CN110944981A

CN110944981A - Benzotriazole ultraviolet absorbent, preparation method and application thereof

Info

Publication number: CN110944981A
Application number: CN201880044864.XA
Authority: CN
Inventors: 康小林; 刘敏; 刘鹏; 陈佩兴; 曹立
Original assignee: Dongguan HEC Tech R&D Co Ltd
Current assignee: Dongguan HEC Tech R&D Co Ltd
Priority date: 2017-10-27
Filing date: 2018-10-26
Publication date: 2020-03-31
Also published as: WO2019080926A1

Abstract

The invention provides a benzotriazole ultraviolet absorbent, a preparation method thereof, a polymer containing the benzotriazole ultraviolet absorbent and application of the polymer. The benzotriazole ultraviolet absorbent has an excellent ultraviolet absorption function, contains a polymerizable group, and is not easy to migrate, dissolve out and diffuse in a polymer.

Description

Benzotriazole ultraviolet absorbent, preparation method and application thereof

Technical Field

The invention relates to the field of ultraviolet absorbers, in particular to a benzotriazole ultraviolet absorber, a preparation method and application thereof.

Background

Eye lens products have been developed for many years, the natural lens of human eye has strong ultraviolet absorption capability to protect retina from ultraviolet light, and the existing eye lens products, such as artificial lens, usually also add ultraviolet absorbent to make the eye lens products have ultraviolet light blocking function. Currently known uv absorbers for use in the field of implantable ophthalmic lenses are primarily benzotriazole, benzophenone, and triazine type absorbers, which typically incorporate conventional ethylenically polymerizable groups, such as methacrylate, acrylate, methacrylamide, acrylamide, or styrene groups, and the like, such that the ethylenically group containing uv absorber can be incorporated into the polymer chain by free radical polymerization with the other components of the ophthalmic lens material, which is covalently bonded to the polymeric network of the lens material, such that the uv absorber is not readily migrated, leached, or separated from the lens material. This stability is particularly important for implantable ophthalmic lenses, and migration, leaching or detachment can not only cause the implant to lose uv blocking activity, but can also present toxicological concerns.

The introduction of different kinds of other functional groups on the ultraviolet absorbent can affect the light absorption performance, the stability, the solubility and the activity of the absorbent, the existing ultraviolet absorbent has the problems of poor light absorption performance, instability, low solubility and the like, and the yellow color is also a common problem of the existing benzotriazole ultraviolet absorbent, so the ultraviolet absorbent for eye medical devices still needs to be improved.

Disclosure of Invention

Summary of The Invention

The invention provides a benzotriazole ultraviolet absorbent with a novel structure, which can be copolymerized with other acrylic monomer raw materials to be combined into a material in a covalent bonding manner, so that the ultraviolet absorbent is prevented from migrating and diffusing in the material; in addition, the ultraviolet absorbent is white crystal, so that the problem of yellowing of the color of the benzotriazole ultraviolet absorbent in the prior art is solved, the transparency of the ophthalmic product is improved, and the application range of the ophthalmic product is expanded; in addition, the benzotriazole ultraviolet absorbent provided by the invention has higher solubility and stronger absorption capacity.

In one aspect, the invention provides a benzotriazole ultraviolet absorbent, which is a compound shown in formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a hydrate and a solvate of the compound shown in formula (I),

wherein:

R¹is H or C_1-12An alkyl group;

R²is O or S;

A₁is a bond or C_1-12An alkylene group; a. the₂Is H or C_1-12An alkyl group;

m is 0 to 100; n is 0 or 1;

R³and R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-8Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl, sulfonic acid or COOR⁵；R⁵Is H or C_1-4An alkyl group;

wherein R is¹、A₂、R³、R⁴And R⁵C in (1)_1-4Alkyl radical, C_1-8Alkyl radical, C_1-12Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl or amino is independently optionally substituted with 1,2,3 or 4 substituents selected from hydrogen, deuterium, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-4Alkylamino or C_6-10Aryl group.

In some of these embodiments, R is¹Is H or C_1-8An alkyl group; r²Is O; a. the₁Is a bond or C_1-8An alkyl group; a. the₂Is H or C_1-8An alkyl group; m is 0 to 50; n is 0 or 1; r³And R⁴Have the meaning as described in the present invention.

In other embodiments, the present invention provides a benzotriazole uv absorber that is a compound of formula (Ia) or a stereoisomer, tautomer, nitroxide, hydrate, solvate of a compound of formula (Ia):

wherein R is¹、A₂、m、R³And R⁴Have the meaning as described in the present invention.

In some of these embodiments, R is¹Is H or C_1-8Alkyl groups of (a); a. the₂Is H or C_1-8An alkyl group; m is 0 to 50; r³And R⁴Have the meaning as described in the present invention.

In still other embodiments, the present invention provides a benzotriazole uv absorber that is a compound of formula (Ib) or a stereoisomer, tautomer, nitroxide, hydrate, solvate of a compound of formula (Ib):

wherein:

R¹is H or C_1-8Alkyl groups of (a);

R⁶is H or C_1-12An alkyl group;

wherein R is¹、R³、R⁴、R⁵And R⁶C in (1)_1-4Alkyl radical, C_1-8Alkyl radical, C_1-12Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl or amino is independently optionally substituted with 1,2,3 or 4 substituents selected from hydrogen, deuterium, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-4Alkylamino or C_6-10Aryl group.

In still other embodiments, the present invention provides a benzotriazole uv absorber that is a compound of formula (Ic) or a stereoisomer, tautomer, nitroxide, hydrate, solvate of a compound of formula (Ic):

wherein R is¹、R³、⁴And R⁶Having a composition as described in the present inventionAnd (5) defining.

In some embodiments, R¹Is H, methyl, ethyl or n-propyl. In some embodiments, R⁶Is H or C_1-8An alkyl group. In other embodiments, R⁶Is C_1-6An alkyl group. In still other embodiments, R⁶Is C_1-4An alkyl group.

In still other embodiments, R⁶Is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

In some embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Halogenoalkyl of, C_6-10Aryl or C_1-6An alkylamino group of (a).

In other embodiments, R³And R⁴Each independently is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

In another aspect, the present invention provides a polymer comprising any one of the benzotriazole uv absorber compounds described above or a stereoisomer, tautomer, nitroxide, hydrate, solvate thereof.

In some embodiments, the monomers comprising the polymer further comprise a bulk monomer comprising at least one of a (meth) acrylate-based monomer, a vinyl-based monomer, or an allyl-based monomer.

In other embodiments, the polymer further comprises at least one of a crosslinker, a blue-light absorber, and an initiator.

In another aspect, the invention features an ocular medical device that includes any of the polymers described above.

In some embodiments, the ocular medical device is an intraocular lens, contact lens, corneal modifier, intracorneal lens, corneal inlay, corneal ring, or glaucoma filter.

In another aspect, the present invention provides a process for the preparation of the benzotriazole UV absorbers of formula (Ib) above.

In another aspect, the present invention also relates to the use of the above benzotriazole uv absorbers in coatings, inks, resins, plastics, rubbers, elastomers, films, cosmetics, photovoltaic or medical materials.

The foregoing merely summarizes certain aspects of the invention and is not intended to be limiting. These and other aspects will be more fully described below.

Description of the drawings:

FIG. 1 shows a graph of the spectral transmittance test of Polymer A1 prepared in example 7;

FIG. 2 shows a graph of the spectral transmittance test of Polymer A2 prepared in example 8;

FIG. 3 shows a graph of the spectral transmittance test of Polymer A3 prepared in example 9;

FIG. 4 shows a graph of the spectral transmittance test of Polymer A4 prepared in example 10;

FIG. 5 shows a graph of the spectral transmittance test of Polymer A5 prepared in example 11;

FIG. 6 shows a graph of the spectral transmittance test of Polymer A6 prepared in example 12; and

FIG. 7 shows a graph of the spectral transmittance test of Polymer A0 prepared in comparative example.

Detailed description of the invention

Definitions and general terms

Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. Those skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described herein. In the event that one or more of the incorporated documents, patents, and similar materials differ or contradict this application (including but not limited to defined terminology, application of terminology, described techniques, and the like), this application controls.

