WO2015064674A1

WO2015064674A1 - Method for manufacturing polymerizable uv-absorbing dye

Info

Publication number: WO2015064674A1
Application number: PCT/JP2014/078851
Authority: WO
Inventors: 正宏田村; 隆英尾下
Original assignee: 興和株式会社
Priority date: 2013-10-30
Filing date: 2014-10-30
Publication date: 2015-05-07
Also published as: JPWO2015064674A1; JP6492367B2

Abstract

Provided are a novel manufacturing method capable of obtaining a polymerizable UV-absorbing dye in high yields, and an intraocular lens material obtained by copolymerizing a polymerizable UV-absorbing dye, which is obtained using said manufacturing method, with another polymerizable monomer. A method for manufacturing a polymerizable UV-absorbing dye comprising: a diazotization step for diazotizing a polymerizable group-containing aminoaryl compound; and a diazo-coupling step for diazo-coupling the diazonium salt obtained in said diazotization step with a specified benzophenone compound using a weak base as catalyst.

Description

Method for producing polymerizable ultraviolet absorbing dye

The present invention mainly relates to a method for producing a polymerizable ultraviolet absorbing dye for coloring an ophthalmic lens material.

When the lens becomes clouded due to cataracts, the entire field of view becomes foggy. As 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. As the intraocular lens material used for treatment, an acrylic or silicon polymer is used.

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.

In order to satisfy such a requirement, 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). ). In 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). Then, 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.

On the other hand, in 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.

Japanese Patent Laid-Open No. 2-232056 JP 2006-291006 A

In the synthesis method disclosed in Patent Document 1, an intermediate having one primary alcoholic hydroxy group and two phenolic hydroxy groups in the azo compound having a specific structure is passed through an ester condensation reaction in the next step, In addition to the target compound that has reacted with the primary alcoholic hydroxy group, many by-products have been generated that have reacted with the phenolic hydroxy group. As a result, there is a problem that the yield of the target compound is remarkably lowered.

On the other hand, although the method of 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. However, in this method, 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. As a result, a new problem has arisen in which 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.

That is, 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) A diazo coupling step to obtain a compound,
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.

(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 a group selected from the groups represented by the following general formulas (2) to (7). In 2) to (7), R ⁴ is a hydrogen atom or a methyl group, m is an integer of 0 to 4, and 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.

(In the formula, 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):

(Wherein R ³ is the same group as described above, and R is a hydrogen atom or a protecting group.)

One of the reactions shown below,
a-1) Esterification reaction between amino-substituted aromatic alcohol and (meth) acrylic acid, a-2) Esterification reaction between amino-substituted aromatic alkyl alcohol and (meth) acrylic acid, a-3) Amino-substituted aromatic Esterification reaction between aromatic alcohol and (meth) acrylic acid chloride, a-4) esterification reaction between amino-substituted aromatic alkyl alcohol and (meth) acrylic acid chloride;
b-1) amidation reaction between amino-substituted aromatic amine and (meth) acrylic acid, b-2) amidation reaction between amino-substituted aromatic alkylamine and (meth) acrylic acid, b-3) amino-substituted aromatic Amidation reaction of aromatic amine and (meth) acrylic acid chloride, b-4) amidation reaction of amino-substituted aromatic alkylamine and (meth) acrylic acid chloride;
c-1) Esterification reaction between amino-substituted aromatic carboxylic acid and hydroxy-substituted alkyl (meth) acrylate, c-2) Esterification reaction between amino-substituted aromatic alkyl carboxylic acid and hydroxy-substituted alkyl (meth) acrylate ;
d-1) amidation reaction of amino-substituted aromatic carboxylic acid and amino-substituted alkyl (meth) acrylate, d-2) amidation reaction of amino-substituted aromatic alkyl carboxylic acid and amino-substituted alkyl (meth) acrylate ;
e-1) Esterification reaction of amino-substituted aromatic alcohol and (meth) acrylic acid carboxylic acid-substituted alkyl, e-2) Esterification reaction of amino-substituted aromatic alkyl alcohol and (meth) acrylic acid carboxylic acid-substituted alkyl ;
f-1) Amidation reaction between amino-substituted aromatic amine and (meth) acrylic acid carboxylic acid-substituted alkyl, f-2) Amidation reaction between amino-substituted aromatic alkylamine and (meth) acrylic acid carboxylic acid-substituted alkyl ;
g-1) Reaction of reducing nitro to amine after amidation reaction of nitro-substituted aromatic amine and (meth) acrylic acid, g-2) Amidation of nitro-substituted aromatic alkylamine and (meth) acrylic acid After reaction, reaction to reduce nitro to amine, g-3) reaction to reduce nitro to amine after amidation reaction of nitro-substituted aromatic amine and (meth) acrylic acid chloride, g-4) nitro-substituted aromatic A reaction in which nitro is reduced to an amine after an amidation reaction between alkylamine and (meth) acrylic acid chloride;
h-1) Reaction of reducing nitro to amine after amidation reaction of nitro-substituted aromatic amine and (meth) acrylic acid carboxylic acid-substituted alkyl, or h-2) nitro-substituted aromatic alkylamine and (meth) acrylic It is preferable to use a product obtained by a reaction of reducing nitro to an amine after an amidation reaction with an acid carboxylate-substituted alkyl.

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.

According to the production method of the present invention, 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. 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. In 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. In 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 | blended the pigment | dye compound obtained in Example 18. 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. In polymer synthesis example 2, it is a chart showing the ultraviolet visible absorption spectrum of the polymer sheet (polymerizable ultraviolet absorption pigment | dye: HBZ-PHM) which mix | blended the pigment | dye compound obtained in Example 34. It is a chart which shows the pH stability of a HBZ-PHM or a BMAC mixing | blending polymer sheet.

Hereinafter, the present invention will be described in detail.
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.
In the diazo coupling step, 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).

In the 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, and R ³ is a group selected from the groups represented by the following general formulas (2) to (7).

In the general formulas (2) to (7), R ⁴ is a hydrogen atom or a methyl group, m is an integer of 0 to 4, and 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. In the specification of the present invention, 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.

In the general formula (1), 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.
In the general formula (1), 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.
In the general formula (1), the substituent R ³ is preferably a group represented by the general formula (2) or (3).
In the general formulas (2) to (7), 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.
In the general formula (1), the substituent R ³ is preferably bonded to the 3rd or 4th position of the azophenyl group.

In the general formula (1), 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.
Here, as the spacer, an alkylene group having 1 to 4 carbon atoms, an alkylene group having 1 to 8 carbon atoms, an alkylene group having 1 to 4 carbon atoms, an alkylene group having 1 to 8 carbon atoms, an oxycarbonyl carbon number of 1 An alkylene group having 1 to 8 carbon atoms, an alkyleneoxycarbonyl group having 1 to 4 carbon atoms, an alkylene group having 1 to 8 carbon atoms, an alkylene group having 1 to 8 carbonylamino carbon atoms, an alkylenecarbonylamino group having 1 to 8 carbon atoms 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 detail of each process in the manufacturing method of this invention is shown below.
<Diazotization process>
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),

One of the reactions shown below,
a-1) Esterification reaction between amino-substituted aromatic alcohol and (meth) acrylic acid, a-2) Esterification reaction between amino-substituted aromatic alkyl alcohol and (meth) acrylic acid, a-3) Amino-substituted aromatic Esterification reaction between aromatic alcohol and (meth) acrylic acid chloride, a-4) esterification reaction between amino-substituted aromatic alkyl alcohol and (meth) acrylic acid chloride;
b-1) amidation reaction between amino-substituted aromatic amine and (meth) acrylic acid, b-2) amidation reaction between amino-substituted aromatic alkylamine and (meth) acrylic acid, b-3) amino-substituted aromatic Amidation reaction of aromatic amine and (meth) acrylic acid chloride, b-4) amidation reaction of amino-substituted aromatic alkylamine and (meth) acrylic acid chloride;
c-1) Esterification reaction between amino-substituted aromatic carboxylic acid and hydroxy-substituted alkyl (meth) acrylate, c-2) Esterification reaction between amino-substituted aromatic alkyl carboxylic acid and hydroxy-substituted alkyl (meth) acrylate ;
d-1) amidation reaction of amino-substituted aromatic carboxylic acid and amino-substituted alkyl (meth) acrylate, d-2) amidation reaction of amino-substituted aromatic alkyl carboxylic acid and amino-substituted alkyl (meth) acrylate ;
e-1) Esterification reaction of amino-substituted aromatic alcohol and (meth) acrylic acid carboxylic acid-substituted alkyl, e-2) Esterification reaction of amino-substituted aromatic alkyl alcohol and (meth) acrylic acid carboxylic acid-substituted alkyl ;
f-1) Amidation reaction between amino-substituted aromatic amine and (meth) acrylic acid carboxylic acid-substituted alkyl, f-2) Amidation reaction between amino-substituted aromatic alkylamine and (meth) acrylic acid carboxylic acid-substituted alkyl ;
g-1) Reaction of reducing nitro to amine after amidation reaction of nitro-substituted aromatic amine and (meth) acrylic acid, g-2) Amidation of nitro-substituted aromatic alkylamine and (meth) acrylic acid After reaction, reaction to reduce nitro to amine, g-3) reaction to reduce nitro to amine after amidation reaction of nitro-substituted aromatic amine and (meth) acrylic acid chloride, g-4) nitro-substituted aromatic A reaction in which nitro is reduced to an amine after an amidation reaction between alkylamine and (meth) acrylic acid chloride;
h-1) Reaction of reducing nitro to amine after amidation reaction of nitro-substituted aromatic amine and (meth) acrylic acid carboxylic acid-substituted alkyl, or h-2) nitro-substituted aromatic alkylamine and (meth) acrylic A reaction of reducing nitro to an amine after an amidation reaction with an acid carboxylate-substituted alkyl;
Etc. can be obtained.
In the above a-1) to f-2), as the 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.
In addition, amino-substituted aromatic alkenes such as 4-aminostyrene and 4-allylaniline can also be used as the polymerizable group-containing aminoaryl compound.

In the above, (meth) acrylic acid means acrylic acid or methacrylic acid. Thereafter, the same display is used. Similarly, (meth) acryloyl is used in the meaning of acryloyl or methacryloyl, and (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.

(Meth) acrylic acid 4-aminophenyl, (meth) acrylic acid 4-aminophenylmethyl, (meth) acrylic acid 2- (4-aminophenyl) ethyl, (meth) acrylic acid 3- (4-aminophenyl) propyl 4- (4-phenyl) butyl (meth) acrylate, (3-aminophenyl) (meth) acrylate, 2- (3-aminophenyl) methyl (meth) acrylate, 2- (meth) acrylate 2- ( 3-aminophenyl) ethyl, 3- (3-aminophenyl) propyl (meth) acrylate, or 4- (3-aminophenyl) butyl (meth) acrylate.

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.

(Meth) acrylic acid (4-aminobenzoyloxy) methyl, (meth) acrylic acid 2- (4-aminobenzoyloxy) ethyl, (meth) acrylic acid 3- (4-aminobenzoyloxy) propyl, (meth) acrylic 4- (4-aminobenzoyloxy) butyl acid, 5- (4-aminobenzoyloxy) pentyl (meth) acrylate, 6- (4-aminobenzoyloxy) hexyl (meth) acrylate, (meth) acrylic acid 7 -(4-aminobenzoyloxy) heptyl, 8- (4-aminobenzoyloxy) octyl (meth) acrylate, (3-aminobenzoyloxy) methyl (meth) acrylate, 2- (3- Aminobenzoyloxy) ethyl, 3- (3-aminobenzoyloxy) propyl (meth) acrylate, 4- (3-aminobenzoyloxy) butyl (meth) acrylate, 5- (3-aminobenzoyloxy) pentyl (meth) acrylate, 6- (3-aminobenzoyloxy) hexyl (meth) acrylate, (meth) 7- (3-aminobenzoyloxy) heptyl acrylate, 8- (3-aminobenzoyloxy) octyl (meth) acrylate, [(4-aminophenyl) acetoxy] methyl (meth) acrylate, (meth) acrylic acid [2- (4-aminophenyl) acetoxy] ethyl, [meth (acrylic acid) [3- (4-aminophenyl) acetoxy] propyl, (meth) acrylic acid [4- (4-aminophenyl) acetoxy] butyl, [Meth] acrylic acid [5- (4-aminophenyl) acetoxy] pentyl, (meth) acrylic acid [6- (4 Aminophenyl) acetoxy] hexyl, (meth) acrylic acid [7- (4-aminophenyl) acetoxy] heptyl, (meth) acrylic acid [8- (4-aminophenyl) acetoxy] octyl, (meth) acrylic acid [( 3-aminophenyl) acetoxy] methyl, (meth) acrylic acid [2- (3-aminophenyl) acetoxy] ethyl, (meth) acrylic acid [3- (3-aminophenyl) acetoxy] propyl, (meth) acrylic acid [4- (3-aminophenyl) acetoxy] butyl, (meth) acrylic acid [5- (3-aminophenyl) acetoxy] pentyl, (meth) acrylic acid [6- (3-aminophenyl) acetoxy] hexyl, ( [Meth] acrylic acid [7- (3-aminophenyl) acetoxy] heptyl, or (meth) acrylic acid [ 8- (3-Aminophenyl) acetoxy] octyl.

