CN109641855B - Azo compounds, polymers, and processes for their preparation and use - Google Patents

Abstract

The invention provides an azo compound, a polymer, a preparation method and application. The structural formula of the azo compound is shown as a formula (I), wherein R¹、R²、R³And m has the meaning described in the specification. The azo compound has good blue light intercepting performance, and the compound is a polymerizable azo compound and is not easy to migrate and diffuse in a polymer.

Description

Azo compounds, polymers, and processes for their preparation and use

Technical Field

The invention relates to the field of ophthalmic medical devices, in particular to an azo compound, a polymer polymerized by the azo compound, and a preparation method and application of the azo compound and the polymer.

Background

In recent years, with the popularization and development of electronic display devices, the damage of the blue light part in visible light to human eyes, particularly to retinas, has attracted more and more attention. Studies have shown that blue light in visible light can cause damage to the human eye, particularly the retina, resulting in decreased vision and even blindness. Therefore, the adhesive film capable of intercepting blue light or the component capable of intercepting blue light is added in the eye medical devices such as glasses lenses, so that the blue light is prevented from damaging eyes.

However, there is still a need for improved ophthalmic medical devices having blue light blocking capabilities and polymers for making ophthalmic medical devices.

Disclosure of Invention

The present application is based on the discovery and recognition by the inventors of the following facts and problems:

although spectacle lenses having a blue light blocking function are popular at present, products having a blue light blocking function are still rare in ocular medical devices such as intraocular lenses which are in direct contact with human eyes. The inventor finds that the blue light blocking function is mainly due to the fact that the yellow dye with the blue light absorbing function is added to the eye medical device to achieve the blue light blocking function generally. In the eye medical device directly contacting with human eyes, the added yellow dye is required not to diffuse and migrate in the eye medical device, that is, it is required to ensure that the added yellow dye stably exists in the eye medical device and does not enter human eyes, so as to ensure the safety performance of the eye medical device. The yellow dyes that can meet the above requirements are very limited, thus limiting the development of ocular medical devices with blue light interception functionality.

The present invention is directed to solving, at least to some extent, one of the above technical problems in the related art. Therefore, the invention provides an azo compound which has better blue light interception performance, is a polymerizable azo compound, is not easy to migrate and diffuse in a polymer, and can be used as a blue light absorber in an eye medical device such as an artificial lens.

The present invention also provides a polymer which contains the above azo compound and thus has a function of intercepting blue light. And the azo compound is a polymerizable compound, so that the azo compound is not easy to diffuse and migrate in the polymer provided by the invention.

The invention also provides the use of the polymers of the invention for the preparation of ophthalmic medical devices. The polymer is used for preparing the eye medical device, so that the blue light interception function can be realized on the premise of not influencing the use function of the eye medical device, and the eye medical device has better safety.

The invention also relates to a method for producing the polymers according to the invention.

Drawings

FIG. 1 shows a graph of the spectral transmittance of inventive polymers A3, A5, A10 and A0 in comparison;

FIG. 2 shows a graph of the spectral transmittance of inventive polymers A4, A8, A11 and A0 in comparison;

FIG. 3 shows a graph of the spectral transmittance of inventive polymers A1, A6, A9 and A0 in comparison;

FIG. 4 shows a comparison of the spectral transmittances of the polymers of the invention A4 before and after extraction with A11; and

FIG. 5 shows a comparison of the spectral absorption losses at 450nm before and after extraction of the polymers A1, A2, A4, A6, A9, A11 according to the invention.

Detailed description of the invention

Definitions and general terms

Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety. The term "comprising" or "comprises" is open-ended, i.e. comprising what is specified in the present invention, but not excluding other aspects. In the present invention, all numbers disclosed herein are approximate values, regardless of whether the word "about" or "approximately" is used. There may be differences below 10% in the value of each number or reasonably considered by those skilled in the art, such as differences of 1%, 2%, 3%, 4% or 5%.

In the invention, the azo compound provided by the invention has a general formula shown in formula (Ia) or formula (I), and also comprises a stereoisomer or a tautomer of the compound conforming to the general formula shown in formula (Ia) or formula (I). "stereoisomers" refers to compounds having the same chemical structure but differing in the arrangement of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis/trans), atropisomers, and the like.

The stereochemical definitions and rules used in the present invention generally follow the general definitions of S.P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; stereochemical definitions and rules as described in and Eliel, e.and Wilen, s, "Stereochemistry of Organic Compounds", John Wiley & Sons, inc, New York, 1994.

Many organic compounds exist in an optically active form, i.e., they have the ability to rotate the plane of plane polarized light. In describing optically active compounds, the prefixes D and L, or R and S, are used to denote the absolute configuration of a molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are the symbols used to specify the rotation of plane polarized light by the compound, where (-) or l indicates that the compound is left-handed. Compounds prefixed with (+) or d are dextrorotatory. A particular stereoisomer is an enantiomer and a mixture of such isomers is referred to as an enantiomeric mixture. A50: 50 mixture of enantiomers is referred to as a racemic mixture or racemate, which may occur when there is no stereoselectivity or stereospecificity in the chemical reaction or process.

Any asymmetric atom (e.g., carbon, etc.) of a compound disclosed herein can exist in racemic or enantiomerically enriched forms, such as the (R) -, (S) -or (R, S) -configuration. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess in the (R) -or (S) -configuration.

Depending on the choice of starting materials and methods, the compounds of the invention may exist as one of the possible isomers or as mixtures thereof, for example as racemates and mixtures of non-corresponding isomers (depending on the number of asymmetric carbon atoms). Optically active (R) -or (S) -isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituents may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the substituents of the cycloalkyl group may have cis or trans configuration.

Any resulting mixture of stereoisomers may be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, depending on differences in the physicochemical properties of the components, for example, by chromatography and/or fractional crystallization.

The racemates of any of the resulting end products or intermediates can be resolved into the optical enantiomers by known methods using methods familiar to those skilled in the art, e.g., by separation of the diastereomeric salts obtained. The racemic product can also be separated by chiral chromatography, e.g., High Performance Liquid Chromatography (HPLC) using a chiral adsorbent. In particular, Enantiomers can be prepared by asymmetric synthesis, for example, see Jacques, et al, Enantiomers, racemes and solutions (Wiley Interscience, New York, 1981); principles of Asymmetric Synthesis (2)^nd Ed.Robert E.Gawley，Jeffrey Aubé，Elsevier，Oxford，UK，2012)；Eliel，E.L.Stereochemistry of Carbon Compounds(McGraw-Hill，NY，1962)；Wilen，S.H.Tables of Resolving Agents and Optical Resolutions p.268(E.L.Eliel，Ed.，Univ.of Notre Dame Press，Notre Dame，IN 1972)；Chiral Separation Techniques：A Practical Approach(Subramanian，G.Ed.，Wiley-VCH Verlag GmbH & Co.KGaA，Weinheim，Germany，2007)。

The term "tautomer" or "tautomeric form" refers to structural isomers having different energies that can interconvert by a low energy barrier (low energy barrier). If tautomerism is possible (e.g., in solution), then the chemical equilibrium of the tautomer can be reached. For example, proton tautomers (also known as proton transfer tautomers) include interconversions by proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers (valenctautomers) include interconversion by recombination of some of the bonding electrons. A specific example of keto-enol tautomerism is the tautomerism of the pentan-2, 4-dione and 4-hydroxypent-3-en-2-one tautomers. Another example of tautomerism is phenol-ketone tautomerism. One specific example of phenol-ketone tautomerism is the tautomerism of pyridin-4-ol and pyridin-4 (1H) -one tautomers. Unless otherwise indicated, all tautomeric forms of the compounds of the invention are within the scope of the invention.

In the invention, the term "blue light" refers to visible light with a wavelength range of 400-550 nm, and the terms such as "blocking blue light", "absorbing blue light" and the like refer to that when the visible light containing blue light enters and passes through the material from one side of the surface of the material composed of the azo compound or the polymer and the like provided by the invention, the light intensity of the blue light in emergent light on the other side surface of the material is obviously reduced compared with that of the blue light in the incident light, and even the emergent light does not contain the blue light. The "room temperature" in the present invention refers to a temperature that can be reached by placing, for example, a reaction solution, a mixed solution, etc. in an indoor environment for a certain period of time without additional cooling or heating treatment during synthesis, preparation, etc. For example, in some embodiments, the "room temperature" temperature is from about 10 degrees Celsius to about 40 degrees Celsius. In some embodiments, "room temperature" refers to a temperature of from about 20 degrees celsius to about 30 degrees celsius; in some other embodiments, "room temperature" refers to 20 degrees celsius, 22.5 degrees celsius, 25 degrees celsius, 27.5 degrees celsius, and the like.

In the present invention, the term "optional" or "optionally" means that the subsequently described event or circumstance may, but need not, occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, "optionally substituted alkylene" means that the alkylene group may be unsubstituted or substituted with any substituent group such as alkyl, halogen, nitro, cyano, aldehyde, amino, alkoxy, haloalkyl, haloalkoxy, and the like.

In the various parts of this specification, substituents of the disclosed compounds are disclosed in terms of group type or range. It is specifically intended that the invention includes each and every independent subcombination of the various members of these groups and ranges. For example, the term "C₁-C₆Alkyl "means in particular independently disclosed methyl, ethyl, C₃Alkyl radical, C₄Alkyl radical, C₅Alkyl and C₆An alkyl group.

