WO2019080926A1 - Benzotriazole ultraviolet absorber, preparation method and use thereof - Google Patents

Abstract

Disclosed are a benzotriazole ultraviolet absorber and a preparation method therefor, a polymer comprising the benzotriazole ultraviolet absorber, and the use thereof. The benzotriazole ultraviolet absorber has an excellent ultraviolet absorption function, comprises a polymerizable group, and does not tends to migrate, dissolve and diffuse in a polymer.

Description

Benzotriazole ultraviolet absorber, preparation method and use thereof Technical field

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

Background technique

Ophthalmic lens products have been developed for many years. The natural lens of the human eye has strong ultraviolet absorption capacity to protect the retina from ultraviolet light. In existing ophthalmic lens products, such as intraocular lenses, ultraviolet absorbers are usually added. The ophthalmic lens product has the function of blocking ultraviolet light. The ultraviolet absorbers currently known in the field of ophthalmic lenses for implantation are mainly benzotriazole, benzophenone and triazine-based absorbents, and conventional olefin-polymerizable groups are usually introduced into these absorbents. a group such as a methacrylate, acrylate, methacrylamide, acrylamide or styrene group, etc., such that an ultraviolet group containing an olefinic group can be radically polymerized with other components of the ophthalmic lens material. The reaction is incorporated into a polymer chain which is covalently bonded to the polymeric network of the lens material such that the ultraviolet absorber is less susceptible to migration, filtration or separation from the lens material. This stability is of particular importance for implantable ophthalmic lenses, and migration, filtration or separation can not only result in loss of UV blocking activity of the implant, but can also pose toxicological problems.

The introduction of different kinds of other functional groups on the ultraviolet absorber has an effect on the light absorption performance, stability performance, solubility property and activity of the absorbent, and the existing ultraviolet absorber has problems such as poor light absorption performance, instability, and low solubility. The yellowish color is also a common problem with benzotriazole ultraviolet absorbers, so the ultraviolet absorber used in eye medical devices still needs to be improved.

Summary of the invention

Summary of invention

The invention provides a benzotriazole ultraviolet absorber having a novel structure, which can be copolymerized with other acrylic monomer raw materials to be covalently bonded to the material, thereby preventing ultraviolet rays. The absorbent migrates and diffuses in the material; in addition, the ultraviolet absorber is white crystal, which overcomes the yellowing problem of the ubiquitous color of the benzotriazole ultraviolet absorber in the prior art, and improves the transparency of the ophthalmic product. The scope of application thereof is expanded; in addition, the benzotriazole-based ultraviolet absorber proposed by the present invention has higher solubility and stronger absorption capacity.

In one aspect, the invention provides a benzotriazole ultraviolet absorber which is a compound of formula (I) or a stereoisomer, tautomer, oxynitride of a compound of formula (I) , hydrate, solvate,

among them:

R ¹ is H or C _1-12 alkyl;

R ² is O or S;

A ₁ is a bond or a C _1-12 alkylene group; A ₂ is H or a C _1-12 alkyl group;

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

R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or C _1-4 alkyl;

Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , A ₂ , R ³ , R ⁴ and R ⁵ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.

In some embodiments, R ¹ is H or C _1-8 alkyl; R ² is O; A ₁ is a bond or C _1-8 alkyl; A ₂ is H or C _1-8 alkyl; 0 to 50; n is 0 or 1; and R ³ and R ⁴ have the meanings as described in the present invention.

In other embodiments, the present invention provides a benzotriazole ultraviolet absorber which is a compound of formula (Ia) or a stereoisomer, tautomer of a compound of formula (Ia) Body, nitrogen oxides, hydrates, solvates:

Wherein R ¹ , A ₂ , m, R ³ and R ⁴ have the meanings as described herein.

In some embodiments, R ¹ is H or C _1-8 alkyl; A ₂ is H or C _1-8 alkyl; m is 0-50; R ³ and R ⁴ have the meanings as described herein .

In still other embodiments, the present invention provides a benzotriazole ultraviolet absorber which is a compound represented by the formula (Ib) or a stereoisomer, a tautomer of a compound represented by the formula (Ib) Structure, nitrogen oxides, hydrates, solvates:

among them:

R ¹ is H or a C _1-8 alkyl group;

R ⁶ is H or C _1-12 alkyl;

R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or C _1-4 alkyl;

Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , R ³ , R ⁴ , R ⁵ and R ⁶ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.

In still other embodiments, the present invention provides a benzotriazole ultraviolet absorber which is a compound represented by the formula (Ic) or a stereoisomer, a tautomer of a compound of the formula (Ic) Structure, nitrogen oxides, hydrates, solvates:

Wherein R ¹ , R ³ , ⁴ and R ⁶ have the meanings as described herein.

In some embodiments, R ¹ is H, methyl, ethyl or n-propyl. In some embodiments, R ⁶ is H or C _1-8 alkyl. In other embodiments, R ⁶ is C _1-6 alkyl. In yet other embodiments, R ⁶ is C _1-4 alkyl.

Still some embodiments, R ⁶ is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

In some embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, C _1-6 alkyl, C _1-6 alkoxy, a C _1-6 haloalkyl group, a C _6-10 aryl group or a C _1-6 alkylamino group.

In other embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, positive Butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

In another aspect, the invention provides a polymer comprising any of the above benzotriazole ultraviolet absorber compounds or stereoisomers, tautomers, oxynitrides, hydrates thereof Solvent.