(Meth) acrylic acid (4-aminobenzoylamino) methyl, (meth) acrylic acid 2- (4-aminobenzoylamino) ethyl, (meth) acrylic acid 3- (4-aminobenzoylamino) propyl, (meth) acrylic 4- (4-aminobenzoylamino) butyl acid, 5- (4-aminobenzoylamino) pentyl (meth) acrylate, 6- (4-aminobenzoylamino) hexyl (meth) acrylate, (meth) acrylic acid 7 -(4-aminobenzoylamino) heptyl, 8- (4-aminobenzoylamino) octyl (meth) acrylate, (3-aminobenzoylamino) methyl (meth) acrylate, 2- (3- Aminobenzoylamino) ethyl, 3- (3-aminobenzoylamino) propyl (meth) acrylate, 4- (3-aminobenzoylamino) butyl (meth) acrylate, 5- (3-aminobenzoylamino) pentyl (meth) acrylate, 6- (3-aminobenzoylamino) hexyl (meth) acrylate, (meth) 7- (3-Aminobenzoylamino) heptyl acrylate, 8- (3-aminobenzoylamino) octyl (meth) acrylate, (meth) acrylic acid [(4-aminophenyl) acetamido] methyl, (meth) acrylic acid [2- (4-aminophenyl) acetamido] ethyl, (meth) acrylic acid [3- (4-aminophenyl) acetamido] propyl, (meth) acrylic acid [4- (4-aminophenyl) acetamido] butyl, [Meth] acrylic acid [5- (4-aminophenyl) acetamide] pentyl, (meth) acrylic acid [6- (4 Aminophenyl) acetamido] hexyl, (meth) acrylic acid [7- (4-aminophenyl) acetamido] heptyl, (meth) acrylic acid [8- (4-aminophenyl) acetamido] octyl, (meth) acrylic acid [( 3-aminophenyl) acetamido] methyl, (meth) acrylic acid [2- (3-aminophenyl) acetamido] ethyl, (meth) acrylic acid [3- (3-aminophenyl) acetamido] propyl, (meth) acrylic acid [4- (3-aminophenyl) acetamido] butyl, (meth) acrylic acid [5- (3-aminophenyl) acetamido] pentyl, (meth) acrylic acid [6- (3-aminophenyl) acetamido] hexyl, (Meth) acrylic acid [7- (3-aminophenyl) acetamide] heptyl, or (meth) acrylic acid [ 8- (3-Aminophenyl) acetamide] octyl.

(Meth) acrylic acid (4-aminophenoxycarbonyl) methyl, (meth) acrylic acid 2- (4-aminophenoxycarbonyl) ethyl, (meth) acrylic acid 3- (4-aminophenoxycarbonyl) propyl, (meth) acrylic 4- (4-aminophenoxycarbonyl) butyl acid, 5- (4-aminophenoxycarbonyl) pentyl (meth) acrylate, 6- (4-aminophenoxycarbonyl) hexyl (meth) acrylate, (meth) acrylic acid 7 -(4-aminophenoxycarbonyl) heptyl, 8- (4-aminophenoxycarbonyl) octyl (meth) acrylate, (3-aminophenoxycarbonyl) methyl (meth) acrylate, 2- (3- (meth) acrylic acid Aminophenoxycarbonyl) ethyl, (meth) acrylic acid 3- 3-aminophenoxycarbonyl) propyl, 4- (3-aminophenoxycarbonyl) butyl (meth) acrylate, 5- (3-aminophenoxycarbonyl) pentyl (meth) acrylate, 6- (3- Aminophenoxycarbonyl) hexyl, 7- (3-aminophenoxycarbonyl) heptyl (meth) acrylate, 8- (3-aminophenoxycarbonyl) octyl (meth) acrylate, (meth) acrylic acid (4-aminobenzyloxycarbonyl) ) Methyl, 2- (4-aminobenzyloxycarbonyl) ethyl (meth) acrylate, 3- (4-aminobenzyloxycarbonyl) propyl (meth) acrylate, 4- (4-aminobenzyloxy) (meth) acrylate Carbonyl) butyl, (meth) acrylic acid 5- ( -Aminobenzyloxycarbonyl) pentyl, 6- (4-aminobenzyloxycarbonyl) hexyl (meth) acrylic acid, 7- (4-aminobenzyloxycarbonyl) heptyl (meth) acrylic acid, 8- (meth) acrylic acid 4-aminobenzyloxycarbonyl) octyl, (meth) acrylic acid (3-aminobenzyloxycarbonyl) methyl, (meth) acrylic acid [2- (3-aminobenzyloxycarbonyl) ethyl, (meth) acrylic acid [3- (3-aminobenzyloxycarbonyl) propyl, (meth) acrylic acid [4- (3-aminobenzyloxycarbonyl) butyl, (meth) acrylic acid [5- (3-aminobenzyloxycarbonyl) pentyl, (meth) acrylic Acid [6- (3-aminobenzyloxycarbonyl) Xyl, (meth) acrylic acid [7- (3-aminobenzyloxycarbonyl) heptyl, (meth) acrylic acid [8- (3-aminobenzyloxycarbonyl) octyl, (meth) acrylic acid [2- (4-amino Phenyl) ethoxycarbonyl] methyl, 2- (2- (4-aminophenyl) ethoxycarbonyl] methyl (meth) acrylate, 3- [2- (4-aminophenyl) ethoxycarbonyl] propyl (meth) acrylate, ( 4- [2- (4-aminophenyl) ethoxycarbonyl] butyl (meth) acrylate, 5- [2- (4-aminophenyl) ethoxycarbonyl] pentyl (meth) acrylate, 6- [2 (meth) acrylic acid -(4-Aminophenyl) ethoxycarbonyl] hexyl, (meth) acrylic acid 7- [2- (4-aminophen L) ethoxycarbonyl] heptyl, 8- (2- (4-aminophenyl) ethoxycarbonyl] octyl (meth) acrylate, (2- (3-aminophenyl) ethoxycarbonyl] methyl (meth) acrylate, (meth) 2- [2- (3-aminophenyl) ethoxycarbonyl] methyl acrylate, 3- [2- (3-aminophenyl) ethoxycarbonyl] propyl (meth) acrylate, 4- [2- (meth) acrylic acid 3-aminophenyl) ethoxycarbonyl] butyl, 5- [2- (3-aminophenyl) ethoxycarbonyl] pentyl (meth) acrylate, 6- [2- (3-aminophenyl) ethoxycarbonyl] (meth) acrylate Hexyl, (meth) acrylic acid 7- [2- (3-aminophenyl) ethoxycarbonyl] heptyl, Others (meth) acrylic acid 8- [2- (3-aminophenyl) ethoxycarbonyl] octyl.

[(4-Aminophenyl) aminocarbonyl] methyl (meth) acrylate, 2-[(4-aminophenyl) aminocarbonyl] ethyl (meth) acrylate, 3-[(4-aminophenyl) (meth) acrylate Aminocarbonyl] propyl, 4-((4-aminophenyl) aminocarbonyl] butyl (meth) acrylate, 5-[(4-aminophenyl) aminocarbonyl] pentyl (meth) acrylate, 6- (meth) acrylic acid [(4-aminophenyl) aminocarbonyl] hexyl, 7-[(4-aminophenyl) aminocarbonyl] heptyl (meth) acrylate, 8-[(4-aminophenyl) aminocarbonyl] octyl (meth) acrylate, (Meth) acrylic acid [(3-aminophenyl) aminocarbonyl] methyl, (meth) acrylic 2-[(3-aminophenyl) aminocarbonyl] ethyl acid, 3-[(3-aminophenyl) aminocarbonyl] propyl (meth) acrylate, 4-[(3-aminophenyl) aminocarbonyl (meth) acrylate ] Butyl, (meth) acrylic acid 5-[(3-aminophenyl) aminocarbonyl] pentyl, (meth) acrylic acid 6-[(3-aminophenyl) aminocarbonyl] hexyl, (meth) acrylic acid 7-[( 3-aminophenyl) aminocarbonyl] heptyl, 8-[(3-aminophenyl) aminocarbonyl] octyl (meth) acrylic acid, [(4-aminobenzyl) aminocarbonyl] methyl (meth) acrylic acid, (meth) acrylic Acid 2-[(4-aminobenzyl) aminocarbonyl] ethyl, (meth) acrylic acid 3-[( -Aminobenzyl) aminocarbonyl] propyl, (meth) acrylic acid 4-[(4-aminobenzyl) aminocarbonyl] butyl, (meth) acrylic acid 5-[(4-aminobenzyl) aminocarbonyl] pentyl, (meth) Acrylic acid 6-[(4-aminobenzyl) aminocarbonyl] hexyl, (meth) acrylic acid 7-[(4-aminobenzyl) aminocarbonyl] heptyl, (meth) acrylic acid 8-[(4-aminobenzyl) amino Carbonyl] octyl, (meth) acrylic acid [(3-aminobenzyl) aminocarbonyl] methyl, (meth) acrylic acid 2-[(3-aminobenzyl) aminocarbonyl] ethyl, (meth) acrylic acid 3-[(3 -Aminobenzyl) aminocarbonyl] propyl, (meth) acrylic acid 4-[(3-aminobenzene) Benzyl) aminocarbonyl] butyl, 5-((3-aminobenzyl) aminocarbonyl] pentyl (meth) acrylate, 6-[(3-aminobenzyl) aminocarbonyl] hexyl (meth) acrylate, (meth) acrylic acid 7-[(3-aminobenzyl) aminocarbonyl] heptyl, 8-[(3-aminobenzyl) aminocarbonyl] octyl (meth) acrylate, 2- [2- (4-aminophenyl) ethyl (meth) acrylate Aminocarbonyl] methyl, 2- [2- (4-aminophenyl) ethylaminocarbonyl] ethyl (meth) acrylate, 3- [2- (4-aminophenyl) ethylaminocarbonyl] propyl (meth) acrylate, ( 4- (2- (4- (Aminophenyl) ethylaminocarbonyl) butyl methacrylate) 5- [2- (4-aminophenyl) ethylaminocarbonyl] pentyl acrylate, 6- [2- (4-aminophenyl) ethylaminocarbonyl] hexyl (meth) acrylic acid, 7- [2 (meth) acrylic acid -(4-aminophenyl) ethylaminocarbonyl] heptyl, 8- [2- (4-aminophenyl) ethylaminocarbonyl] octyl (meth) acrylate, 2- [2- (3-aminophenyl) ethylamino acrylate Carbonyl] methyl, 2- [2- (3-aminophenyl) ethylaminocarbonyl] ethyl (meth) acrylate, 3- [2- (3-aminophenyl) ethylaminocarbonyl] propyl (meth) acrylate, (meth ) 4- [2- (3-Aminophenyl) ethylaminocarbonyl] butyl acrylate, (meth) acrylic Acid 5- [2- (3-aminophenyl) ethylaminocarbonyl] pentyl, (meth) acrylic acid 6- [2- (3-aminophenyl) ethylaminocarbonyl] hexyl, (meth) acrylic acid 7- [2- (3-Aminophenyl) ethylaminocarbonyl] heptyl or 8- [2- (3-aminophenyl) ethylaminocarbonyl] octyl (meth) acrylate.

4-aminostyrene, 4-allylaniline, 4- (3-butenyl) aniline, 4- (4-pentenyl) aniline, 4- (5-hexenyl) aniline, 4- (6-heptenyl) aniline, 4- (7 -Octenyl) aniline, 3-aminostyrene, 3-allylaniline, or 3- (3-butenyl) aniline.

In the present invention, a known method can be employed for the diazotization step.
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.
In the diazotization step, when a protective group is bonded to the polymerizable group-containing aminoaryl compound of the reactant, it is preferable to treat with a acid such as hydrochloric acid in advance and allow the diazotizing agent to act after deprotection.

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.

<Diazo coupling process>
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.

In the production method of the present invention, the diazo coupling step needs to be performed under weak base conditions. In the production process of the compound represented by the general formula (1) of the present invention, when a strong base such as sodium hydroxide, triethylamine, dimethylaminopyridine or the like usually employed as a catalyst is used, 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. In response to the problem of decomposition of the ester or amide structure, by performing a diazo coupling reaction using a weak base, formation of decomposition products is remarkably suppressed and sufficient reactivity is exhibited, resulting in a reaction yield. I thought that it would improve dramatically.

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.
In the diazo coupling step, 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.

Examples of the reaction solvent in the diazo coupling reaction 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). Solvents, sulfone 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 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):

(In the formula, 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.

Of these, 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.
Methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, butyl (meth) acrylate, t-butyl (meth) acrylate, isobutyl (meth) acrylate, pentyl (meth) acrylate, t-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 alkyl (meth) acrylates such as acrylate, stearyl (meth) acrylate, cyclopentyl (meth) acrylate, cyclohexyl (meth) acrylate;

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 Door like;

Trifluoroethyl (meth) acrylate, tetrafluoropropyl (meth) acrylate, pentafluoropropyl (meth) acrylate, hexafluoroisopropyl (meth) acrylate, tetrafluoro-t-pentyl (meth) acrylate, hexafluorobutyl (meth) acrylate , Hexafluoro-t-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 DOO, 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, 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.

Among these, 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.

When copolymerizing the polymerizable UV-absorbing dye obtained by the method of the present invention with the above-mentioned “other polymerizable monomer”, a known polymerizable UV absorber (mainly absorbing the UV portion) or polymerization Sexual dyes (those that absorb the light mainly in the blue region without UV absorption ability) can also be used in combination. 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. Examples of polymerizable ultraviolet absorbers that can be used in combination for this purpose include benzophenone-based polymerizable ultraviolet absorbers disclosed in JP-A No. 2003-253248 and benzotriazole-based polymerizable UV absorbers disclosed in Japanese Patent No. 2658980. Can be used. As the polymerizable dye, polymerizable group-containing azo, anthraquinone, nitro and phthalocyanine type polymerizable dyes disclosed in JP-A-10-251537 can be used.

When copolymerizing the polymerizable ultraviolet-absorbing dye obtained by the method of the present invention with the above other polymerizable monomer, if necessary, 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.

As the crosslinking agent, a polyfunctional monomer having two or more polymerizable groups in the molecule can be used. Examples of such 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, α-methylene-N-vinylpyrrolidone, etc. Can be given.

These 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. In the polymerization, a radical polymerization initiator is appropriately used, and temperature rising polymerization can be employed as necessary.

Examples of the radical polymerization initiator 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.

<Synthesis of polymerizable group-containing aminoaryl compound>
A synthesis example of a polymerizable group-containing aminoaryl compound used in synthesizing a polymerizable ultraviolet absorbing dye by the method of the present invention is shown below.