The term "alkyl" or "alkyl group" denotes a saturated straight or branched chain hydrocarbon group. In one embodiment, the alkyl group contains 1 to 20 carbon atoms; in another embodiment, the alkyl group contains 1 to 12 carbon atoms; in another embodiment, the alkyl group contains 1 to 8 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 6 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 3 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me, -CH)₃) Ethyl group (Et, -CH)₂CH₃) N-propyl (n-Pr, -CH)₂CH₂CH₃) Isopropyl group (i-Pr, -CH (CH)₃)₂) N-butyl (n-Bu, -CH)₂CH₂CH₂CH₃) Isobutyl (i-Bu, -CH)₂CH(CH₃)₂) Sec-butyl (s-Bu, -CH (CH)₃)CH₂CH₃) Tert-butyl (t-Bu, -C (CH)₃)₃) N-pentyl (-CH)₂CH₂CH₂CH₂CH₃) 2-pentyl (-CH (CH)₃)CH₂CH₂CH₃) 3-pentyl (-CH (CH)₂CH₃)₂) 2-methyl-2-butyl (-C (CH)₃)₂CH₂CH₃) 3-methyl-2-butyl (-CH (CH)₃)CH(CH₃)₂) 3-methyl-1-butyl (-CH)₂CH₂CH(CH₃)₂) 2-methyl-1-butyl (-CH)₂CH(CH₃)CH₂CH₃) N-hexyl (-CH)₂CH₂CH₂CH₂CH₂CH₃) 2-hexyl (-CH (CH)₃)CH₂CH₂CH₂CH₃) 3-hexyl (-CH (CH)₂CH₃)(CH₂CH₂CH₃) 2-methyl-2-pentyl (-C (CH))₃)₂CH₂CH₂CH₃) 3-methyl-2-pentyl (-CH (CH)₃)CH(CH₃)CH₂CH₃) 4-methyl-2-pentyl (-CH (CH)₃)CH₂CH(CH₃)₂) 3-methyl-3-pentyl (-C (CH)₃)(CH₂CH₃)₂) 2-methyl-3-pentyl (-CH (CH)₂CH₃)CH(CH₃)₂) 2, 3-dimethyl-2-butyl (-C (CH)₃)₂CH(CH₃)₂) 3, 3-dimethyl-2-butyl (-CH (CH)₃)C(CH₃)₃) N-heptyl, n-octyl, and the like.

The term "alkylene" denotes a saturated divalent hydrocarbon radical resulting from the removal of two hydrogen atoms from a saturated straight or branched chain hydrocarbon. In one embodiment, the alkylene group contains 1 to 12 carbon atoms. In another embodiment, the alkylene group contains 1 to 6 carbon atoms; in another embodiment, the alkylene group contains 1 to 4 carbon atoms; in yet another embodiment, the alkylene group contains 1 to 3 carbon atoms; in yet another embodiment, the alkylene group contains 1 to 2 carbon atoms. Non-limiting examples include methylene (-CH)₂-, ethylene (-CH)₂CH₂-, isopropylidene (-CH (CH)₃)CH₂-) and the like.

The terms "heteroalkylene" and "heteroalkylene" refer to alkylene and alkylene chains into which one or more heteroatoms such as O, N, S may be inserted, and/or, wherein optionally one or more-CH groups₂-by-NH-, -C (═ O), -S (═ O)₂And isoradical substitution, wherein alkylene and alkylene chain have the meaning as described herein. Unless otherwise specified, the heteroalkylene or heteroalkylene group contains 1 to 12 carbon atoms, in some embodiments the heteroalkylene group contains 1 to 10 carbon atoms, in other embodiments the heteroalkylene group contains 1 to 5 carbon atoms, and in yet other embodiments the heteroalkylene group contains 1 to 4 carbon atoms. Examples include, but are not limited to, -CH₂-O-、-CH₂-O-CH₂-、-C(CH₃)₂-O-、-C(CH₃)(OH)-O-、-CH(CH₃)-O-CH₂-、-C(CH₃)₂-O-CH₂-、-CH₂-NH-、-CH₂-NH-CH₂-、-C(CH₃)₂-NH-、-CH(CH₃)-NH-CH₂-、-C(CH₃)₂-NH-CH₂-、-C(CH₃)(OH)-NH-、-C(＝O)-NH-、-C(＝O)-NH-CH₂-、-CH₂-NH-C (═ O) -. And the like.

The term "alkenyl" denotes at least one carbon-carbon sp²A linear or branched hydrocarbon group of a double bond, which includes the positioning of "cis" and "tan", or the positioning of "E" and "Z". In one embodiment, the alkenyl group contains 2 to 20 carbon atoms; in another embodiment, the alkenyl group contains 2 to 12 carbon atoms; in yet another embodiment, the alkenyl group contains 2 to 8 carbon atoms; in yet another embodiment, the alkenyl group contains 2 to 6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-CH ═ CH)₂) Allyl (-CH)₂CH＝CH₂) And so on.

The term "alkynyl" denotes a straight or branched chain hydrocarbon group having at least one carbon-carbon sp triple bond. In one embodiment of the process of the present invention,alkynyl groups contain 2-20 carbon atoms; in another embodiment, alkynyl groups contain 2-12 carbon atoms; in yet another embodiment, alkynyl groups contain 2-8 carbon atoms; in yet another embodiment, alkynyl groups contain 2-6 carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (-C.ident.CH), propargyl (-CH)₂C.ident.CH), 1-propynyl (-C.ident.C-CH)₃) And so on.

The term "alkoxy" means an alkyl group attached to the rest of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. Unless otherwise specified, the alkoxy group contains 1 to 12 carbon atoms. In one embodiment, the alkoxy group contains 1 to 6 carbon atoms; in another embodiment, the alkoxy group contains 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group contains 1 to 3 carbon atoms. The alkoxy group is optionally substituted with one or more substituents described herein. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH)₃) Ethoxy (EtO, -OCH)₂CH₃) 1-propoxy (n-PrO, n-propoxy, -OCH)₂CH₂CH₃) 2-propoxy (i-PrO, i-propoxy, -OCH (CH)₃)₂) And so on.

The term "alkylthio" refers to C_1-6The linear or branched alkyl group is attached to the rest of the molecule through a sulfur atom. In one embodiment, alkylthio is lower C_1-4Alkylthio groups, and such examples include, but are not limited to, methylthio (CH)₃S-)。

The term "alkylamino" or "alkylamino" includes "N-alkylamino" and "N, N-dialkylamino" wherein the amino groups are each independently substituted with one or two alkyl groups, wherein the alkyl groups have the meaning as described herein. In one embodiment, alkylamino is one or two C_1-6Lower alkylamino groups in which the alkyl group is attached to the nitrogen atom. In another embodiment, alkylamino is C_1-4Lower alkylamino groups of (a). Suitable alkylamino groups may be monoalkylamino or dialkylamino groupsExamples include, but are not limited to, N-methylamino, N-ethylamino, N, N-dimethylamino, N, N-diethylamino, and the like. The alkylamino group is optionally substituted with one or more substituents described herein.

The terms "halogen" and "halo" refer to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

The terms "haloalkyl", "haloalkenyl" or "haloalkoxy" mean alkyl, alkenyl or alkoxy groups, respectively, substituted with one or more halogen atoms, wherein alkyl, alkenyl and alkoxy groups have the meaning described herein, and examples include, but are not limited to, difluoromethyl, trifluoromethyl, trifluoromethoxy, 2, 2, 2-trifluoroethoxy, 2, 2, 3, 3-tetrafluoropropoxy, and the like. The haloalkyl, haloalkenyl, or haloalkoxy group is optionally substituted with one or more substituents described herein.

The term "alkoxyalkyl" means an alkyl group substituted with one or more alkoxy groups, wherein the alkyl group and alkoxy group have the meaning as described herein, examples of which include, but are not limited to, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, and the like.

The term "aryl" denotes monocyclic, bicyclic and tricyclic carbon ring systems containing 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, wherein at least one ring system is aromatic, wherein each ring system comprises a ring of 3 to 7 atoms with one or more attachment points to the rest of the molecule. Examples of the aryl group may include phenyl, naphthyl and anthracenyl. When the aryl group may be optionally substituted, the substituted group may be fluorine, chlorine, bromine, iodine, cyano, azido, nitro, amino, hydroxyl, mercapto, alkylamino, alkoxy, alkylthio, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl.

The term "arylalkyl" means an alkyl group substituted with one or more aryl groups; wherein the alkyl group and the aryl group have the meanings as described herein, and examples of the arylalkyl group include, but are not limited to, benzyl, phenethyl and the like.

The term "aryloxy" or "aryloxy" refers to an optionally substituted aryl group, as defined herein, attached to and linked from an oxygen atom to the rest of the molecule, wherein the aryl group has the meaning as described herein. Examples of aryloxy groups include, but are not limited to, phenoxy, halophenoxy, cyano-substituted phenoxy, hydroxy-substituted phenoxy, and the like.

The term "aryloxyalkyl" refers to an alkyl group substituted with one or more aryloxy groups; wherein the aryloxy and alkyl groups have the meaning as described herein. Examples of aryloxyalkyl groups include, but are not limited to, phenoxymethyl, fluorophenoxymethyl (such as (2-fluorophenoxy) methyl, (3-fluorophenoxy) methyl, or (4-fluorophenoxy) methyl), chlorophenoxymethyl, and the like.

The term "arylalkoxy" means that the alkoxy group is substituted with one or more aryl groups; wherein the alkoxy groups and aryl groups have the meaning as described in the present invention. Examples of the arylalkoxy group include, but are not limited to, benzyloxy, fluorobenzyloxy, chlorobenzyloxy, cyano-substituted benzyloxy, methanesulfonyl-substituted benzyloxy, phenylethoxy, and the like.