It will be further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

The following definitions as used herein should be applied unless otherwise indicated. For the purposes of the present invention, the chemical elements are in accordance with the CAS version of the periodic Table of the elements and the handbook of chemistry and Physics, 75 th edition, 1994. In addition, general principles of Organic Chemistry can be referred to as described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausaltito: 1999, and "March's Advanced Organic Chemistry" by Michael B.Smith and Jerry March, John Wiley & Sons, New York:2007, the entire contents of which are incorporated herein by reference.

The articles "a," "an," and "the" as used herein are intended to include "at least one" or "one or more" unless otherwise indicated or clearly contradicted by context. Thus, as used herein, the articles refer to one or to more than one (i.e., to at least one) of the objects. For example, "a component" refers to one or more components, i.e., there may be more than one component contemplated for use or use in embodiments of the described embodiments.

The term "comprising" is open-ended, i.e. includes the elements indicated in the present invention, but does not exclude other elements.

"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.

"chiral" is a molecule having the property of not overlapping its mirror image; and "achiral" refers to a molecule that can overlap with its mirror image.

"enantiomer" refers to two isomers of a compound that are not overlapping but are in mirror image relationship to each other.

"diastereomer" refers to a stereoisomer having two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers may be separated by high resolution analytical procedures such as electrophoresis and chromatography, e.g., HPLC.

"solvate" refers to an association of one or more solvent molecules with a compound of the invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. The term "hydrate" refers to an association of solvent molecules that is water.

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 diastereomeric mixtures (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 (2nd Ed. Robert E. Gawley, Jeffrey Aub é, Elsevier, Oxford, UK, 2012); eliel, E.L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); wilen, S.H.tables of solving Agents and Optical solutions 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.

The compounds of the invention may be optionally substituted with one or more substituents, as described herein, in compounds of the general formula above, or as specifically exemplified, sub-classes, and classes of compounds encompassed by the invention. It is understood that the term "optionally substituted" may be used interchangeably with the term "substituted or unsubstituted". In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced with a particular substituent. Unless otherwise indicated, an optional substituent group may be substituted at each substitutable position of the group. When more than one position in a given formula can be substituted with one or more substituents selected from a particular group, the substituents may be substituted at each position, identically or differently. When substituents are described as being "independently selected from" groups, then each substituent is selected independently of the other, and thus each substituent may be the same or different from each other.

In addition, unless otherwise explicitly indicated, the descriptions of the terms "… independently" and "… independently" and "… independently" used in the present invention are interchangeable and should be understood in a broad sense to mean that the specific items expressed between the same symbols do not affect each other in different groups or that the specific items expressed between the same symbols in the same groups do not affect each other.

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 "C_1-6Alkyl "means in particular independently disclosed methyl, ethyl, C₃Alkyl radical, C₄Alkyl radical, C₅Alkyl and C₆An alkyl group. In each of the parts of the invention, linking substituents are described. Where the structure clearly requires a linking group, the markush variables listed for that group are understood to be linking groups. For example, if the structure requires a linking group and the markush group definition for the variable recites "alkyl" or "aryl," it is understood that the "alkyl" or "aryl" represents an attached alkylene group or arylene group, respectively.

The term "alkyl" or "alkyl group" as used herein, denotes a saturated, straight or branched chain monovalent hydrocarbon radical containing from 1 to 20 carbon atoms, wherein the alkyl group may be optionally substituted with one or more substituents as described herein. Unless otherwise specified, alkyl groups contain 1-20 carbon atoms. In one embodiment, the alkyl group contains 1 to 12 carbon atoms; in another embodiment, the alkyl group contains 1 to 6 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 4 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 (Et-CH)₂CH₃) N-propyl (n-Pr, -CH)₂CH₂CH₃) Isopropyl (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) T-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 "alkenyl" denotes radicals containing 2 to 12 carbon atomsStraight or branched chain monovalent hydrocarbon radicals having at least one site of unsaturation, i.e. having one carbon-carbon sp²A double bond, wherein the alkenyl group may be optionally substituted with one or more substituents described herein, including the positioning of "cis" and "trans", or the positioning of "E" and "Z". In one embodiment, the alkenyl group contains 2 to 8 carbon atoms; in another embodiment, the alkenyl group contains 2 to 6 carbon atoms; in yet another embodiment, the alkenyl group contains 2 to 4 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 monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one site of unsaturation, i.e. a carbon-carbon sp triple bond, wherein said alkynyl radical may optionally be substituted with one or more substituents as described herein. In one embodiment, alkynyl groups contain 2-8 carbon atoms; in another embodiment, alkynyl groups contain 2-6 carbon atoms; in yet another embodiment, alkynyl groups contain 2-4 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 "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing from 3 to 12 carbon atoms. In one embodiment, the cycloalkyl group contains 3 to 12 carbon atoms; in another embodiment, cycloalkyl groups contain 3 to 10 carbon atoms; in another embodiment, cycloalkyl contains 3 to 8 carbon atoms; in yet another embodiment, the cycloalkyl group contains 3 to 6 carbon atoms. The cycloalkyl groups may be independently unsubstituted or substituted with one or more substituents described herein.

The terms "heterocyclyl" and "heterocycle" are used interchangeably herein and refer to a saturated or partially unsaturated monocyclic, bicyclic, or tricyclic ring containing 3 to 15 ring atoms, wherein no aromatic ring is included in the monocyclic, bicyclic, or tricyclic ring, and at least one ring atom is selected from the group consisting of nitrogen, sulfur, and oxygen atoms. Unless otherwise stated in the context of the present invention,the heterocyclic group may be carbon-based or nitrogen-based, and-CH₂The group may optionally be replaced by-c (o) -. The sulfur atom of the ring may optionally be oxidized to the S-oxide. The nitrogen atom of the ring may optionally be oxidized to an N-oxygen compound.

Examples of heterocyclyl groups include, but are not limited to: oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuryl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxolanyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thiaxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thietanyl, oxazepanyl, and the like

Radical diaza

Radical, sulfur nitrogen hetero

Yl, 2-oxa-5-azabicyclo [2.2.1]Hept-5-yl. In heterocyclic radicals of-CH₂Examples of-groups substituted by-C (O) -include, but are not limited to, 2-oxopyrrolidinyl, oxo-1, 3-thiazolidinyl, 2-piperidinonyl, 3, 5-dioxopiperidinyl and pyrimidinedione. Examples of the sulfur atom in the heterocyclic group being oxidized include, but are not limited to, sulfolane group, 1-dioxothiomorpholinyl group. The heterocyclyl group may be optionally substituted with one or more substituents as described herein. Where the structure clearly requires a linking group, the markush variables listed for that group are understood to be linking groups. For example, if the structure requires a linking group and the Markush group definition for that variable recites "heterocyclyl", it is to be understood thatThe "heterocyclyl" represents an attached heterocyclylene group.

The term "n-atomic" where n is an integer typically describes the number of ring-forming atoms in a molecule in which the number of ring-forming atoms is n. For example, piperidinyl is a heterocyclic group consisting of 6 atoms.

The term "unsaturated" as used herein means that the group contains one or more unsaturations.

The term "heteroatom" refers to O, S, N, P and Si, including N, S and any oxidation state form of P; primary, secondary, tertiary amines and quaternary ammonium salt forms; or a form in which a hydrogen on a nitrogen atom in the heterocycle is substituted, for example, N (like N in 3, 4-dihydro-2H-pyrrolyl), NH (like NH in pyrrolidinyl) or NR (like NR in N-substituted pyrrolidinyl).

The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

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. The term "aryl" may be used interchangeably with the term "aromatic ring". Examples of the aryl group may include phenyl, naphthyl and anthracenyl. The aryl group may independently be optionally substituted with one or more substituents described herein.

The term "heteroaryl" denotes monocyclic, bicyclic and tricyclic ring systems containing 5 to 12 ring atoms, or 5 to 10 ring atoms, or 5 to 6 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring of 5 to 7 atoms with one or more attachment points to the rest of the molecule. The term "heteroaryl" may be used interchangeably with the terms "heteroaromatic ring" or "heteroaromatic compound". The heteroaryl group is optionally substituted with one or more substituents described herein. In one embodiment, a heteroaryl group of 5-10 atoms contains 1,2,3, or 4 heteroatoms independently selected from O, S, and N.

