invention, the novel manufacturing method of the compound represented by General formula (1) is provided. 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. Thus, a polymer can be obtained, and the polymer is useful as a material for an intraocular lens.

3 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet obtained in Production Example 1. FIG. 6 is a chart showing an ultraviolet-visible absorption spectrum of a polymer sheet obtained in Production Example 2. It is a chart showing the ultraviolet visible absorption spectrum of the filtrate after alkali-treating a polymer.

Hereinafter, the present invention will be described in detail.
<1> Dye compound produced by the production method of the present invention The dye compound produced by the production method of the present invention is represented by the following general formula (1).

In the general formula (1), R ¹ represents a hydrogen atom, a hydroxyl group, a carboxyl 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. Among these, a hydrogen atom, a methyl group, or an ethyl group is preferable from the viewpoint of reaction efficiency in production.
In general formula (1), R < ² > is a hydrogen atom, a hydroxy group, or a C1-C4 alkoxy group. Among these, a hydrogen atom, a hydroxy group, a methoxy group, or an ethoxy group is preferable from the viewpoint of reaction efficiency in production, and a hydroxy group is particularly preferable from the viewpoint of light absorption characteristics.
As shown in the general formula (1), the dye compound of the present invention has a benzophenone skeleton and an azobenzene skeleton, and these are dye parts.
In the general formula (1), R ³ is represented by the following formula (2).

In the general formula (2), R ⁴ is a hydrogen atom or a methyl group.
In the general formula (2), R ⁵ is a single bond or a substituent alkylene group of good 1 to 4 carbon atoms have, preferably no substituents alkylene group having 1 to 4 carbon atoms is there. A C1-C4 alkylene group specifically means a methylene group, an ethylene group, a propylene group, or a butylene group. Such an alkylene group may or may not have a substituent, and in the case of having a substituent, an alkylene group having 1 to 2 carbon atoms, a halogen group, a carboxyl group, or a carboxy carbon atom having 1 to 2 carbon atoms. The aspect which substituents, such as a 2 alkyl group, a hydroxy group, a C1-C2 hydroxyalkyl group, an amino group, a C1-C2 aminoalkyl group, has couple | bonded is mentioned.
Thus, the substituent R ³ is a group in which a spacer is bonded to the polymerizable group (meth) acryloylamino group, and is a site involved in copolymerization in the dye compound of the present invention. Due to the structure represented by the general formula (2), the dye compound of the present invention has a property of high reaction efficiency with other polymerizable monomers.
In addition, (meth) acryloyl means acryloyl or methacryloyl.
In the general formula (1), the substituent R ³ is preferably bonded to the 3rd or 4th position of the azophenyl group.

  Although the pigment | dye compound of this invention represented by General formula (1) is not specifically limited, For example, what has a structure shown by the following (1-1)-(1-16) is mention | raise | lifted preferably.

The dye compound represented by the general formula (1) has, in one molecule, a benzophenone skeleton (ultraviolet absorption part) having ultraviolet absorption capability and an azobenzene skeleton (chromophore) having blue region light absorption capability. Due to the presence of these dye sites, the dye compound of the present invention has the performance (light absorption characteristics) of suppressing transmission in the ultraviolet region (wavelength 380 nm or less) and the blue region (wavelength 380 to 500 nm). The dye compound of the present invention is a conventional dye compound (for example, 2,4-dihydroxy-5- (4- (2- (N-2-methacryloyloxyethyl) carbamoyloxy) ethylphenylazo) described in Patent Document 6). Compared to benzophenone (BMAC)), it has more excellent light absorption characteristics. Specifically, when an ultraviolet-visible absorption spectrum is measured, the rise of the chart appears sharply around 420 to 500 nm, and the light transmission suppression ability in the ultraviolet / blue region is excellent.
In addition, since the dye compound represented by the general formula (1) has an ultraviolet absorbing portion and a chromophore (collectively referred to as a dye moiety) in one molecule, the chromophore is damaged by ultraviolet rays, and the dye fades over time. It is difficult to occur.
In the dye compound represented by the general formula (1), the polymerizable group and the dye part are connected by an amide bond. Since such a bond is stable even under alkaline conditions, the dye moiety is not detached from the polymer of the present invention described later. As a result, the stability under alkaline conditions, which is poor with conventional dye compounds having ester bonds and copolymers using the same, is realized.

  A first embodiment according to the production method of the present invention is characterized by using a compound represented by the following general formula (3) as a starting material or an intermediate.

一般式（３）中、Ｒ⁶は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基であり、アルキレン基の具体例は、メチレン基、エチレン基、プロピレン基、ブチレン基である。

In the general formula (3), R ⁶ is an alkylene group of a single bond or a substituent having 1 to 4 carbon atoms which may have a specific example of the alkylene groups include methylene, ethylene, propylene, butylene It is a group.

  Moreover, the second embodiment according to the production method of the present invention is characterized by using a compound represented by the following general formula (4) as a starting material or an intermediate.

一般式（４）中、Ｒ⁷は水素原子またはメチル基である。また、Ｒ⁸は単結合又は置換基を有していてもよい炭素数１〜４のアルキレン基であり、アルキレン基の具体例は、メチレン基、エチレン基、プロピレン基、ブチレン基である。

In the general formula (4), R ⁷ is a hydrogen atom or a methyl group. Also, R ⁸ is an alkylene group of a single bond or a substituent having 1 to 4 carbon atoms which may have a specific example of the alkylene groups include methylene, ethylene, propylene, butylene group.

(Synthesis method 1)
In the first embodiment according to the production method of the present invention, a nitroaryl compound represented by the general formula (3) is used as a starting material or an intermediate, and an acrylic acid compound or a methacrylic acid compound is amidated to this. The amidation step in which a polymerizable group is introduced by reaction, a reduction step in which the nitro group of the resulting polymerizable nitroaryl compound is reduced to an amino group, and the resulting polymerizable aminoaryl compound is diazotized to obtain a diazonium salt A diazotization step and a diazo coupling step of diazo coupling the obtained diazonium salt with a benzophenone compound to obtain a dye compound represented by the general formula (1) may be included.

(Synthesis method 2)
In the second embodiment of the production method of the present invention, the polymerizable nitroaryl compound represented by the general formula (4) is used as a starting material or an intermediate, and the nitro group of the polymerizable nitroaryl compound is A reduction step of reducing to an amino group, a diazotization step of diazotizing the obtained polymerizable aminoaryl compound to obtain a diazonium salt, and diazo coupling of the obtained diazonium salt with a benzophenone compound are represented by the general formula (1). A diazo coupling step to obtain a dye compound to be prepared.
The outline of the synthesis methods 1 and 2 is shown in the following reaction formula. In the formula, R ′ represents a hydroxy group or a halogen atom, and R ^{1 to} R ⁸ represent the same substituents as described above.