In some embodiments, the monomer constituting the polymer further includes a bulk monomer including at least a (meth) acrylate monomer, a vinyl monomer, or an allyl monomer. one.

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

In another aspect, the invention provides an ocular medical device comprising any of the polymers described above.

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

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

In another aspect, the invention relates to the use of the above benzotriazole ultraviolet absorber in paints, inks, resins, plastics, rubbers, elastomers, films, cosmetics, optoelectronic or medical materials.

The foregoing description merely summarizes certain aspects of the invention, but is not limited thereto. These and other aspects are described in more detail below.

BRIEF DESCRIPTION OF THE DRAWINGS:

1 is a graph showing the spectral transmittance of the polymer A1 prepared in Example 7;

2 is a graph showing the spectral transmittance of the polymer A2 prepared in Example 8;

Figure 3 is a graph showing the spectral transmittance of the polymer A3 prepared in Example 9;

4 is a graph showing the spectral transmittance of the polymer A4 prepared in Example 10;

Figure 5 is a graph showing the spectral transmittance of the polymer A5 prepared in Example 11;

Figure 6 is a graph showing the spectral transmittance test of the polymer A6 prepared in Example 12;

Figure 7 is a graph showing the spectral transmittance test of the polymer A0 prepared in the comparative example.

Detailed description of the invention

Definitions and general terms

Some embodiments of the invention are now described in detail, examples of which are illustrated by the accompanying structural formulas and formulas. The invention is intended to cover all alternatives, modifications, and equivalents, which are 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 invention. The invention is in no way limited to the methods and materials described herein. Where one or more of the incorporated literature, patents, and similar materials are different or inconsistent with the present application (including but not limited to defined terms, terminology applications, described techniques, etc.), The application shall prevail.

It will be further appreciated that certain features of the invention are described in the various embodiments of the invention, and may be described in combination in a single embodiment. On the contrary, the various features of the invention are described in a single embodiment for the sake of brevity, but may be provided separately or in any suitable sub-combination.

The following definitions used herein should be applied unless otherwise stated. For the purposes of the present invention, chemical elements are consistent with the CAS version of the Periodic Table of the Elements and the Handbook of Chemistry and Physics, 75th Edition, 1994. In addition, the general principles of organic chemistry can be found in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007. The description is fully incorporated herein by reference.

The articles "a", "an" and "sai" are used, and are meant to include "at least one" or "one or more", unless otherwise indicated. Accordingly, the articles used in the present invention are intended to mean one or more than one (i. For example, "a component" refers to one or more components, that is, there may be more than one component contemplated for use or use in embodiments of the embodiments.

The term "comprising" is an open-ended expression that includes the subject matter of the invention, but does not exclude other aspects.

"Stereoisomer" refers to a compound that has the same chemical structure but differs in the way the atoms or groups are spatially aligned. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotomers), geometric isomers (cis/trans) isomers, atropisomers, etc. .

"Chirality" is a molecule that has properties that cannot overlap with its mirror image; "non-chiral" refers to a molecule that can overlap with its mirror image.

"Enantiomer" refers to two isomers of a compound that are not superimposable but are mirror images of each other.

"Diastereomer" refers to a stereoisomer that has two or more centers of chirality and whose molecules are not mirror images of each other. Diastereomers have different physical properties such as melting point, boiling point, spectral properties and reactivity. The mixture of diastereomers can be separated by high resolution analytical procedures such as electrophoresis and chromatography, such as HPLC.

"Solvate" means an association of one or more solvent molecules with a compound of the invention. Solvent-forming solvents include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. The term "hydrate" means that the solvent molecule is an association formed by water.

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

Many organic compounds exist in optically active forms, i.e., they have the ability to rotate a plane of plane polarized light. In describing optically active compounds, the prefixes D and L or R and S are used to indicate the absolute configuration of the molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are symbols for specifying the rotation of plane polarized light caused by the compound, wherein (-) 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 a mixture of enantiomers. A 50:50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.

Any asymmetric atom (e.g., carbon, etc.) of the compounds disclosed herein may exist in racemic or enantiomerically enriched form, such as the (R)-, (S)- or (R, S)-configuration presence. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess in the (R)- or (S)-configuration, 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.

Depending on the choice of starting materials and methods, the compounds of the invention may be one of the possible isomers or mixtures thereof, such as racemates and mixtures of diastereomers (depending on the number of asymmetric carbon atoms) The form exists. 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 substituent may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the substituent of the cycloalkyl group may have a cis or trans configuration.

The resulting mixture of any stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, for example, by chromatography, depending on the difference in physicochemical properties of the components. Method and / or step crystallization.

The racemate of any of the resulting end products or intermediates can be resolved into the optical antipodes by methods known to those skilled in the art by known methods, for example, by obtaining the diastereomeric salts thereof. Separation. Racemic products can also be separated by chiral chromatography, such as 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, Racemates and Resolutions (Wiley Interscience, New York, 1981); Principles of Asymmetric Synthesis (2nd Ed. Robert E .Gawley, Jeffrey Aubé, Elsevier, Oxford, UK, 2012); Eliel, ELStereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, SHTables of Resolving Agents and Optical Resolutions p.268 (ELEliel, 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 are interconvertible by a low energy barrier. If tautomerism is possible (as in solution), the chemical equilibrium of the tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include interconversions by proton transfer, such as keto-enol isomerization and imine-ene Amine isomerization. Valence tautomers include interconversions by recombination of some bonding electrons. A specific example of keto-enol tautomerization is the interconversion of a pentane-2,4-dione and a 4-hydroxypent-3-en-2-one tautomer. Another example of tautomerization is phenol-keto tautomerization. A specific example of phenol-keto tautomerization is the interconversion of pyridin-4-ol and pyridine-4(1H)-one tautomers. All tautomeric forms of the compounds of the invention are within the scope of the invention unless otherwise indicated.