Detailed description of the invention

In one aspect of the present invention, an azo compound is provided. The azo compound has a formula corresponding to formula (Ia), or is a stereoisomer or tautomer of a compound having a formula corresponding to formula (Ia):

wherein,

R¹is hydrogen or alkyl; r²Is an alkyl group;

x is O, NH or NR⁵(ii) a Y is O, S, NH or NR⁵(ii) a Wherein each R⁵Independently is C_1-10An alkyl group;

w is a single bond, alkylene or heteroalkylene; w is optionally substituted with 1, 2, 3, 4 or 5 fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, oxo (═ O), C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Alkylthio or C_1-6Alkyl amino substituted;

R³、R⁴each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR^aR^b、-C(＝O)R^c、-S(＝O)₂-R^c、-C(＝O)-NR^aR^b、-S(＝O)₂-NR^aR^b、C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_6-12Aryl radical, C_6-12Aryl radical C_1-6Alkyl radical, C_6-12Aryloxy radical, C_6-12Aryloxy radical C_1-6Alkyl or C_6-12Aryl radical C_1-6An alkoxy group; and

each R^a、R^bAnd R^cIndependently hydrogen, hydroxy, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy radical, C_6-10Aryl or C_6-10Aryl radical C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4;

m is 0, 1, 2, 3, 4 or 5.

In some embodiments, R¹Is hydrogen or C_1-4An alkyl group. In other embodiments, R¹Is hydrogen or methyl.

In some embodiments, R²Is an alkyl group. In other embodiments, R²Is C_1-6An alkyl group. In still other embodiments, R²Is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

In some embodiments, X is O, NH or NR⁵. In other embodiments, X is O or NH.

In some casesIn embodiments, Y is O, S, NH or NR⁵. In other embodiments, Y is O, S or NH.

In some embodiments, each R is⁵Independently is C_1-10An alkyl group.

In some embodiments, W is a single bond, alkylene, or heteroalkylene; w is optionally substituted with 1, 2, 3, 4 or 5 fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, oxo (═ O), C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Alkylthio or C_1-6Alkylamino.

In other embodiments, W is a single bond, C_1-12Alkylene or C_1-12A heteroalkylene group; w is optionally substituted with 1, 2, 3, 4 or 5 fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, oxo (═ O), C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Alkylthio or C_1-6Alkylamino.

In still other embodiments, W is- (CR)^dR^e)_r-、-(CR^dR^e)_r-O-(CR^fR^g)_t-、-(CR^dR^e)_r-C(＝O)-(CR^fR^g)_t-、-(CR^dR^e)_r-N(R^h)-(CR^fR^g)_t-、-C(＝O)-N(R^h)-(CR^fR^g)_t-、-(CR^dR^e)_r-N(R^h) -C (═ O) -or- (CR)^dR^e)_r-N(R^h)-S(＝O)₂-；

Each r is independently 1, 2, 3 or 4;

each t is independently 0, 1, 2 or 3;

each R^d、R^e、R^fAnd R^gIndependently hydrogen, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxyl, nitro, amino, carboxyl, oxo (═ O), C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_1-3Alkoxy or C_1-3An alkylamino group; and

each R^hIndependently of one another is hydrogen, C_1-4Alkyl radical, C_2-4Alkenyl or C_2-4Alkynyl.

In yet other embodiments, W is-CH₂-、-(CH₂)₂-、-C(CH₃)₂-、-CH₂-C(CH₃)₂-、-C(CH₃)(OH)-、-CH₂-O-、-CH₂-O-CH₂-、-C(CH₃)₂-O-、-C(CH₃)(OH)-O-、-CH(CH₃)-O-CH₂-、-C(CH₃)₂-O-CH₂-、-CH₂-NH-、-CH₂-NH-CH₂-、-C(CH₃)₂-NH-、-CH(CH₃)-NH-CH₂-、-C(CH₃)₂-NH-CH₂-、-C(CH₃)(OH)-NH-、-C(＝O)-NH-、-C(＝O)-NH-CH₂-、-CH₂-NH-C(＝O)-。

In some embodiments, R³、R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR^aR^b、-C(＝O)R^c、-S(＝O)₂R^c、-C(＝O)NR^aR^b、-S(＝O)₂NR^aR^b、C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_6-12Aryl radical, C_6-12Aryl radical C_1-6Alkyl radical, C_6-12Aryloxy radical, C_6-12Aryloxy radical C_1-6Alkyl or C_6-12Aryl radical C_1-6An alkoxy group; and

each R^a、R^bAnd R^cIndependently hydrogen, hydroxy, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy radical, C_6-10Aryl or C_6-10Aryl radical C_1-6An alkyl group.

In some embodiments, R³、R⁴Are respectively and independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde group,Nitro, cyano, -NR^aR^b、-C(＝O)R^c、-S(＝O)₂R^c、-C(＝O)NR^aR^b、-S(＝O)₂NR^aR^b、C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy radical, C_1-4Alkoxy radical C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl radical, C_6-10Aryloxy radical, C_6-10Aryloxy radical C_1-4Alkyl or C_6-10Aryl radical C_1-4An alkoxy group;

each R^a、R^bAnd R^cIndependently hydrogen, hydroxy, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_1-4Alkoxy radical, C_6-10Aryl or C_6-10Aryl radical C_1-4An alkyl group. In some embodiments, R³、R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde group, nitro, cyano or-NH₂、-N(CH₃)₂、-C(＝O)CH₃、-C(＝O)OH、-C(＝O)OCH₃、-CONH₂、-CON(CH₃)₂Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, trifluoromethyl, trifluoromethoxy, trifluoroethyl, trifluoroethoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, phenyl, phenylmethyl, phenylethyl, phenylpropyl, phenoxy, phenoxymethyl, phenoxyethyl, phenylmethoxy or phenylethoxy.

In some embodiments, the present invention provides an azo compound. The azo compound has a general formula shown in a formula (I), or is a stereoisomer or a tautomer of a compound shown in the formula (I).

In the formula (I), R¹Is H or alkyl; r²Is an alkyl group; ³Reach independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR^aR^b、-C(＝O)R^c、-S(＝O)₂R^c、-C(＝O)NR^aR^b、-S(＝O)₂NR^aR^bAlkyl, alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_6-12Aryl radical, C_6-12Aryl radical C_1-6Alkyl radical, C_6-12Aryloxy radical, C_6-12Aryloxy radical C_1-6Alkyl or C_6-12Aryl radical C_1-6An alkoxy group; and

each R^a、R^bAnd R^cIndependently hydrogen, hydroxy, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy radical, C_6-10Aryl or C_6-10Aryl radical C_1-6An alkyl group;

m is 0, 1, 2, 3, 4 or 5.

The azo compound with the structure is a polymerizable yellow dye, can play a good role in blue light absorption/interception, and can form a copolymer with other materials (such as monomers or additives for forming ocular medical devices such as intraocular lenses) so as to reduce the risk of migration of the azo compound in the ocular medical devices, and thus, the azo compound can be used for preparing the ocular medical devices with the blue light interception function.

In one embodiment of the invention, R¹Is H or alkyl; in another embodiment, R¹Is H or C_1-6An alkyl group; in yet another embodiment, R¹Is H or methyl.

In one embodiment of the invention, R²Is an alkyl group; in another embodiment, R²Is C_1-6An alkyl group; in another embodiment, R²Is methyl, ethyl or n-propylAlkyl, isopropyl, n-butyl or isobutyl.

In one embodiment of the invention, m is 0, 1, 2, 3, 4 or 5,

R³each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR^aR^b、-C(＝O)R^c、-S(＝O)₂R^c、-C(＝O)NR^aR^b、-S(＝O)₂NR^aR^b、C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_6-12Aryl radical, C_6-12Aryl radical C_1-6Alkyl radical, C_6-12Aryloxy radical, C_6-12Aryloxy radical C_1-6Alkyl or C_6-12Aryl radical C_1-6An alkoxy group; and

each R^a、R^bAnd R^cIndependently hydrogen, hydroxy, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy radical, C_6-10Aryl or C_6-10Aryl radical C_1-6An alkyl group.

In another embodiment, m is 0, 1, 2, 3, 4 or 5, R³Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR^aR^b、-C(＝O)R^c、-S(＝O)₂R^c、-C(＝O)NR^aR^b、-S(＝O)₂NR^aR^b、C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy radical, C_1-4Alkoxy radical C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl radical, C_6-10Aryloxy radical, C_6-10Aryloxy radical C_1-4Alkyl or C_6-10Aryl radical C_1-4An alkoxy group; and

each R^a、R^bAnd R^cIndependently hydrogen, hydroxy, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_1-4Alkoxy radical, C_6-10Aryl or C_6-10Aryl radical C_1-4An alkyl group.

In still other embodiments, m is 0, 1, 2, 3, 4, or 5, R³Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, hydroxyl, nitro, aldehyde group, -NH₂、-N(CH₃)₂、-C(＝O)CH₃、-C(＝O)OH、-C(＝O)OCH₃、-CONH₂、-CON(CH₃)₂Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, trifluoromethyl, trifluoromethoxy, trifluoroethyl, trifluoroethoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, phenyl, benzyl, phenethyl, phenylpropyl, phenoxy, phenoxymethyl, phenoxyethyl, benzyloxy, or phenylethoxy.

In one embodiment of the invention, R¹Is H or methyl, R²Is methyl or ethyl, m is 1 or 2, R³Each independently is hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, methoxyethyl, trifluoromethyl, trifluoromethoxy, fluoro, chloro, or bromo.

In the above embodiments of the present invention, R³Are independent of each other, and when m is greater than 1, a plurality of R in the azo compound³May or may not be the same.

In another embodiment of the present invention, the azo compound of the present invention may be a compound satisfying the general formulae represented by the following formulae (1) to (20), or a stereoisomer or tautomer of a compound satisfying the following general formulae:

the compounds satisfying the general formulae (1) to (20) above, or azo compounds satisfying stereoisomers or tautomers of the compounds of the general formulae above, have a more desirable blue light-blocking effect, and can be added as a blue light absorber to raw materials for synthesizing an ophthalmic medical device. The azo compounds are all polymerizable azo compounds, and the inventor finds that the azo compounds can be polymerized with other raw materials for forming the eye medical device when the eye medical device is prepared through a large number of experiments, and then the azo compounds can stably exist in the obtained eye medical device, so that the risk of entering human eyes due to the migration of the azo compounds in the using process can be greatly reduced. And the compound does not cause negative influence on optical properties (refractive index, spectral transmittance and the like) and mechanical properties (tensile strength, elongation at break, elastic modulus and the like) of the eye medical device, so that the compound can be used for preparing flexible eye medical devices such as foldable artificial crystals and the like.