Examples of heteroaryl groups include, but are not limited to, 2-furyl, 3-furyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyridazinyl (e.g., 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl), triazolyl (e.g., 3-triazolyl and 5-triazolyl), and the like, 2-thienyl, 3-thienyl, pyrazolyl (e.g., 2-pyrazolyl), isothiazolyl, 1,2, 3-oxadiazolyl, 1,2, 5-oxadiazolyl, 1,2, 4-oxadiazolyl, 1,2, 3-triazolyl, 1,2, 3-thiadiazolyl, 1,3, 4-thiadiazolyl, 1,2, 5-thiadiazolyl, pyrazinyl, 1,3, 5-triazinyl; the following bicyclic rings are also included, but are in no way limited to these: benzimidazolyl, benzofuranyl, benzothienyl, indolyl (e.g., 2-indolyl), purinyl, quinolyl (e.g., 2-quinolyl, 3-quinolyl, 4-quinolyl), isoquinolyl (e.g., 1-isoquinolyl, 3-isoquinolyl, or 4-isoquinolyl), imidazo [1,2-a ] pyridyl, pyrazolo [1,5-a ] pyrimidinyl, imidazo [1,2-b ] pyridazinyl, [1,2,4] triazolo [4,3-b ] pyridazinyl, [1,2,4] triazolo [1,5-a ] pyrimidinyl, [1,2,4] triazolo [1,5-a ] pyridyl, and the like.

The term "alkylamino" or "alkylamino" includes "N-alkylamino" and "N, N-dialkylamino" in which the amino groups are each independently substituted with one or two alkyl groups. In some of these embodiments, the alkylamino group is one or two C_1-6Lower alkylamino groups in which the alkyl group is attached to the nitrogen atom. In other embodiments, the alkylamino group is C_1-3Lower alkylamino groups of (a). Suitable alkylamino groups can be monoalkylamino or dialkylamino, and such examples include, but are not limited to, N-methylamino, N-ethylamino, N-dimethylamino, N-diethylamino, and the like.

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 may be 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) 1-butoxy (n-BuO, n-butoxy, -OCH)₂CH₂CH₂CH₃) 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH)₂CH(CH₃)₂) 2-butoxy (s-BuO, s-butoxy, -OCH (CH)₃)CH₂CH₃) 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC (CH)₃)₃) 1-pentyloxy (n-pentyloxy, -OCH)₂CH₂CH₂CH₂CH₃) 2-pentyloxy (-OCH (CH)₃)CH₂CH₂CH₃) 3-pentyloxy (-OCH (CH))₂CH₃)₂) 2-methyl-2-butoxy (-OC (CH))₃)₂CH₂CH₃) 3-methyl-2-butoxy (-OCH (CH)₃)CH(CH₃)₂) 3-methyl-l-butoxy (-OCH)₂CH₂CH(CH₃)₂) 2-methyl-l-butoxy (-OCH)₂CH(CH₃)CH₂CH₃) And so on.

The term "haloalkyl" denotes an alkyl group substituted with one or more halogen atoms, examples of which include, but are not limited to, trifluoromethyl and the like. The term "amino" (alone or in combination with other terms) means-NH₂. The term "sulfonic acid group" means-SO₃H。

Detailed description of the invention

(1) The benzotriazole ultraviolet absorbent of the invention and the preparation method thereof

wherein:

R¹is H or C_1-12Alkyl groups of (a);

R²is O or S;

m is 0 to 100; n is 0 or 1;

wherein R is¹、A₂、R³、R⁴And R⁵C in (1)_1-4Alkyl radical, C_1-8Alkyl radical, C_1-12Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl or amino is independently optionally substituted with 1,2,3 or 4 substituents selected from hydrogen, deuterium, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-4Alkylamino or C_6-10Substituent of arylAnd (4) substitution.

In some embodiments, R¹Is H or C_1-8An alkyl group. In other embodiments, R¹Is H or C_1-6An alkyl group. In still other embodiments, R¹Is H or C_1-4An alkyl group. In still other embodiments, R¹Is H, methyl, ethyl or n-propyl.

In some embodiments, a is₁Is a bond. In other embodiments, A₁Is C_1-12An alkylene group. In still other embodiments, A₁Is C_1-8An alkylene group. In still other embodiments, A₁Is C_1-6An alkylene group. In still other embodiments, A₁Is C_1-4An alkylene group.

In some embodiments, a is₂Is H or C_1-12An alkyl group. In still other embodiments, A₂Is C_1-8An alkyl group. In still other embodiments, A₂Is C_1-6An alkyl group. In still other embodiments, A₂Is C_1-4An alkyl group.

In some embodiments, m is 0 to 100. In other embodiments, m is 0 to 50. In still other embodiments, m is 0 to 30. In still other embodiments, m is from 0 to 20. In still other embodiments, m is 0 to 10.

In some embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_6-10Aryl or C_1-6An alkylamino group. In other embodiments, R³And R⁴Each independently is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

wherein:

R¹is H or C_1-12Alkyl groups of (a);

A₂is H or C_1-12An alkyl group;

m is 0 to 100;

R³and R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-8Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl, sulfonic acid or COOR⁵；R⁵Is H or C_1-4Alkyl groups of (a);

In some embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_6-10Aryl radical, C_6-10Aryloxy radical or C_1-6An alkylamino group. In other embodiments, R³And R⁴Each independently is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

wherein:

R¹is H or C_1-8An alkyl group;

R⁶is H or C_1-12An alkyl group;

R³and R⁴Each independently of the others is hydrogen, fluorine, chlorineBromine, iodine, hydroxy, amino, nitro, cyano, C_1-8Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl, sulfonic acid or COOR⁵；R⁵Is H or C_1-4An alkyl group;

In some embodiments, R¹Is H or C_1-8An alkyl group. In other embodiments, R¹Is C_1-6An alkyl group. In still other embodiments, R¹Is C_1-4An alkyl group. In still other embodiments, R¹Is H or methyl or ethyl or n-propyl.

In some embodiments, R⁶Is H or C_1-8An alkyl group. In another embodiment, R⁶Is C_1-6An alkyl group. In still other embodiments, R⁶Is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, tert-pentyl, n-hexyl.

In some embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_6-10Aryl or C_1-6An alkylamino group. In other embodiments, R³And R⁴Each of which isIndependently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

wherein R is¹、R³、⁴And R⁶Have the meaning as described in the present invention.

The ultraviolet absorbing compound of the present invention represented by the general formula (I), (Ia), (Ib) or (Ic) is not particularly limited, however

Preferred examples include compounds having the following structure:

or stereoisomers, tautomers, nitroxides, hydrates and solvates thereof.

The compounds satisfying the general formula (I), (Ia), (Ib) or (Ic) or the compounds having the formulae (1) to (38) or the stereoisomers, tautomers, nitrogen oxides, hydrates and solvates thereof have a desirable ultraviolet light blocking effect, and specifically, when the ultraviolet visible light absorption spectrum is measured, the spectral transmittance at 400nm or less is almost zero and ultraviolet rays are almost completely blocked; in addition, the benzotriazole ultraviolet absorbent provided by the invention has a polymerizable group, and can be subjected to copolymerization reaction with other monomers in the polymer, so that the phenomena of migration and dissolution of the ultraviolet absorbent from the polymer are avoided. In addition, the benzotriazole ultraviolet absorbent provided by the invention takes asymmetric ether bonds as connecting groups, so that the solubility of the compound is greatly increased, the polymerization efficiency in the copolymerization reaction is greatly improved, and the polymer molecules obtained after polymerization can keep quite flexible; in addition, the inventor discovers through a large amount of researches that the ultraviolet absorbing compound obtained by the invention is pure white due to the introduction of the flexible chain in the molecule, overcomes the problem of yellowing of the color commonly existing in benzotriazole ultraviolet absorbers in the prior art, improves the transparency, the light transmission effect, the visual effect and the like of the material, and greatly expands the application range of the ultraviolet absorber; therefore, the benzotriazole ultraviolet absorbent provided by the invention can be used as an ultraviolet absorbent to be added into raw materials for synthesizing the eye medical device, and can be subjected to copolymerization reaction with other polymerization monomers, such as a bulk monomer of a polymer, a blue light absorbent and the like, so that the obtained polymer is used for manufacturing the eye medical device, and the ultraviolet absorbent can 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 benzotriazole ultraviolet absorbent is one of ideal materials for preparing flexible eye medical devices such as foldable intraocular lenses and the like.