As described herein, the compounds of the present invention may be optionally substituted with one or more substituents, such as the compounds of the above formula, or specific examples, subclasses, and inclusions of the present invention. A class of compounds. It should be understood that the term "optionally substituted" and the term "substituted or unsubstituted" are used interchangeably. In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced by a particular substituent. Unless otherwise indicated, an optional substituent group can be substituted at each substitutable position of the group. When more than one position in the given formula can be substituted by one or more substituents selected from a particular group, the substituents may be substituted at the various positions, either identically or differently. When a substituent is described as a "independently selected" group, each substituent is selected independently of each other, and thus each substituent may be the same or different from each other.

In addition, it should be noted that the descriptions of the "individually" and "individually" and "independently" are interchangeable, unless otherwise explicitly indicated in the present invention. It should be understood in a broad sense, which can mean that the specific options expressed between the same symbols in different groups do not affect each other, and can also represent specific options expressed in the same group and between the same symbols. There is no influence between each other.

In each part of the specification, the substituents of the compounds disclosed herein are disclosed in terms of the type or range of groups. In particular, the invention includes each individual sub-combination of each member of the group and range of such groups. For example, the term "C _1-6 alkyl" refers particularly to the disclosure independently methyl, ethyl, C ₃ alkyl, C ₄ alkyl, C ₅ alkyl, and C ₆ alkyl. In various parts of the invention, linking substituents are described. When the structure clearly requires a linking group, the Markush variable recited for that group is understood to be a linking group. For example, if the structure requires a linking group and the definition of the Markush group for the variable is "alkyl" or "aryl", it should be understood that the "alkyl" or "aryl" respectively represent the attached An alkylene group or an arylene group.

The term "alkyl" or "alkyl group" as used herein, denotes a saturated straight or branched monovalent hydrocarbon group containing from 1 to 20 carbon atoms, wherein the alkyl group may be optionally selected The ground is replaced by one or more substituents described herein. Unless otherwise specified, an alkyl group contains from 1 to 20 carbon atoms. In one embodiment, the alkyl group contains from 1 to 12 carbon atoms; in another embodiment, the alkyl group contains from 1 to 6 carbon atoms; in yet another embodiment, the alkyl group contains 1 - 4 carbon atoms; also in one embodiment, the alkyl group contains 1-3 carbon atoms.

Examples of alkyl groups include, but are not limited to, methyl (Me, -CH ₃ ), ethyl (Et, -CH ₂ CH ₃ ), n-propyl (n-Pr, -CH ₂ CH ₂ CH ₃ ), isopropyl (i-Pr, -CH(CH ₃ ) ₂ ), n-butyl (n-Bu, -CH ₂ CH ₂ CH ₂ CH ₃ ), isobutyl (i-Bu, -CH ₂ CH) (CH ₃ ) ₂ ), sec-butyl (s-Bu, -CH(CH ₃ )CH ₂ CH ₃ ), tert-butyl (t-Bu, -C(CH ₃ ) ₃ ), n-pentyl (-CH) ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-pentyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₃ ), 3-pentyl (-CH(CH ₂ CH ₃ ) ₂ ), 2-methyl -2-butyl (-C(CH ₃ ) ₂ CH ₂ CH ₃ ), 3-methyl-2-butyl (-CH(CH ₃ )CH(CH ₃ ) ₂ ), 3-methyl-1- Butyl (-CH ₂ CH ₂ CH(CH ₃ ) ₂ ), 2-methyl-1-butyl (-CH ₂ CH(CH ₃ )CH ₂ CH ₃ ), n-hexyl (-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-hexyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₂ CH ₃ ), 3-hexyl (-CH(CH ₂ CH ₃ )(CH ₂ CH ₂ CH ₃ )), 2-methyl-2-pentyl (-C(CH ₃ ) ₂ CH ₂ CH ₂ CH ₃ ), 3-methyl-2-pentyl (-CH(CH ₃ )CH(CH ₃ )CH ₂ CH ₃ ), 4-methyl-2-pentyl (-CH(CH ₃ )CH ₂ CH(CH ₃ ) ₂ ), 3-methyl-3-pentyl (-C(CH ₃ )(CH ₂ CH ₃ ) _2), 2-methyl-3-pentyl _{(-CH (CH 2 CH 3)} CH (CH 3) 2), 2,3- dimethyl 2-butyl _{(-C (CH 3) 2 CH} (CH 3) 2), 3,3- dimethyl-2-butyl _{(-CH (CH 3) C (} CH 3) 3), n-heptyl Base, positive octyl, and so on.

The term "alkenyl" denotes a straight or branched chain monovalent hydrocarbon radical containing from 2 to 12 carbon atoms, wherein at least one site of unsaturation, i.e., has a carbon-carbon sp ² double bond, wherein the alkenyl group The 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 2-8 carbon atoms; in another embodiment, the alkenyl group contains 2-6 carbon atoms; in yet another embodiment, the alkenyl group comprises 2 - 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-CH = CH _2), allyl (-CH ₂ CH = CH ₂₎ and the like.