  In addition, in the production method of the present invention, the aliphatic amine of a nitroaryl compound having an aminoalkyl group is substituted with an appropriate protecting group, the nitro group is reduced to an amino group, and then the aminoamine in which the aliphatic amine is protected. A diazotization step to diazotize a compound to obtain a diazonium salt, a diazo coupling step to obtain a diazo compound by diazo coupling the obtained diazonium salt and a benzophenone compound, a deprotection to remove the protecting group of the aliphatic amine by acid treatment, etc. It can also be produced by a synthesis method including a step and an amidation step in which an acrylic acid compound or a methacrylic acid compound is reacted with the obtained diazo compound by an amidation reaction to introduce a polymerizable group.

In addition, the diazotization process in each synthetic method mentioned above can be performed by a well-known method.
As 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. to 50 ° C., preferably in the range of −20 ° C. to 20 ° C., and more preferably in the range of −20 ° C. to 10 ° 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.

The diazo coupling step in the synthesis method is preferably carried out under weak base conditions using a weak base as a catalyst. This is because the amide structure contained in the diazonium salt of the polymerizable aminoaryl compound is decomposed or eliminated by a strong base such as sodium hydroxide or potassium hydroxide generally used in the diazo coupling reaction. When the yield decreases, the use of a weak base can remarkably suppress the decomposition and ensure sufficient reactivity, and as a result, the reaction yield can be dramatically increased. is there. Furthermore, the vinyl group contained in the diazonium salt is also known to polymerize in the presence of the strong base as described above, which causes a significant decrease in yield, but a weak base can be used instead of the strong base. This is because this can also be suppressed.
The weak base used here is a salt composed of a strong alkali and a weak acid, and its aqueous solution does not hydrolyze an amide bond at 1 atm, 0 ° C. to 25 ° C., and does not cause a vinyl group polymerization reaction. Without being limited, it is preferable to use a weak base such as sodium carbonate, sodium bicarbonate, potassium carbonate, sodium acetate or potassium acetate. The amount of the 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. Moreover, the reaction temperature in a diazo coupling process is the range of -10 degreeC-10 degreeC, and it is more preferable that it is the range of -5 degreeC-5 degreeC.

  Examples of the reaction solvent in the diazo coupling step include organic solvents (alcohol solvents such as methanol, ethanol, isopropyl alcohol, amides such as N, N-dimethylacetamide, N, N-dimethylformamide, and 1-methyl-2-pyrrolidone). Solvents, sulfolane 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, α-picoline and 2,6-lutidine, etc.) alone or as a mixed system of a plurality of types, or further, a mixed system of an organic solvent and water and a single water system Can be used , Alcohol solvents are preferable 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 nitroaryl compound is represented by (i) in the above reaction formula. The polymerizable nitroaryl compound is represented by the same (ii), the polymerizable aminoaryl compound is represented by the same (iii), and the benzophenone compound is represented by the same (vi). It is what is done.

The polymerizable aminoaryl compound or polymerizable nitroaryl compound is an amino-substituted aromatic amine or an amidation reaction between a nitro-substituted aromatic amine and (meth) acrylic acid, an amino-substituted aromatic alkylamine or a nitro-substituted aromatic alkylamine. An amidation reaction of (meth) acrylic acid with an amino-substituted aromatic amine or nitro-substituted aromatic amine and (meth) acrylic acid chloride, an amino-substituted aromatic alkylamine or a nitro-substituted aromatic alkylamine It can be obtained by an amidation reaction with (meth) acrylic acid chloride.
In the amino-substituted aromatic compound, the amino group is t-butoxycarbonyl group, benzyloxycarbonyl group, 9-fluorenylmethyloxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, allyloxycarbonyl group, p -The thing substituted by protecting groups, such as a toluenesulfonyl group and 2-nitrobenzenesulfonyl group, can be used.

Examples of the polymerizable aminoaryl compound include N- (4-aminophenyl) (meth) acrylamide, N-[(4-aminophenyl) methyl] (meth) acrylamide, and 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, N- [4- ( 3-aminophenyl) butyl] (meth) acrylamide and the like.
Examples of the polymerizable nitroaryl compound include N- (4-nitrophenyl) (meth) acrylamide, N-[(4-nitrophenyl) methyl] (meth) acrylamide, and N- [2- (4-nitrophenyl). ) Ethyl] (meth) acrylamide, N- [3- (4-nitrophenyl) propyl] (meth) acrylamide, N- [4- (4-nitrophenyl) butyl] (meth) acrylamide, N-[(3- Nitrophenyl) methyl] (meth) acrylamide, N- [2- (3-nitrophenyl) ethyl] (meth) acrylamide, N- [3- (3-nitrophenyl) propyl] (meth) acrylamide, N- [4 -(3-nitrophenyl) butyl] (meth) acrylamide and the like.

In the production method of the present invention, a synthesis method in which an amidation step is performed before the diazo coupling step as in the synthesis method 1 or the synthesis method 2 is preferable. This is because generation of by-products can be avoided. As a result, according to synthesis method 1 or synthesis method 2, the reaction efficiency is good, and the dye compound of the present invention can be obtained in a high yield.
The nitroaryl compound used as a starting material in the synthesis method 1 is less expensive than the aminoaryl compound. Furthermore, in the amidation reaction, when a polymerizable group is introduced, a by-product in which two molecules of the polymerizable group are introduced with respect to the amino group is formed, but this occurs when a nitroaryl compound is amidated. Removal of by-products is easier than when, for example, an aminoaryl compound is amidated. Therefore, when the viewpoint of such economical efficiency and easy operation is taken into consideration, the production method of the present invention is advantageous as compared with the conventional method.
The production method of the present invention enables industrial production of the compound represented by the general formula (1), and can be used as a useful dye or a polymerizable ultraviolet absorbing dye monomer.

<2> Polymer The dye compound represented by the general formula (1) can be copolymerized with one or more other copolymerization monomers to form a polymer.
The dye compound represented by the general formula (1) does not inhibit polymerization because the chromophore and the polymerizable group are sterically separated. Therefore, it can be used as a copolymerizable monomer having good reactivity with other copolymerizable monomers.
Although it will not restrict | limit especially as said other copolymerization monomer if it is normally used, For example, the following are mentioned.

Methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, butyl (meth) acrylate, tert-butyl (meth) acrylate, isobutyl (meth) acrylate, pentyl (meth) acrylate, tert-pentyl (meth) acrylate, hexyl (meth) acrylate, heptyl (meth) acrylate, octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, dodecyl (meth) Linear, branched and cyclic such as acrylate, stearyl (meth) acrylate, cyclopentyl (meth) acrylate, cyclohexyl (meth) acrylate, phenoxy (meth) acrylate Alkyl (meth) acrylates;
Pentamethyldisiloxanylmethyl (meth) acrylate, pentamethyldisiloxanylpropyl (meth) acrylate, methylbis (trimethylsiloxy) silylpropyl (meth) acrylate, tris (trimethylsiloxy) silylpropyl (meth) acrylate, mono ( Methylbis (trimethylsiloxy) siloxy) bis (trimethylsiloxy) silylpropyl (meth) acrylate, tris (methylbis (trimethylsiloxy) siloxy) silylpropyl (meth) acrylate, methylbis (trimethylsiloxy) silylpropylglyceryl (meth) acrylate, tris ( Trimethylsiloxy) silylpropylglyceryl (meth) acrylate, mono (methylbis (trimethylsiloxy) siloxy) bis (trimethylsiloxy) Rupropylglyceryl (meth) acrylate, trimethylsilylethyltetramethyldisiloxanylpropylglyceryl (meth) acrylate, trimethylsilylmethyl (meth) acrylate, trimethylsilylpropyl (meth) acrylate, trimethylsilylpropyl glyceryl (meth) acrylate, pentamethyldisiloxa Nylpropylglyceryl (meth) acrylate, methylbis (trimethylsiloxy) silylethyltetramethyldisiloxanylmethyl (meth) acrylate, tetramethyltriisopropylcyclotetrasiloxanylpropyl (meth) acrylate, tetramethyltriisopropylcyclotetrasiloxybis Silicon-containing (meth) acrylates such as (trimethylsiloxy) silylpropyl (meth) acrylate Kind;
Trifluoroethyl (meth) acrylate, tetrafluoropropyl (meth) acrylate, pentafluoropropyl (meth) acrylate, hexafluoroisopropyl (meth) acrylate, tetrafluoro-tert-pentyl (meth) acrylate, hexafluorobutyl (meth) acrylate , Hexafluoro-tert-hexyl (meth) acrylate, octafluoropentyl (meth) acrylate, 2,3,4,5,5,5-hexafluoro-2,4-bis (trifluoromethyl) pentyl (meth) acrylate , Dodecafluoroheptyl (meth) acrylate, 2-hydroxyoctafluoro-6-trifluoromethylheptyl (meth) acrylate, 2-hydroxydodecafluoro-8-trifluoromethylnonyl (meth) ) Acrylate, fluorine-containing (meth) acrylates such as 2-hydroxy-hexadecafluoro-10-trifluoromethyl undecyl (meth) acrylate;
Styrene, pentafluorostyrene, methylstyrene, trimethylstyrene, trifluoromethylstyrene, (pentamethyl-3,3-bis (trimethylsiloxy) trisiloxanyl) styrene, (hexamethyl-3-trimethylsiloxytrisiloxanyl) styrene, dimethylaminostyrene Styrene derivatives such as;
Hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, hydroxybutyl (meth) acrylate, dihydroxypropyl (meth) acrylate, dihydroxybutyl (meth) acrylate, diethylene glycol mono (meth) acrylate, triethylene glycol mono (meth) acrylate Hydroxy group-containing (meth) acrylates such as dipropylene glycol mono (meth) acrylate;
(Meth) acrylic acid;

Vinyl lactams such as N-vinylpyrrolidone, α-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, methoxydiethylene glycol (meth) acrylate;
Aromatic ring-containing (meth) acrylates such as benzyl (meth) acrylate;
Alkyl esters that may be 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;
Tetrahydrofurfuryl (meth) acrylate;
4-vinylpyridine;
Heterocyclic N-vinyl monomers such as vinylimidazole, N-vinylpiperidone, N-vinylpiperidine, N-vinylsuccinimide;
N- (meth) acryloylpiperidine;
N- (meth) acryloylmorpholine.

“(Meth) acrylate” means “acrylate” or “methacrylate”, and the same applies to (meth) acrylic acid derivatives.
Alternatively, one or more of the above copolymerization monomers may be selected and polymerized to form a macromonomer, which may be used as one of the copolymerization monomers for polymer production.

The polymer of the dye compound represented by the general formula (1) is prepared by blending the dye compound represented by the general formula (1) and one or more other copolymerization monomers in an arbitrary amount. After mixing, it can be obtained by copolymerization.
In the copolymerization of the polymer of the dye compound represented by the general formula (1), the proportion of the dye compound represented by the general formula (1) is the thickness of the polymer application, for example, an intraocular lens. Although it is influenced also, it is preferable that it is 0.001-5 weight part with respect to 100 weight part of all the copolymerization monomer mixtures, It is more preferable that it is 0.005-2 weight part, More preferably, it is -0.06 weight part. If it is less than 0.001 part by weight, the color of the polymer may be deteriorated. On the other hand, when the amount exceeds 5 parts by weight, the color of the polymer becomes too dark and the transparency is lowered, the physical properties (for example, strength) of the polymer are lowered, or the dye compound of the present invention is easily eluted from the polymer. There is a risk of

  The polymer of the dye compound represented by the general formula (1) can be synthesized by a method usually performed in the technical field. For example, the dye compound represented by the general formula (1) and one or more other copolymerization monomers are uniformly mixed, and a polymerization initiator is added as necessary, and the temperature is from room temperature to about 130 ° C. Polymerization can be carried out by gradually heating in the temperature range or by irradiating electromagnetic waves such as microwaves, ultraviolet rays and radiation (gamma rays). For the polymerization, various methods commonly used by those skilled in the art, such as radical polymerization, bulk polymerization, or solvent polymerization, can be employed. In the case of heat polymerization, the temperature is raised stepwise. You may let them.

  Examples of the polymerization initiator include azobisisobutyronitrile, azobisdimethylvaleronitrile, 2,2′-azobis (2,4-dimethylvaleronitrile), benzoyl peroxide, tert-butyl hydroperoxide, cumene hydro Radical polymerization initiators such as peroxide and benzoyl peroxide can be mentioned, and one or more of these can be used. The amount used is preferably in the range of about 0.01 to 1 part by weight with respect to 100 parts by weight of all the comonomer mixture. Moreover, when superposing | polymerizing using a light etc., it is preferable to add a photoinitiator and a sensitizer further.

When synthesizing the polymer of the dye compound represented by the general formula (1), a known polymerizable ultraviolet absorber (mainly absorbing the ultraviolet part) or a polymerizable dye (mainly blue having no ultraviolet absorption ability) That absorb the light in the region) or a polymerizable ultraviolet-absorbing dye can be used in combination. The combined use of these polymerizable UV absorbers, polymerizable dyes and polymerizable UV absorbing dyes makes it possible to finely adjust the balance between the UV absorption performance and the blue region light absorption performance of the finally obtained polymer. In particular, when the polymer of the dye compound represented by the general formula (1) is used as a material for an intraocular lens as described later, the color tone of the intraocular lens is adjusted or the ultraviolet absorbing ability is sufficiently imparted. In addition, such a combination is useful.
The addition amount is preferably adjusted to be 0.01 parts by weight or more, more preferably 0.05 parts by weight or more with respect to 100 parts by weight of all the comonomer mixture, and a sufficient polymerization rate and degree of polymerization. Is preferably adjusted to 5 parts by weight or less, more preferably 3 parts by weight or less with respect to 100 parts by weight of all copolymerization monomers.