In another aspect of the present invention, the present invention provides a method for preparing the benzotriazole uv absorber shown in (Ib) above. The method has simple operation and high yield, and is particularly suitable for industrial scale-up production. The synthesis method is represented by a chemical reaction formula as follows:

wherein R is¹、R⁶、R⁷、R⁸、R³And R⁴Having the above definitions of the invention, further description is omitted here.

The method comprises the following steps: firstly, carrying out diazotization reaction on the compound of the formula (VII) under the condition of nitrous acid or nitrite strong acid medium to form azo ions, then adjusting the pH value to be under the alkaline condition, carrying out coupling reaction on the azo ions and the formula (VI), and finally reducing nitro groups into amino groups under the action of active metals (such as zinc, iron and the like) and realizing ring closure to obtain a compound (IV);

step two: carrying out substitution reaction on the compound (IV) and the compound (V) in an inorganic base and a protic solvent to generate a compound shown as a formula (II); in some embodiments of the present invention, the above substitution reaction is carried out in a protic solvent, for example, the protic solvent may include at least one of ethanol, isopropanol, N-butanol, N-dimethylformamide, dimethyl sulfoxide, acetone, methyl ethyl ketone, and dioxane. In another embodiment of the present invention, the above substitution reaction is carried out in the presence of a protic solvent and an inorganic base, which may include at least one of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide and calcium hydroxide. In another embodiment of the present invention, in order to accelerate the reaction, a catalyst such as potassium iodide or sodium iodide is usually added to the substitution reaction, and iodine is exchanged with chlorine to accelerate the reaction.

Step three: the compound shown in the formula (II) and the acrylic acid compound shown in the formula (III) are coupled to obtain the benzotriazole ultraviolet absorbent shown in the formula (Ib) of the invention. In one embodiment of the present invention, the condensation reaction is carried out in an aprotic solvent. The aprotic solvent includes at least one of dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, 1,1, 1-trichloroethane, chlorobenzene, dichlorobenzene, pentane, n-hexane, methylcyclohexane, 1, 1-diethoxypropane, 1, 1-dimethoxymethane, 2-dimethoxypropane, 1,2,3, 4-tetrahydronaphthalene, decahydronaphthalene, benzene, toluene, xylene, cumene, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1, 4-dioxane, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethyl acetate, and butyl acetate. In another embodiment of the present invention, the above condensation reaction is carried out in the presence of an aprotic solvent and an acid, which may include p-toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoroacetic acid, acetic acid, propionic acid, and the like.

(2) Polymers of the invention

In another aspect of the present invention, there is provided a polymer, wherein the monomers comprising the polymer comprise any one of the benzotriazole UV absorbers described above. Specifically, the polymer is prepared by copolymerizing the polymerizable benzotriazole ultraviolet absorber disclosed by the invention and one or more than two bulk monomers or other polymerizable monomers. Since the polymerizable benzotriazole ultraviolet absorber has an ultraviolet absorbing effect, a polymer containing the polymerizable benzotriazole ultraviolet absorber also has an ultraviolet absorbing effect. In addition, the polymerizable benzotriazole ultraviolet absorbent has groups capable of participating in polymerization, and can perform copolymerization reaction with a body monomer or other additives in raw materials for synthesizing a polymer, so that the risk of migration, filtering or separation of the benzotriazole ultraviolet absorbent in the polymer is greatly reduced, and the safety performance of a device which is prepared from the polymer and is directly contacted with a human body is improved. Preferably, the polymer can be used for preparing intraocular medical devices such as an intraocular lens and the like, so that the intraocular lens also has an ultraviolet absorption function, and further the damage of ultraviolet light to human eyes can be reduced.

In the present invention, the UV absorbers according to the present invention may be used in an amount of 0.1 to 2% by weight, based on the total weight of monomers used to synthesize the polymer. The proportion of the ultraviolet absorber and the bulk monomer in the polymer can be adjusted according to actual conditions. The term "bulk monomer" refers specifically to the principal monomer material used to form the bulk of the polymer. The bulk monomer is a main component capable of forming the polymer proposed by the present invention by polymerization, and is capable of undergoing a copolymerization reaction with the ultraviolet absorber during the polymerization process. Since the uv absorber contains a polymerizable group, monomers commonly used for forming a polymer can be copolymerized with the uv absorber of the present invention, and thus, in the present invention, the specific type of the bulk monomer is not particularly limited, and may include at least one of a (meth) acrylate monomer, a vinyl monomer, and an allyl monomer. In one embodiment of the present invention, the bulk monomer is a (meth) 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 another embodiment of the present invention, the bulk monomer may include at least one of 2-phenylethyl acrylate, 2-phenylethyl methacrylate, and ethoxyethyl methacrylate. In another embodiment 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 yet another embodiment of the present invention, the bulk monomer is an allylic monomer, which 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.

In the present invention, "other polymerizable monomers" means other polymerizable monomers constituting the polymer raw material proposed in the present invention, such as a polymerizable blue-light absorber, a crosslinking agent, an initiator, and the like, in addition to the bulk monomer.

In the raw materials constituting the polymer proposed by the present invention, a crosslinking agent, an initiator and a blue light absorber may be further included. The crosslinking agent, the initiator, the blue light absorber, the bulk monomer and the ultraviolet absorber are mixed and polymerized to form the polymer provided by the invention.

In one embodiment of the present invention, the crosslinking agent may include, but is not limited to, at least one of 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. The cross-linking agent can play a better role in cross-linking each monomer, thereby further improving the performance of the polymer. In one embodiment, the crosslinking agent may be used in an amount of 2 to 7% by weight, based on the total weight of monomers used to synthesize the polymer. When the amount of the crosslinking agent is within the above range, a good crosslinking reaction effect can be obtained, and the obtained polymer has high mechanical strength and is less likely to undergo plastic deformation.

In one embodiment of the present invention, the initiator may be a photoinitiator or a thermal initiator. The initiator may include benzoyl peroxide, t-butyl hydroperoxide, cumyl hydroperoxide, bis (4-t-butylcyclohexyl) peroxydicarbonate, azobisisobutyronitrile, phenylbis (2,4, 6-trimethylbenzoyl) phosphine oxide, (2,4, 6-trimethylbenzoyl) diphenylphosphine oxide, ethyl 2,4, 6-trimethylbenzoylphosphonate, 2-methyl-1- [ 4-methylthiophenyl ] -2-morpholinyl-1-propanone, 2-phenylbenzyl-2-dimethylamine-1- (4-morpholinobenzylphenyl) butanone, 2-hydroxy-1- (4- (2-hydroxy-2-methylpropionylphenyl) benzyl) -2-methyl-1-propanone, N-methyl-2-methylbenzoylphenyl) propanone, N-methyl-2-methyl-1-propanone, N-methyl-2-propanone, N-methyl-1, Bis 2, 6-difluoro-3-pyrrolylphenyltitanocene, ethyl (4-dimethylamino) -benzoate, 4-phenylbenzophenone, 4-chlorobenzophenone, benzophenone, methyl o-benzoylbenzoate, benzoin dimethyl ether, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 1-hydroxy-cyclohexyl-phenyl ketone, 2-isopropylthioxanthone, and azobis (2, 4-dimethylvaleronitrile). In one embodiment, the initiator may be used in an amount of 0.1 to 5% by weight, based on the total weight of monomers used to synthesize the polymer.

In one embodiment of the present invention, the blue light absorber may include a polymerizable azo-based compound. In the present invention, the "polymerizable azo-based compound" means a compound having a corresponding group (azo group) which is copolymerizable with at least one of the above-mentioned monomers of the present invention (including the benzotriazole uv absorber monomer, bulk monomer, as set forth above in the present invention), an initiator, and a crosslinking agent. The skilled person will be able to select suitable compounds as blue-light absorbers within the above-mentioned ranges depending on the actual situation, e.g. on the specific requirements of the ophthalmic medical device for the polymer. In some embodiments, blue-light absorbers may include N- (4-hydroxy-3- (o-tolylazene) phenethyl) methacrylamide, methyl 4-hydroxy-3-methyl-5- (phenyldiazenyl) phenoxy) methacrylate, (E) -2- (4- (phenyldiazenyl) phenoxy) ethyl methacrylate, (E) -N- (4- (4-hydroxyphenyl) diazenyl) phenyl) methacrylamide, (E) -N- (4- ((4-hydroxy-3-methoxyphenyl) diazenyl) phenyl) methacrylamide, 2-hydroxy-3- (4-methoxyphenyl) diazenyl) methacrylate-5-methylbenzyl ester, At least one of benzyl 2-hydroxy-5-methyl-3- ((3,4, 5-trimethoxyphenyl) diazenyl) methacrylate. The blue light absorbent is added into the raw material of the polymer, so that most of blue light can be absorbed, and the retina of an eye is prevented from being damaged by exposure to the blue light. The blue-light absorber may be used in an amount of 0.1 to 2% by weight, based on the total weight of monomers used to synthesize the polymer. When the content of the blue light absorber is within the above range, most of the blue light can be efficiently absorbed without adversely affecting the refractive index and flexibility of the polymer.