In another aspect, the present invention features a polymer. The monomers constituting the polymer include a bulk monomer and a blue light absorber, which is the azo compound of the present invention described above. In other words, the monomers constituting the polymer include monomers forming the bulk of the polymer (bulk monomers) as well as the azo compound proposed in the foregoing of the present invention. Thus, the polymer has an effect of intercepting blue light. In addition, in the process of synthesizing the polymer, the blue light absorbent can be subjected to copolymerization reaction with a body monomer or other additives in raw materials for synthesizing the polymer, so that the risk of migration of the blue light absorbent in the polymer can be greatly reduced, and the safety performance of a device which is prepared by using the polymer and is directly contacted with a human body can be improved. For example, the polymer can be used for preparing eye medical devices such as artificial lenses, so that the eye medical devices also have the function of intercepting blue light, and further the damage of the blue light in visible light to organs such as human eyes can be reduced.

In the present invention, the ratio of the blue-light absorber and the bulk monomer in the polymer can be adjusted according to the actual situation. The term "bulk monomer" particularly refers to the principal monomer material used to form the bulk of the polymer. The bulk monomer is a main component capable of constituting the above-mentioned polymer proposed by the present invention by polymerization, and is capable of undergoing a copolymerization reaction with the blue-light absorber during the polymerization. Since the blue-light absorber contains a polymerizable group, monomers commonly used for forming a polymer can be copolymerized with the blue-light absorber proposed in the present invention, and thus, the specific type of the bulk monomer is not particularly limited in the present invention. In some embodiments of the present invention, the bulk monomer is an acrylate monomer, which may include, but is not limited to, at least one of the following monomers: methyl methacrylate, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, butyl methacrylate, t-butyl methacrylate, isobutyl methacrylate, pentyl methacrylate, t-pentyl methacrylate, hexyl methacrylate, heptyl methacrylate, octyl methacrylate, 2-ethylhexyl methacrylate, nonyl methacrylate, decyl methacrylate, dodecyl methacrylate, stearyl methacrylate, cyclopentyl methacrylate, cyclohexyl methacrylate, phenoxy methacrylate; methoxyethyl methacrylate, ethoxyethyl acrylate, methoxydiglycol methacrylate, 2-ethylphenoxy acrylate, 2-ethylthiophene methacrylate, 2-ethylthiophene acrylate, 2-ethylaminophenyl methacrylate, 2-ethylaminophenyl acrylate, phenyl methacrylate, benzyl methacrylate, 2-phenylethyl acrylate, 3-phenylpropyl methacrylate, 4-phenylbutyl methacrylate, 4-methylphenyl methacrylate, 4-methylbenzyl methacrylate, 2-phenylethyl acrylate, 3-phenylpropyl methacrylate, 4-phenylbutyl methacrylate, and the like, 2, 2-methylphenylethyl methacrylate, 2, 3-methylphenylethyl methacrylate, 2, 4-methylphenylethyl methacrylate, 2- (4-propylphenyl) ethyl methacrylate, 2- (4- (1-methylethyl) phenyl) ethyl methacrylate, 2- (4-methoxyphenyl) ethyl methacrylate, 2- (4-cyclohexylphenyl) ethyl methacrylate, 2- (2-chlorophenyl) ethyl methacrylate, 2- (3-chlorophenyl) ethyl methacrylate, 2- (4-bromophenyl) ethyl methacrylate, and mixtures thereof, 2- (3-phenylphenyl) ethyl methacrylate, 2- (4-phenylphenyl) ethyl methacrylate, and 2- (4-benzylphenyl) ethyl methacrylate. In other embodiments of the present invention, the bulk monomer may include at least one of 2-phenylethyl acrylate, 2-phenylethyl methacrylate, and ethoxyethyl methacrylate. In other embodiments of the present invention, the bulk monomer is a vinyl monomer, and may include, but is not limited to, at least one of the following monomers: styrene, 4-butylstyrene, phenylpropylene, vinyl acetate, 4-ethoxymethylstyrene, 4-hexyloxymethylstyrene, 4-hexyloxyethylstyrene, vinyl ether, N-butyl vinyl ether, isobutyl vinyl ether, tert-butyl vinyl ether, cyclohexene vinyl ether, butanediol divinyl ether, N-vinylcaprolactam, dodecyl vinyl ether, octadecyl vinyl ether, divinyl glycol divinyl ether, trivinyl glycol divinyl ether. In still other embodiments of the present invention, the bulk monomer is an allylic monomer, and may include, but is not limited to, at least one of the following monomers: methyl crotonate, ethyl crotonate, phenylethyl crotonate, allyl acetate, allyl propionate, allyl butyrate, allyl valerate, allyl hexanoate and 3-phenyl-2-propenyl butyrate. The bulk monomer has better optical and mechanical properties, and can further improve the service performance of the polymer.

The raw materials for forming the polymer of the present invention may further include at least one of a crosslinking agent, an ultraviolet absorber, and an initiator. The crosslinking agent, the ultraviolet absorber and the initiator can be mixed with the bulk monomer and the blue light absorber to form the polymer provided by the invention through polymerization. In one embodiment of the present invention, the crosslinking agent may include, but is not limited to, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1, 3-propanediol dimethacrylate, 1, 6-hexanediol dimethacrylate, 1, 3-butanediol dimethacrylate, 1, 4-butanediol diacrylate, trimethylolpropane trimethacrylate, 1, 5-bis (methacryloyloxy) -2, 2, 3, 3, 4, 4-hexafluorohexane, 1, 6-bis (acryloyloxy) -2, 2, 3, 3, 4, 4, 5, 5-octafluorohexane, and pentaerythritol tetraacrylate. UV absorbers may include, but are not limited to, 2- (2 ' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 2- [3- (2H-benzotriazol-2-yl) -4-hydroxyphenyl ] ethyl 2-methacrylate, 2- (2H-benzotriazol-2-yl) -4-methyl-6- (2-propenyl) phenol, 2- (5-chloro-2H-benzo [ d ] [1, 2, 3] triazole) -4-methyl-6- (2-allyl) phenol, 4-allyl-2- (5-chloro-2H-benzo [ d ] [1, 2, 3] triazole) -6-methoxyphenol, 2- (5-chloro-2H-1, 2, 3-benzo [ d ] [1, 2, 3] triazole) -4-methyl-6-allylphenol, 2-hydroxy-4- (methacryloyloxy) benzophenone, and 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate. Initiators may include, but are not limited to, benzoyl peroxide, t-butyl hydroperoxide, cumyl hydroperoxide, bis (4-t-butylcyclohexyl) peroxydicarbonate, azobisisobutyronitrile, and azobis (2, 4-dimethylvaleronitrile). Thereby, the properties of the polymer can be further improved.

In another aspect, the present disclosure is directed to an ophthalmic medical device. The ocular medical device comprises the polymer as set forth above. Thus, the ocular medical device has all of the features and advantages of the polymers described above and will not be described in further detail herein. Specifically, the eye medical device has ideal mechanical property and optical property, and can intercept blue light components in visible light, so that damage of the blue light to organs such as human eyes can be reduced. The eye medical device has better safety performance, and the blue light absorbent in the polymer provided by the invention is not easy to migrate and diffuse in the polymer, so that the azo compound forming the blue light absorbent can be prevented from being directly contacted with a human body.

In one embodiment of the present invention, the ocular medical device may be an intraocular lens, a contact lens, a corneal modifier, an intracorneal lens, a corneal inlay, a corneal ring, or a glaucoma filtering device.

In yet another aspect, the present invention provides a method of making the polymer of the present invention. The raw material mixture is subjected to a heating treatment or a photocuring treatment. In some embodiments, the method comprises: the raw material mixture is subjected to a gradient heating treatment to obtain a polymer. Wherein the raw material mixture contains the bulk monomer and the blue light absorber. The specific types of bulk monomers and blue-light absorbers have been described in detail above and will not be described further herein. In the process proposed by the present invention, the ratio of the bulk monomer and the blue-light absorber is also not particularly limited. The ratio can be adjusted by one skilled in the art according to the physicochemical properties of the specific polymer to be prepared and the specific types of the bulk monomer and the blue light absorber. In order to further improve the properties of the polymer prepared by the method, at least one of a crosslinking agent, an initiator and an ultraviolet absorber may be further included in the raw material mixture. The method has simple and convenient operation steps and short production period, and the obtained polymer has ideal physical and chemical properties (such as optical and mechanical properties and blue light interception function).

In some embodiments, the gradient heat treatment may include:

a first reaction stage:

in the first reaction stage, the raw material mixture is heated to 40-120 ℃ for reaction, preferably at 40-70 ℃, and the reaction time can be 1-48 hours. The reaction at a lower temperature can prevent the reaction rate from being too fast, and is beneficial to forming a sample with uniform appearance, thereby improving the performance of the polymer.

And a second reaction stage:

in the second reaction stage, the raw material mixture after the first reaction stage is heated to 40-140 ℃, preferably 80-120 ℃, and the reaction time can be 1-48 hours. Therefore, the method is beneficial to promoting the further reaction of the residual raw materials, improves the conversion rate of the raw materials and can further improve the performance of the polymer prepared by the method.

The scheme of the invention will be explained with reference to the examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the invention only and should not be taken as limiting the scope of the invention. The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.

In the examples described below, all temperatures are given in degrees Celsius unless otherwise indicated. The reagents used are either commercially available or can be prepared by the methods described herein.