(Synthesis of polymerizable group-containing aminoaryl compound 1)

4- (tert-Butoxycarbonylamino) benzyl alcohol (3.80 g) and triethylamine (1.72 g) are dissolved in chloroform (50 mL), and a solution of methacryloyl chloride (1.99 g) in chloroform (20 mL) is added dropwise under ice cooling. did. The mixture was stirred at 4 ° C. for 4 hours, then transferred to a separatory funnel, washed with 5% potassium hydrogen sulfate, saturated sodium hydrogen carbonate, and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography using hexane-ethyl acetate (8: 1 v / v) and concentrated under reduced pressure. The precipitated powder was dried under reduced pressure to obtain the desired product.
Yield: 3.00 g (60%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.52 (s, 9H), 1.55 (s, 3H), 5.13 (s, 2H), 5.56 (quintet, 1H, J = 1) .5 Hz), 6.12 (s, 1H), 6.48 (br.s, 1H), 7.31 (d, 2H, J = 8.3 Hz), 7.36 (d, 2H, J = 8) .8 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 2)

4- (tert-Butoxycarbonylamino) benzyl alcohol (3.80 g) was reacted with acryloyl chloride (1.77 g) in the same manner as in the synthesis of 4- (tert-butoxycarbonylamino) benzyl methacrylate (raw material synthesis 1). The target product was obtained as white needle crystals.
Yield: 4.13 g (87%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.52 (s, 9H), 5.14 (s, 2H), 5.83 (dd, 1H, J = 10.7 Hz, 1.4 Hz), 6 .14 (dd, 1H, J = 17.1 Hz, 10.7 Hz), 6.43 (dd, 1H, J = 17.1 Hz, 1.4 Hz), 6.49 (br.s, 1H), 7. 31 (d, 2H, J = 8.8 Hz), 7.36 (d, 2H, J = 8.3 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 3)

2- [4- (tert-Butoxycarbonylamino) phenyl] ethanol (3.36 g) and triethylamine (1.72 g) were dissolved in chloroform (50 mL), and methacryloyl chloride (1.63 g) in chloroform (20 mL) was cooled with ice. ) The solution was added dropwise. The mixture was stirred at 4 ° C. for 4 hours, then transferred to a separatory funnel, washed with 5% potassium hydrogen sulfate, saturated sodium hydrogen carbonate, and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography using hexane-ethyl acetate (8: 1 v / v) and concentrated under reduced pressure. The precipitated powder was dried under reduced pressure to obtain the desired product.
Yield: 2.97 g (69%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.50 (s, 9H), 1.91 (t, 3H, J = 1.2 Hz), 2.91 (t, 2H, J = 6.8 Hz) 4.11 (q, 2H, J = 7.2 Hz), 5.52 (q, 1H, J = 1.2 Hz), 6.06 (s, 1H), 6.41 (br.s, 1H) 7.14 (d, 2H, J = 8.8 Hz), 7.28 (d, 2H, 8.8 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 4)

2- [4- (tert-butoxycarbonylamino) phenyl] ethanol (2.83 g) was synthesized from 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl methacrylate (polymerizable group-containing aminoaryl compound 3). In the same manner as in the synthesis, acryloyl chloride (1.49 g) was reacted to obtain the desired product.
Yield: 2.63 g (76%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.51 (s, 9H), 2.92 (t, 2H, J = 6.9 Hz), 4.33 (t, 2H, J = 7.3 Hz) 5.81 (dd, 1 H, J = 10.8 Hz, 1.5 Hz), 6.10 (dd, 1 H, J = 17.2 Hz, 10.8 Hz), 6.38 (dd, 1 H, J = 17) .5 Hz, 1.5 Hz), 6.44 (br.s, 1 H), 7.15 (d, 2 H, J = 8.3 Hz), 7.29 (d, 2 H, J = 8.3 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 5)

4- (tert-Butoxycarbonylamino) benzoic acid (2.37 g), 2-hydroxyethyl methacrylate (1.30 g), and 4-dimethylaminopyridine (0.12 g) were dissolved in chloroform (50 mL) and ice-cooled. Lower water soluble carbodiimide (1.92 g) was added. The mixture was stirred at 4 ° C. for 2 hours, then at room temperature overnight and transferred to a separatory funnel. The mixture was washed with 5% sodium hydrogen sulfate, saturated sodium hydrogen carbonate, and saturated brine in that order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography using hexane-ethyl acetate (4: 1 v / v) to obtain the desired product as white needle crystals.
Yield: 2.54 g (73%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.52 (s, 9H), 1.93 (t, 3H, J = 1.2 Hz), 4.45-4.48 (m, 2H), 4 .52-4.54 (m, 2H), 5.57 (quintet, 1H, J = 1.6 Hz), 6.13 (t, 1H, J = 0.8 Hz), 6.64 (br.s, 1H), 7.42 (dt, 2H, J = 8.8 Hz, 2.0 Hz), 7.96 (dt, J = 9.2 Hz, 2.0 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 6)

As in the synthesis of 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (synthesis of polymerizable aryl group-containing aminoaryl compound 5), 4-hydroxyethyl acrylate (1.16 g) was converted into 4 Reaction with-(tert-butoxycarbonylamino) benzoic acid (2.37 g) gave the desired product.
Yield: 2.26 g (67%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.51 (s, 9H), 3.745 (q, J = 5.6 Hz), 4.37 (t, 2H, J = 5.2 Hz), 5 .87 (dd, 1H, J = 10.8 Hz, 1.6 Hz), 6.14 (dd, 1H, J = 17.6 Hz, 10.4 Hz), 6.44 (dd, 1H, J = 18.0 Hz) 1.6 Hz), 6.62 (s, 1H), 7.42 (d, 2H, J = 8.8 Hz), 7.70 (d, 2H, J = 8.8 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 7)

4- (tert-Butoxycarbonylamino) benzoic acid (2.37 g), 2-aminoethyl methacrylate hydrochloride (1.66 g) and triethylamine (1.11 g) were dissolved in chloroform (50 mL) and dissolved in water under ice-cooling. Carbodiimide (1.92 g) was added. The mixture was stirred at 4 ° C. for 2 hours, then at room temperature overnight and transferred to a separatory funnel. The mixture was washed with 5% sodium hydrogen sulfate, saturated sodium hydrogen carbonate, and saturated brine in that order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography using hexane-ethyl acetate (2: 1 v / v) to obtain the desired product as white needle crystals.
Yield: 2.87 g (82%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.51 (s, 9H), 1.94 (t, 3H, J = 1.2 Hz), 3.75 (q, 2H, J = 4.8 Hz) 4.37 (t, 2H, J = 5.6 Hz), 5.59 (t, 1H, J = 1.6 Hz), 6.13 (t, 1H, J = 0.8 Hz), 6.47 ( br.s, 1H), 6.62 (br.s, 1H), 7.42 (d, 2H, J = 8.8 Hz), 7.70 (d, 2H, J = 8.8 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 8)

2- (tert-Butoxycarbonylamino) ethanol (3.62 g) and triethylamine (3.04 g) are dissolved in chloroform (80 mL), and a solution of acryloyl chloride (2.30 g) in chloroform (20 mL) is added dropwise under ice cooling. did. The mixture was stirred at 4 ° C. for 1 hour and concentrated under reduced pressure. The residue was dissolved in ethyl acetate, transferred to a separatory funnel, washed with 5% potassium hydrogen sulfate and saturated brine, and dried over anhydrous sodium sulfate. . 3. Sodium sulfate was removed by filtration and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using hexane-ethyl acetate (4: 1 v / v) and then hexane-ethyl acetate (2: 1 v / v). 25 g of a colorless oil was obtained. This was dissolved in ethyl acetate (10 mL), and 4M hydrogen chloride in ethyl acetate (40 mL) was added. The mixture was stirred for 90 minutes at room temperature and then concentrated under reduced pressure to obtain 2.18 g of white prism crystals. This was dissolved in chloroform (40 mL), 4- (tert-butoxycarbonylamino) benzoic acid (3.41 g) and triethylamine (2.40 g) were added, and then water-soluble carbodiimide (2.76 g) was added under ice cooling. ) Was added. The mixture was stirred at 4 ° C. for 2 hours, then at room temperature overnight and then concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate and transferred to a separatory funnel. The organic layer was washed with 5% sodium hydrogen sulfate, saturated sodium hydrogen carbonate and saturated brine in that order, dried over anhydrous sodium sulfate and concentrated under reduced pressure. 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.
Yield: 3.77 g (78%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.53 (s, 9H), 3.76 (q, 2H, J = 5.4 Hz), 4.39 (t, 2H, J = 5.4 Hz) 5.88 (dd, 1 H, J = 10.2 Hz, 1.0 Hz), 6.15 (dd, 1 H, J = 17.6 Hz, 10.2 Hz), 6.45 (dd, 1 H, J = 17) .6 Hz (1.0 Hz), 6.49 (br.t, 1H, J = 5.4 Hz), 6.65 (br.s, 1H), 7.29 (d, 2H, J = 8.8 Hz) , 7.72 (d, 2H, J = 8.8 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 9)

2- [4- (tert-Butoxycarbonyl) phenyl] ethylamine (3.54 g) and methacrylic acid (1.57 g) were dissolved in chloroform (80 mL), and water-soluble carbodiimide (2.88 g) was added under ice cooling. The mixture was stirred at 4 ° C. for 1 hour, then at room temperature overnight and concentrated in vacuo. The residue was washed with 5% potassium hydrogen sulfate, saturated sodium bicarbonate, and saturated brine in that order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography with hexane-ethyl acetate. (2: 1 v / v) Then, elution was performed using hexane-ethyl acetate (1: 1 v / v) to obtain the desired product as white needle crystals.
Yield: 2.92 g (64%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.52 (s, 9H), 1.91 (s, 3H), 2.80 (t, 2H, J = 6.8 Hz), 3.54 (q , 2H, J = 6.8 Hz), 5.28 (t, 1H, J = 1.4 Hz), 5.59 (s, 1H), 5.76 (br.s, 1H), 6.46 (br .S, 1H), 7.12 (d, 2H, J = 8.3 Hz), 7.31 (d, 2H, J = 8.3 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 10)

2- [4- (tert-butoxycarbonyl) phenyl] ethylamine (2.36 g) and acrylic acid (1.06 g) were combined with N- [2- [4- (tert-butoxycarbonylamino) phenyl] ethyl] methacrylamide. The reaction was carried out in the same manner as in the synthesis (synthesis of polymerizable group-containing aminoaryl compound 9) to obtain the desired product as white needle crystals.
Yield: 2.02 g (70%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.52 (s, 9H), 2.80 (t, 2H, J = 6.8 Hz), 3.57 (q, 2H, J = 6.8 Hz) 5.51 (br.s, 1H), 5.62 (dd, 1H, J = 10.5 Hz, 0.9 Hz), 6.01 (dd, 1H, J = 17.4 Hz, 10.5 Hz), 6.26 (dd, 1H, J = 17.4 Hz, 0.9 Hz), 6.45 (br.s, 1H), 7.12 (d, 2H, J = 8.2 Hz), 7.30 (d , 2H, J = 8.2 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 11)

3- (tert-Butoxycarbonylamino) benzyl alcohol (4.47 g) was synthesized in the same manner as the synthesis of 2- [4- (tert-butoxycarbonylamino) phenyl] methyl methacrylate (synthesis of polymerizable aryl group-containing aminoaryl compound 1). Was reacted with methacryloyl chloride (2.30 g) to give 5.16 g of a colorless oil. This was dissolved in ethyl acetate (20 mL), 4M hydrogen chloride in ethyl acetate (45 mL) was added, and the mixture was stirred at room temperature for 1.5 hr and concentrated under reduced pressure. Ether was added to the crystalline residue and collected by filtration to obtain the desired product as white prism crystals.
Yield: 2.72 g (60%)
¹ H-NMR (400 MHz, CD ₃ OD) δ: 1.96 (t, 3H, J = 1.0 Hz), 5.27 (s, 2H), 5.68 (quintet, 1H, J = 1.4 Hz) ), 6.16 (t, 1H, J = 1.0 Hz), 7.37 (d, 1H, J = 7.8 Hz), 7.45 (s, 1H), 7.51-7.58 (m) , 2H).

(Synthesis of polymerizable group-containing aminoaryl compound 12)

Synthesis of 3- [tert-butoxycarbonylamino) benzoic acid (2.85 g) of 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (synthesis of polymerizable aryl group-containing aminoaryl compound 5) In the same manner as above, the reaction product was reacted with 2-hydroxyethyl methacrylate (1.56 g) to obtain the desired product as white needle crystals.
Yield: 3.23 g (77%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.53 (s, 9H), 1.95 (t, 3H, J = 1.2 Hz), 4.47-4.51 (m, 2H), 4 .54-4.58 (m, 2H), 5.59 (quintet, 1H, J = 1.4 Hz), 6.15 (t, 1H, J = 1.2 Hz), 6.56 (br.s, 1H), 7.38 (t, 1H, J = 7.8 Hz), 7.71 (dt, 2H, J = 7.8 Hz, 1.0 Hz), 7.90 (t, 1H, J = 2.0 Hz) ).

(Synthesis of polymerizable group-containing aminoaryl compound 13)

4- [tert-Butoxycarbonylamino) benzoic acid (2.85 g) and 2-aminoethyl methacrylate hydrochloride (1.99 g) were combined with 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate. In the same manner as in the synthesis of (polymerizable group-containing aminoaryl compound 7), the target product was obtained as white needle crystals.
Yield: 3.31 g (79%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.53 (s, 9H), 1.96 (s, 3H), 3.77 (q, 2H, J = 5.4 Hz), 4.37 (t , 2H, J = 5.5 Hz), 5.61 (t, 1H, J = 1.5 Hz), 6.16 (s, 1H), 6.58 (br.t, 1H), 6.65 (br .S, 1H), 7.35 (t, 1H, J = 7.8 Hz), 7.42 (dt, 1H, J = 7.8 Hz, 1.5 Hz), 7.53 (d, 1H, J = 8.3 Hz), 7.81 (t, 1H, J = 1.9 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 14)

Synthesis of 3- (tert-butoxycarbonylamino) phenylacetic acid (3.77 g) of 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (synthesis of polymerizable aryl group-containing aminoaryl compound 5) In the same manner as above, it was reacted with 2-hydroxyethyl methacrylate (1.74 g) to obtain 4.59 g of a colorless oil. This was dissolved in ethyl acetate (40 mL), and 4M hydrogen chloride in ethyl acetate (50 mL) was added. The mixture was stirred at room temperature for 90 minutes and then concentrated under reduced pressure to obtain the desired product as white prism crystals.
Yield: 3.48 g (77%)
¹ H-NMR (400 MHz, CD ₃ OD) δ: 1.89 (t, 3H, J = 1.2 Hz), 3.77 (s, 2H), 4.33-4.39 (m, 4H), 5.61 (t, 1H, J = 1.4 Hz), 6.04 (s, 1H), 7.29-7.51 (m, 4H).