The term "alkynyl" means a straight or branched chain monovalent hydrocarbon radical containing from 2 to 12 carbon atoms, wherein at least one site of unsaturation, i.e., has a carbon-carbon sp triple bond, wherein the alkynyl group It may be optionally substituted with one or more of the substituents described herein. In one embodiment, the alkynyl group contains 2-8 carbon atoms; in another embodiment, the alkynyl group contains 2-6 carbon atoms; in yet another embodiment, the alkynyl group comprises 2 - 4 carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (-C≡CH), propargyl (-CH ₂ C≡CH), 1-propynyl (-C≡C-CH ₃ ), and the like. .

The term "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic system containing from 3 to 12 carbon atoms. In one embodiment, the cycloalkyl group contains from 3 to 12 carbon atoms; in another embodiment, the cycloalkyl group contains from 3 to 10 carbon atoms; in another embodiment, the cycloalkyl group contains from 3 to 8 Carbon atom; In yet another embodiment, the cycloalkyl group contains from 3 to 6 carbon atoms. The cycloalkyl group can be independently unsubstituted or substituted with one or more substituents described herein.

The terms "heterocyclyl" and "heterocycle" are used interchangeably herein to refer to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing from 3 to 15 ring atoms, wherein monocyclic, bicyclic or tricyclic The ring does not contain an aromatic ring, and at least one ring atom is selected from the group consisting of nitrogen, sulfur and oxygen atoms. Unless otherwise stated, a heterocyclic group can be a carbyl or a nitrogen group, and a -CH ₂ - group can be optionally substituted with -C(O)-. The sulfur atom of the ring can be optionally oxidized to an S-oxide. The nitrogen atom of the ring can be optionally oxidized to an N-oxygen compound.

Examples of heterocyclic groups include, but are not limited to, oxiranyl, azetidinyl, oxetanyl, thioheterobutyl, pyrrolidinyl, 2-pyrroline, 3-pyrrolyl , pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothienyl, 1,3-dioxocyclopentyl, disulfide Pentyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxoalkyl, dithiaalkyl, thia Oxanyl, homopiperazinyl, homopiperidinyl, oxetanyl, thiecycloheptyl, oxazepine

Base, diaza

Base

Base, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl. Examples of the -CH ₂ - group in the heterocyclic group substituted by -C(O)- include, but are not limited to, 2-oxopyrrolidinyl, oxo-1,3-thiazolidinyl, 2-piperidone Base, 3,5-dioxopiperidinyl and pyrimidindione. Examples of the sulfur atom in the heterocyclic group being oxidized include, but are not limited to, a sulfolane group and a 1,1-dioxothiomorpholinyl group. The heterocyclyl group can be optionally substituted with one or more substituents described herein. When the structure clearly requires a linking group, the Markush variable recited for that group is understood to be a linking group. For example, if the structure requires a linking group and the "Heterocyclyl" is recited for the Markush group definition of the variable, it is understood that the "heterocyclyl" represents a linked heterocyclylene group.

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

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

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

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

The term "aryl" denotes a monocyclic, bicyclic and tricyclic carbocyclic ring system containing from 6 to 14 ring atoms, or from 6 to 12 ring atoms, or from 6 to 10 ring atoms, wherein at least one ring system is aromatic Of the family, wherein each ring system comprises a ring of 3-7 atoms and one or more attachment points are attached to the remainder of the molecule. The term "aryl" can be used interchangeably with the term "aromatic ring". Examples of the aryl group may include a phenyl group, a naphthyl group, and an anthracenyl group. The aryl group may be independently and optionally substituted with one or more substituents described herein.

The term "heteroaryl" denotes a monocyclic, bicyclic and tricyclic ring system containing from 5 to 12 ring atoms, or from 5 to 10 ring atoms, or from 5 to 6 ring atoms, wherein at least one ring system is aromatic, And at least one ring system comprises one or more heteroatoms, wherein each ring system comprises a ring of 5-7 atoms and one or more attachment points are attached to the remainder of the molecule. The term "heteroaryl" can be used interchangeably with the terms "heteroaryl 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 comprises 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 (eg 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (such as 5-tetrazolyl), triazolyl (such as 3-triazolyl and 5-triazolyl), 2-thienyl, 3-thienyl, pyrazolyl (such as 2-pyrazolyl), isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3- Triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, 1,3,5- Triazine group; also includes the following bicyclic rings, but is by no means limited to these bicyclic rings: benzimidazolyl, benzofuranyl, benzothienyl, fluorenyl (such as 2-indenyl), fluorenyl, quinolyl (eg 2-quinolyl, 3-quinolinyl, 4-quinolinyl), isoquinolinyl (eg 1-isoquinolinyl, 3-isoquinoline) Or 4-isoquinolinyl), imidazo[1,2-a]pyridyl, pyrazolo[1,5-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]pyridinyl, and the like.

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. In some embodiments, the alkylamino group is a lower alkylamino group having one or two _C1-6 alkyl groups attached to the nitrogen atom. In other embodiments, the alkylamino group is a lower alkylamino group of _C1-3 . Suitable alkylamino groups may be monoalkylamino or dialkylamino, examples of which include, but are not limited to, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N - Diethylamino and the like.