In the present invention, the structure is dominant if there is any difference between the chemical name and the chemical structure.

The following shorthand words are used throughout the present invention

g

mL of

mmol millimole

h hours

min for

s second

Boc tert-butyloxycarbonyl group

EtOAc ethyl acetate

n-Hex n-hexane

wt% wt.%

Example 1

1- (4- ((4-hydroxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl methacrylate

Step 1: synthesis of compound 1- (4-nitrophenoxy) -3-methoxypropan-2-ol

4-nitrophenol (41.7g, 0.3mol), potassium carbonate (56.5g, 0.1mol) and absolute ethanol (200mL) were added in this order to a three-necked flask, and after the mixture was stirred under reflux for 1 hour, 1-chloro-3-methoxy-2-propanol (25.0g, 0.2mol) was slowly added dropwise thereto, and stirring was continued for 24 hours. The reaction was cooled to room temperature, filtered, the filtrate was rotary evaporated to remove ethanol, the crude product was diluted with dichloromethane (250mL) and washed with aqueous sodium hydroxide (5 wt%, 150 mL. times.2). The organic phase was dried over anhydrous magnesium sulfate overnight, filtered and the solvent removed by rotary evaporation to give a pale yellow viscous liquid (27g, 59.1%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：250[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：8.21-8.19(m，2H)，7.01-6.98(m，2H)，4.24-4.18(m，1H)，4.16-4.09(m，2H)，3.62-3.55(m，2H)，3.43(s，3H)，2.74-2.73(d，1H)。

step 2: synthesis of compound 1- (4-aminophenoxy) -3-methoxypropan-2-ol

1- (4-Nitrophenoxy) -3-methoxypropan-2-ol (27g, 118.9mmol), 5% palladium on carbon (25.2g, 11.9mmol), ammonium formate (44.9g, 713.4mmol) and tetrahydrofuran (100mL) were added sequentially to a single-neck flask, the mixture was stirred at room temperature for 5 minutes, and then the reaction was transferred to a 60 ℃ oil bath for 2 hours. The reaction was filtered, the filter cake was washed with tetrahydrofuran (100mL), the collected filtrate was washed with saturated aqueous sodium bicarbonate (100mL × 1), the aqueous phase after separation was extracted with dichloromethane (100mL × 3), the organic phase was mixed and washed with saturated brine (100mL × 2), the aqueous phase after separation was extracted with dichloromethane (100mL × 1), the organic phase was slightly concentrated and dried over anhydrous magnesium sulfate overnight, and the solvent was removed by rotary evaporation after filtration to give a pink liquid (22.7g, 99%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：198[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：6.79-6.76(m，2H)，6.66-6.64(m，2H)，4.17-4.12(m，1H)，3.99-3.92(m，2H)，3.60-3.52(m，2H)，3.42(s，3H)。

and step 3: synthesis of compound 1- (4-tert-butoxycarbonylaminophenoxy) -3-methoxypropan-2-ol

To a single-neck flask were added 1- (4-aminophenoxy) -3-methoxypropan-2 ol (22.0g, 111.7mmol), and methanol (200mL) in that order. BOC anhydride (37.4g, 171.3mmol) was diluted with methanol (30mL) and added dropwise, and the mixture was stirred at room temperature for 3 h. The mixture was slightly concentrated and added dropwise to n-hexane (400mL), stirred for 10min, filtered, the filter cake washed with n-hexane (100mL), and the collected solid dried under vacuum at 40 ℃ for 2h to give an off-white solid (30g, 87.6%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：320[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.28-7.27(m，2H)，6.88-6.85(m，2H)，6.41(s，1H)，4.20-4.14(m，1H)，4.04-3.97(m，2H)，3.61-3.53(m，2H)，3.43(s，3H)，2.60-2.59(d，1H)，1.53(s，9H)。

and 4, step 4: synthesis of compound 1- (4-tert-butoxycarbonylaminophenoxy) -3-methoxyprop-2-yl methacrylate

1- (4-tert-Butoxycarbonylaminophenoxy) -3-methoxypropan-2-ol (15.0g, 50.5mmol), triethylamine (10.1g, 100.0mmol), 4-dimethylaminopyridine (1.2g, 10.0mmol) and tetrahydrofuran (150mL) were added in this order to a single-neck flask, and after sufficient dissolution, methacryloyl chloride (10.5g, 100.9mmol) was slowly added dropwise thereto, followed by stirring at 0 ℃ for 1 hour, then returning to room temperature and further stirring for 24 hours. To the mixture was added 50% aqueous sodium bicarbonate (10mL) to terminate the reaction, after stirring for 10 minutes, the reaction was filtered, tetrahydrofuran was removed by rotary evaporation, and the crude product was purified by column chromatography (n-hexane/EtOAc (v/v) ═ 5/1) to give a colorless, transparent, viscous liquid (17g, 92.4%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：388[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.28-7.26(m，2H)，6.87-6.85(m，2H)，6.46(s，1H)，6.16(s，1H)，5.60(s，1H)，5.37-5.32(m，1H)，4.17-4.11(m，2H)，3.71-3.70(d，2H)，3.41(s，3H)，1.96(s，3H)，1.52(s，9H)。

and 5: synthesis of compound preparation 1- (4-aminophenoxy) -3-methoxyprop-2-yl methacrylate

1- (4-tert-Butoxycarbonylaminophenoxy) -3-methoxyprop-2-yl methacrylate (17.0g, 46.6mmol) and methylene chloride (100mL) were sequentially added to a single-neck flask, and after sufficient dissolution, trifluoroacetic acid (70mL) was added and the mixture was stirred at room temperature for 15 min. After the reaction was completed, the mixture was neutralized with an aqueous sodium hydroxide solution, separated, the aqueous phase was extracted with dichloromethane (50 mL. times.1), and the organic phase was dried over anhydrous magnesium sulfate for 2 hours, filtered, and the solvent was removed by rotary evaporation to obtain a pale red viscous liquid (12.5g, 98%). Mass spectral data of the resulting product are as follows:

LC-MS(ESI，pos.ion)m/z：266[M+H]⁺。

step 6: synthesis of the Compound 1- (4- ((4-hydroxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl methacrylate

A three-necked flask was charged with a mixed solution (20mL) of 1- (4-aminophenoxy) -3-methoxyprop-2-yl methacrylate (3.00g, 11.30mmol), potassium bromide (1.35g, 11.30mmol), concentrated hydrochloric acid (5.70g, 56.50mmol) and acetone/water (v/v, 1/1) in this order, the mixed solution was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, a solution of sodium nitrite (0.93g, 13.60mmol) in water (20mL) was slowly dropped into the reaction solution and stirring was continued for 0.5 h. A solution of phenol (1.09g, 11.30mmol), sodium hydroxide (1.11g, 28.30mmol), and sodium carbonate (1.50g, 14.10mmol) in water (20mL) was added dropwise to the above diazonium solution while maintaining the temperature of the solution at not higher than 5 ℃. Stirring was continued overnight, the mixture was poured into dichloromethane (100mL) and after separation the organic phase was stirred and purified by column chromatography (n-hexane/EtOAc (v/v) ═ 5/1) to give a yellow solid powder (2.01g, 53.1%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：371[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.88-7.83(m，4H)，7.04-7.02(m，2H)，6.96-6.94(m，2H)，6.19(s，1H)，5.63(s，1H)，5.44-5.39(m，1H)，4.29-4.28(d，2H)，3.75-.374(d，2H)，3.44(s，3H)，1.98(s，3H)。

example 2

The compound 1- (4- ((4-hydroxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl acrylate

Step 1: synthesis of compound 1- (4-tert-butoxycarbonylaminophenoxy) -3-methoxyprop-2-yl acrylate

1- (4-tert-Butoxycarbonylaminophenoxy) -3-methoxypropan-2-ol (8.00g, 26.94mmol), triethylamine (5.45g, 53.96mmol), 4-dimethylaminopyridine (0.65g, 2.50mmol) and tetrahydrofuran (150mL) were added to a single-neck flask in this order, and after sufficient dissolution, acryloyl chloride (4.80g, 46.12mmol) was slowly added dropwise thereto, followed by stirring at 0 ℃ for 1h, then returning to room temperature and further stirring for 24 h. To the mixture was added 50% aqueous sodium bicarbonate (10mL) to terminate the reaction, after stirring for 10 minutes, the reaction was filtered, tetrahydrofuran was removed by rotary evaporation, and the product was purified by column chromatography (n-hexane/EtOAc (v/v) ═ 5/1) to give a pale red, transparent, viscous liquid (8.05g, 81.9%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：374[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.28-7.26(m，2H)，6.88-6.86(m，2H)，6.49-6.45(d，1H)，6.22-6.15(m，1H)，5.89-5.86(d，1H)，5.41-5.36(m，1H)，4.19-4.13(m，2H)，3.71-3.70(d，2H)，3.41(s，3H)，1.52(s，9H)。

step 2: synthesis of Compound 1- (4-aminophenoxy) -3-methoxyprop-2-yl acrylate

1- (4-tert-Butoxycarbonylaminophenoxy) -3-methoxyprop-2-yl acrylate (8.0g, 31.87mmol) and methylene chloride (100mL) were sequentially added to a single-neck flask, and after being sufficiently dissolved, trifluoroacetic acid (70mL) was added thereto, and the mixture was stirred at room temperature for 15 min. After the reaction was completed, the mixture was neutralized with an aqueous sodium hydroxide solution, separated, the aqueous phase was extracted with dichloromethane (50 mL. times.1), and the organic phase was dried over anhydrous magnesium sulfate for 2 hours, filtered, and the solvent was removed by rotary evaporation to obtain a pale red viscous liquid (4.60g, 80%). The mass spectra and nuclear magnetic data of the resulting product are as follows:

LC-MS(ESI，pos.ion)m/z：252[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：6.79-6.77(m，2H)，6.65-6.63(m，2H)，6.49-6.45(d，1H)，6.23-6.16(m，1H)，5.88-5.86(d，1H)，5.39-5.34(m，1H)，4.13-4.11(m，2H)，3.71-3.70(d，2H)，3.41(s，3H)。

and step 3: synthesis of the Compound 1- (4- ((4-hydroxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl acrylate

A three-necked flask was charged with a mixed solution (20mL) of 1- (4-aminophenoxy) -3-methoxyprop-2-yl acrylate (1.50g, 5.90mmol), potassium bromide (0.70g, 5.90mmol), concentrated hydrochloric acid (2.99g, 29.50mmol) and acetone/water (v/v, 1/1) in this order, the mixed solution was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, sodium nitrite (0.48g, 7.80mmol) was dissolved in water (20mL), and the solution was slowly added dropwise to the reaction mixture and stirred for 0.5 h. Phenol (0.55g, 5.90mmol), sodium hydroxide (0.59g, 14.75mmol), anhydrous sodium carbonate (0.77g, 7.34mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution, maintaining the solution temperature at not higher than 5 ℃. Stirring was continued overnight, the mixture was poured into dichloromethane (100mL) and after separation the organic phase was stirred and purified by column chromatography (n-hexane/EtOAc (v/v) ═ 5/1) to give a yellow solid powder (1.26g, 73.5%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：357[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.89-7.83(m，4H)，7.05-7.02(m，2H)，6.96-6.94(m，2H)，6.52-6.47(d，1H)，6.24-6.17(m，1H)，5.91-5.89(d，1H)，5.46-5.43(m，1H)，4.29-4.28(m，2H)，3.76-3.74(d，2H)，3.44(s，3H)。

example 3

1- (4- ((2, 4-dihydroxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl acrylate

The procedure of example 1 was repeated, except that in step (6), a mixed solution (20mL) of 1- (4-aminophenoxy) -3-methoxyprop-2-yl methacrylate (3.00g, 11.30mmol), potassium bromide (1.35g, 11.30mmol), concentrated hydrochloric acid (5.70g, 56.50mmol) and acetone/water (v/v, 1/1) was sequentially added to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and when the internal temperature reached 0 ℃ or less, sodium nitrite (0.93g, 13.60mmol) was dissolved in water (20mL), and the mixture was slowly added dropwise to the reaction mixture, followed by stirring for 0.5 h. Resorcinol (1.23g, 11.30mmol), sodium hydroxide (1.11g, 28.30mmol), sodium carbonate (1.50g, 14.10mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution, maintaining the solution temperature not higher than 5 ℃. Stirring was continued overnight, the mixture was poured into dichloromethane (100mL) and after separation the organic phase was stirred and chromatographed (n-hexane/EtOAc (v/v) ═ 3/1) to give a red solid (2.1g, 53.8%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：387[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.80-7.73(m，3H)，7.04-7.02(m，2H)，6.56-6.53(d，1H)，6.44-6.43(s，1H)，6.18(s，1H)，5.63(s，1H)，5.43-5.38(m，1H)，4.29-4.27(d，2H)，3.75-3.73(d，2H)，3.44(s，3H)，1.98(s，3H)。

example 4

1- (4- ((2, 4-dihydroxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl acrylate

The procedure of example 2 was repeated, except that in step (3), a mixed solution (20mL) of 1- (4-aminophenoxy) -3-methoxyprop-2-yl acrylate (1.00g, 3.90mmol), potassium bromide (0.47g, 3.90mmol), concentrated hydrochloric acid (2.00g, 19.50mmol) and acetone/water (v/v, 1/1) was added in this order to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and when the internal temperature reached 0 ℃ or less, sodium nitrite (0.32g, 4.68mmol) was dissolved in water (20mL), slowly added dropwise to the reaction mixture, and the stirring was continued for 0.5 h. Resorcinol (0.73g, 3.90mmol), sodium hydroxide (0.39g, 9.75mmol), anhydrous sodium carbonate (0.51g, 4.87mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution, maintaining the solution temperature not higher than 5 ℃. Stirring was continued overnight, the mixture was poured into dichloromethane (100mL) and after separation the organic phase was stirred and purified by column chromatography (n-hexane/EtOAc (v/v) ═ 3/1) to give the title compound as a red solid powder (1.15g, 77.7%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：373[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.79-7.71(m，3H)，7.03-7.01(m，2H)，6.55-6.53(t，1H)，6.52-6.48(d，1H)，6.43-6.42(d，1H)，6.24-6.17(m，1H)，5.93-5.90(d，1H)，5.47-5.42(m，1H)，4.30-4.25(m，2H)，3.76-3.75(d，2H)，3.45(s，3H)。

example 5

1- (4- ((4-hydroxy-2-methoxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl methacrylate and 1- (4 ((2-hydroxy-4-methoxyphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl methacrylate

The procedure of example 1 was repeated, except that in step (6), a mixed solution (20mL) of 1- (4-aminophenoxy) -3-methoxyprop-2-ylmethacrylate (2.00g, 7.50mmol), potassium bromide (0.89g, 7.50mmol), concentrated hydrochloric acid (3.80g, 37.7mmol) and acetone/water (v/v, 1/1) was sequentially added to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and when the internal temperature reached 0 ℃ or less, sodium nitrite (0.62g, 9.00mmol) was dissolved in water (20mL), and the mixture was slowly added dropwise to the reaction mixture, and the stirring was continued for 0.5 h. Metamethoxyphenol (0.93g, 7.5mmol), sodium hydroxide (0.75g, 18.70mmol), and sodium carbonate (0.99g, 9.40mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution while maintaining the solution temperature at not higher than 5 ℃. Stirring was continued overnight, the mixture was poured into dichloromethane (100mL), and after separation the organic phase was stirred and chromatographed (n-hexane/EtOAc (v/v) ═ 3/1) to give a yellow solid (0.47g, 17%) identified by mass spectrometry and nuclear magnetic identification as compound (11) and a red viscous liquid (0.21g, 7.7%) identified by mass spectrometry and nuclear magnetic identification as compound (5), respectively. Mass spectra and nmr H spectra data of compound (11) are as follows:

LC-MS(ESI，pos.ion)m/z：401[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.81-7.76(m，3H)，7.05-7.03(m，2H)，6.64-6.61(m，1H)，6.52-6.49(m，1H)，6.18(s，1H)，5.63(s，1H)，5.43-5.38(m，1H)，4.29-4.28(d，2H)，3.88(s，3H)，3.74-3.73(d，2H)，3.44(s，3H)，1.98(s，3H)。

mass spectra and nmr H spectra data of compound (5) are as follows:

LC-MS(ESI，pos.ion)m/z：401[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.87-7.86(m，2H)，7.69-7.68(m，1H)，7.02-7.01(m，2H)，6.58(s，1H)，6.48-6.47(m，1H)，6.18(s，1H)，5.63(s，1H)，5.42-5.39(m，1H)，4.28-4.27(d，2H)，4.01(s，3H)，3.74-3.73(d，2H)，3.43(s，3H)，1.98(s，3H)。

example 6

1- (4- ((4-hydroxy-2-methylphenyl) diazenyl) phenoxy) -3-methoxyprop-2-yl methacrylate

The procedure of example 1 was repeated, except that in step (6), a mixed solution (20mL) of 1- (4-aminophenoxy) -3-methoxyprop-2-ylmethacrylate (2.00g, 7.50mmol), potassium bromide (0.89g, 7.50mmol), concentrated hydrochloric acid (3.80g, 37.70mmol) and acetone/water (v/v, 1/1) was sequentially added to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and when the internal temperature reached 0 ℃ or less, sodium nitrite (0.62g, 9.00mmol) was dissolved in water (20mL), and the mixture was slowly added dropwise to the reaction mixture, and the stirring was continued for 0.5 h. M-methylphenol (0.82g, 7.50mmol), sodium hydroxide (0.75g, 18.70mmol), sodium carbonate (0.99g, 9.40mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution while maintaining the solution temperature at not higher than 5 ℃. Stirring was continued overnight, the mixture was poured into dichloromethane (100mL) and after separation the organic phase was stirred and chromatographed (n-hexane/EtOAc (v/v) ═ 5/1) to give a red viscous liquid (2.06g, 79.2%). The mass spectrum and nuclear magnetic resonance H spectrum data of the obtained product are as follows:

LC-MS(ESI，pos.ion)m/z：385[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.87-7.85(m，2H)，7.65-7.62(d，1H)，7.03-7.01(m，2H)，6.78(s，1H)，6.73-6.70(d，1H)，6.19(s，1H)，5.63(s，1H)，5.44-5.39(m，1H)，4.29-4.27(d，2H)，3.76-3.75(d，2H)，3.44(s，3H)，2.68(s，3H)，1.99(s，3H)。

example 7

1-ethoxy-3- (4- ((4-hydroxyphenyl) diazenyl) phenoxy) prop-2-ylmethacrylate

Step 1: synthesis of compound 1-ethoxy-3- (4-nitrophenoxy) propan-2-ol

4-nitrophenol (28.0g, 0.2mol), potassium carbonate (14.0g, 0.1mol) and absolute ethanol (200mL) were added in this order to a three-necked flask, and after the mixture was stirred under reflux for 1 hour, 1-chloro-3-ethoxy-2-propanol (13.9g, 0.1mol) was slowly added dropwise thereto, and stirring was continued for 24 hours. The reaction was cooled to room temperature, filtered, the filtrate was rotary evaporated to remove ethanol, the crude product was diluted with dichloromethane (200mL) and washed with aqueous sodium hydroxide (10 wt%, 80 mL. times.3). The organic phase was dried over anhydrous sodium sulfate for 2h, filtered and the solvent removed by rotary evaporation to give a pale red viscous liquid (13.3g, 55%).