(Synthesis of polymerizable group-containing aminoaryl compound 15)

4- (tert-Butoxycarbonylamino) benzylamine (5.38 g) and methacrylic acid (1.89 g) were dissolved in chloroform (80 mL), and water-soluble carbodiimide (2.88 g) was added under ice cooling. The mixture was stirred at 4 ° C. for 1 hour, then at room temperature overnight and concentrated in vacuo. The residue was washed with 5% potassium hydrogen sulfate, saturated sodium bicarbonate, and saturated brine in that order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography with hexane-ethyl acetate. (2: 1 v / v) Then, elution was performed using hexane-ethyl acetate (1: 1 v / v) to obtain the desired product as white needle crystals.
Yield: 4.15 g (56%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.50 (s, 9H), 1.96 (s, 3H), 4.43 (d, 2H, J = 5.4 Hz), 5.32 (t , 1H, J = 0.3 Hz), 5.68 (s, 1H), 5.96 (br.s, 1H), 6.46 (br.s, 1H), 7.21 (d, 2H, J = 8.8 Hz), 7.32 (d, 2H, J = 8.8 Hz).

(Synthesis of polymerizable group-containing aminoaryl compound 16)

4-Nitrobenzylamine hydrochloride (1.51 g) and sodium hydrogencarbonate (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.
Yield: 1.05 g (60%)
¹ H-NMR (400 MHz, 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 580 mg (89%)
¹ H-NMR (400 MHz, 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 group-containing aminoaryl compound 17)

2- (4-Nitrophenyl) ethylamine hydrochloride (1.72 g) and sodium bicarbonate (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 to obtain N- [2- (4-nitrophenyl) ethyl] methacrylamide as yellowish white crystals.
Yield: 1.25 g (63%)
¹ H-NMR (400 MHz, 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.
Yield: 1.01 g (97%)
¹ H-NMR (400 MHz, 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).

<Synthesis of polymerizable ultraviolet absorbing dye>
Using the polymerizable group-containing aminoaryl compound obtained by synthesizing the polymerizable group-containing aminoaryl compounds 1 to 17, a polymerizable ultraviolet absorbing dye as a target product was synthesized by the production method of the present invention. Examples 1 to 60 are shown below. Further, polymerizable ultraviolet absorbing dyes not according to the present invention were synthesized and shown as Comparative Examples 1 and 2.

Example 1 2-Hydroxy-5- [4- (methacryloyloxymethyl) phenylazo] benzophenone (NBZ-BNM)

4- (tert-Butoxycarbonylamino) benzyl methacrylate (583 mg) was dissolved in ethyl acetate (2 mL), and 4M hydrogen chloride in ethyl acetate (5 mL) was added. The mixture was stirred at room temperature for 40 minutes and then concentrated under reduced pressure. This concentrated residue was dissolved in 1M hydrochloric acid (4 mL), a solution of sodium nitrite (145 mg) in water (10 mL) was added dropwise under ice cooling, and the mixture was stirred at 4 ° C. for 40 minutes to prepare a diazonium salt. Subsequently, 2-hydroxybenzophenone (396 mg) was dissolved in ethanol (20 mL), and a solution of sodium carbonate (423 mg) in water (20 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 4 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. This precipitate was dissolved in chloroform without drying, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Methanol was added to the concentrated residue and the mixture was allowed to stand at 4 ° C. overnight, and the precipitated target product was obtained as pale brown crystals.
Yield: 599 mg (75%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.98 (s, 3H), 5.25 (s, 2H), 5.61 (t, 1H, J = 1.4 Hz), 6.18 (s , 1H), 7.20 (d, 1H, J = 9.3 Hz), 7.28 (d, 2H, J = 8.4 Hz), 7.55-7.58 (m, 2H), 7.65 (T, 1H, J = 7.8 Hz), 7.77-7.79 (m, 2H), 7.84 (d, 2H, J = 8.3 Hz), 8.16 (dd, 1H, J = 8.8 Hz, 2.5 Hz), 8.27 (d, 1 H, J = 2.4 Hz), 12.45 (s, 1 H).

Example 2 2,4-Dihydroxy-5- [4- (methacryloyloxymethyl) phenylazo] benzophenone (HBZ-BNM)

Similar to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl methacrylate (583 mg) was acid-treated, then diazonium chloride, and diazo-coupled with 2,4-dihydroxybenzophenone (437 mg) to give the desired product. Got.
Yield: 324 mg (40%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.98 (s, 3H), 5.25 (s, 2H), 5.62 (t, 1H, J = 1.4 Hz), 6.18 (s , 1H), 6.59 (s, 1H), 7.49 (d, 2H, J = 8.3 Hz), 7.57 (t, 2H, J = 6.8 Hz), 7.65 (t, 1H) , J = 7.3 Hz), 7.73-7.81 (m, 4H), 8.24 (s, 1H), 12.91 (s, 1H), 13.90 (s, 1H).

Example 3 2-Hydroxy-5- [4- (methacryloyloxymethyl) phenylazo] -4-methoxybenzophenone (MBZ-BNM)

Similar to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl methacrylate (583 mg) was acid-treated and then diazonium chloride, and diazo coupling with 2-hydroxy-4-methoxybenzophenone (456 mg) was performed. The desired product was obtained.
Yield: 582 mg (68%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.98 (s, 3H), 4.09 (s, 3H), 5.42 (s, 2H), 5.60 (t, 1H, J = 1) .5 Hz), 6.17 (s, 1 H), 6.71 (s, 1 H), 7.45-7.55 (m, 4 H), 7.61 (t, 1 H, J = 7.8 Hz), 7.69-7.72 (m, 2H), 7.79 (d, 2H, J = 8.3 Hz), 8.03 (s, 1H), 12.91 (s, 1H).

Example 4 4-Ethoxy-2-hydroxy-5- [4- (methacryloyloxymethyl) phenylazo] benzophenone (EBZ-BNM)

Similarly to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl methacrylate (583 mg) was acid-treated and then diazonium chloride, followed by diazo coupling with 4-ethoxy-2-hydroxybenzophenone (485 mg). The desired product was obtained.
Yield: 613 mg (70%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.58 (t, 3H, J = 6.8 Hz), 1.98 (s, 3H), 4.33 (q, 2H, J = 6.8 Hz) , 5.23 (s, 2H), 5.61 (t, 1H, J = 1.5 Hz), 6.17 (s, 1H), 6.68 (s, 1H), 7.45-7.54. (M, 4H), 7.61 (t, 1H, J = 7.3 Hz), 7.
70 (d, 2H, J = 7.3 Hz), 7.81 (d, 2H, J = 8.8 Hz), 8.03 (s, 1H), 12.90 (s, 1H).

Example 5 5- [4- (acryloyloxymethyl) phenylazo] -2-hydroxybenzophenone (NBZ-BNA)

Similarly to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl acrylate (555 mg) was acid-treated and then diazonium chloride, and diazo coupling with 2-hydroxybenzophenone (396 mg) to obtain the desired product. It was.
Yield: 507 mg (65%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 5.26 (s, 2H), 5.88 (dd, 1H, J = 10.3 Hz, 1.5 Hz), 6.19 (dd, 1H, J = 17.1 Hz, 10.3 Hz), 6.47 (dd, 1 H, J = 17.1 Hz, 1.5 Hz), 7.20 (d, 1 H, J = 9.3 Hz), 7.49 (d, 2 H) , J = 8.3 Hz), 7.57 (t, 2H, J = 7.8 Hz), 7.66 (t, 1H, J = 7.8 Hz), 7.77-7.79 (m, 2H) 7.84 (d, 2H, J = 8.3 Hz), 8.16 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.27 (d, 1H, J = 2.6 Hz), 12.46 (s, 1H).

Example 6 5- [4- (acryloyloxymethyl) phenylazo] -2,4-dihydroxybenzophenone (HBZ-BNA)

Similar to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl acrylate (555 mg) was acid-treated, then diazonium-chlorinated, and diazo-coupled with 2,4-dihydroxybenzophenone (437 mg) to give the desired product. Got.
Yield: 326 mg (41%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 5.26 (s, 2H), 5.89 (dd, 1H, J = 10.7 Hz, 1.5 Hz), 6.19 (dd, 1H, J = 17.6 Hz, 10.7 Hz), 6.48 (dd, 1 H, J = 17.6 Hz, 1.5 Hz), 6.59 (s, 1 H), 7.50 (d, 2 H, J = 8.8 Hz) ), 7.57 (t, 2H, J = 7.8 Hz), 7.65 (t, 1H, J = 7.3 Hz), 7.73-7.75 (m, 2H), 7.79 (d , 2H, J = 8.8 Hz), 8.24 (s, 1H), 12.91 (s, 1H), 13.89 (s, 1H).

Example 7 5- [4- (acryloyloxymethyl) phenylazo] -2-hydroxy-4-methoxybenzophenone (MBZ-BNA)

Similarly to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl acrylate (555 mg) was acid-treated and then diazonium chloride, followed by diazo coupling with 2-hydroxy-4-methoxybenzophenone (456 mg). The desired product was obtained.
Yield: 460 mg (55%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 4.09 (s, 3H), 5.25 (s, 2H), 5.88 (dd, 1H, J = 10.3 Hz, 1.5 Hz), 6 .18 (dd, 1H, J = 17.1 Hz, 10.3 Hz), 6.46 (dd, 1H, J = 17.1 Hz, 1.5 Hz), 6.71 (s, 1H), 7.46 ( d, 2H, J = 8.8 Hz), 7.53 (t, 2H, J = 7.8 Hz), 7.61 (t, 1H, J = 6.6 Hz), 7.70-7.72 (m , 2H), 7.80 (d, 2H, J = 8.3 Hz), 8.04 (s, 1H), 12.92 (s, 1H).

Example 8 5- [4- (acryloyloxymethyl) phenylazo] -4-ethoxy-2-hydroxybenzophenone (EBZ-BNA)

Similarly to the synthesis of NBZ-BNM, 4- (tert-butoxycarbonylamino) benzyl acrylate (555 mg) was acid-treated and then diazonium chloride, and diazo coupling with 4-ethoxy-2-hydroxybenzophenone (485 mg) was performed. The desired product was obtained.
Yield: 477 mg (55%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.58 (t, 3H, J = 7.4 Hz), 4.33 (q, 2H, J = 7.4 Hz), 5.25 (s, 2H) 5.88 (dd, 1H, J = 10.8 Hz, 1.5 Hz), 6.18 (dd, 1H, J = 17.6 Hz, 10.8 Hz), 6.47 (dd, 1H, J = 17) .6 Hz, 1.5 Hz), 6.68 (s, 1 H), 7.47 (d, 2 H, J = 8.8 Hz), 7.53 (t, 2 H, J = 7.3 Hz), 7.61 (T, 1H, J = 7.4 Hz), 7.69-7.71 (m, 2H), 7.81 (d, 2H, J = 8.3 Hz), 8.03 (s, 1H), 12 .90 (s, 1H).

Example 9 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethyl] phenylazo] benzophenone (NBZ-PEM)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl methacrylate (610 mg) was acid-treated, then diazonium-chlorinated, and diazo-coupled with 2-hydroxybenzophenone (396 mg). The target was obtained.
Yield: 605 mg (73%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.92 (t, 3H, J = 1.5 Hz), 3.05 (t, 2H, J = 7.4 Hz), 4.39 (t, 2H, J = 6.8 Hz), 5.54 (quintet, 1H, J = 1.5 Hz), 6.07 (t, 1H, J = 1.0 Hz), 7.19 (d, 1H, J = 8.8 Hz) ), 7.35 (d, 2H, J = 8.3 Hz), 7.56 (tt, 2H, J = 7.8 Hz, 1.5 Hz), 7.65 (tt, 1H, J = 7.3 Hz) 2.0 Hz), 7.77-7.81 (m, 4H), 8.15 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.25 (d, 1H, J = 2.4 Hz) ), 12.43 (s, 1H).

Example 10 2,4-Dihydroxy-5- [4- [2- (methacryloyloxy) ethyl] phenylazo] benzophenone (HBZ-PEM)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl methacrylate (610 mg) was diazonium salified and subjected to diazo coupling with 2,4-dihydroxybenzophenone (437 mg). I got a thing.
Yield: 392 mg (41%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.91 (s, 3H), 3.04 (t, 2H, J = 6.8 Hz), 4.38 (t, 2H, J = 6.8 Hz) 5.54 (q, 1H, J = 1.6 Hz), 6.06 (s, 1H), 6.57 (s, 1H), 7.36 (d, 2H, J = 8.8 Hz), 7 .55 (t, 2H, J = 6.8 Hz), 7.63 (tt, 1H, J = 72 Hz, 2.0 Hz), 7.18-7.45 (m, 4H), 8.21 (s, 1H), 12.88 (s, 1H), 13.95 (s, 1).