The term "alkoxy" denotes an alkyl group attached to the remainder of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. Unless otherwise specified, the alkoxy group contains from 1 to 12 carbon atoms. In one embodiment, the alkoxy group contains from 1 to 6 carbon atoms; in another embodiment, the alkoxy group contains from 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group The group contains 1-3 carbon atoms. The alkoxy group can 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 ₂ CH ₃ ), 1-propoxy (n-PrO, n- Propyloxy, -OCH ₂ CH ₂ CH ₃ ), 2-propoxy (i-PrO, i-propoxy, -OCH(CH ₃ ) ₂ ), 1-butoxy (n-BuO, n- Butoxy, -OCH ₂ CH ₂ CH ₂ CH ₃ ), 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH ₂ CH(CH ₃ ) ₂ ), 2-butyl Oxygen (s-BuO, s-butoxy, -OCH(CH ₃ )CH ₂ CH ₃ ), 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC (CH) ₃ ) ₃ ), 1-pentyloxy (n-pentyloxy, -OCH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-pentyloxy (-OCH(CH ₃ )CH ₂ CH ₂ CH ₃ ), 3-pentyloxy (-OCH(CH ₂ CH ₃ ) ₂ ), 2-methyl-2-butoxy (-OC(CH ₃ ) ₂ CH ₂ CH ₃ ), 3-methyl-2-butoxy (-OCH(CH ₃ )CH(CH ₃ ) ₂ ), 3-methyl-l-butoxy (-OCH ₂ CH ₂ CH(CH ₃ ) ₂ ), 2-methyl-l-butoxy (-OCH ₂ CH(CH ₃ )CH ₂ CH ₃ ), and so on.

The term "haloalkyl" denotes an alkyl group substituted by 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 -NH _2. The term "sulfonic acid group" refers to -SO ₃ H.

Detailed description of the invention

(1) Benzotriazole ultraviolet absorber of the present invention and preparation method thereof

In one aspect, the invention provides a benzotriazole ultraviolet absorber which is a compound of formula (I) or a stereoisomer, tautomer, oxynitride of a compound of formula (I) , hydrate, solvate,

among them:

R ¹ is H or a C _1-12 alkyl group;

R ² is O or S;

A ₁ is a bond or a C _1-12 alkylene group; A ₂ is H or a C _1-12 alkyl group;

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

R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or C _1-4 alkyl;

Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , A ₂ , R ³ , R ⁴ and R ⁵ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.

In some embodiments, R ¹ is H or C _1-8 alkyl. In other embodiments, R ¹ is H or C _1-6 alkyl. In yet other embodiments, R ¹ is H or C _1-4 alkyl. Some embodiments still another embodiment, R ¹ is H, methyl, ethyl or n-propyl.

In some embodiments, A ₁ is a bond. In other embodiments, A ₁ is a C _1-12 alkylene group. In still other embodiments, A ₁ is a C _1-8 alkylene group. In still other embodiments, A ₁ is C _1-6 alkylene. In still other embodiments, A ₁ is C _1-4 alkylene.

In some embodiments, A ₂ is H or C _1-12 alkyl. In still other embodiments, A ₂ is C _1-8 alkyl. In still other embodiments, A ₂ is C _1-6 alkyl. In still other embodiments, A ₂ is C _1-4 alkyl.

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

In some embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl, C _6-10 aryl or C _1-6 alkylamino. In other embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, positive Butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

In other embodiments, the present invention provides a benzotriazole ultraviolet absorber which is a compound of formula (Ia) or a stereoisomer, tautomer of a compound of formula (Ia) Body, nitrogen oxides, hydrates, solvates:

among them:

R ¹ is H or a C _1-12 alkyl group;

A ₂ is H or C _1-12 alkyl;

m is 0 to 100;

R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or a C _1-4 alkyl group;

Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , A ₂ , R ³ , R ⁴ and R ⁵ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.

In some embodiments, R ¹ is H or C _1-8 alkyl. In other embodiments, R ¹ is H or C _1-6 alkyl. In yet other embodiments, R ¹ is H or C _1-4 alkyl. Some embodiments still another embodiment, R ¹ is H, methyl, ethyl or n-propyl.

In some embodiments, A ₂ is H or C _1-12 alkyl. In still other embodiments, A ₂ is C _1-8 alkyl. In still other embodiments, A ₂ is C _1-6 alkyl. In still other embodiments, A ₂ is C _1-4 alkyl.

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

In some embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl, C _6-10 aryl, C _6-10 aryloxy or C _1-6 alkylamino. In other embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, positive Butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

In still other embodiments, the present invention provides a benzotriazole ultraviolet absorber which is a compound represented by the formula (Ib) or a stereoisomer, a tautomer of a compound represented by the formula (Ib) Structure, nitrogen oxides, hydrates, solvates:

among them:

R ¹ is H or C _1-8 alkyl;

R ⁶ is H or C _1-12 alkyl;

R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or C _1-4 alkyl;

Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , R ³ , R ⁴ , R ⁵ and R ⁶ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.

In some embodiments, R ¹ is H or C _1-8 alkyl. In other embodiments, R ¹ is C _1-6 alkyl. In still other embodiments, R ¹ is C _1-4 alkyl. Some embodiments still another embodiment, R ¹ is H or methyl or ethyl or n-propyl.

In some embodiments, R ⁶ is H or C _1-8 alkyl. In another embodiment, R ⁶ is C _1-6 alkyl. Some embodiments still another embodiment, R ⁶ is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, tert-pentyl, n-hexyl.

In some embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl, C _6-10 aryl or C _1-6 alkylamino. In other embodiments, R ³ and R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, amino, nitro, cyano, methyl, ethyl, propyl, isopropyl, positive Butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl, phenyl, methylamino or ethylamino.