As described above, the polymerizable benzotriazole uv absorber of the present invention has excellent absorption characteristics in the uv (wavelength of 400nm or less), and the polymer of the present invention comprises a benzotriazole uv absorber having the above-mentioned properties, and therefore, the polymer of the present invention also has excellent absorption characteristics in the region of 400nm or less, specifically, the uv-visible absorption spectrum of the polymer of the present invention is as shown in fig. 1 to 6, and the transmittance of light of 400nm or less reaches 0%, and the uv is almost completely blocked. In addition, the benzotriazole ultraviolet absorbent provided by the invention has a polymerizable group, and can generate copolymerization reaction with other monomers in the polymer, so that the phenomena of migration and dissolution of the benzotriazole ultraviolet absorbent from the polymer are avoided. In addition, the benzotriazole ultraviolet absorbent provided by the invention takes asymmetric ether bonds as connecting groups, so that the solubility of the benzotriazole ultraviolet absorbent is greatly increased, the polymerization efficiency in the copolymerization reaction is greatly improved, and the polymer molecules obtained after polymerization can keep considerable flexibility; in addition, the inventor discovers through a great deal of research that the ultraviolet absorbing compound obtained by the invention is pure white due to the introduction of the flexible chain in the molecule, the problem of common yellow color of benzotriazole ultraviolet absorbers in the prior art is solved, the white ultraviolet absorber is added into the polymer, the transparency, the light transmission effect, the visual effect and the like of the polymer material are improved, and the application effect of the polymer in various fields is enhanced.

In summary, the above polymers have very strong ultraviolet light blocking ability, while the spectral transmittance is high in the visible light range. In addition, the polymer also has higher tensile strength, proper elastic modulus and larger elongation at break, and the foldable intraocular lens prepared by the polymer provided by the invention can not damage human eyes due to too violent opening, can not influence the use effect due to poor mechanical properties, and is very suitable for manufacturing eye medical devices with specific functions, such as intraocular lenses and the like.

In another aspect of the invention, the invention features an ocular medical device that includes the polymer previously set forth herein. Thus, the ocular medical device has all of the features and advantages of the polymers previously described. Specifically, the eye medical device has ideal mechanical and optical properties, and can intercept ultraviolet components in visible light, so that the damage of ultraviolet rays to organs such as human eyes and the like can be reduced; the eye medical device has better safety performance, and because the benzotriazole ultraviolet absorbent in the polymer provided by the invention is not easy to migrate and diffuse in the polymer, the benzotriazole ultraviolet absorbent can be prevented from being in direct contact with a human body. The eye treatment also has the characteristics of low hardness, good flexibility, easy folding and the like, thereby facilitating the treatment in the operation.

The ocular medical device may be an intraocular lens, contact lens, corneal modifier, intracorneal lens, corneal inlay, corneal ring, or glaucoma filter, etc. More preferably, the polymer of the present invention can be used as a material for an artificial crystal. When the polymer of the present invention is used as a material for an artificial crystal, it can be molded by a known method. For example, a method of obtaining a polymer in a rod shape, a block shape, or a plate shape by performing a polymerization reaction in an appropriate mold or a container, then processing the polymer into a desired shape by a processing method such as cutting, polishing, or laser processing, or a method of obtaining a polymer by performing a polymerization reaction in a mold corresponding to a desired shape, and then performing further fine processing as necessary.

In a further aspect of the invention, the invention provides the use of the aforementioned ultraviolet absorbing compounds in materials such as coatings, inks, resins, plastics, rubbers, elastomers, films, cosmetics, optoelectronics, and medical applications. The benzotriazole ultraviolet absorber provided by the invention can be added into materials for manufacturing the eye medical device, and can also be added into materials such as paint, ink, resin, plastic, rubber, elastomer, film, cosmetics, photoelectricity, medical materials and the like, so that the materials have an ultraviolet absorption function.

General synthetic procedure

In general, the compounds of the invention can be prepared by the processes described herein, unless otherwise indicated, wherein the substituents have the meanings as described herein. The following reaction schemes and examples serve to further illustrate the context of the invention. Those skilled in the art will recognize that: the chemical reactions described herein may be used to suitably prepare a number of other compounds of the invention, and other methods for preparing the compounds of the invention are considered to be within the scope of the invention. For example, the synthesis of those non-exemplified compounds according to the present invention can be successfully accomplished by those skilled in the art by modification, such as appropriate protection of interfering groups, by the use of other known reagents in addition to those described herein, or by some routine modification of reaction conditions. In addition, the reactions disclosed herein or known reaction conditions are also recognized as being applicable to the preparation of other compounds of the present invention.

The examples described below, unless otherwise indicated, are all temperatures set forth in degrees Celsius. Reagents were purchased from commercial suppliers such as Aldrich Chemical Company, Inc., Arco Chemical Company and Alfa Chemical Company and were used without further purification unless otherwise indicated. General reagents were purchased from Shantou Wen Long chemical reagent factory, Guangdong Guanghua chemical reagent factory, Guangzhou chemical reagent factory, Tianjin HaoLiyu Chemicals Co., Ltd, Qingdao Tenglong chemical reagent Co., Ltd, and Qingdao Kaseiki chemical plant. The anhydrous tetrahydrofuran, dioxane, toluene and ether are obtained through reflux drying of metal sodium. The anhydrous dichloromethane and chloroform are obtained by calcium hydride reflux drying. Ethyl acetate, petroleum ether, N-hexane, N-dimethylacetamide and N, N-dimethylformamide were used by being dried beforehand over anhydrous sodium sulfate.

The following reactions are generally carried out under positive pressure of nitrogen or argon or by sleeving a dry tube over an anhydrous solvent (unless otherwise indicated), the reaction vial being stoppered with a suitable rubber stopper and the substrate being injected by syringe. The glassware was dried.

The column chromatography is performed using a silica gel column. Silica gel (300 and 400 meshes) was purchased from Qingdao oceanic chemical plants. Nuclear magnetic resonance spectroscopy with CDC1₃、DMSO-d₆、CD₃OD or acetone-d₆As solvent (reported in ppm) TMS (0ppm) or chloroform (7.26ppm) was used as reference standard. When multiple peaks occur, the following abbreviations will be used: s(s)ingelet, singlet), d (doublet ), t (triplet, triplet), q (quartet ), m (multiplet, multiplet), br (broad), dd (doublet of doublets), dt (doublet of triplets). Coupling constants are expressed in hertz (Hz).

Low resolution Mass Spectral (MS) data were measured by an Agilent6320 series LC-MS spectrometer equipped with a G1312A binary pump and a G1316A TCC (column temperature maintained at 30 ℃), a G1329A autosampler and a G1315B DAD detector were applied for analysis, and an ESI source was applied to the LC-MS spectrometer.

Low resolution Mass Spectral (MS) data were determined by Agilent6120 series LC-MS spectrometer equipped with a G1311A quaternary pump and a G1316A TCC (column temperature maintained at 30 ℃), a G1329A autosampler and a G1315D DAD detector were used for analysis, and an ESI source was used for the LC-MS spectrometer.

Both spectrometers were equipped with an Agilent Zorbax SB-C18 column, 2.1X 30mm, 5 μm. The injection volume is determined by the sample concentration; the flow rate is 0.6 mL/min; peaks of HPLC were recorded by UV-Vis wavelength at 210nm and 254 nm. The mobile phases were 0.1% formic acid in acetonitrile (phase a) and 0.1% formic acid in ultrapure water (phase B). Gradient elution conditions

As shown in table 1:

TABLE 1

Time (min)	A(CH ₃CN，0.1％HCOOH)	B(H ₂O，0.1％HCOOH)
0-3	5-100	95-0
3-6	100	0
6-6.1	100-5	0-95
6.1-8	5	95

Compound purification was assessed by Agilent 1100 series High Performance Liquid Chromatography (HPLC) with UV detection at 210nm and 254nm, a Zorbax SB-C18 column, 2.1X 30mm, 4 μm, 10 min, flow rate 0.6mL/min, 5-95% (0.1% formic acid in acetonitrile) in (0.1% formic acid in water), the column temperature was maintained at 40 ℃.