Example 11 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethyl] phenylazo] -4-methoxybenzophenone (MBZ-PEM)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl methacrylate (610 mg) was diazonium salified and diazo-coupled with 2-hydroxy-4-methoxybenzophenone (456 mg). The target was obtained.
Yield: 631 mg (71%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.90 (s, 3H), 3.02 (t, 2H, J = 7.2 Hz), 4.08 (s, 3H), 4.37 (t , 2H, J = 6.8 Hz), 5.53 (t, 1H, J = 1.6 Hz), 6.05 (s, 1H), 6.69 (s, 1H), 7.31 (d, 2H) , J = 8.4 Hz), 7.51 (t, 2H, J = 7.6 Hz), 7.60 (t, 1H, J = 7.2 Hz), 7.69 (d, 2H, J = 6. 8 Hz), 7.74 (d, 2H, J = 8.4 Hz), 8.02 (s, 1H), 12.90 (s, 1H).

Example 12 4-Ethoxy-2-hydroxy-5- [4- [2- (methacryloyloxy) ethyl] phenylazo] benzophenone (EBZ-PEM)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl methacrylate (610 mg) was acid-treated and then diazonium chloride to give 4-ethoxy-2-hydroxybenzophenone (485 mg) and diazo Coupling was performed to obtain the target product.
Yield: 632 mg (69%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.58 (t, 3H, J = 7.6 Hz), 1.92 (t, 3H, J = 1.5 Hz), 3.04 (t, 2H, J = 6.8 Hz), 4.33 (q, 2H, J = 7.3 Hz), 3.28 (t, 2H, J = 6.8 Hz), 5.54 (quintet, 1H, J = 1.6 Hz) ), 6.08 (q, 1H, J = 1.1 Hz), 6.68 (s, 1H), 7.32 (d, 2H, J = 8.3 Hz), 7.52 (t, 2H, J = 6.8 Hz), 7.60 (tt, 1H, J = 7.3 Hz, 2.0 Hz), 7.69-7.71 (m, 2H), 7.76 (d, 2H, J = 8. 8 Hz), 8.02 (s, 1H), 12.89 (s, 1H).

Example 13 5- [4- [2- (Acryloyloxy) ethyl] phenylazo] -2-hydroxybenzophenone (NBZ-PEA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl acrylate (583 mg) was acid-treated, then diazonium chloride, and diazo-coupled with 2-hydroxybenzophenone (396 mg). The target was obtained.
Yield: 561 mg (70%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 3.05 (t, 2H, J = 6.8 Hz), 4.41 (t, 2H, J = 6.8 Hz), 5.82 (dd, 1H, J = 10.7 Hz, 1.5 Hz), 6.10 (dd, 1 H, J = 17.6 Hz, 10.2 Hz), 6.39 (dd, 1 H, J = 17.6 Hz, 1.4 Hz), 7 .20 (d, 1H, J = 9.3 Hz), 7.35 (d, 2H, J = 8.8 Hz), 7.56 (t, 2H, J = 7.8 Hz), 7.65 (tt, 1H, J = 7.3 Hz, 2.0 Hz), 7.77-7.80 (m, 4H), 8.15 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.25 (d , 1H, J = 2.4 Hz), 12.43 (s, 1H).

Example 14 5- [4- [2- (acryloyloxy) ethyl] phenylazo] -2,4-dihydroxybenzophenone (HBZ-PEA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl acrylate (583 mg) was acid-treated and then diazonium chloride, and 2,4-dihydroxybenzophenone (437 mg) was combined with diazo coupling. To obtain the target product.
Yield: 342 mg (41%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 3.05 (t, 2H, J = 7.0 Hz), 4.41 (t, 2H, J = 7.0 Hz), 5.83 (dd, 1H, J = 10.2 Hz, 1.5 Hz), 6.10 (dd, 1 H, J = 17.6 Hz, 10.2 Hz), 6.39 (dd, 1 H, J = 17.6 Hz, 1.5 Hz), 6 .58 (s, 1H), 7.35 (d, 2H, J = 8.8 Hz), 7.56 (t, 2H, J = 7.8 Hz), 7.64 (tt, 1H, J = 7. 3 Hz, 1.5 Hz), 7.73-7.75 (m, 4H), 8.22 (s, 1H), 12.89 (s, 1H), 13.95 (s, 1H).

Example 15 5- [4- [2- (acryloyloxy) ethyl] phenylazo] -2-hydroxy-4-methoxycybenzophenone (MBZ-PEA)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl acrylate (583 mg) was acid-treated and then diazonium chloride to give 2-hydroxy-4-methoxybenzophenone (456 mg) and diazo Coupling was performed to obtain the target product.
Yield: 621 mg (72%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 3.03 (t, 2H, J = 7.3 Hz), 4.09 (s, 3H), 4.40 (t, 2H, J = 7.3 Hz) 5.82 (dd, 1H, J = 10.2 Hz, 1.5 Hz), 6.09 (dd, 1H, J = 17.6 Hz, 10.2 Hz), 6.38 (dd, 1H, J = 17) .6 Hz, 1.5 Hz), 6.70 (s, 1 H), 7.32 (d, 2 H, J = 8.3 Hz), 7.52 (t, 2 H, J = 7.3 Hz), 7.61 (Tt, 1H, J = 7.8 Hz, 1.5 Hz), 7.69-7.76 (m, 4H), 8.02 (s, 1H), 12.91 (s, 1H).

Example 16 5- [4- [2- (acryloyloxy) ethyl] phenylazo] -4-ethoxy-2-hydroxybenzophenone (EBZ-PEA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) phenyl] ethyl acrylate (583 mg) was acid-treated and then diazonium chloride, and 4-ethoxy-2-hydroxybenzophenone (485 mg) and diazo Coupling was performed to obtain the target product.
Yield: 577 mg (65%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.58 (t, 3H, J = 6.8 Hz), 3.04 (t, 2H, J = 7.3 Hz), 4.33 (q, 2H, J = 6.8 Hz), 4.40 (t, 2H, J = 7.3 Hz), 5.82 (dd, 1H, J = 10.3 Hz, 1.5 Hz), 6.10 (dd, 1H, J = 17.6 Hz, 10.3 Hz), 6.38 (dd, 1 H, J = 17.6 Hz, 1.5 Hz), 6.68 (s, 1 H), 7.32 (d, 2 H, J = 8. 8 Hz), 7.52 (t, 2H, J = 7.8 Hz), 7.60 (tt, 1H, J = 7.3 Hz, 1.5 Hz), 7.69-7.71 (m, 2H), 7.76 (d, 2H, J = 8.3 Hz), 8.02 (s, 1H), 12.89 (s, 1H).

Example 17 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] benzophenone (NBZ-EMA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium salified to give 2-hydroxybenzophenone (396 mg) and diazo coupling. The target product was obtained.
Yield: 623 mg (68%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 196 (s, 3H), 4.50-4.52 (m, 2H), 4.59-4.61 (m, 2H), 5.60 (t , 1H, J = 1.5 Hz), 6.15 (s, 1H), 7.22 (d, 1H, J = 8.8 Hz), 7.58 (t, 2H, J = 7.8 Hz), 7 .67 (t, 1H, J = 7.3 Hz), 7.79 (d, 2H, J = 7.3 Hz), 7.88 (d, 2H, J = 8.3 Hz), 8.15-8. 19 (m, 3H), 8.31 (d, 1H, J = 1.9 Hz), 12.52 (s, 1H).

Example 18 2,4-Dihydroxy-5- [4- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] benzophenone (HBZ-EMA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was subjected to acid treatment followed by diazonium chloride to give 2,4-dihydroxybenzophenone (437 mg) and diazo cup. Ringing was performed to obtain the target product.
Yield: 392 mg (41%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.94 (s, 3H), 4.49-4.51 (m, 2H), 4.58-4.60 (m, 2H), 5.58 (T, 1H, J = 1.2 Hz), 6.13 (t, 1H, J = 1.6 Hz), 6.59 (s, 1H), 7.56 (tt, 2H, J = 7.6 Hz, 1.2 Hz), 7.64 (tt, 1H, J = 7.6 Hz, 2.4 Hz), 7.72-774 (m, 2H), 7.83 (dt, 2H, J = 8.4 Hz, 2 .0 Hz), 8.15 (dt, 2H, J = 8.8 Hz, 2.0 Hz), 8.27 (s, 1H), 12.93 (s, 1H), 13.77 (s, 1H).

Example 19 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] -4-methoxybenzophenone (MBZ-EMA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium salified with 2-hydroxy-4-methoxybenzophenone (456 mg). Diazo coupling was performed to obtain the target product.
Yield: 622 mg (64%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.94 (s, 3H), 4.10 (s, 3H), 4.48-4.52 (m, 2H), 4.56-4.59 (M, 2H), 5.58 (t, 1H, J = 1.6 Hz), 6.13 (s, 1H), 6.71 (s, 1H), 7.53 (t, 2H, J = 7) .6 Hz), 7.61 (t, 1H, J = 7.6 Hz), 7.70 (d, 2H, J = 6.8 Hz), 7.82 (d, 2H, J = 8.8 Hz), 8 .08 (s, 1H), 8.12 (dt, 2H, J = 8.8 Hz, 2.0 Hz), 12.94 (s, 1H).

Example 20 4-Ethoxy-2-hydroxy-5- [4- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] benzophenone (EBZ-EMA)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium salified with 4-ethoxy-2-hydroxybenzophenone (485 mg). Diazo coupling was performed to obtain the target product.
Yield: 673 mg (67%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.60 (t, 3H, J = 6.8 Hz), 1.95 (dd, 3H, J = 1.5 Hz, 1.0 Hz), 4.34 ( q, 2H, J = 7.3 Hz), 4.50-4.53 (m, 2H), 4.57-4.61 (m, 2H), 5.59 (quintet, 1H, J = 1.5 Hz) ), 6.15 (t, 1H, J = 1.0 Hz), 6.69 (s, 1H), 7.54 (t, 2H, J = 7.8 Hz), 7.62 (tt, 1H, J = 7.3 Hz, 1.5 Hz), 7.70-7.72 (m, 2H), 7.84 (dt, 2H, J = 8.8 Hz, 2.0 Hz), 8.09 (s, 1H) 8.13 (dt, 2H, J = 8.6 Hz, 2.0 Hz), 12.94 (s, 1H).

Example 21 5- [4- [2- (acryloyloxy) ethoxycarbonyl] phenylazo] -2-hydroxybenzophenone (NBZ-EAC)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl acrylate (671 mg) was acid-treated and then diazonium-chlorinated to give 2-hydroxybenzophenone (396 mg) and diazo coupling. The target product was obtained.
Yield: 718 mg (81%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 4.50-4.61 (m, 4H), 5.87 (dd, 1H, J = 10.2 Hz, 1.4 Hz), 6.17 (dd, 1H, J = 17.6 Hz, 10.2 Hz), 6.46 (dd, 1 H, J = 17.6 Hz, 1.4 Hz), 7.22 (d, 1 H, J = 9.3 Hz), 7.58 (T, 2H, J = 7.4 Hz), 7.67 (tt, 1H, J = 7.3 Hz, 1.5 Hz), 7.76-7.80 (m, 2H), 7.88 (d, 2H, J = 8.8 Hz), 8.15-8.20 (m, 3H), 8.32 (d, 1H, J = 2.4 Hz), 12.52 (s, 1H).

Example 22 5- [4- [2- (acryloyloxy) ethoxycarbonyl] phenylazo] -2,4-dihydroxybenzophenone (HBZ-EAC)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl acrylate (671 mg) was acid-treated and then diazonium-chlorinated to give 2,4-dihydroxybenzophenone (437 mg) and diazo cup. Ringing was performed to obtain the target product.
Yield: 294 mg (32%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 4.52-4.54 (m, 2H), 4.58-4.61 (m, 2H), 5.87 (dd, 1H, J = 10. 8 Hz, 1.5 Hz), 6.16 (dd, 1 H, J = 17.6 Hz, 10.8 Hz), 6.46 (dd, 1 H, J = 17.6 Hz, 10.8 Hz), 6.60 (s) , 1H), 7.58 (d, 2H, J = 7.8 Hz), 7.66 (tt, 1H, J = 7.3 Hz, 1.5 Hz), 7.74-7.76 (m, 2H) 7.85 (d, 2H, J = 8.8 Hz), 8.16 (d, 2H, J = 8.8 Hz), 8.28 (s, 1H), 12.95 (s, 1H), 13 .74 (s, 1H).

Example 23 5- [4- [2- (acryloyloxy) ethoxycarbonyl] phenylazo] -2-hydroxy-4-methoxybenzophenone (MBZ-EAC)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl acrylate (671 mg) was acid-treated and then diazonium salified with 2-hydroxy-4-methoxybenzophenone (456 mg). Diazo coupling was performed to obtain the target product.
Yield: 656 mg (69%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 4.11 (s, 3H), 4.44-4.60 (m, 4H), 5.87 (dd, 1H, J = 10.2 Hz, 1. 5 Hz), 6.16 (dd, 1 H, J = 17.6 Hz, 10.7 Hz), 6.45 (dd, 1 H, J = 17.6 Hz, 1.5 Hz), 6.72 (s, 1 H), 7.54 (t, 2H, J = 7.3 Hz), 7.63 (t, 1H, J = 7.3 Hz), 7.70-7.72 (m, 2H), 7.78 (d, 2H) , J = 8.8 Hz), 8.09 (s, 1H), 8.13 (d, 2H, J = 8.8 Hz), 12.96 (s, 1H).

Example 24 5- [4- [2- (acryloyloxy) ethoxycarbonyl] phenylazo] -4-ethoxy-2-hydroxybenzophenone (EBZ-EAC)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoyloxy] ethyl acrylate (671 mg) was acid-treated and then diazonium salified with 4-ethoxy-2-hydroxybenzophenone (485 mg). Diazo coupling was performed to obtain the target product.
Yield: 644 mg (66%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.60 (t, 3H, J = 6.8 Hz), 4.35 (q, 2H, J = 6.8 Hz), 4.51-4.54 ( m, 2H), 4.57-4.60 (m, 2H), 5.87 (dd, 1H, J = 10.7 Hz, 1.4 Hz), 6.16 (dd, 1H, J = 17.6 Hz) , 10.7 Hz), 6.46 (dd, 1 H, J = 17.6 Hz, 1.4 Hz), 6.69 (s, 1 H), 7.54 (t, 2 H, J = 6.8 Hz), 7 .62 (tt, 1H, J = 7.3 Hz, 1.4 Hz), 7.70-7.72 (m, 2H), 7.84 (d, 2H, J = 8.7 Hz), 8.10 (S, 1H), 8.14 (d, 2H, J = 8.7 Hz), 12.94 (s, 1H).