  Examples of the polymerizable ultraviolet absorber that can be used in combination for the above purpose include, for example, a benzophenone-based polymerizable ultraviolet absorber disclosed in Japanese Patent Application Laid-Open No. 2003-253248 and a benzotriazole-based polymerizable ultraviolet absorber disclosed in Japanese Patent No. 2685980. Can be used. Specific examples include, for example, 2-hydroxy-4- (meth) acryloyloxybenzophenone, 2-hydroxy-4- (meth) acryloyloxy-5-t-butylbenzophenone, 2-hydroxy-4- (meth) acryloyloxy. Benzophenone-based polymerizable ultraviolet absorbers such as -2 ', 4'-dichlorobenzophenone, 2-hydroxy-4- (2'-hydroxy-3'-(meth) acryloyloxypropoxy) benzophenone; 2- (2'-hydroxy -5 ′-(meth) acryloyloxyethylphenyl) -2H-benzotriazole, 2- (2′-hydroxy-5 ′-(meth) acryloyloxyethylphenyl) -5-chloro-2H-benzotriazole, 2- ( 2'-hydroxy-5 '-(meth) acryloyloxypropylphenyl) -2H- Benzotriazole, 2- (2′-hydroxy-5 ′-(meth) acryloyloxypropyl-3′-t-butylphenyl) -5-chloro-2H-benzotriazole, 2- (2′-hydroxy-5′- (2 "-methacryloyloxyethoxy) -3'-t-butylphenyl) -5-methyl-2H-benzotriazole and other benzotriazole-based polymerizable UV absorbers; 2-hydroxy-4-methacryloyloxymethylbenzoate phenyl and the like Salicylic acid derivative-based polymerizable UV absorbers; 2-cyano-3-phenyl-3- (3 ′-(meth) acryloyloxyphenyl) propenyl acid methyl ester, etc. These may be used alone or in combination of two or more. Can be used.

Examples of polymerizable dyes that can be used in combination for the above purpose include azo-type, anthraquinone-type, nitro-type, and phthalocyanine-type polymerizable dyes disclosed in JP-A-10-251537. These can be used alone or in admixture of two or more.
Specific examples of the polymerizable azo dye include, for example, 1-phenylazo-4- (meth) acryloyloxynaphthalene, 1-phenylazo-2-hydroxy-3- (meth) acryloyloxynaphthalene, 1-naphthylazo-2-hydroxy. -3- (Meth) acryloyloxynaphthalene, 1- (α-anthrylazo) -2-hydroxy-3- (meth) acryloyloxynaphthalene, 1-((4 ′-(phenylazo) -phenyl) azo) -2-hydroxy -3- (meth) acryloyloxynaphthalene, 1- (2 ′, 4′-xylylazo) -2- (meth) acryloyloxynaphthalene, 1- (o-tolylazo) -2- (meth) acryloyloxynaphthalene, 2- (M- (Meth) acryloylamide-anilino) -4,6-bis (1 ′-(o-tolyl) Zo) -2'-naphthylamino) -1,3,5-triazine, 2- (m-vinylanilino) -4- (4'-nitrophenylazo) -anilino) -6-chloro-1,3,5- Triazine, 2- (1 ′-(o-tolylazo) -2′-naphthyloxy) -4- (m-vinylanilino) -6-chloro-1,3,5-triazine, 2- (p-vinylanilino) -4 -(1 '-(o-tolylazo) -2'naphthylamino) -6-chloro-1,3,5-triazine, N- (1'-(o-tolylazo) -2'-naphthyl) -3-vinylphthal Acid monoamide, N- (1 ′-(o-tolylazo) -2′-naphthyl) -6-vinylphthalic acid monoamide, 3-vinylphthalic acid- (4 ′-(p-sulfophenylazo) -1′-naphthyl) mono Ester, 6-vinylphthalic acid- (4 ′-(p- Ruphophenylazo) -1′-naphthyl) monoester, 3- (meth) acryloylamide-4-phenylazophenol, 3- (meth) acryloylamide-4- (8′-hydroxy-3 ′, 6′-disulfo-1) '-Naphthylazo) -phenol, 3- (meth) acryloylamide-4- (1'-phenylazo-2'-naphthylazo) -phenol, 3- (meth) acryloylamide-4- (p-tolylazo) phenol, 2- Amino-4- (m- (2′-hydroxy-1′-naphthylazo) anilino) -6-isopropenyl-1,3,5-triazine, 2-amino-4- (N-methyl-p- (2 ′ -Hydroxy-1'-naphthylazo) anilino) -6-isopropenyl-1,3,5-triazine, 2-amino-4- (m- (4'-hydroxy-1'-pheny) Azo) anilino) -6-isopropenyl-1,3,5-triazine, 2-amino-4- (N-methyl-p- (4′-hydroxyphenylazo) anilino) -6-isopropenyl-1,3 , 5-triazine, 2-amino-4- (m- (3′-methyl-1′-phenyl-5′-hydroxy-4′-pyrazolylazo) anilino) -6-isopropenyl-1,3,5- Triazine, 2-amino-4- (N-methyl-p- (3′-methyl-1′-phenyl-5′-hydroxy-4′-pyrazolylazo) anilino) -6-isopropenyl-1,3,5 -Triazine, 2-amino-4- (p-phenylazoanilino) -6-isopropenyl-1,3,5-triazine, 4-phenylazo-7- (meth) acryloylamide-1-naphthol, etc. .