LC-MS(ESI，pos.ion)m/z：264[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：8.24-8.20(m，2H)，7.12-6.98(m，2H)，4.23-4.14(m，1H)，4.13-4.11(m，2H)，3.64-3.58(m，4H)，2.64(s，1H)，1.26-1.19(t，3H)。

Step 2: synthesis of compound 1- (4-aminophenoxy) -3-ethoxypropan-2-ol

1-ethoxy-3- (4-nitrophenoxy) propan-2-ol (13.3g, 55.2mmol), 5% palladium on carbon (11.7g, 5.5mmol), ammonium formate (20.9g, 33.1mmol), and tetrahydrofuran (50mL) were added sequentially to a single-neck flask, and the mixture was stirred at 45 ℃ for 1 h. The reaction was filtered, the filter cake was washed with dichloromethane (100mL), the collected filtrate was diluted to 250mL with dichloromethane and washed with saturated brine (80mL × 4), the organic phase after separation was dried over anhydrous sodium sulfate for 2h, and the solvent was removed by rotary evaporation after filtration to give a pink solid (10g, 86%).

LC-MS(ESI，pos.ion)m/z：212[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：6.79-6.77(m，2H)，6.67-6.64(m，2H)，4.17-4.12(m，1H)，4.00-3.93(m，2H)，3.64-3.55(m，4H)，3.47(s，2H)，2.65(s，1H)，1.30-1.22(t，3H)。

And step 3: synthesis of compound 1- (4-tert-butoxycarbonylaminophenoxy) -3-ethoxypropan-2-ol

1- (4-Aminophenoxy) -3-ethoxypropan-2-ol (10.0g, 47.4mmol), BOC anhydride (12.5g, 56.9mmol), and methanol (50mL) were added in this order to a single-neck flask, and the mixture was stirred at room temperature for 1 h. The reaction was added to n-hexane (300mL), stirred for 10min, filtered, the filter cake washed with n-hexane (200mL), and the collected solid dried under vacuum at 40 ℃ for 2h to give a white solid (11.0g, 74%).

LC-MS(ESI，pos.ion)m/z：334[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.28-7.27(m，2H)，6.89-6.86(m，2H)，6.37(s，1H)，4.18-4.14(m，1H)，4.04-3.97(m，2H)，3.65-3.56(m，4H)，2.58-2.56(d，1H)，1.53(s，9H)，1.26-1.22(t，3H)。

And 4, step 4: synthesis of compound 1- (4-tert-butoxycarbonylaminophenoxy) -3-ethoxypropan-2-yl methacrylate

To a one-necked flask were added 1- (4-tert-butoxycarbonylaminophenoxy) -3-ethoxypropan-2-ol (11.0g, 33.2mmol), diisopropylethylamine (14.2g, 108.5mmol), 4-dimethylaminopyridine (0.86g, 7.0mmol) and tetrahydrofuran (70mL) in this order, and after sufficient dissolution, methacryloyl chloride (18.4g, 176.9mmol) was slowly added dropwise thereto and stirring was continued for 24 h. The reaction was filtered, the tetrahydrofuran removed by rotary evaporation and the product purified by column chromatography (n-hexane/EtOAc (v/v) ═ 5/1) to give a light yellow viscous liquid (9.0g, 64%).

LC-MS(ESI，pos.ion)m/z：402[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.28-7.26(m，2H)，6.89-6.86(m，2H)，6.37(s，1H)，6.16(s，1H)，5.60(s，1H)，5.37-5.31(m，1H)，4.18-4.12(m，2H)，3.74-3.73(d，2H)，3.60-3.53(m，2H)，1.97(s，3H)，1.53(s，9H)，1.30-1.19(t，3H)。

And 5: synthesis of Compound 1- (4-aminophenoxy) -3-ethoxypropan-2-yl methacrylate

To a single-neck flask were added 1- (4-tert-butoxycarbonylaminophenoxy) -3-ethoxypropan-2-ylmethacrylic acid (9.0g, 23.7mmol) and a trifluoroacetic acid/dichloromethane mixed solution (v/v, 3/4, 35mL) in this order, and the mixture was dissolved sufficiently and stirred at room temperature for 15 min. The reaction was diluted to 200mL with dichloromethane and neutralized with saturated sodium bicarbonate, separated, the organic phase dried over anhydrous sodium sulfate for 2h, filtered, the solvent removed by rotary evaporation, and the product purified by column chromatography (n-hexane/EtOAc (v/v) ═ 1: 1) to give a brown viscous liquid (5.4g, 75%).

LC-MS(ESI，pos.ion)m/z：280[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：6.79-6.76(m，2H)，6.66-6.63(m，2H)，6.16(s，1H)，5.60(s，1H)，5.35-5.30(m，1H)，4.17-4.09(m，2H)，3.74-3.72(d，2H)，3.62-3.51(m，2H)，1.97(s，3H)，1.22-1.19(t，3H)。

Step 6: synthesis of the Compound 1-ethoxy-3- (4- ((4-hydroxyphenyl) diazenyl) phenoxy) prop-2-ylmethacrylate

A three-necked flask was charged with a mixed solution (20mL) of 1- (4-aminophenoxy) -3-ethoxypropan-2-yl methacrylate (0.84g, 3.00mmol) obtained in step (5), potassium bromide (0.41g, 3.40mmol), concentrated hydrochloric acid (1.12g, 11.00mmol) and acetone/water (v/v, 1/1) in this order, the mixed solution was stirred in a low-temperature bath at-5 ℃ C, when the internal temperature reached 0 ℃ or less, sodium nitrite (0.23g, 3.30mmol) was dissolved in water (10mL), and slowly added dropwise to the reaction solution, and stirring was continued for 0.5 h. Phenol (0.32g, 3.30mmol), sodium hydroxide (0.13g, 3.30mmol) were dissolved in water (15mL) and added dropwise to the above diazonium solution, maintaining the solution temperature at no higher than 5 ℃ during the addition. After stirring for an additional 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was passed through column chromatography (n-hexane/EtOAc (v/v) ═ 5/1) to give an orange viscous liquid (0.40g, 34%).

LC-MS(ESI，pos.ion)m/z：407[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.88-7.83(m，4H)，7.05-7.02(d，2H)，6.96-6.94(d，2H)，6.18(s，1H)，5.62(s，1H)，5.43-5.38(m，1H)，4.31-4.18(m，2H)，3.78-3.77(m，2H)，3.63-3.56(m，2H)，1.98(s，3H)，1.25-1.21(t，3H)。

Example 8

1- (4- ((2, 4-dihydroxyphenyl) diazenyl) phenoxy) -3-ethoxypropan-2-yl methacrylate

The procedure of example 7 was repeated, except that in step (6), a mixed solution (20mL) of 1- (4-aminophenoxy) -3-ethoxypropan-2-yl methacrylate (0.84g, 3.00mmol), potassium bromide (0.41g, 3.40mmol), concentrated hydrochloric acid (1.12g, 11.00mmol) and acetone/water (v/v, 1/1) was added in this order to a three-necked flask, the mixture was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, sodium nitrite (0.23g, 3.30mmol) was dissolved in water (10mL), and the mixture was slowly added dropwise to the reaction mixture, and stirring was continued for 0.5 h. M-biphenol (0.36g, 3.30mmol), sodium hydroxide (0.26g, 6.60mmol) were dissolved in water (15mL) and added dropwise to the above diazonium salt solution, maintaining the solution temperature at no higher than 5 ℃ during the addition. After stirring for a further 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was passed through column chromatography (n-hexane/EtOAc (v/v) ═ 1/1) to give an orange solid (0.30g, 22%).

LC-MS(ESI，pos.ion)m/z：423[M+Na]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.77-7.75(d，2H)，7.71-7.70(d，1H)，7.02-7.00(d，2H)，6.54-6.52(t，1H)，6.42-6.42(d，1H)，6.19(s，1H)，5.64(s，1H)，5.42-5.39(m，1H)，4.30-4.26(m，2H)，3.79-3.78(m，2H)，3.64-3.57(m，2H)，1.99(s，3H)，1.25-1.23(t，3H)。

Example 9

1-ethoxy-3- (4- ((4-hydroxy-2-methoxyphenyl) diazenyl) phenoxy) prop-2-ylmethacrylate

The procedure of example 7 was repeated, except that in step (6), a mixed solution (20mL) of 1- (4-aminophenoxy) -3-ethoxypropan-2-yl methacrylate (0.84g, 3.0mmol), potassium bromide (0.41g, 3.40mmol), concentrated hydrochloric acid (1.20g, 11.80mmol) and acetone/water (v/v, 1/1) was charged in this order into a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, sodium nitrite (0.23g, 3.30mmol) was dissolved in water (10mL), and the mixture was slowly added dropwise to the reaction mixture, and stirring was continued for 0.5 h. Metamethoxyphenol (0.41g, 3.30mmol), sodium hydroxide (0.13g, 3.3mmol) were dissolved in water (15mL) and added dropwise to the above diazonium salt solution while maintaining the solution temperature at not higher than 5 ℃. After stirring for a further 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was passed through column chromatography (n-hexane/EtOAc (v/v) ═ 3/1) to give an orange solid (0.30g, 24%).