Example 25 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] benzophenone (NBZ-AMA)

As in the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified to give 2-hydroxybenzophenone (396 mg) and diazo coupling. The target product was obtained.
Yield: 521 mg (57%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 2.00 (s, 3H), 3.80 (q, 2H, J = 5.4 Hz), 4.42 (t, 2H, J = 5.8 Hz) , 5.62 (t, 1H, J = 1.5 Hz), 6.16 (t, 1H, J = 1.5 Hz), 6.65 (br.t, J = 4.9 Hz), 7.21 ( d, 1H, J = 8.8 Hz), 7.58 (t, 2H, J = 7.3 Hz), 7.66 (tt, 1H, J = 7.3 Hz, 1.5 Hz), 7.77-7 .79 (m, 2H), 7.89 (s, 4H), 8.17 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.30 (d, 1H, J = 2.4 Hz) , 12.51 (s, 1H).

Example 26 2,4-Dihydroxy-5- [4- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] benzophenone (HBZ-AMA)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified to give 2,4-dihydroxybenzophenone (437 mg) and diazo cup. Ringing was performed to obtain the target product.
Yield: 274 mg (29%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.97 (t, 3H, J = 1.2 Hz), 3.80 (q, 2H, J = 5.4 Hz), 4.42 (t, 2H, J = 5.4 Hz), 5.63 (quintet, 1H, J = 1.7 Hz), 6.16 (s, 1H), 6.60 (s, 1H), 6.67 (br.t, 1H, J = 5.4 Hz), 7.57 (t, 2H, J = 7.3 Hz), 7.65 (tt, 1H, J = 7.4 Hz, 2.0 Hz), 7.73-7.76 (m , 2H), 7.87 (dd, 4H, J = 17.6 Hz, 8.8 Hz), 8.21 (s, 1H), 12.93 (s, 1H), 13.79 (s, 1H).

Example 27 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] -4-methoxybenzophenone (MBZ-AMA)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified with 2-hydroxy-4-methoxybenzophenone (456 mg). Diazo coupling was performed to obtain the target product.
Yield: 585 mg (60%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.96 (s, 3H), 3.80 (q, 2H, J = 5.4 Hz), 4.11 (s, 3H), 4.42 (t , 2H, J = 5.4 Hz), 5.62 (t, 1H, J = 1.7 Hz), 6.16 (s, 1H), 6.63 (br.t, 1H, J = 5.5 Hz) 6.72 (s, 1H), 7.54 (t, 2H, J = 6.8 Hz), 7.63 (tt, 1H, J = 7.8 Hz, 1.5 Hz), 7.85-7. 86 (m, 4H), 8.08 (s, 1H), 12.95 (s, 1H).

Example 28 4-Ethoxy-2-hydroxy-5- [4- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] benzophenone (EBZ-AMA)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified with 4-ethoxy-2-hydroxybenzophenone (485 mg). Diazo coupling was performed to obtain the target product.
Yield: 547 mg (55%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.58 (t, 3H, J = 6.8 Hz), 1.95 (t, 3H, J = 1.2 Hz), 3.79 (q, 2H, J = 5.2 Hz), 4.33 (q, 2H, J = 7.2 Hz), 4.40 (t, 2H, J = 5.2 Hz), 5.61 (t, 1H, J = 1.6 Hz) ), 6.14 (s, 1H), 6.61 (br.t, 1H, J = 5.2 Hz), 6.68 (s, 1H), 7.52 (t, 2H, J = 7.2 Hz) ), 7.61 (tt, 1H, J = 7.6 Hz, 2.4 Hz), 7.69 (d, 2H, J = 7.2 Hz), 7.85 (s, 4H) 8.07 (s, 1H), 12.91 (s, 1H).

Example 29 5- [4- [2- (acryloyloxy) ethylaminocarbonyl] phenylazo] -2-hydroxybenzophenone (NBZ-AAC)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl acrylate (669 mg) was acid-treated and then diazonium-chlorinated to give 2-hydroxybenzophenone (396 mg) and diazo coupling. The target product was obtained.
Yield: 479 mg (54%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 3.80 (q, 2H, J = 4.9 Hz), 4.43 (t, 2H, J = 4.9 Hz), 5.90 (dd, 1H, J = 10.2 Hz, 1.5 Hz), 6.17 (dd, 1 H, J = 17.1 Hz, 10.2 Hz), 6.47 (dd, 1 H, J = 17.1 Hz, 1.5 Hz), 6 .64 (br.t, 1H, J = 5.8 Hz), 7.21 (d, 1H, J = 5.8 Hz), 7.58 (t, 1H, J = 8.8 Hz), 7.67 ( t, 1H, J = 7.3 Hz), 7.77-7.80 (m, 2H), 7.89 (s, 4H), 8.18 (dd, 1H, J = 9.3 Hz, 2.4 Hz) ), 8.30 (d, 1H, J = 2.4 Hz), 12.50 (s, 1H).

Example 30 5- [4- [2- (acryloyloxy) ethylaminocarbonyl] phenylazo] -2,4-dihydroxybenzophenone (HBZ-AAC)

Similar to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl acrylate (669 mg) was acid-treated and then diazonium chloride, and 2,4-dihydroxybenzophenone (437 mg) and diazocup Ringing was performed to obtain the target product.
Yield: 258 mg (28%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 3.80 (q, 2H, J = 5.4 Hz), 4.43 (t, 2H, J = 5.4 Hz), 5.90 (dd, 1H, J = 10.2 Hz, 1.5 Hz), 6.17 (dd, 1 H, J = 17.6 Hz, 10.2 Hz), 6.48 (dd, 1 H, J = 17.6 Hz, 1.5 Hz), 6 .60 (s, 1H), 6.67 (br.t, 1H, J = 5.4 Hz), 7.58 (t, 2H, J = 7.3 Hz), 7.66 (t, 1H, J = 7.8 Hz), 7.74-7.76 (m, 2H), 7.85 (d, 2H, J = 8.8 Hz), 7.90 (d, 2H, J = 8.8 Hz), 8. 27 (s, 1H), 12.94 (s, 1H), 13.80 (s, 1H).

Example 31 5- [4- [2- (acryloyloxy) ethylaminocarbonyl] phenylazo] -2-hydroxy-4-methoxybenzophenone (MBZ-AAC)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl acrylate (669 mg) was acid-treated and then diazonium salified with 2-hydroxy-4-methoxybenzophenone (456 mg). Diazo coupling was performed to obtain the target product.
Yield: 743 mg (78%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 3.80 (q, 2H, J = 5.4 Hz), 4.11 (s, 3H), 4.42 (t, 2H, J = 5.4 Hz) 5.89 (dd, 1H, J = 10.8 Hz, 1.5 Hz), 6.16 (dd, 1H, J = 17.6 Hz, 10.8 Hz), 6.47 (dd, 1H, J = 17) .6 Hz, 1.5 Hz), 6.63 (br.t, 1H, J = 5.4 Hz), 6.72 (s, 1H), 7.54 (t, 2H, J = 7.3 Hz), 7 .63 (t, 1H, J = 7.8 Hz), 7.70-7.72 (m, 2H), 7.86 (d, 4H, J = 2.9 Hz), 8.08 (s, 1H) , 12.05 (s, 1H).

Example 32 5- [4- [2- (acryloyloxy) ethylaminocarbonyl] phenylazo] -4-ethoxy-2-hydroxybenzophenone (EBZ-AAC)

Similarly to the synthesis of NBZ-BNM, 2- [4- (tert-butoxycarbonylamino) benzoylamino] ethyl acrylate (669 mg) was acid-treated and then diazonium salified with 4-ethoxy-2-hydroxybenzophenone (485 mg). Diazo coupling was performed to obtain the target product.
Yield: 601 mg (62%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.60 (t, 3H, J = 7.3 Hz), 3.80 (q, 2H, J = 5.3 Hz), 4.34 (q, 2H, J = 7.3 Hz), 4.42 (t, 2H, J = 5.3 Hz), 5.90 (dd, 1H, J = 10.7 Hz, 1.5 Hz), 6.17 (dd, 1H, J = 17.6 Hz, 10.7 Hz), 6.47 (dd, 1H, J = 17.6 Hz, 1.5 Hz), 6.62 (br.t, 1H), 6.69 (s, 1H), 7 .54 (t, 2H, J = 7.8 Hz), 7.62 (t, 1H, J = 7.8 Hz), 7.70-7.72 (m, 2H), 7.86 (s, 4H) , 8.08 (s, 1H), 12.94 (s, 1H).

Example 33 2-Hydroxy-5- [4- [2- (methacrylamide) ethyl] phenylazo] benzophenone (NBZ-PHM)

Similar to the synthesis of NBZ-BNM, 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.
Yield: 630 mg (76%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.92 (s, 3H), 2.93 (t, 2H, J = 6.8 Hz), 3.61 (q, 2H, J = 6.8 Hz) , 5.29 (t, 1H, J = 1.2 Hz), 5.61 (s, 1H), 5.79 (br.t, 1H), 7.20 (d, 1H, J = 8.8 Hz) 7.32 (d, 2H, J = 8.3 Hz), 7.57 (t, 2H, J = 7.3 Hz), 7.66 (t, 1H, J = 7.3 Hz), 7.77- 7.81 (m, 4H), 8.15 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.26 (d, 1H, J = 2.4 Hz), 12.44 (s, 1H) ).

Example 34 2,4-Dihydroxy-5- [4- [2- (methacrylamide) ethyl] phenylazo] benzophenone (HBZ-PHM)

Similar to the synthesis of NBZ-BNM, 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.
Yield: 326 mg (38%)
¹ H-NMR (400 MHz, 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), 5.80 (br.t, 1H), 6. 58 (s, 1H), 7.33 (d, 2H, J = 8.8 Hz), 7.56 (t, 2H, J = 7.2 Hz), 7.64 (tt, 1H, J = 7.3 Hz) , 2.4 Hz), 7.73-7.76 (m, 4H), 8.23 (s, 1H), 12.89 (s, 1H), 13.94 (s, 1H).

Example 35 2-Hydroxy-5- [4- [2- (methacrylamide) ethyl] phenylazo] -4-methoxybenzophenone (MBZ-PHM)

Similarly to the synthesis of NBZ-BNM, 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.
Yield: 553 mg (62%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.92 (s, 3H), 2.92 (t, 2H, J = 6.8 Hz), 3.60 (q, 2H, J = 6.8 Hz) , 4.09 (s, 3H), 5.29 (t, 1H, J = 1.4 Hz), 5.60 (s, 1H), 5.76 (br.t, 1H), 6.71 (s , 1H), 7.29 (d, 2H, J = 8.8 Hz), 7.53 (t, 2H, J = 8.8 Hz), 7.61 (t, 1H, J = 7.8 Hz), 7 .71 (d, 2H, J = 6.8 Hz), 7.76 (d, 2H, J = 6.8 Hz), 8.03 (s, 1H), 12.91 (s, 1H).

Example 36 4-Ethoxy-2-hydroxy-5- [4- [2- (methacrylamide) ethyl] phenylazo] benzophenone (EBZ-PHM)

In the same manner as in the synthesis of NBZ-BNM, 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.
Yield: 652 mg (71%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.59 (t, 3H, J = 6.8 Hz), 1.92 (s, 3H), 2.92 (t, 2H, J = 6.8 Hz) 3.60 (q, 2H, J = 6.8 Hz), 4.33 (q, 2H, J = 6.8 Hz), 5.29 (t, 1H, J = 1.2 Hz), 5.60 ( s, 1H), 5.77 (br.t, 1H), 6.68 (s, 1H), 7.30 (d, 2H, J = 8.3 Hz), 7.53 (t, 2H, J = 7.3 Hz), 7.61 (t, 1H, J = 7.3 Hz), 7.71 (d, 2H, J = 7.3 Hz), 7.78 (d, 2H, J = 8.4 Hz), 8.03 (s, 1H), 12.90 (s, 1H).

Example 37 5- [4- [2- (acrylamide) ethyl] phenylazo] -2-hydroxybenzophenone (NBZ-PHA)

Similarly to the synthesis of NBZ-BNM, 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.
Yield: 525 mg (66%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 2.94 (t, 2H, J = 6.8 Hz), 3.64 (q, 2H, J = 6.8 Hz), 5.56 (br.t, 1H), 5.63 (dd, 1H, J = 10.3 Hz, 1.5 Hz), 6.02 (dd, 1H, J = 17.1 Hz, 10.3 Hz), 6.27 (dd, 1H, J = 17.1 Hz, 1.5 Hz), 7.20 (d, 1 H, J = 9.3 Hz), 7.32 (d, 2 H, J = 8.3 Hz), 7.57 (tt, 2 H, J = 7.3 Hz, 1.5 Hz), 7.66 (t, 1 H, J = 7.8 Hz), 7.77-7.81 (m, 4 H), 8.15 (dd, 1 H, J = 9.3 Hz) , 2.4 Hz), 8.26 (d, 1H, J = 2.4 Hz), 12.45 (s, 1H).

Example 38 5- [4- [2- (Acrylamide) ethyl] phenylazo] -2,4-dihydroxybenzophenone (HBZ-PHA)

Similar to the synthesis of NBZ-BNM, 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.
Yield: 313 mg (38%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 2.94 (t, 2H, J = 6.8 Hz), 3.64 (q, 2H, J = 6.4 Hz), 5.56 (br.t, 1H), 5.64 (dd, 1H, J = 10.8 Hz, 1.5 Hz), 6.03 (dd, 1H, J = 17.1 Hz, 10.8 Hz), 6.28 (dd, 1H, J = 17.1 Hz, 1.5 Hz), 6.58 (s, 1H), 7.33 (d, 2H, J = 8.3 Hz), 7.54-7.59 (m, 2H), 7.65 (T, 1H, J = 78 Hz), 7.73-7.76 (m, 4H), 8.23 (s, 1H), 12.90 (s, 1H), 13.94 (s, 1H).