  Specific examples of the polymerizable anthraquinone dye include 1,5-bis ((meth) acryloylamino) -9,10-anthraquinone, 1- (4′-vinylbenzoylamide) -9,10-anthraquinone, 4 -Amino-1- (4'-vinylbenzoylamide) -9,10-anthraquinone, 5-amino-1- (4'-vinylbenzoylamide) -9,10-anthraquinone, 8-amino-1- (4 ' -Vinylbenzoylamide) -9,10-anthraquinone, 4-nitro-1- (4'-vinylbenzoylamide) -9,10-anthraquinone, 4-hydroxy-1- (4'-vinylbenzoylamide) -9, 10-anthraquinone, 1- (3′-vinylbenzoylamide) -9,10-anthraquinone, 1- (2′-vinylbenzoylamide) -9, 0-anthraquinone, 1- (4′-isopropenylbenzoylamide) -9,10-anthraquinone, 1- (3′-isopropenylbenzoylamide) -9,10-anthraquinone, 1- (2′-isopropenylbenzoylamide) ) -9,10-anthraquinone, 1,4-bis (4′-vinylbenzoylamide) -9,10-anthraquinone, 1,4-bis (4′-isopropenylbenzoylamide) -9,10-anthraquinone, 1 , 5′-bis (4′-vinylbenzoylamide) -9,10-anthraquinone, 1,5-bis (4′-isopropenylbenzoylamide) -9,10-anthraquinone, 1-methylamino-4- (3 '-Vinylbenzoylamide) -9,10-anthraquinone, 1-methylamino-4- (4'-vinylbenzoyloxye) Ruamino) -9,10-anthraquinone, 1-amino-4- (3′-vinylphenylamino) -9,10-anthraquinone-2-sulfonic acid, 1-amino-4- (4′-vinylphenylamino)- 9,10-anthraquinone-2-sulfonic acid, 1-amino-4- (2′-vinylbenzylamino) -9,10-anthraquinone-2-sulfonic acid, 1-amino-4- (3 ′-(meth)) Acryloylaminophenylamino) -9,10-anthraquinone-2-sulfonic acid, 1-amino-4- (3 ′-(meth) acryloylaminobenzylamino) -9,10-anthraquinone-2-sulfonic acid, 1- ( β-ethoxycarbonylallylamino) -9,10-anthraquinone, 1- (β-carboxyallylamino) -9,10-anthraquinone, 1,5-di- ( β-carboxyallylamino) -9,10-anthraquinone, 1- (β-isopropoxycarbonylallylamino) -5-benzoylamide-9,10-anthraquinone, 2- (3 ′-(meth) acryloylamide-anilino) -4- (3 '-(3 "-sulfo-4" -aminoanthraquinone-1 "-yl) -amino-anilino) -6-chloro-1,3,5-triazine, 2- (3'-(meta ) Acryloylamido-anilino) -4- (3 '-(3 "-sulfo-4" -aminoanthraquinone-1 "-yl) -amino-anilino) -6-hydrazino-1,3,5-triazine, 2, 4-bis-((4 "-methoxyanthraquinone-1" -yl) -amino) -6- (3'-vinylanilino) -1,3,5-triazine, 2- (2'-vinylphenoxy) -4- (4 '-(3 “-Sulfo-4” -aminoanthraquinone-1 ”-yl-amino) -anilino) -6-chloro-1,3,5-triazine and the like.

Specific examples of the polymerizable nitro dye include o-nitroanilinomethyl (meth) acrylate and the like.
Specific examples of the polymerizable phthalocyanine dye include (meth) acryloylated tetraamino copper phthalocyanine, (meth) acryloylated (dodecanoylated tetraamino copper phthalocyanine), and the like.

  Specific examples of polymerizable UV-absorbing dyes that can be used in combination for the above purpose include, for example, 2,4-dihydroxy-3 (p-styrenoazo) benzophenone, 2,4-dihydroxy-5- (p-styrenoazo). ) Benzophenone, 2,4-dihydroxy-3- (p- (meth) acryloyloxymethylphenylazo) benzophenone, 2,4-dihydroxy-5- (p- (meth) acryloyloxymethylphenylazo) benzophenone, 2,4 -Dihydroxy-3- (p- (meth) acryloyloxyethylphenylazo) benzophenone, 2,4-dihydroxy-5- (p- (meth) acryloyloxyethylphenylazo) benzophenone, 2,4-dihydroxy-3- ( p- (Meth) acryloyloxypropylphenylazo) benzof Non, 2,4-dihydroxy-5- (p- (meth) acryloyloxypropylphenylazo) benzophenone, 2,4-dihydroxy-3- (o- (meth) acryloyloxymethylphenylazo) benzophenone, 2,4- Dihydroxy-5- (o- (meth) acryloyloxymethylphenylazo) benzophenone, 2,4-dihydroxy-3- (o- (meth) acryloyloxyethylphenylazo) benzophenone, 2,4-dihydroxy-5- (o -(Meth) acryloyloxyethylphenylazo) benzophenone, 2,4-dihydroxy-3- (o- (meth) acryloyloxypropylphenylazo) benzophenone, 2,4-dihydroxy-5- (o- (meth) acryloyloxy Propylphenylazo) benzofe 2,4-dihydroxy-3- (p- (N, N-di (meth) acryloyloxyethylamino) phenylazo) benzophenone, 2,4-dihydroxy-5- (p- (N, N-di (meta ) Acryloyloxyethylamino) phenylazo) benzophenone, 2,4-dihydroxy-3- (o- (N, N-di (meth) acryloyloxyethylamino) phenylazo) benzophenone, 2,4-dihydroxy-5- (o-) (N, N-di (meth) acryloylethylamino) phenylazo) benzophenone, 2,4-dihydroxy-3- (p- (N-ethyl-N- (meth) acryloyloxyethylamino) phenylazo) benzophenone, 2,4 -Dihydroxy-5- (p- (N-ethyl-N- (meth) acryloyloxyethylamino) fur Enylazo) benzophenone, 2,4-dihydroxy-3- (o- (N-ethyl-N- (meth) acryloyloxyethylamino) phenylazo) benzophenone, 2,4-dihydroxy-5- (o- (N-ethyl-) N- (meth) acryloyloxyethylamino) phenylazo) benzophenone, 2,4-dihydroxy-3- (p- (N-ethyl-N- (meth) acryloylamino) phenylazo) benzophenone, 2,4-dihydroxy-5 (P- (N-ethyl-N- (meth) acryloylamino) phenylazo) benzophenone, 2,4-dihydroxy-3- (o- (N-ethyl-N- (meth) acryloylamino) phenylazo) benzophenone, 2, 4-dihydroxy-5- (o- (N-ethyl-N- (meth) acryloylamino) ) Phenylazo) and benzophenone type polymerizable ultraviolet absorbing dyes such as benzophenone, 2-hydroxy-4-(p-Suchirenoazo) benzoic acid type polymerizable ultraviolet absorbing dyes phenyl benzoate and the like. These can be used alone or in admixture of two or more.

In addition, a crosslinking agent is blended at the time of copolymerization of the polymer of the dye compound represented by the general formula (1), or a macromonomer having two or more polymerizable groups in the molecule is used as the copolymerization monomer. Thus, a three-dimensional crosslinked structure can be formed in the obtained polymer. Thereby, the mechanical strength and hardness of the polymer can be improved, and the elution of the monomer (including the dye compound of the present invention) from the polymer can be suppressed. In addition, when the polymer of the dye compound represented by the general formula (1) is used as a material for an intraocular lens as described later, an intraocular lens having a uniform, transparent, and distortion-free optical property can be obtained. In addition, durability (chemical resistance, heat resistance, solvent resistance) can be imparted to the intraocular lens.
When a crosslinking agent or a macromonomer is blended, the blending ratio is preferably within a range of 0.01 to 10 parts by weight per 100 parts by weight of all copolymer monomer mixtures. If it is less than 0.01 part by weight, the effect is difficult to obtain, and if it exceeds 10 parts by weight, the resulting polymer tends to be brittle.