In still other embodiments, the present invention provides a benzotriazole ultraviolet absorber which is a compound represented by the formula (Ic) or a stereoisomer, a tautomer of a compound of the formula (Ic) Structure, nitrogen oxides, hydrates, solvates:

Wherein R ¹ , R ³ , ⁴ and R ⁶ have the meanings as described herein.

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

As a preferred embodiment, a compound having the following structure can be mentioned:

Or their stereoisomers, tautomers, nitrogen oxides, hydrates and solvates.

a compound satisfying the above formula (I), (Ia), (Ib) or (Ic) or a compound represented by the above formulas (1) to (38), or satisfying their stereoisomers, tautomerism The compounds of the body, nitrogen oxides, hydrates and solvates have an ideal ultraviolet light blocking effect. Specifically, when the ultraviolet visible light absorption spectrum is measured, the spectral transmittance is almost zero below 400 nm, and is almost completely blocked. In addition, the benzotriazole ultraviolet absorber proposed by the present invention has a polymerizable group and can be copolymerized with other monomers in the polymer, so that the ultraviolet absorber does not migrate or dissolve from the polymer. phenomenon. In addition, the benzotriazole ultraviolet absorber proposed by the invention has an asymmetric ether bond as a linking group, which greatly increases the solubility of the compound, greatly improves the polymerization efficiency when the copolymerization reaction is carried out, and enables the polymerization after polymerization. The obtained polymer molecule maintains considerable flexibility; in addition, the inventors have found through extensive research that it is precisely because of the introduction of the flexible chain in the molecule that the ultraviolet absorbing compound obtained by the present invention is pure white, overcoming the present There is a ubiquitous color yellowing problem in the benzotriazole ultraviolet absorber in the prior art, which improves the transparency, light transmission effect and visual effect of the material, and greatly expands the application range of the ultraviolet absorber; therefore, the invention proposes The benzotriazole ultraviolet absorber can be added as an ultraviolet absorber to the raw material of the synthetic ocular medical device, and copolymerized with other polymerizable monomers, such as bulk monomers of the polymer, blue light absorber, etc., and the obtained polymerization Used to make eye medical devices, and the above ultraviolet absorbers do not have optical properties (refractive index and spectral transmittance, etc.) for ophthalmic medical treatment. Mechanical properties (tensile strength, elongation at break and elastic modulus) adversely affected, so is the ideal material prepared foldable intraocular lens and other eye of the flexible medical device.

In another aspect of the present invention, the present invention provides a process for producing a benzotriazole ultraviolet absorber represented by the above (Ib). The method is simple in operation and high in yield, and is particularly suitable for industrial scale production. The synthetic method is expressed by the chemical reaction formula as follows:

Wherein R ¹ , R ⁶ , R ⁷ , R ⁸ , R ³ and R ⁴ have the definitions previously described in the present invention and will not be further described herein.

Step 1: First, the compound of the above formula (VII) is subjected to diazotization under nitrous acid or nitrite strong acid medium to form azo ions, and then the pH is adjusted to alkaline conditions, azo ions and (VI) The coupling reaction occurs, and finally the nitro group is reduced to an amino group by a reactive metal (such as zinc, iron, etc.) and the ring is closed to obtain the compound (IV);

Step 2: The compound (IV) and the compound (V) are subjected to a substitution reaction in an inorganic base or a protic solvent to form a compound of the formula (II); in some embodiments of the present invention, the above substitution reaction is in a protic solvent. For example, the protic solvent may include at least one of ethanol, isopropanol, n-butanol, N,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, and the inorganic base may include sodium carbonate, sodium hydrogencarbonate, potassium carbonate, potassium hydrogencarbonate, cesium carbonate, sodium hydroxide. At least one of potassium hydroxide and calcium hydroxide. In still another embodiment of the present invention, in order to accelerate the progress of the reaction, a certain amount of a catalyst such as potassium iodide or sodium iodide is usually added to the above substitution reaction, and iodine is exchange-reacted with chlorine to accelerate the reaction.

Step 3: The compound represented by the formula (II) is coupled with the acrylic compound represented by the formula (III) to obtain a benzotriazole ultraviolet absorber represented by the formula (Ib) of the present invention. In one embodiment of the invention, the condensation reaction described above is carried out in an aprotic solvent. The above aprotic solvents include dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, 1,1,1-trichloroethane, chlorobenzene. , dichlorobenzene, pentane, n-hexane, methylcyclohexane, 1,1-diethoxypropane, 1,1-dimethoxymethane, 2,2-dimethoxypropane, 1,2 , 3,4-tetrahydronaphthalene, decalin, benzene, toluene, xylene, cumene, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, ethylene glycol diethyl ether At least one of 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, and the acid may include p-toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoroacetic acid, acetic acid, and C. Acid, etc.

(2) The polymer of the present invention

Another aspect of the invention provides a polymer, the monomer constituting the polymer comprising any of the benzotriazole ultraviolet absorbers described above. Specifically, the polymer is obtained by copolymerizing a polymerizable benzotriazole ultraviolet absorber according to the present invention with one or two or more bulk monomers or other polymerizable monomers. Since the above polymerizable benzotriazole ultraviolet absorber has an ultraviolet absorbing effect, the polymer containing the above polymerizable benzotriazole ultraviolet absorber also has an ultraviolet absorbing effect. In addition, since the above-mentioned polymerizable benzotriazole ultraviolet absorber has a group which can participate in polymerization, it can copolymerize with other monomers in the bulk monomer or the raw material of the synthetic polymer, thereby greatly reducing benzotriazole The risk of migration, filtration or separation of the UV absorber in the polymer increases the safety of the direct contact with the human body prepared from the polymer. Preferably, the polymer can be used to prepare an ocular medical device such as an artificial lens, so that the artificial lens also has an ultraviolet absorbing function, thereby reducing the damage of ultraviolet light to the human eye.