The following acronyms are used throughout the invention:

examples

example 1

Acrylic acid 1- (4- (2H-benzo [ d ] [1,2,3] triazol-2-yl) -3-hydroxyphenoxy) -3-ethoxy-2-propyl ester

The synthetic route is as follows:

step 1: synthesis of Compound (1-1)

In an ice-water bath, o-nitroaniline (5.05g, 36.2mmol), concentrated hydrochloric acid (11mL, 37%), sodium nitrite (3.13g, 43.5mmol) and water (50mL) are added into a single-neck flask to be mixed, m-diphenol (3.99g, 36.2mmol) and sodium hydroxide (1.74g, 43.5mmol) are prepared into an aqueous solution (50mL), then the aqueous solution is added into the reaction solution and stirred for 3h, then Zn powder (14.12g, 144.8mmol) is added, stirring is carried out for 12h at room temperature, and a solid crude product is obtained by suction filtration. The crude product was purified by column chromatography on silica gel eluting with petroleum ether ethyl acetate (V: V) ═ 20:1, giving the product as a pale yellow solid (2.5g, yield 30.09%).

MS(ESI,pos.ion)m/z:228[M+1]⁺。

¹H-NMR (400MHz,d₆-DMSO)δ(ppm)：10.43(s,1H),9.99(s,1H),8.17–7.88(m,2H),7.62(d,J＝8.8Hz,1H),7.58–7.44(m,2H),6.55(d,J＝2.5Hz,1H),6.45(dd,J＝8.8,2.5Hz,1H)。

Step 2: synthesis of Compound (1-2)

The compound (1-1) (2.4g, 10.57mmol), K₂CO₃(1.61g, 11.67mmol), 1-chloro-3-ethoxy-2-propanol (1.61g, 11.67mmol) and ethanol (100mL) were added to a single vial, stirred at 80 ℃ for 8h, then the heating was stopped, dichloromethane extracted, rotary evaporated to dryness and the crude product purified by column chromatography on silica gel eluting with petroleum ether, ethyl acetate (V: V) ═ 2: 1, the product was obtained as a pale yellow solid (1.4g, yield 40.2%).

MS(ESI,pos.ion)m/z:330[M+1]⁺。

¹H-NMR (400MHz,CDCl₃)δ(ppm)：11.46(s,1H),8.32(d,J＝9.2Hz,1H),7.94(dd,J＝6.4,2.9Hz,2H),7.69–7.37(m,2H),6.75(d,J＝2.5Hz,1H),6.67(dd,J＝9.0,2.4Hz,1H),4.22(d,J＝4.8Hz,1H),4.11(p,J＝9.6Hz,2H),3.72–3.63(m,2H),3.61(dd,J＝14.6,7.9Hz,2H),2.59(d,J＝4.9Hz,1H),1.48–1.10(m,3H)。

And step 3: synthesis of Compound (1)

Compound (1-2) (0.8g, 2.43mmol), p-toluenesulfonic acid (0.13g, 0.698mmol), acrylic acid (0.6g, 6.98mmol), and toluene (100mL) were added to a single vial under reflux for 12h, followed by rotary evaporation to remove toluene, and the resulting crude product was purified by silica gel column chromatography with petroleum ether, ethyl acetate (V: V) ═ 2: 1, the product was obtained as a white solid (0.3g, yield 32.2%).

MS(ESI,pos.ion)m/z:384[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.44(s,1H),8.30(t,J＝11.2Hz,1H),8.02–7.89(m,2H),7.58–7.43(m,2H),6.77(t,J＝10.4Hz,1H),6.66(dd,J＝9.1,2.7Hz,1H),6.49(dd,J＝17.3,1.3Hz,1H),6.21(dd,J＝17.3,10.4Hz,1H),6.00–5.83(m,1H),5.51–5.37(m,1H),4.37–4.01(m,2H),3.77(t,J＝4.7Hz,2H),3.67–3.51(m,2H),1.45–1.10(m,3H)。

Example 2

Acrylic acid 1- (4- (2H-benzo [ d ] [1,2,3] triazol-2-yl) -3-hydroxyphenoxy) -3-methoxy-2-propyl ester

The synthetic route is as follows:

step 1: synthesis of Compound (1-1)

Reference example 1, step 1.

Step 2: synthesis of Compound (2-1)

The compound (1-1) (5.20g, 22.91mmol), K₂CO₃(3.48g, 25.20mmol), 1-chloro-3-methoxy-2-propanol (3.12g, 25.20mmol) and ethanol (100mL) were added to a single vial, stirred at 80 ℃ under reflux for 8h, then heating was discontinued, dichloromethane was extracted, rotary evaporated to dryness and the crude product purified by column chromatography on silica gel eluting with petroleum ether ethyl acetate (V: V) ═ 2: 1, the product was obtained as a pale yellow solid (3.0g, yield 41.58%).

MS(ESI,pos.ion)m/z:316[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.45(s,1H),8.32(d,J＝9.1Hz,1H),7.94(dd,J＝6.5,3.1Hz,2H),7.61–7.39(m,2H),6.75(d,J＝2.6Hz,1H),6.67(dd,J＝9.1,2.7Hz,1H),4.21(tt,J＝13.7,7.0Hz,1H),4.17–4.03(m,2H),3.69–3.54(m,2H),3.50–3.40(m,3H),2.53(dd,J＝24.3,4.4Hz,1H)。

And step 3: synthesis of Compound (2)

Compound (2-1) (2.4g, 7.62mmol), p-toluenesulfonic acid (0.16g, 0.91mmol), acrylic acid (0.67g, 9.14mmol), and toluene (100mL) were added to a single vial under reflux for 12h, followed by rotary evaporation to remove toluene, and the resulting crude product was purified by silica gel column chromatography with petroleum ether, ethyl acetate (V: V) ═ 2: 1, the product was obtained as a white solid (0.7g, yield 24.9%).

MS(ESI,pos.ion)m/z:370[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.44(s,1H),8.31(d,J＝9.1Hz,1H),7.93(dd,J＝6.5,3.0Hz,2H),7.63–7.36(m,2H),6.89–6.70(m,1H),6.66(dd,J＝9.1,2.4Hz,1H),6.46(dd,J＝27.5,12.8Hz,1H),6.19(dt,J＝30.8,15.4Hz,1H),6.02–5.82(m,1H),5.65–5.21(m,1H),4.35–4.20 (m,2H),3.81–3.68(m,2H),3.51–3.37(m,3H)。

Example 3

1- (4- (2H-benzo [ d ] [1,2,3] triazol-2-yl) -3-hydroxyphenoxy) -3-methoxy-2-propyl methacrylate

The synthetic route is as follows:

step 1: synthesis of Compound (1-1)

Reference example 1, step 1.

Step 2: synthesis of Compound (2-1)

Reference example 2, step 2.

And step 3: synthesis of Compound (3)

Compound (2-1) (5.95g, 18.88mmol), p-toluenesulfonic acid (0.49g, 0.28mmol), methacrylic acid (4.87g, 56.64mmol), and toluene (100mL) were added to a single vial under reflux for 12h, followed by rotary evaporation to remove toluene, and the resulting crude product was purified by silica gel column chromatography with the eluent petroleum ether ethyl acetate (V: V) ═ 2: 1, the product was obtained as a white solid (5.50g, yield 73.39%).