  Examples of the macromonomer as described above include butanediol di (meth) acrylate, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, and propylene glycol di (meth). ) Acrylate, dipropylene glycol di (meth) acrylate, diallyl fumarate, allyl (meth) acrylate, vinyl (meth) acrylate, trimethylolpropane tri (meth) acrylate, methacryloyloxyethyl (meth) acrylate, divinylbenzene, diallyl phthalate , Diallyl adipate, triallyl diisocyanate, α-methylene-N-vinylpyrrolidone, 4-vinylbenzyl (meth) acrylate, 3-vinylbenzyl ) Acrylate, 2,2-bis ((meth) acryloyloxyphenyl) hexafluoropropane, 2,2-bis ((meth) acryloyloxyphenyl) propane, 1,4-bis (2- (meth) acryloyloxyhexafluoro) Isopropyl) benzene, 1,3-bis (2- (meth) acryloyloxyhexafluoroisopropyl) benzene, 1,2-bis (2- (meth) acryloyloxyhexafluoroisopropyl) benzene, 1,4-bis (2- (Meth) acryloyloxyisopropyl) benzene, 1,3-bis (2- (meth) acryloyloxyisopropyl) benzene, 1,2-bis (2- (meth) acryloyloxyisopropyl) benzene and the like.

Further, by selecting an appropriate copolymerization monomer, various functionalities can be imparted to the polymer of the dye compound represented by the general formula (1).
In the case where oxygen permeability is imparted to the polymer of the dye compound represented by the general formula (1), silicon-containing monomers such as silicon-containing (meth) acrylates and silicon-containing styrene derivatives and fluorine-containing alkyl ( What is necessary is just to select meth) acrylates.
When increasing the strength of the polymer or adjusting the hardness, alkyl (meth) acrylates, styrene derivatives including styrene, (meth) acrylic acid, or the like may be selected as a copolymerization monomer.
When a fluorine-containing monomer such as fluorine-containing alkyl (meth) acrylates or fluorine-containing styrene derivatives is selected as a copolymerization monomer, the anti-lipid contamination function is obtained when the polymer of the present invention is used as a material for an intraocular lens as described later. Can be provided.

When imparting hydrophilicity to the polymer of the dye compound represented by the general formula (1), hydroxy (meth) acrylates, (meth) acrylamides, aminoalkyl (meth) acrylates, (meth) are used as copolymerization monomers. Monomers having a hydrophilic group such as acrylates and N-vinyl lactams may be selected. When the polymer of the dye compound represented by the general formula (1) is used as a material for an intraocular lens as described later, water content is contained. A flexible intraocular lens can be obtained.
If a monomer containing an aromatic ring, such as a styrene monomer or an aromatic ring-containing (meth) acrylate, is selected as a copolymerization monomer, the polymer of the present invention can be used as a lens material having a high refractive index. .
When the copolymerization monomer for imparting various functionalities to the polymer of the dye compound represented by the general formula (1) is selected and blended as described above, with respect to 100 parts by weight of all the copolymerization monomer mixture Is preferably 0.01 parts by weight or more, more preferably 0.05 parts by weight or more, and preferably 5 parts by weight or less, and more preferably 3 parts by weight or less, with respect to 100 parts by weight of all copolymerization monomer mixtures. Adjust as appropriate.

  As described above, since the dye compound represented by the general formula (1) has light absorption characteristics in the ultraviolet region (wavelength 380 nm or less) and the blue region (wavelength 380 to 500 nm), it is represented by the general formula (1). The polymer of the dye compound can block ultraviolet light and reduce the intensity of blue region light. Specifically, the light transmittance decreases from around 500 nm, and it is preferable that the light transmittance is 0% below 400 nm. More preferably, when an ultraviolet-visible absorption spectrum is measured, the rise of the chart appears sharply around 420 to 500 nm, and the light transmission suppression ability in the ultraviolet / blue region is superior to conventional dye compounds (such as BMAC). Furthermore, it is preferable to use another ultraviolet absorber so as not to transmit light having a wavelength of 400 nm or less. Therefore, when the material for an intraocular lens is used as will be described later, the adverse effect of light rays on the eye can be suppressed.

In the polymer of the dye compound represented by the general formula (1), since the dye compound represented by the general formula (1) is directly bonded to the polymer chain by copolymerization, the dye compound represented by the general formula (1) The dye compound represented by the general formula (1) does not elute from the polymer. This can be confirmed by the fact that the light transmittance spectrum does not change before and after the polymer of the dye compound represented by the general formula (1) is immersed in ethanol at 40 ° C. for 24 hours.
In addition, in the dye compound represented by the general formula (1) as described above, the amide bond that connects the polymerizable group and the dye portion is stable even under alkaline conditions (for example, pH 12 or higher). The dye portion is not detached from the polymer of the dye compound represented by As a result, stability under alkaline conditions, which was poor with conventional copolymers using dye compounds having an ester bond, is realized, and high light absorption characteristics are maintained even in polymers after alkali treatment. This can be confirmed by the fact that the light transmittance in the immersion liquid after immersion of the polymer of the present invention in 4N aqueous sodium hydroxide solution at room temperature for 4 hours is substantially 100%.

<3> Intraocular lens The polymer of the pigment compound represented by formula (1) can be used as an intraocular lens material.
In general, when a dye compound increases its hardness when added to a polymer, the dye compound represented by the general formula (1) is excellent in flexibility, so the polymer of the dye compound represented by the general formula (1) An intraocular lens molded using the material as an intraocular lens material can be expected to retain flexibility, and can be easily handled during treatment.
In addition, the polymer of the dye compound represented by the general formula (1) exhibits excellent resistance to light and chemical agents, has high fastness, and the dye part does not elute from the polymer. An excellent intraocular lens without decolorization or discoloration can be obtained.
In addition, the pigment compound represented by the general formula (1) can be used as a material for glasses, sunglasses, contact lenses, etc., and can also be used for paints, building materials, and the like.
In addition, the polymer of the dye compound represented by the general formula (1) has a chemically stable dye part, and is deteriorated even in an outdoor or harsh environment where temperature change and pH change are expected to be severe. It can be used without.

When the polymer of the dye compound represented by the general formula (1) is used as an intraocular lens material, it can be molded by a known method. For example, a polymerization reaction is performed in an appropriate mold or container to obtain a rod-like, block-like, or plate-like polymer, which is then processed into a desired shape by mechanical processing such as cutting or polishing, or desired shape A method of performing a polymerization reaction in a mold corresponding to the above to obtain a polymer molded product, and then mechanically finishing as required.
Further, the support portion of the intraocular lens may be manufactured separately from the intraocular lens and attached later, or may be molded simultaneously (integrally) with the intraocular lens.