Example 39 5- [4- [2- (acrylamide) ethyl] phenylazo] -2-hydroxy-4-methoxybenzophenone (MBZ-PHA)

Similarly to the synthesis of NBZ-BNM, 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.
Yield: 510 mg (59%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 2.92 (t, 2H, J = 6.8 Hz), 3.62 (q, 2H, J = 6.8 Hz), 4.09 (s, 3H) 5.56 (br.t, 1H), 5.53 (dd, 1H, J = 10.2 Hz, 1.5 Hz), 6.02 (dd, 1H, J = 17.1 Hz, 10.2 Hz), 6.26 (dd, 1H, J = 17.1 Hz, 1.5 Hz), 6.70 (s, 1H), 7.29 (d, 2H, J = 8.3 Hz), 7.53 (t, 2H) , J = 7.3 Hz), 7.61 (t, 1H, J = 7.8 Hz), 7.70-7.76 (m, 4H), 8.03 (s, 1H), 12.92 (s) , 1H).

Example 40 5- [4- [2- (Acrylamide) ethyl] phenylazo] -4-ethoxy-2-hydroxybenzophenone (EBZ-PHA)

Similarly to the synthesis of NBZ-BNM, 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.
Yield: 583 mg (66%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.59 (t, 3H, J = 7.1 Hz), 2.93 (t, 2H, J = 6.9 Hz), 3.64 (q, 2H, J = 6.9 Hz), 4.33 (q, 2H, J = 7.1 Hz), 5.52 (br.t, 1H), 5.63 (dd, 1H, J = 10.4 Hz, 1.3 Hz) ), 6.02 (dd, 1H, J = 16.9 Hz, 10.4 Hz), 6.27 (dd, 1H, J = 16.9 Hz, 1.3 Hz), 6.68 (s, 1H), 7 .29 (d, 2H, J = 8.5 Hz), 7.50-7.55 (m, 2H), 7.61 (t, 1H, J = 7.4 Hz), 7.69-7.72 ( m, 2H), 7.96 (d, 2H, J = 8.3 Hz), 8.02 (s, 1H), 12.89 (s, 1H).

Example 41 2-Hydroxy-5- [3- (methacryloyloxymethyl) phenylazo] benzophenone (NBZ-3BM)

In the same manner as in the synthesis of NBZ-BNM, 3-aminobenzyl methacrylate (455 mg) was acid-treated and then diazonium-chlorinated, followed by diazo coupling with 2-hydroxybenzophenone (396 mg) to obtain the desired product.
Yield: 604 mg (75%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.98 (s, 3H), 5.23 (s, 2H), 5.61 (t, 1H, J = 1.5 Hz), 6.18 (s , 1H), 7.20 (d, 1H, J = 9.3 Hz), 7.48-7.51 (m, 2H), 7.57 (t, 2H, J = 7.3 Hz), 7.66. (T, 1H, J = 7.3 Hz), 7.78-7.82 (m, 3H), 7.85 (s, 1H), 8.16 (dd, 1H, J = 9.3 Hz, 2. 4 Hz), 8.28 (d, 1 H, J = 2.0 Hz), 12.47 (s, 1 H).

Example 42 2,4-Dihydroxy-5- [3- (methacryloyloxymethyl) phenylazo] benzophenone (HBZ-3BM)

In the same manner as in the synthesis of NBZ-BNM, 3-aminobenzyl methacrylate hydrochloride (455 mg) was subjected to acid treatment followed by diazonium chloride, and diazo coupling with 2,4-dihydroxybenzophenone (437 mg) to obtain the desired product.
Yield: 314 mg (37%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.98 (s, 3H), 5.26 (s, 2H), 5.61 (t, 1H, J = 1.5 Hz), 6.18 (s , 1H), 6.59 (s, 1H), 7.47-7.52 (m, 2H), 7.57 (t, 2H, J = 7.8 Hz), 7.65 (tt, 1H, J = 7.3 Hz, 2.0 Hz), 7.74-7.77 (m, 3H), 7.80 (s, 1H), 8.25 (s, 1H), 12.91 (s, 1H), 13.87 (s, 1H).

Example 43 2-Hydroxy-5- [3- (methacryloyloxymethyl) phenylazo] -4-methoxybenzophenone (MBZ-3BM)

In the same manner as in the synthesis of NBZ-BNM, 3-aminobenzyl methacrylate (455 mg) was acid-treated and then diazonium-chlorinated, followed by diazo coupling with 2-hydroxy-4-methoxybenzophenone (456 mg) to obtain the desired product. It was.
Yield: 679 mg (79%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.98 (s, 3H), 4.10 (s, 3H), 5.26 (t, 1H, J = 1.5 Hz), 5.60 (s , 1H), 6.17 (s, 1H), 6.71 (s, 1H), 7.43-7.49 (m, 2H), 7.53 (t, 2H, J = 7.3 Hz), 7.62 (t, 1H, J = 7.8 Hz), 7.70-7.72 (m, 2H), 7.76 (dt, 1H, J = 6.8 Hz, 2.0 Hz), 7.80 (S, 1H), 8.05 (s, 1H), 12.93 (s, 1H).

Example 44 4-Ethoxy-2-hydroxy-5- [3- (methacryloyloxymethyl) phenylazo] benzophenone (EBZ-3BM)

Similar to the synthesis of NBZ-BNM, 3-aminobenzyl hydrochloride (455 mg) methacrylate was acid-treated, then diazonium salified, and diazo-coupled with 4-ethoxy-2-hydroxybenzophenone (485 mg) to obtain the desired product. It was.
Yield: 607 mg (68%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.59 (t, 3H, J = 6.8 Hz), 1.98 (t, 3H, J = 1.4 Hz), 4.33 (q, 2H, J = 6.8 Hz), 5.26 (s, 2H), 5.60 (t, 1H, J = 1.7 Hz), 6.18 (s, 1H), 6.69 (s, 1H), 7 .42-7.49 (m, 2H), 7.53 (t, 2H, J = 7.8 Hz), 7.61 (tt, 1H, J = 7.3 Hz, 2.0 Hz), 7.69- 7.71 (m, 2H), 7.78 (dt, 1H, J = 7.3 Hz, 2.0 Hz), 7.81 (s, 1H), 8.04 (s, 1H), 12.91 ( s, 1H).

Example 45 2-Hydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] benzophenone (NBZ-3EM)

As in the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium salified to give 2-hydroxybenzophenone (396 mg) and diazo coupling. The target product was obtained.
Yield: 672 mg (73%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.93 (s, 3H), 4.50-4.52 (m, 2H), 4.60-4.63 (m, 2H), 5.56 (T, 1H, J = 1.5 Hz), 6.14 (s, 1H), 7.22 (d, 1H, J = 8.8 Hz), 7.58 (dt, 3H, J = 7.8 Hz, 2.0 Hz), 7.67 (t, 1 H, J = 7.3 Hz), 7.78-7.80 (m, 2 H), 8.04 (d, 1 H, J = 8.8 Hz), 8. 12 (d, 1H, J = 7.8 Hz), 8.18 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.31 (d, 1H, J = 2.4 Hz), 8.49 (T, 1H, J = 2.0 Hz), 12.50 (s, 1H).

Example 46 2,4-Dihydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] benzophenone (HBZ-3EM)

Similar to the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium chloride, and 2,4-dihydroxybenzophenone (437 mg) and diazocup Ringing was performed to obtain the target product.
Yield: 228 mg (24%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.93 (s, 3H), 4.50-4.53 (m, 2H), 4.61-4.63 (m, 2H), 5.56 (T, 1H, J = 1.3 Hz), 6.13 (s, 1H), 6.61 (s, 1H), 7.56-7.61 (m, 2H), 8.00 (d, 1H , J = 8.1 Hz), 8.12 (d, 1H, J = 7.8 Hz), 8.28 (s, 1H), 8.44 (t, 1H, J = 1.5 Hz), 12.94. (S, 1H), 13.71 (s, 1H).

Example 47 2-Hydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] -4-methoxybenzophenone (MBZ-3EM)

Similarly to the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium salified with 2-hydroxy-4-methoxybenzophenone (456 mg). Diazo coupling was performed to obtain the target product.
Yield: 695 mg (71%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ 1.94 (s, 3H), 4.10 (s, 3H), 4.49-4.52 (m, 2H), 4.60-4.62 (m , 2H), 5.58 (t, 1H, J = 1.7 Hz), 6.14 (s, 1H), 6.72 (s, 1H), 7.52-7.56 (m, 3H), 7.63 (tt, 1H, J = 7.8 Hz, 2.4 Hz), 7.70-7.72 (m, 2H), 7.99 (ddd, 1H, J = 8.0 Hz, 2.0 Hz, 1.0 Hz), 8.08-8.10 (m, 2H), 8.40 (dd, 1H, J = 2.0 Hz, 1.41 Hz), 12.95 (s, 1H).

Example 48 4-Ethoxy-2-hydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonyl] phenylazo] benzophenone (EBZ-3EM)

Similar to the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoyloxy] ethyl methacrylate (699 mg) was acid-treated and then diazonium salified with 4-ethoxy-2-hydroxybenzophenone (485 mg). Diazo coupling was performed to obtain the target product.
Yield: 719 mg (72%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.59 (t, 3H, J = 7.3 Hz), 1.94 (s, 3H), 4.34 (q, 2H, J = 7.3 Hz) 4.49-4.52 (m, 2H), 4.60-4.62 (m, 2H), 5.58 (t, 1H, J = 2.0 Hz), 6.14 (s, 1H) 6.69 (s, 1H), 7.54 (dt, 3H, J = 7.8 Hz, 2.4 Hz), 7.62 (t, 1H, J = 7.3 Hz), 7.70-7. 75 (m, 2H), 8.00 (d, 1H, J = 8.1 Hz), 8.07 (s, 1H), 8.09 (d, 1H, J = 7.8 Hz), 8.46 ( t, 1H, J = 1.7 Hz), 12.93 (s, 1H).

Example 49 2-Hydroxy-5- [3- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] benzophenone (NBZ-3AM)

As in the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified to give 2-hydroxybenzophenone (396 mg) and diazo coupling. The target product was obtained.
Yield: 491 mg (54%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.94 (s, 3H), 3.81 (q, 2H, J = 5.4 Hz), 4.41 (t, 2H, J = 5.4 Hz) , 5.58 (t, 1H, J = 1.5 Hz), 6.14 (s, 1H), 6.63 (br.t, 1H), 7.22 (d, 1H, J = 8.8 Hz) 7.58 (t, 3H, J = 8.3 Hz), 7.67 (t, 1H, J = 7.8 Hz), 7.78-7.80 (m, 2H), 7.87 (d, 1H, J = 8.3 Hz), 8.00 (dt, 1H, J = 7.8 Hz, 1.9 Hz), 8.17 (dd, 1H, J = 9.3 Hz, 2.4 Hz), 8.20 (T, 1H, J = 2.2 Hz), 8.30 (d, 1H, J = 2.4 Hz), 12.50 (s, 1H).

Example 50 2,4-Dihydroxy-5- [3- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] benzophenone (HBZ-3AM)

As in the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified to give 2,4-dihydroxybenzophenone (437 mg) and diazocup Ringing was performed to obtain the target product.
Yield: 289 mg (31%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.93 (s, 3H), 3.80 (q, 2H, J = 5.4 Hz), 4.41 (t, 2H, J = 5.4 Hz) , 5.58 (t, 1H, J = 2.0 Hz), 6.14 (s, 1H), 6.60 (s, 1H), 6.66 (br.t, 1H), 7.56-7 .60 (m, 3H), 7.65 (tt, 1H, J = 7.3 Hz, 2.0 Hz), 7.73-7.75 (m, 2H), 7.84 (dt, 1H, J = 7.8 Hz, 1.5 Hz), 7.93 (d, 1 H, J = 8.3 Hz), 8.19 (t, 1 H, J = 1.9 Hz), 8.27 (s, 1 H), 12. 93 (s, 1H), 13.72 (s, 1H).

Example 51 2-Hydroxy-5- [3- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] -4-methoxybenzophenone (MBZ-3AM)

Similar to the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified with 2-hydroxy-4-methoxybenzophenone (456 mg). Diazo coupling was performed to obtain the target product.
Yield: 447 mg (46%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.95 (s, 3H), 3.80 (q, 2H, J = 5.4 Hz), 4.10 (s, 3H), 4.40 (t , 2H, J = 5.4 Hz), 5.60 (t, 1H, J = 1.5 Hz), 6.15 (t, 1H, J = 1.5 Hz), 6.62 (br.t, 1H) , 6.72 (s, 1H), 7.52-7.56 (m, 3H), 7.62 (tt, 1H, J = 7.8 Hz, 2.4 Hz), 7.70-7.72 ( m, 2H), 7.85 (dt, 1H, J = 8.3 Hz, 1.5 Hz), 7.94 (ddd, 1H, J = 8.3 Hz, 2.0 Hz, 1.0 Hz), 8.07 (S, 1H), 8.14 (t, 1H, J = 1.5 Hz), 12.95 (s, 1H).

Example 52 4-Ethoxy-2-hydroxy-5- [3- [2- (methacryloyloxy) ethylaminocarbonyl] phenylazo] benzophenone (EBZ-3AM)

Similar to the synthesis of NBZ-BNM, 2- [3- (tert-butoxycarbonylamino) benzoylamino] ethyl methacrylate (669 mg) was acid-treated and then diazonium salified with 4-ethoxy-2-hydroxybenzophenone (485 mg). Diazo coupling was performed to obtain the target product.
Yield: 510 mg (51%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.58 (t, 3H, J = 6.4 Hz), 1.95 (s, 3H), 3.80 (q, 2H, J = 5.4 Hz) , 4.34 (q, 2H, J = 6.8 Hz), 4.40 (t, 2H, J = 5.4 Hz), 5.60 (t, 1H, J = 1.5 Hz), 6.14 ( s, 1H), 6.61 (br.t, 1H), 6.69 (s, 1H), 7.54 (t, 3H, J = 7.8 Hz), 7.62 (t, 1H, J = 7.3 Hz), 7.69-7.75 (m, 2H), 7.84 (d, 1H, J = 7.8 Hz), 7.94 (d, 1H, J = 7.8 Hz), 8. 06 (s, 1H), 8.16 (s, 1H), 12.92 (s, 1H).