MS(ESI,pos.ion)m/z:384[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.45(s,1H),8.32(d,J＝9.1Hz,1H),8.02–7.84(m,2H), 7.63–7.41(m,2H),6.86–6.61(m,2H),6.32–6.13(m,1H),5.78–5.56(m,1H),5.52–5.31(m,1H),4.36–4.18(m,2H),3.86–3.67(m,2H),3.45(d,J＝10.6Hz,3H),2.08–1.93(m,3H)。

Example 4

1-ethoxy-3- (3-hydroxy-4- (5-methoxy-2H-benzo [ d ] [1,2,3] triazol-2-yl) phenoxy) -2-propyl methacrylate

The synthetic route is as follows:

step 1: synthesis of Compound (4-1)

In an ice-water bath, 4-methoxy-2-nitroaniline (9.00g, 53.6mmol), concentrated hydrochloric acid (16mL, 37%), sodium nitrite (4.44g, 64.3mmol) and water (50mL) were added to a single vial and mixed, an aqueous solution (50mL) of resorcinol (7.07g, 64.3mmol) and sodium hydroxide (3.08g, 77.2mmol) was added thereto, the mixture was stirred for 3 hours, then Zn powder (17.42g, 268mmol) was added thereto, the mixture was stirred at room temperature for 12 hours, and then a solid crude product was obtained by suction filtration and purified by silica gel column chromatography, and the eluent was petroleum ether ethyl acetate (V: V) ═ 20:1, the product was obtained as a pale yellow solid (4.7g, yield 34.1%).

MS(ESI,pos.ion)m/z:258[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.40(s,1H),8.18(t,J＝19.9Hz,1H),7.80(d,J＝9.0Hz,1H),7.17(t,J＝3.7Hz,1H),7.15(s,1H),6.66(d,J＝2.6Hz,1H),6.55(dd,J＝8.9,2.7Hz,1H), 5.28(d,J＝71.8Hz,1H),3.95(s,3H)。

Step 2: synthesis of Compound (4-2)

The compound (4-1) (4.7g, 18.3mmol), K₂CO₃(3.03g, 21.9mmol), 1-chloro-3-methoxy-2-propanol (3.03g, 21.9mmol) and ethanol (100mL) were added to a single vial, stirred at 80 ℃ under reflux for 8h, then heating was discontinued, dichloromethane was extracted, rotary evaporated to dryness and the crude product purified by column chromatography on silica gel eluting with petroleum ether ethyl acetate (V: V) ═ 2: 1, the product was obtained as a pale yellow solid (2.2g, yield 33.5%).

MS(ESI,pos.ion)m/z:360[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.39(s,1H),8.33(t,J＝53.3Hz,1H),7.80(d,J＝9.0Hz,1H),7.22–7.15(m,1H),7.15(s,1H),6.73(d,J＝2.6Hz,1H),6.65(dd,J＝9.1,2.7Hz,1H),4.29–4.14(m,1H),4.23–4.05(m,2H),3.94(s,3H),3.81–3.47(m,4H),2.56(t,J＝15.1Hz,1H),1.49–1.10(m,3H)。

And step 3: synthesis of Compound (4)

Compound (4-2) (2.2g, 6.13mmol), p-toluenesulfonic acid (0.13g, 0.74mmol), methacrylic acid (0.63g, 7.32mmol), and toluene (100mL) were added to a single vial under reflux for 12h, followed by rotary evaporation to remove toluene, and the resulting crude product was purified by silica gel column chromatography with the eluent petroleum ether ethyl acetate (V: V) ═ 2: 1, the product was obtained as a white solid (0.66g, yield 25.15%).

MS(ESI,pos.ion)m/z:428[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.37(s,1H),8.22(d,J＝9.1Hz,1H),7.78(d,J＝9.1Hz,1H),7.15(dd,J＝8.9,2.0Hz,1H),7.13(d,J＝2.2Hz,1H),6.85–6.70(m,1H),6.70–6.58(m,1H),5.65(tt,J＝13.7,6.8Hz,2H),5.39(p,J＝5.1Hz,1H),4.44–4.13(m,2H),3.93(s,3H),3.74(dd,J＝12.4,5.2Hz,2H),3.69–3.46(m,2H),2.17–1.81(m,3H),1.24(dt,J＝14.0,7.0Hz,3H)。

Example 5

1- (4- (5-chloro-2H-benzo [ d ] [1,2,3] triazol-2-yl) -3-hydroxyphenoxy) -3-ethoxy-2-propyl methacrylate

The synthetic route is as follows:

step 1: synthesis of Compound (5-1)

In an ice-water bath, 4-chloro-2-nitroaniline (7.84g, 45.6mmol), concentrated hydrochloric acid (14mL, 37%), sodium nitrite (3.94g, 54.7mmol) and water (50mL) were added to a single-neck flask and mixed, an aqueous solution (50mL) prepared from resorcinol (9.97g, 91.2mmol) and sodium hydroxide (2.34g, 54.7mmol) was added thereto, the mixture was stirred for 3 hours, then Zn powder (14.82g, 228mmol) was added thereto, the mixture was stirred at room temperature for 12 hours, and then a solid crude product was obtained by suction filtration and purified by silica gel column chromatography, and the eluent was petroleum ether ethyl acetate (V: V) ═ 20:1, the product was obtained as a pale yellow solid (1.4g, yield 11.8%).

MS(ESI,pos.ion)m/z:262[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.17(s,1H),8.24(d,J＝8.9Hz,1H),7.93(d,J＝1.1Hz,1H),7.87(d,J＝9.0Hz,1H),7.43(dd,J＝9.0,1.8Hz,1H),7.21–7.10(m,1H),6.67(t,J＝4.8Hz,1H),6.58(dd,J＝9.0,2.6Hz,1H)。

Step 2: synthesis of Compound (5-2)

The compound (5-1) (1.75g, 6.70mmol), K₂CO₃(1.11g, 8.05mmol), 1-chloro-3-ethoxy-2-propanol (1.11g, 8.05mmol) and ethylAlcohol (100mL) was added to a single-neck flask and stirred under reflux at 80 ℃ for 8h, then heating was discontinued, dichloromethane was extracted, rotary evaporated and dried, and the crude product was purified by column chromatography on silica gel eluting with petroleum ether, ethyl acetate (V: V) ═ 2: 1, the product was obtained as a pale yellow solid (0.8g, yield 32.7%).

MS(ESI,pos.ion)m/z:364[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.21(s,1H),8.29(d,J＝9.1Hz,1H),7.94(d,J＝1.2Hz,1H),7.88(d,J＝9.0Hz,1H),7.44(dd,J＝9.0,1.8Hz,1H),6.74(d,J＝2.6Hz,1H),6.67(dd,J＝9.1,2.7Hz,1H),4.35–4.17(m,1H),4.18–3.96(m,2H),3.72–3.40(m,4H),2.54(dd,J＝24.7,4.4Hz,1H),1.32–1.21(m,3H)。

And step 3: synthesis of Compound (5)

Compound (5-2) (0.8g, 2.20mmol), p-toluenesulfonic acid (0.05g, 0.26mmol), methacrylic acid (0.23g, 2.64mmol), and toluene (100mL) were added to a single vial under reflux for 12h, followed by rotary evaporation to remove toluene, and the resulting crude product was purified by silica gel column chromatography with the eluent petroleum ether ethyl acetate (V: V) ═ 2: 1, the product was obtained as a white solid (0.14g, yield 14.7%).

MS(ESI,pos.ion)m/z:432[M+1]⁺。

¹H-NMR(400MHz,CDCl₃)δ(ppm)：11.19(s,1H),8.28(d,J＝9.1Hz,1H),7.92(t,J＝5.9Hz,1H),7.88(d,J＝9.0Hz,1H),7.44(dd,J＝9.0,1.7Hz,1H),6.74(d,J＝2.6Hz,1H),6.66(dd,J＝9.2,2.6Hz,1H),6.29–6.09(m,1H),5.81–5.53(m,1H),5.51–5.29(m,1H),4.39–4.20(m,2H),3.76(d,J＝5.2Hz,2H),3.63–3.50(m,2H),1.97(d,J＝13.6Hz,3H),1.27–1.19(m,3H)。

Example 6

1- (4- (2H-benzo [ d ] [1,2,3] triazol-2-yl) -3-hydroxyphenoxy) -3-ethoxy-2-propyl methacrylate

The synthetic route is as follows:

step 1: synthesis of Compound (1-1)

Reference example 1, step 1.

Step 2: synthesis of Compound (1-2)

Reference example 1, step 2.

And step 3: synthesis of Compound (6)

Compound (1-2) (2.83g, 8.6mmol), p-toluenesulfonic acid (0.25g, 1.5mmol), methacrylic acid (2.43g, 28.3mmol) and toluene (100mL) were added to a single vial under reflux for 12h, followed by rotary evaporation to remove toluene, and the resulting crude product was purified by silica gel column chromatography with the eluent petroleum ether ethyl acetate (V: V) ═ 2: 1, the product was obtained as a white solid (2.13g, yield 64.6%).