In the present invention, the ultraviolet absorber of the present invention may be used in an amount of from 0.1 to 2% by weight based on the total mass of the monomers used for the synthetic polymer. The ratio of the ultraviolet absorber and the bulk monomer in the above polymer can be adjusted according to actual conditions. The term "bulk monomer" specifically refers to the primary monomer material used to form the polymer body. The bulk monomer is a main component capable of constituting the above-mentioned polymer proposed by the present invention by polymerization, which is capable of undergoing copolymerization with an ultraviolet absorber during polymerization. Since the ultraviolet absorber contains a polymerizable group, the monomers commonly used for forming the polymer can be copolymerized with the ultraviolet absorber proposed by the present invention. Therefore, in the present invention, the specific type of the bulk monomer is not particularly limited. At least one of a (meth) acrylate monomer, a vinyl monomer, and an allyl monomer may be contained. In an embodiment of the 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, methyl Propyl acrylate, isopropyl methacrylate, butyl methacrylate, t-butyl methacrylate, isobutyl methacrylate, amyl methacrylate, t-amyl methacrylate, hexyl methacrylate, Heptyl methacrylate, octyl methacrylate, 2-ethylhexyl methacrylate, decyl methacrylate, decyl methacrylate, dodecyl methacrylate, stearyl methacrylate , cyclopentyl methacrylate, cyclohexyl methacrylate, phenoxy methacrylate; methoxyethyl methacrylate, ethoxyethyl methacrylate, ethoxyethyl acrylate, methyl Methoxydiglycol acrylate, 2-ethylphenoxy methacrylate, 2-ethylphenoxy acrylate, 2-ethylthiophene methacrylate, 2-ethyl acrylate Thiophene ester, 2-ethylaminophenyl methacrylate, 2-ethylaminobenzene acrylate Ester, phenyl methacrylate, benzyl methacrylate, 2-phenylethyl methacrylate, 2-phenylethyl acrylate, 3-phenylpropyl methacrylate, methacrylic acid-4 -Phenylbutyl ester, 4-methylphenyl methacrylate, 4-methylbenzyl methacrylate, 2,2-methylphenylethyl methacrylate, methacrylic acid-2,3 -methylphenylethyl ester, 2,4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(meth) methacrylate 1-methylethyl)phenyl)ethyl ester, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenyl)ethyl methacrylate, methyl 2-(2-chlorophenyl)ethyl acrylate, 2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethyl methacrylate, methacrylic acid- 2-(4-Bromophenyl)ethyl ester, 2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate, methacrylic acid- 2-(4-Benzylphenyl)ethyl ester. 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-based monomer, which may include, but is not limited to, at least one of the following monomers: styrene, 4-butylstyrene, styrene, vinyl acetate, 4-ethoxymethylstyrene, 4-hexyloxymethylstyrene, 4-hexyloxyethylstyrene, vinyl ether, n-butyl vinyl ether, isobutyl vinyl ether, uncle Butyl vinyl ether, cyclohexene vinyl ether, butanediol divinyl ether, N-vinyl caprolactam, dodecyl vinyl ether, octadecyl vinyl ether, divinyl glycol divinyl Ether ether, trivinyl glycol divinyl ether. In still another embodiment of the present invention, the bulk monomer is an allyl monomer, which may include, but is not limited to, at least one of the following monomers: methyl crotonate, ethyl crotonate, benzene crotonate. Ethyl ester, propylene acetate, propylene propionate, propylene butyrate, propylene valerate, propylene hexanoate, 3-phenyl-2-propenyl butyrate. The above bulk monomer has better optical and mechanical properties, and can further improve the performance of the polymer.

In the present invention, "other polymerizable monomer" means, in addition to the bulk monomer, other polymerizable monomers constituting the polymer raw material proposed by the present invention, such as a polymerizable blue light absorber, a crosslinking agent, and the initiation. Agents, etc.

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

In an embodiment of the 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 dimethacrylate, 1,4-butyl Diol diacrylate, trimethylolpropane trimethacrylate, 1,5-bis(methacryloyloxy)-2,2,3,3,4,4-hexafluorohexane, 1, At least one of 6-bis(acryloyloxy)-2,2,3,3,4,4,5,5-octafluorohexane and pentaerythritol tetraacrylate. The above crosslinking agent can function to better crosslink each monomer, so that the performance of the polymer can be further improved. In one embodiment, the crosslinking agent can be used in an amount of from 2 to 7% by weight based on the total weight of the 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 an embodiment of the invention, the initiator may be a photoinitiator or a thermal initiator. The initiator may include benzoyl peroxide, t-butyl hydroperoxide, cumyl hydroperoxide, bis(4-tert-butylcyclohexyl)peroxydicarbonate, azobisisobutyronitrile, phenyl bis ( 2,4,6-trimethylbenzoyl)phosphine oxide, (2,4,6-trimethylbenzoyl)diphenylphosphine oxide, 2,4,6-trimethylbenzoylphosphonic acid Ethyl ester, 2-methyl-1-[4-methylthiophenyl]-2-morpholinyl-1-propanone, 2-phenylbenzyl-2-dimethylamine-1-(4-morpholine Benzyl phenyl) butanone, 2-hydroxy-1-(4-(2-hydroxy-2-methylpropanoylphenyl)benzyl)-2-methyl-1-propanone, bis 2,6-difluoro -3 pyrrolyl phenyl titanocene, (4-dimethylamino)-benzoic acid ethyl ester, 4-phenyl benzophenone, 4-chlorobenzophenone, benzophenone, o-benzoylbenzoic acid Methyl ester, benzoin dimethyl ether, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 1-hydroxy-cyclohexyl-phenyl ketone, 2-isopropylthioxanthone, and even At least one of nitrogen bis(2,4-dimethylvaleronitrile). In one embodiment, the initiator may be used in an amount of from 0.1 to 5% by weight based on the total weight of the monomers used to synthesize the polymer.