  When the polymer of the dye compound represented by the general formula (1) is molded into an intraocular lens, a surface modification treatment may be performed as necessary to make the surface of the lens hydrophilic. Treatment or treatment with ultraviolet rays is preferred, and corona discharge treatment, glow discharge treatment or ultraviolet / ozone treatment is more preferred. As a processing apparatus and a processing method at that time, a conventionally known normal apparatus and method can be used.

2- (4-Nitrophenyl) ethylamine hydrochloride (1.72 g) and sodium hydrogen carbonate (5.00 g) were dissolved in water (25 mL), ethyl acetate (25 mL) was added, and the mixture was stirred in an ice bath. Thereto, methacryloyl chloride (1.79 g) was added dropwise. After stirring for 10 minutes, the mixture was extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and the desiccant was removed by suction filtration. Recrystallization was performed using a mixed solvent of hexane and ethyl acetate. N- [2- (4-nitrophenyl) ethyl] methacrylamide was obtained as yellowish white crystals. Yield was 1.25 g (63%). The obtained compound shows a spectral data of ^{1 H-NMR (400MHz, CDCl} 3).
δ: 1.93 (s, 3H), 2.99 (t, 2H, J = 6.8 Hz), 3.60 (q, 2H, J = 6.8 Hz), 5.32 (t, 1H, J = 1.2 Hz), 5.61 (s, 1H), 5.82 (br.s, 1H), 7.37 (d, 2H, J = 8.6 Hz), 8.17 (d, 2H, J = 8.6 Hz).
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. The yield was 1.01 g (97%). The obtained compound shows a spectral data of ^{1 H-NMR (400MHz, CDCl} 3).
δ: 1.91 (s, 3H), 2.74 (t, 2H, J = 6.8 Hz), 3.51 (q, 2H, J = 6.8 Hz), 3.61 (br.s, 2H) ), 5.27 (t, 1H, J = 1.4 Hz), 5.59 (s, 1H), 5.76 (br.s, 1H), 6.64 (d, 2H, J = 8.3 Hz) ), 6.98 (d, 2H, J = 8.3 Hz).

4-Nitrobenzylamine hydrochloride (1.51 g) and sodium bicarbonate (4.13 g) were dissolved in water (25 mL), ethyl acetate (25 mL) was added, and the mixture was stirred in an ice bath. Thereto, methacryloyl chloride (1.26 g) was added dropwise. After stirring for 10 minutes, the mixture was extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and the desiccant was removed by suction filtration. Thereafter, recrystallization was performed using a mixed solvent of hexane and ethyl acetate. N- (4-nitrobenzyl) methacrylamide was obtained as yellowish white crystals. The yield was 1.05 g (60%). The obtained compound shows a spectral data of ^{1 H-NMR (400MHz, CDCl} 3).
δ: 2.01 (s, 3H), 4.61 (d, 2H, J = 6.0 Hz), 5.41 (t, 1H, J = 1.0 Hz), 5.76 (t, 1H, J = 1.0 Hz), 6.29 (br.s, 1H), 7.45 (d, 2H, J = 8.8 Hz), 8.17 (d, 2H, J = 8.8 Hz).
N- (4-nitrobenzyl) methacrylamide (811 mg) was then dissolved in ethanol (12 mL) and water (4 mL). 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. Yield was 580 mg (89%). The obtained compound shows a spectral data of ^{1 H-NMR (400MHz, CDCl} 3).
δ: 1.97 (t, 3H, J = 1.3 Hz), 3.67 (br.s, 2H), 4.37 (d, 2H, J = 5.6 Hz), 5.31 (t, 1H) , J = 1.4 Hz), 5.68 (br.t, 1H), 5.92 (br.s, 1H), 6.65 (d, 2H, J = 8.3 Hz), 7.09 (d , 2H, J = 8.3 Hz).

<Synthesis of polymerizable ultraviolet absorbing dye>
A polymerizable ultraviolet absorbing dye was synthesized using the polymerizable aminoaryl compound synthesized as described above. Hereinafter, it shows as Example 1 and 2.

Example 1 Synthesis of 2,4-dihydroxy-5- [4- [2- (methacrylamide) ethyl] phenylazo] benzophenone (HBZ-PHM)

1-M hydrochloric acid (15 mL) was added to N- [2- (4-aminophenyl) ethyl] methacrylamide (930 mg), and a solution of sodium nitrite (355 mg) in water (5 mL) was added dropwise under ice cooling for 4 hours. The mixture was stirred at 0 ° C. to prepare a diazonium salt. Then, 2,4-dihydroxybenzophenone (975 mg) was dissolved in ethanol (40 mL), and a solution of sodium carbonate (970 mg) in water (40 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. for 1 hour and then at room temperature for 2 hours and the pH was adjusted to 6 by dropwise addition of 4M hydrochloric acid. Water (40 mL) was added to the mixture, and the precipitate was collected by filtration and washed with water. After drying, the product was dissolved in chloroform, adsorbed on silica gel, and purified by column chromatography with ethyl acetate to obtain orange crystals. Methanol was added to the crystals and refluxed, and the mixture was allowed to stand at room temperature overnight to obtain the precipitated target product as orange crystals. Yield was 774 mg (40%). The obtained compound shows a spectral data of ^{1 H-NMR (400MHz, CDCl} 3).
δ: 1.93 (t, 3H, J = 1.0 Hz), 2.94 (t, 2H, J = 6.8 Hz), 3.61 (q, 2H, J = 6.8 Hz), 5.31 (T, 1H, J = 1.0 Hz), 5.61 (t, 1H, J = 1.0 Hz), 5.81 (br.t, 1H), 6.58 (s, 1H), 7.33 (D, 2H, J = 8.5 Hz), 7.56 (t, 2H, J = 7.2 Hz), 7.64 (tt, 1H, J = 7.2 Hz, 2.4 Hz), 7.72− 7.76 (m, 4H), 8.22 (s, 1H), 12.89 (s, 1H), 13.93 (s, 1H).