LC-MS(ESI,pos.ion)m/z：397[M+Na]⁺。

¹H NMR(400MHz，CDCl₃)δ(ppm):11.46(d,J＝16.2Hz,1H),8.32(t,J＝8.4Hz,1H),7.99–7.86(m,2H),7.58–7.42(m,2H),6.74(dd,J＝11.5,4.2Hz,1H),6.67(dd,J＝9.1,2.7Hz,1H),6.17(d,J＝21.4Hz,1H),5.67–5.59(m,1H),5.39(tt,J＝9.8,4.9Hz,1H),4.35–4.23(m,2H),3.75(t,J＝8.0Hz,2H),3.66–3.53(m,2H),1.98(d,J＝9.7Hz,3H),1.23(t,J＝7.0Hz,3H)。

Example 7 preparation of Polymer A1

2-phenylethyl acrylate (0.60g), 2-phenylethyl methacrylate (0.35g), 1, 4-butanediol diacrylate (0.05g), bis (4-tert-butylcyclohexyl) peroxydicarbonate (0.02g) and the ultraviolet absorber (0.02g) prepared in example 1 were mixed uniformly, and then transferred to a mold composed of two layers of glass and a polytetrafluoroethylene sheet, and the mold was put into an oven at 60 ℃ for reaction for 3 hours, and then the oven was raised to 100 ℃ and kept for 3 hours to obtain a transparent and elastic polymer, and the obtained material was ultrasonically cleaned in anhydrous ethanol and then vacuum-dried at 60 ℃ for 24 hours to obtain polymer a 1.

Examples 8 to 12 preparation of polymers A2 to A6

The procedure was the same as in example 1 except that the ultraviolet absorbers prepared in examples 2,3,4, 5 and 6 were used instead of the ultraviolet absorber in example 1, to prepare polymers A2 to A6, respectively.

Comparative example preparation of Polymer A0

2-phenylethyl acrylate (0.60g), 2-phenylethyl methacrylate (0.35g), 1, 4-butanediol diacrylate (0.05g) and bis (4-tert-butylcyclohexyl) peroxydicarbonate (0.02g) were mixed uniformly, and then transferred to a mold composed of two layers of glass and a polytetrafluoroethylene sheet, and the mold was put into an oven at 60 ℃ for reaction for 3 hours, and then the oven was raised to 100 ℃ and kept for 3 hours to obtain a transparent and elastic polymer, and the obtained material was ultrasonically cleaned in absolute ethanol, and vacuum-dried at 60 ℃ for 24 hours to obtain polymer a 0.

Measurement of spectral transmittance

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

(2) And (3) testing results:

FIGS. 1 to 6 show the results of spectral transmittances of polymers A1 to A6 prepared in examples 7 to 12. FIG. 7 shows the spectral transmittance results of Polymer A0 prepared in the comparative example. As can be seen from the attached drawing, the spectrum of the polymer A0 prepared in the comparative example without the ultraviolet absorbent of the invention starts to have stronger transmittance at 300nm and has weaker or no absorption to ultraviolet light, while the spectrum transmittance of the polymers A1-A6 prepared in the examples 1-6 with the ultraviolet absorbent of the invention is almost zero at 400nm or below, which indicates that the benzotriazole ultraviolet absorbent provided by the invention has very strong ultraviolet absorption capacity.

It will be evident to those skilled in the art that the present disclosure is not limited to the foregoing illustrative embodiments, but may be embodied in other specific forms without departing from the essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing embodiments, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example" or "some examples" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily 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.

Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that those skilled in the art can make changes, modifications, substitutions and alterations to the above embodiments without departing from the principle and spirit of the present invention, the scope of which is defined by the appended claims and their equivalents.

Claims

A benzotriazole ultraviolet absorbent is characterized in that the benzotriazole ultraviolet absorbent is a compound shown in a formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a hydrate and a solvate of the compound shown in the formula (I),

wherein:

R¹is H or C_1-12An alkyl group;

R²is O or S;

A₁is a bond or C_1-12An alkylene group;A₂is H or C_1-12An alkyl group;

m is 0 to 100; n is 0 or 1;

R³and R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-8Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl, sulfonic acid or COOR⁵；R⁵Is H or C_1-4An alkyl group;

wherein R is¹、A₂、R³、R⁴And R⁵C in (1)_1-4Alkyl radical, C_1-8Alkyl radical, C_1-12Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl or amino is independently optionally substituted with 1,2,3 or 4 substituents selected from hydrogen, deuterium, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-4Alkylamino or C_6-10Aryl group.
The benzotriazole UV absorber of claim 1, wherein the benzotriazole UV absorber is a compound of formula (Ia) or a stereoisomer, a tautomer, a nitrogen oxide, a hydrate, a solvate of a compound of formula (Ia),
the benzotriazole UV absorber of claim 1, wherein the benzotriazole UV absorber is a compound of formula (Ib) or a stereoisomer, tautomer, nitroxide, hydrate, solvate of a compound of formula (Ib),

wherein:

R¹is H or C_1-8An alkyl group;

R⁶is H or C_1-12An alkyl group;

R³and R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-8Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl, sulfonic acid or COOR⁵；R⁵Is H or C_1-4An alkyl group;

wherein R is¹、R³、R⁴、R⁵And R⁶C in (1)_1-4Alkyl radical, C_1-8Alkyl radical, C_1-12Alkyl radical, C_1-8Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-10Cycloalkyl radical, C_3-10Heterocyclic group, C_6-10Aryl radical, C_1-9Heteroaryl or amino is independently optionally substituted with 1,2,3 or 4 substituents selected from hydrogen, deuterium, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-4Alkylamino or C_6-10Aryl group.
The benzotriazole UV absorber of claim 3 which is a compound of formula (Ic) or a stereoisomer, tautomer, nitroxide, hydrate, solvate of a compound of formula (Ic),
benzotriazole UV absorber according to any one of claims 1-4 wherein R is selected from the group consisting of¹Is H or methyl.
Benzotriazole UV absorber according to claim 3 or 4 wherein R is selected from the group consisting of⁶Is H or C_1-8An alkyl group.
Benzotriazole UV absorber according to any one of claims 1-6 wherein R is selected from the group consisting of³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_6-10Aryl or C_1-6An alkylamino group.
Benzotriazole UV absorber according to any one of claims 1-7 wherein R is selected from the group consisting of³And R⁴Each independently is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.
Benzotriazole uv absorber according to any one of claims 1-8 wherein said benzotriazole uv absorber has the structure of one of the following:

their stereoisomers, tautomers, nitroxides, hydrates and solvates.
A process for the preparation of the benzotriazole uv absorber of claim 3 which comprises: subjecting a compound of formula (II) to a condensation reaction with a compound of formula (III) to obtain said benzotriazole UV absorber:

wherein R is⁷Is hydroxy, chlorine, bromine or C_1-6An alkoxy group.
The process according to claim 10, wherein the compound of formula (II) is obtained by substitution reaction of a compound of formula (iv) with a compound of formula (v):

wherein R is⁸Is a mixture of chlorine, bromine,
the method according to claim 11, wherein the compound represented by the formula (iv) is obtained by a coupling reaction of a compound represented by the formula (vi) with a compound represented by the formula (vii):
a polymer characterized in that a monomer constituting the polymer comprises the benzotriazole uv absorber of any one of claims 1 to 9.
The polymer of claim 13, wherein the monomers comprising the polymer further comprise a bulk monomer comprising at least one of a (meth) acrylate-based monomer, a vinyl-based monomer, and an allyl-based monomer.
The polymer of any one of claims 13-14, wherein the polymer further comprises at least one of a crosslinker, a blue-light absorber, and an initiator.
An ocular medical device, characterized in that it comprises a polymer according to any of claims 13 to 15.
The ocular medical device of claim 16 wherein the ocular medical device is an intraocular lens, contact lens, corneal modifier, intracorneal lens, corneal inlay, corneal ring, or glaucoma filter.
Use of the UV absorber of any of claims 1 to 9 in coatings, inks, resins, plastics, rubbers, elastomers, films, cosmetics, optoelectronics or medical materials.