Example 53 2-Hydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonylmethyl] phenylazo] benzophenone (NBZ-3PM)

Similarly to the synthesis of NBZ-BNM, 2- (3-aminophenylacetoxy) ethyl methacrylate hydrochloride (600 mg) was acid-treated, then diazonium chloride, and diazo-coupled with 2-hydroxybenzophenone (396 mg) to give the desired product Got.
Yield: 596 mg (63%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.88 (s, 3H), 3.73 (s, 2H), 4.33-4.38 (m, 4H), 5.52 (t, 1H , J = 1.5 Hz), 6.05 (s, 1H), 7.20 (d, 1H, J = 9.3 Hz), 7.37 (d, 1H, J = 7.3 Hz), 7.44 (T, 1H, J = 8.1 Hz), 7.56-7.59 (m, 2H), 7.66 (t, 1H, J = 7.4 Hz), 7.75-7.79 (m, 4H), 8.15 (dd, 1H, J = 8.8 Hz, 2.4 Hz), 8.27 (d, 1H, J = 2.4 Hz), 12.46 (s, 1H).

Example 54 2,4-Dihydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonylmethyl] phenylazo] benzophenone (HBZ-3PM)

Similar to the synthesis of NBZ-BNM, 2- (3-aminophenylacetoxy) ethyl methacrylate (600 mg) methacrylate was acid-treated, then diazonium chloride, and diazocoupled with 2,4-dihydroxybenzophenone (437 mg). The desired product was obtained.
Yield: 407 mg (42%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.89 (s, 3H), 3.73 (s, 2H), 4.33-4.39 (m, 4H), 5.5t3 (t, 1H , J = 1.8 Hz), 6.05 (s, 1H), 6.59 (s, 1H), 7.38 (d, 1H, J = 7.8 Hz), 7.45 (t, 1H, J = 7.8 Hz), 7.55-7.59 (m, 2H), 7.65 (tt, 1H, J = 7.3 Hz, 2.4 Hz), 7.70-7.76 (m, 4H) , 8.24 (s, 1H), 12.91 (s, 1H), 13.89 (s, 1H).

Example 55 2-Hydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonylmethyl] phenylazo] -4-methoxybenzophenone (MBZ-3PM)

Similar to the synthesis of NBZ-BNM, 2- (3-aminophenylacetoxy) ethyl methacrylate hydrochloride (600 mg) was acid-treated and then diazonium-chlorinated to give 2-hydroxy-4-methoxybenzophenone (456 mg) and diazo coupling. The target product was obtained.
Yield: 565 mg (56%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.89 (s, 3H), 3.72 (s, 2H), 4.10 (s, 3H), 4.33-4.37 (m, 4H ), 5.52 (t, 1H, J = 1.7 Hz), 6.06 (s, 1H), 6.71 (s, 1H), 7.35 (d, 1H, J = 7.8 Hz), 7.42 (t, 1H, J = 7.3 Hz), 7.51-7.55 (m, 2H), 7.62 (t, 1H, J = 7.8 Hz), 7.70-7.72 (M, 4H), 8.03 (s, 1H), 12.93 (s, 1H).

Example 56 4-Ethoxy-2-hydroxy-5- [3- [2- (methacryloyloxy) ethoxycarbonylmethyl] phenylazo] benzophenone (EBZ-3PM)

Similar to the synthesis of NBZ-BNM, 2- (3-aminophenylacetoxy) ethyl methacrylate hydrochloride (600 mg) was acid-treated and then diazonium salified to give 4-ethoxy-2-hydroxybenzophenone (485 mg) and diazo coupling. The target product was obtained.
Yield: 551 mg (53%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.59 (t, 3H, J = 6.8 Hz), 1.89 (s, 3H), 2.03 (s, 2H), 4.32-4 .38 (m, 6H), 5.53 (t, 1H, J = 1.7 Hz), 6.06 (s, 1H), 6.69 (s, 1H), 7.36 (d, 1H, J = 7.8 Hz), 7.42 (t, 1H, J = 7.3 Hz), 7.52-7.56 (m, 2H), 7.62 (t, 1H, J = 7.4 Hz), 7 70-7.74 (m, 4H), 8.02 (s, 1H), 12.91 (s, 1H).

Example 57 5- [4- [2- (methacrylamido) methyl] phenylazo] -2,4-dihydroxybenzophenone (HBZ-BZM)

Similar to the synthesis of NBZ-BNM, 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.
Yield: 470 mg (57%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 1.99 (s, 3H), 4.56 (d, 2H, J = 5.9 Hz), 5.37 (s, 1H), 5.73 (s , 1H), 6.13 (br.t, 1H), 6.57 (s, 1H), 7.25 (s, 1H), 7.41 (d, 2H, J = 8.8 Hz), 7. 53-7.57 (m, 2H), 7.63 (t, 1H, J = 7.3 Hz), 7.72-7.76 (m, 4H), 8.22 (s, 1H), 12. 88 (s, 1H), 13.89 (s, 1H).

Example 58 5- [4- [2- (Methacrylamide) methyl] phenylazo] -2-hydroxy-4-methoxybenzophenone (MBZ-BZM)

Similarly to the synthesis of NBZ-BNM, 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.
Yield: 511 mg (59%)
¹ H-NMR (400 MHz, CDCl ₃ ) δ: 2.00 (s, 3H), 4.09 (s, 3H), 4.56 (d, 2H, J = 5.9 Hz), 5.37 (s , 1H), 5.73 (s, 1H), 6.10 (br.t, 1H), 6.70 (s, 1H), 7.39 (d, 2H, J = 8.8 Hz), 7. 51-7.55 (m, 2H), 7.61 (t, 1H, J = 7.8 Hz), 7.69-7.72 (m, 2H), 7.78 (d, 2H, J = 8) .3 Hz), 8.03 (s, 1H), 12.92 (s, 1H).

Example 59 5- [4- [2- (methacrylamido) methyl] phenylazo] -2,4-dihydroxybenzophenone (HBZ-BZM)

To 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. Next, 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: 370 mg (29%)
¹ H-NMR (400 MHz, 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).

Example 60 2,4-Dihydroxy-5- [4- [2- (methacrylamide) ethyl] phenylazo] benzophenone (HBZ-PHM)

1M 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 1 hour. 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: 774 mg (40%)
¹ H-NMR (400 MHz, 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).

(Comparative raw material synthesis 1) 2,4-dihydroxy-5- [4- (2-hydroxyethyl) phenylazo] benzophenone by diazo coupling

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. for 1 hour and at room temperature for 4 hours, 4N hydrochloric acid was added to adjust the pH to 3, and then water (100 mL) was added. The deposited precipitate was collected by filtration and dried overnight, and then the precipitate was dissolved in chloroform (200 mL), and then insoluble matters were removed by Celite filtration. The filtrate was concentrated under reduced pressure, methanol was added, and the mixture was allowed to stand at 4 ° C. overnight, and the precipitated crystals were collected by filtration. The crystals were further purified on a silica gel column using hexane-ethyl acetate (1: 1 v / v) and hexane-ethyl acetate (1: 2 v / v) as eluents to obtain the desired product as orange crystals.
Yield: 1.91 g (26%)

(Comparative Example Raw Material Synthesis 2) 2-Hydroxy-5- [4- (2-hydroxyethyl) phenylazo] -4-methoxybenzophenone by diazo coupling

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 pH of the mixture was lowered to 3 with 4M hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure and crystallized from methanol to obtain the desired product as tan crystals.
Yield: 4.85 g (64%)

Comparative Example 1 2,4-Dihydroxy-5- [4- [2- (methacryloyloxy) ethyl] phenylazo] benzophenone (HBZ-PEM) using methacryloyl chloride

2,4-Dihydroxy-5- [4- (2-hydroxyethyl) phenylazo] benzophenone (362 mg) and triethylamine (303 mg) were dissolved in chloroform (9 mL), and methacryloyl chloride (106 mg) in chloroform (1 mL) was cooled with ice. ) The solution was added dropwise and stirred at 4 ° C. for 2 hours and then at room temperature overnight. 1N hydrochloric acid was added to the mixture, and the chloroform layer was separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. This residue was treated by silica gel column chromatography using hexane-ethyl acetate (4: 1 v / v) as an eluent, and further purified by preparative TLC using hexane-ethyl acetate (2: 1 v / v) as a developing solvent. The target product was obtained as orange crystals.
Yield: 10 mg (2%)

Comparative Example 2 2-Hydroxy-5- [4- [2- (methacryloyloxy) ethyl] phenylazo] -4-methoxybenzophenone using dehydration condensation with methacrylic acid with water-soluble carbodiimide in the presence of 4-dimethylaminopyridine ( MBZ-PEM)

2-hydroxy-5- [4- (2-hydroxyethyl) phenylazo] -4-methoxybenzophenone (1.08 g), methacrylic acid (0.27 g), 4-dimethylaminopyridine (70 mg) in chloroform (10 mL) And water-soluble carbodiimide (0.66 g) was added under ice cooling. The mixture was stirred at 4 ° C. for 2 hours, then at room temperature overnight and concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and purified with hexane-ethyl acetate (4: 1 v / v) to obtain the desired product as tan crystals.
Yield: 50 mg (4%)

<Polymer Synthesis Example 1 (Containing only Polymerizable Benzophenone Dye)>
0.03 part by weight of each polymerizable benzophenone dye (NBZ-EMA, HBZ-EMA, MBZ-EAC, EBZ-PEM, and HBZ-PHM) synthesized in Examples 17, 18, 23, 12, and 34, 60 parts by weight of 2-phenoxyethyl acrylate, 40 parts by weight of ethyl acrylate, 0.5 parts by weight of 2,2′-azobis (2,4-dimethylvaleronitrile) are uniformly blended and polymerized at 80 ° C. for 40 minutes A polymer sheet having a thickness of 1 mm was produced. Using the obtained sheet as a sample, the light transmittance at a wavelength of 220 to 800 nm was measured. The results are shown in FIGS.
Further, the sample lens 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).

<Polymer synthesis example 2 (combination of polymerizable benzophenone and UV absorber)>
Further 0.15 parts by weight of 2- [2′-hydroxy-5 ′-(2 ″ -methacryloyloxyethoxy) -3′-tert-butylphenyl] -5-methyl-2H-benzotriazole as a UV absorber A polymer sheet was prepared in the same manner as in Polymer Synthesis 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 Polymer Synthesis Example 1. The results are shown in FIGS.
The spectrum of light transmittance before and after the elution treatment did not change, and it was confirmed that even when the polymerizable benzophenone dye of the present invention was used in combination with another ultraviolet absorber, it was not eluted after polymerization.

<Solubility test>
BMAC, EBZ-EMA, HBZ-EMA, HBZ-AMA, MBZ-PEM, MBZ-AMA were weighed in 50 mg each, and ethyl acrylate (250 μL, 500 μL, 1.0 mL, 2.5 mL, 5.0 mL, 10 mL, 25 mL, 50 mL). These mixtures, when completely dissolved, are 20 w / v%, 10 w / v%, 5 w / v%, 2 w / v%, 1 w / v%, 0.5 w / v%, 0.2 w / v%, respectively. , 0.1 w / v% ethyl acrylate solution. After each mixture was sonicated for 5 minutes, it was judged that a transparent solution was soluble and that an insoluble material remained was insoluble. The results are summarized in Table 1 below.
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. On the other hand, 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.

<Stability comparison under alkaline conditions>
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.
As a control example, instead of HBZ-PHM, 2,4-dihydroxy-5- (4- (2- (N-N— The polymerization reaction was similarly carried out using 2-methacryloyloxyethyl) carbamoyloxy) ethylphenylazo) benzophenone (BMAC) to obtain a BMAC copolymer.
Each copolymer powder obtained was subjected to Soxhlet extraction with ethanol for 12 hours, and then each powder 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. . Note that the test solution at this time was pH 12 to 14 on the pH test paper. After completion of stirring, the mixture was neutralized with 4N HCl and further ethanol (15 mL) was added. The insoluble material was removed by filtration and the filtrate was observed. As a result, the HBZ-PHM copolymer was colorless and transparent. On the other hand, in the BMAC copolymer, the filtrate was colored yellow. Furthermore, the results of measuring the light transmittance of each filtrate at a wavelength of 220 to 800 nm are 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 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.

Claims

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;
A diazo coupling step of diazo coupling the diazonium salt and benzophenone compound obtained in the diazotization step to obtain a compound represented by the following general formula (1),
In the diazo coupling step, a weak base is used as a catalyst, and the method for producing a compound represented by the following general formula (1):

(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 selected from groups represented by the following formulas (2) to (7), and represented by the general formulas (2) to (7 And R 4 is a hydrogen atom or a methyl group, m is an integer of 0 to 4, and n is an integer of 1 to 8.)
The production method according to claim 1, wherein the weak base used in the diazo coupling step includes one or more selected from sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium acetate and potassium acetate.
The method according to claim 1 or 2, wherein the benzophenone compound is a compound represented by the following general formula (8).

(In the general formula (8), 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.)
The manufacturing method according to any one of claims 1 to 3, wherein the polymerizable group-containing aminoaryl compound is a compound represented by the following general formula (9).

(In the general formula (9), R 3 is selected from groups represented by the following formulas (2) to (7). In the general formulas (2) to (7), R 4 is a hydrogen atom or a methyl group. And m is an integer from 0 to 4, and n is an integer from 1 to 8.)
A compound produced by the production method according to any one of claims 1 to 4.
A polymer obtained by copolymerizing one or more of the compounds according to claim 5 with another polymerizable monomer.
The polymer according to claim 6, which is used for an intraocular lens.