LC-MS(ESI，pos.ion)m/z：415[M+H]⁺；

¹H NMR(400MHz，CDCl₃)δ(ppm)：7.86-7.84(d，2H)，7.67-7.65(d，1H)，7.10-6.99(d，2H)，6.57(s，1H)，6.48-6.46(t，1H)，6.17(s，1H)，5.62(s，1H)，5.41-5.37(m，1H)，4.30-4.27(m，2H)，3.98(s，3H)，3.77-3.76(d，2H)，3.62-3.53(m，2H)，1.98(s，3H)，1.24-1.20(t，3H)。

Comparative example 1 preparation of Polymer A0

2-phenylethyl acrylate (0.3500g), 2-phenylethyl methacrylate (0.2500g), ethoxyethyl methacrylate (0.3500g), 1, 4-butanediol diacrylate (0.0350g), 2- (2H-benzotriazol-2-yl) -4-methyl-6- (2-propenyl) phenol (0.0100g) and bis (4-tert-butylcyclohexyl) peroxydicarbonate (0.0100g) (without addition of azo compounds) were mixed uniformly, and then transferred to a mold composed of two layers of glass and a 0.4mm thick polytetrafluoroethylene sheet, the mold was placed in an oven at 60 ℃ for reaction for 3 hours, the oven was raised to 100 ℃ and kept for 3 hours to obtain a transparent elastic polymer, the obtained material was ultrasonically cleaned in absolute ethanol, vacuum drying at 60 deg.C for 24 hr.

Example 10 preparation of Polymer A1

2-phenylethyl acrylate (0.3500g), 2-phenylethyl methacrylate (0.2500g), ethoxyethyl methacrylate (0.3500g), 1, 4-butanediol diacrylate (0.0350g), 2- (2H-benzotriazol-2-yl) -4-methyl-6- (2-propenyl) phenol (0.0100g), bis (4-tert-butylcyclohexyl) peroxydicarbonate (0.0200g) and the azo compound prepared in example 1 (0.0010g) were mixed well, and then transferred to a mold composed of two layers of glass and a 0.4mm thick polytetrafluoroethylene sheet, and the mold was put into an oven at 60 ℃ for reaction for 3 hours, and the oven was raised to 100 ℃ and kept for 3 hours to obtain a transparent and elastic polymer, the obtained material was ultrasonically cleaned in absolute ethanol and vacuum dried at 60 ℃ for 24 hours to obtain polymer A1.

Examples 11 to 18 preparation of polymers A2 to A9

The other steps are the same as in example 10, except that the azo compounds prepared in examples 2 to 9 were respectively used in place of the azo compound prepared in example 1, to obtain polymers a2 to a 9.

Example 19 preparation of Polymer A10

2-phenylethyl acrylate (0.3500g), 2-phenylethyl methacrylate (0.2500g), ethoxyethyl methacrylate (0.3500g), 1, 4-butanediol diacrylate (0.0350g), 2- (2H-benzotriazol-2-yl) -4-methyl-6- (2-propenyl) phenol (0.0100g), bis (4-tert-butylcyclohexyl) peroxydicarbonate (0.0100g) and the azo compound (0.00150g) prepared in example 3 were mixed well, and then transferred to a mold consisting of two layers of glass and a 0.4mm thick polytetrafluoroethylene sheet, the mold was put into an oven at 60 ℃ for reaction for 3 hours, the oven was raised to 100 ℃ and kept for 3 hours to obtain a transparent elastic polymer, the obtained material is ultrasonically cleaned in absolute ethyl alcohol and then is dried for 24 hours in vacuum at 60 ℃.

Comparative example 2 preparation of Polymer A11

Uniformly mixing 2-phenylethyl acrylate (0.3500g), 2-phenylethyl methacrylate (0.2500g), ethoxyethyl methacrylate (0.3500g), 1, 4-butanediol diacrylate (0.0350g), 2- (2H-benzotriazole-2-yl) -4-methyl-6- (2-propenyl) phenol (0.0100g), bis (4-tert-butylcyclohexyl) peroxydicarbonate (0.0100g) and a conventional dye 4-hydroxyazobenzene (0.0010g), transferring to a mold consisting of two layers of glass and a 0.4 mm-thick polytetrafluoroethylene sheet, placing the mold in an oven at 60 ℃ for reaction for 3 hours, raising the temperature of the oven to 100 ℃ and keeping the temperature for 3 hours to obtain a transparent elastic polymer, the obtained material is ultrasonically cleaned in absolute ethyl alcohol and then is dried for 24 hours in vacuum at 60 ℃.

Example 20 spectral transmittance measurement

(1) The test method comprises the following steps: the spectral transmittance of the material in the light wave range of 200nm-800nm is tested by an Agilent Cary60 ultraviolet-visible spectrophotometer at room temperature.

(2) And (3) testing results:

the spectral transmittances of the polymers prepared in examples 10 to 19 and comparative examples 1 and 2 are shown in Table 1. FIGS. 1-3 show graphs comparing the spectral transmittance of some of the polymers prepared in the examples and comparative polymers. As is clear from the table and the drawing, the spectrum of the comparative test material A0, to which the yellow dye (azo compound) of the present invention was not added, began to have a strong transmittance at 400nm, and the transmittance at 450nm (blue region) was higher than 90%, and there was almost no absorption of blue light. The polymers A1-A10 added with the yellow dye can obviously reduce the spectral transmittance of wavelengths of 400-500nm, have good absorptivity to blue light in the range, and have the maximum value of the spectral transmittance higher than 91% in the visible light range, which indicates that the polymers added with the yellow dye can keep better transparency. Also, the polymer synthesized by the present invention has good blue light absorption property and spectral transmittance, compared to comparative example 2 using the conventional dye.

TABLE 1

Example 21 polymeric Material extraction experiments and test results

(1) The extraction experimental method comprises the following steps:

the polymers A1, A2, A4, A6, A9 and A11 prepared in the previous examples were cut into thin pieces having a length and a width of about 15X 10mm, respectively, and placed in a Soxhlet extractor to be washed with anhydrous ethanol under reflux. The frequency of washing the extraction cannula with the extraction liquid was 2 times/hour. And taking out the sample after extraction for 24 hours, respectively measuring the spectral transmittance of the sample after vacuum drying for 24 hours at 60 ℃, and calculating the absorption efficiency loss rate of each sample at 450nm before and after extraction.

(2) And (3) testing results:

spectral absorption data at 450nm and absorption loss rate at 450nm of each sample before and after extraction of polymers A1, A2, A4, A6, A9 and A11 are shown in Table 2. FIG. 4 is a comparison of spectral transmittances before and after extraction of A4 and A11. The comparison shows that the absorption efficiency of the polymer A11 added with the traditional dye 4-hydroxyazobenzene to blue light is obviously reduced (the absorption efficiency is reduced by 43.8%) after extraction, which indicates that the stability of the traditional dye added in the polymer is poor, so that the risk of the azo compound in the polymer entering human eyes is high if the artificial lens is prepared by using the polymer. The absorption efficiency of the polymer added with the dye of the invention to blue light is not obviously changed before and after extraction (the absorption loss rate is less than 3 percent), which shows that the yellow dye of the invention participates in reaction in the process of forming the polymer due to the polymerizable double bond, and the dye is bonded with the material matrix by covalent bonds, thereby effectively improving the biocompatibility of the yellow crystal material and the stability of blue light absorption. Referring to fig. 5, the absorption loss rate of each polymer synthesized by the present invention before and after extraction is not higher than 3%, while the absorption loss rate of the conventional dye after extraction is as high as nearly 45%. Other polymers synthesized by the present invention were tested and the results were similar to those shown in table 2.

TABLE 2

In the description herein, references to the description of the terms "one embodiment," "another embodiment," "an example," etc., mean that a particular feature, structure, material, or characteristic described in connection with the example or example is included in at least one example or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.

Although embodiments of the present invention and examples have been shown and described above, it is understood that the above embodiments, examples are illustrative and not to be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments, examples by those of ordinary skill in the art within the scope of the present invention.

Claims (11)

1. An azo compound, wherein the azo compound is a compound represented by the formula (Ia):

wherein,

R¹is hydrogen or methyl; r²Is C_1-6An alkyl group;

x is O; y is O; w is a single bond;

the R is³Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy or C_1-4Alkoxy radical C_1-4An alkyl group;

R⁴each independently is hydrogen; and

n is 0, 1, 2, 3 or 4;

m is 0, 1, 2, 3, 4 or 5.

2. The azo compound of claim 1, wherein R is³Each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoroMethyl, trifluoromethoxy, trifluoroethyl, trifluoroethoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl.

3. The azo compound of claim 1, wherein R is¹Is H or methyl, said R²Is methyl or ethyl, m is 1 or 2, R³Each independently is hydroxy, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, methoxyethyl, trifluoromethyl, trifluoromethoxy, fluoro, chloro, or bromo.

4. The azo compound of claim 1, wherein the azo compound is a compound represented by any one of formulae (1) to (20):

5. a polymer, characterized in that the monomers constituting the polymer comprise a bulk monomer and a blue light absorber, wherein the blue light absorber is the azo compound of any one of claims 1 to 4.

6. The polymer of claim 5, wherein the bulk monomer comprises at least one of a (meth) acrylate monomer, a vinyl monomer, and an allyl monomer.

7. The polymer of claim 5 or 6, wherein the raw materials comprising the polymer further comprise at least one of a crosslinking agent, an ultraviolet absorber, and an initiator.

8. An ophthalmic medical device comprising the polymer of any one of claims 5 to 7.

9. The ocular medical device of claim 8 wherein the ocular medical device is an intraocular lens, contact lens, corneal modifier, intracorneal lens, corneal inlay, corneal ring, or glaucoma filter.

10. A process for preparing a polymer according to any one of claims 5 to 7, comprising:

subjecting the raw material mixture to a gradient heating treatment or a photocuring treatment to obtain the polymer,

wherein the raw material mixture contains a bulk monomer, a blue light absorber, and optionally at least one selected from a crosslinking agent, an initiator, and an ultraviolet absorber.

11. The method of claim 10, wherein the gradient heat treatment comprises:

a first reaction stage, wherein the temperature of the first reaction stage is 40-120 ℃, and the reaction time is 1-48 hours; and

and in the second reaction stage, the temperature of the second reaction stage is 40-140 ℃, and the reaction time is 1-48 hours.

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