Example 2 Synthesis of 5- [4- [2- (methacrylamido) methyl] phenylazo] -2-hydroxy-4-methoxybenzophenone (HBZ-BZM)

To N- (4-aminobenzyl) methacrylamide (574 mg), 1M hydrochloric acid (9 mL) was added, and a solution of sodium nitrite (210 mg) in water (3 mL) was added dropwise under ice cooling, followed by stirring at 4 ° C. for 1 hour. A diazonium salt was prepared. Then 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. for 1 hour and then at room temperature for 2 hours and the pH was adjusted to 6 by dropwise addition of 4M hydrochloric acid. Water (25 mL) was added to the mixture, and the precipitate was collected by filtration and washed with water. After drying, the product was dissolved in chloroform, adsorbed on silica gel, and purified by column chromatography with ethyl acetate to obtain orange crystals. Methanol was added to the crystals and refluxed, and the mixture was allowed to stand at room temperature overnight to obtain the precipitated target product as orange crystals. Yield was 370 mg (29%). The obtained compound shows a spectral data of ^{1 H-NMR (400MHz, CDCl} 3).
δ: 2.00 (t, 3H, J = 1.1 Hz), 4.57 (d, 2H, J = 6.0 Hz), 5.38 (t, 1H, J = 1.4 Hz), 5.73 (Br.t, 1H), 6.16 (br.s, 1H), 6.57 (s, 1H), 7.41 (d, 2H, J = 8.5 Hz), 7.56 (t, 2H) , J = 7.4 Hz), 7.63 (tt, 1H, J = 7.3 Hz, 2.4 Hz), 7.71-7.78 (m, 4H), 8.22 (s, 1H), 12 .88 (s, 1H), 13.89 (s, 1H).

<Examples of copolymerization of polymerizable UV-absorbing dye and other polymerizable monomer>
The polymerizable ultraviolet absorbing dye obtained in Example 1 was copolymerized with other polymerizable monomers.
[Production Example 1]
0.03 part by mass of the polymerizable ultraviolet absorbing dye (HBZ-PHM) obtained in Example 1, 60 parts by mass of 2-phenoxyethyl acrylate, 40 parts by mass of ethyl acrylate, 2,2′-azobis (2, 4-dimethylvaleronitrile) 0.5 parts by mass was uniformly mixed and polymerized at 80 ° C. for 40 minutes to prepare a polymer sheet having a thickness of 1 mm. Using the obtained polymer sheet as a sample, the light transmittance at a wavelength of 220 to 800 nm was measured. The results are shown in FIG.
Further, this sample was immersed in ethanol at 40 ° C. for 24 hours for elution treatment, and the light transmittance was measured again. As a result, the spectrum did not change before and after the elution treatment. This indicates that the polymerizable UV-absorbing dye is chemically bonded in the material. Even if 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).

<Examples of copolymerization with polymerizable UV-absorbing dye, polymerized UV absorber and other polymerizable monomers>
The polymerizable ultraviolet absorbing dye obtained in Example 1 was copolymerized with other polymerizable monomers together with other polymerizable ultraviolet absorbers.
[Production Example 2]
Further 0.15 parts by mass of 2- [2′-hydroxy-5 ′-(2 ″ -methacryloyloxyethoxy) -3′-t-butylphenyl] -5-methyl-2H-benzotriazole as an ultraviolet absorber A polymer sheet was produced in the same manner as in Production Example 1 except that. Using the obtained sheet as a sample, the light transmittance at a wavelength of 220 to 800 nm was measured in the same manner as in Production Example 1. The result is shown in FIG. The spectrum of light transmittance before and after the elution treatment does not change, and even if the polymerizable ultraviolet absorbing dye of the present invention is used in combination with other polymerizable ultraviolet absorbers, it is incorporated into the polymer as a copolymer component and polymerized. It was confirmed that it did not elute later.

<Stability comparison under alkaline conditions>
HBZ-PHM (1 part by weight) and methyl methacrylate (26 parts by weight) obtained in Reference Example 1 were mixed with dioxane (52 parts by weight), N, N-dimethylformamide (22 parts by weight) and water (20 parts by weight). Part) was added to the mixed solvent, 2.4 parts by weight of 2,2′-azobis (2,4-dimethylvaleronitrile) was added, and the mixture was polymerized at 75 ° C. for 5 hours in an argon atmosphere to produce an HBZ-PHM copolymer. Got.
As a control example, 2,4-dihydroxy-5- (4- (2- (N--N--N--N--N-- The polymerization reaction was similarly carried out using 2-methacryloyloxyethyl) carbamoyloxy) ethylphenylazo) benzophenone (BMAC) to obtain a BMAC copolymer.
After the Soxhlet extraction of the obtained copolymer powder with ethanol for 12 hours, the powdered polymer (200 mg) was suspended in ethanol (5 mL), 4N-NaOH (5 mL) was added, and the mixture was stirred at room temperature for 4 hours. . The test solution at this time was pH 12 to 14 with pH test paper. After completion of stirring, the mixture was neutralized with 4N HCl and further ethanol (15 mL) was added. When the insoluble material was removed by filtration and the filtrate was observed, the HBZ-PHM copolymer was colorless and transparent. On the other hand, in the BMAC copolymer, the filtrate was colored yellow. Furthermore, the result of having measured the light transmittance of wavelength 220-800nm of each filtrate is shown in FIG. The filtrate after alkali treatment of the BMAC copolymer showed the same transmittance pattern as that of the BMAC copolymer. This strongly suggests that the dye part of BMAC was detached from the copolymer by the alkali treatment. On the other hand, 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 released 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.

  According to the present invention, a novel method for producing a polymerizable UV-absorbing dye monomer that is stable even under alkaline conditions is provided. The dye compound provided by the production method has a benzophenone skeleton having ultraviolet absorption capability, an azobenzene skeleton having blue region light absorption capability, and a polymerizable group in its molecule, and therefore, it is copolymerized with other polymerizable monomers. Thus, the polymer is useful as a material for an intraocular lens.

Claims (5)

A method for producing a compound represented by the following general formula (1),
The manufacturing method using the compound represented by following General formula (3) as a starting material or an intermediate body.

(In the general formula (1), 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, and R ³ is represented by the following formula (2).)

(In the general formula (2), R ⁴ is a hydrogen atom or a methyl group. R ⁵ is a C 1-4 alkylene group which may have a single bond or a substituent.)

(In the general formula (3), R ⁶ is an alkylene group of a single bond or a substituent having 1 to 4 carbon atoms which may have a.) A method for producing a compound represented by the following general formula (1),
The manufacturing method using the compound represented by following General formula (4) as a starting material or an intermediate body.

(In the general formula (1), 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, and R ³ is represented by the following formula (2).)

(In the general formula (2), R ⁴ is a hydrogen atom or a methyl group. R ⁵ is a C 1-4 alkylene group which may have a single bond or a substituent.)

(In General Formula (4), R ⁷ is a hydrogen atom or a methyl group. R ⁸ is a C 1-4 alkylene group which may have a single bond or a substituent.)   A diazo cup obtained by diazo coupling a diazonium salt obtained from the compound represented by the general formula (3) and / or the general formula (4) with a benzophenone compound to obtain a compound represented by the general formula (1) The manufacturing method according to claim 1, comprising a ring step.   The production method according to claim 3, wherein a weak base is used as a catalyst in the diazo coupling step.   The said weak base is a manufacturing method of Claim 4 containing 1 or more types selected from sodium carbonate, sodium hydrogencarbonate, potassium carbonate, sodium acetate, and potassium acetate.

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