In an embodiment of the invention, the blue light absorbing agent may include a polymerizable azo compound. In the present invention, the above "polymerizable azo compound" means the above-mentioned monomer (including the benzotriazole ultraviolet absorber monomer, bulk monomer) of the present invention, an initiator, and a crosslinking agent. At least one of the copolymerized compounds containing the corresponding group (azo group). A person skilled in the art can select an appropriate compound as a blue light absorber within the above range according to actual conditions, for example, according to the specific requirements of the ocular medical device for the polymer. In some embodiments, the blue light absorber can include N-(4-hydroxy-3-(o-tolyl)phenylethyl)methacrylamide, 4-hydroxy-3-methyl-5-(phenyl Dinitroalkenyl)phenoxy)methyl methacrylate, (E)-2-(4-(phenyldiazenyl)phenoxy)ethyl methacrylate, (E)-N-( 4-(4-hydroxyphenyl)diazenol)phenyl)methacrylamide, (E)-N-(4-((4-hydroxy-3-methoxyphenyl)diazenyl) Phenyl)methacrylamide, 2-hydroxy-3-(4-methoxyphenyl)diazenol)-5-methylbenzyl methacrylate, 2-hydroxy-5-methyl-3 At least one of -((3,4,5-trimethoxyphenyl)diazenyl)benzyl methacrylate. Adding the above-mentioned blue light absorbing agent to the raw material of the above polymer can absorb most of the blue light and prevent the retina of the eye from being exposed to blue light and being damaged. The blue light absorber may be used in an amount of from 0.1 to 2% by weight based on the total weight of the monomers used in the synthetic polymer. When the content of the blue light absorbing agent is within the above range, most of the blue light can be effectively absorbed without adversely affecting the refractive index and flexibility of the polymer.

As described above, the polymerizable benzotriazole ultraviolet absorber proposed by the present invention has excellent absorption characteristics in ultraviolet rays (having a wavelength of 400 nm or less), and the polymer proposed by the present invention contains benzotriazole ultraviolet absorption having the above properties. Therefore, the polymer of the present invention also has excellent absorption properties in a region having a wavelength of 400 nm or less. Specifically, the ultraviolet-visible absorption spectrum of the polymer proposed by the present invention is as shown in FIGS. 1 to 6 and is below 400 nm. The light transmission rate reaches 0%, which almost completely blocks the ultraviolet light. In addition, the benzotriazole ultraviolet absorber proposed by the invention has a polymerizable group and can be copolymerized with other monomers in the polymer, so that the benzotriazole ultraviolet absorber does not migrate from the polymer. The phenomenon of dissolution. In addition, the benzotriazole ultraviolet absorber proposed by the invention has an asymmetric ether bond as a linking group, which greatly increases the solubility of the benzotriazole ultraviolet absorber, and the polymerization efficiency when the copolymerization reaction is carried out is greatly increased. In addition, the polymer molecules obtained after the polymerization can be kept relatively compliant; in addition, the inventors have found through extensive research that it is precisely because of the introduction of the flexible chain in the molecule that the ultraviolet absorbing compound obtained by the present invention is obtained. It is pure white, which overcomes the ubiquitous color yellowing problem of benzotriazole ultraviolet absorbers in the prior art. The white ultraviolet absorber is added to the polymer to improve the transparency, light transmission effect and visual effect of the polymer material. Etc., enhances the application of polymers in various fields.

In summary, the above polymer has a very strong ultraviolet light blocking ability, and in the visible light range, the spectral transmittance is high. In addition, the polymer also has high tensile strength, appropriate elastic modulus and large elongation at break, and the foldable intraocular lens prepared by using the polymer proposed by the invention is neither too open nor too severe. Damage to the human eye, it will not affect the use of the effect due to poor mechanical properties, it is very suitable for the production of specific functional eye medical devices such as intraocular lenses.

In another aspect of the invention, the invention provides an ocular medical device comprising the polymer as set forth above in the present invention. Thus, the ocular medical device has all of the features and advantages of the previously described polymers. Specifically, the ocular medical device has ideal mechanical and optical properties, and can intercept ultraviolet light components in visible light, thereby reducing damage of ultraviolet rays to human eyes and the like; the ocular medical device has good safety performance. Because the benzotriazole ultraviolet absorber in the polymer proposed by the present invention is not easy to migrate and diffuse in the polymer, the benzotriazole ultraviolet absorber can be prevented from directly contacting the human body. The eye medical treatment also has the characteristics of low hardness, good flexibility, and easy folding, which makes handling at the time of surgery easier.

The above-mentioned ocular medical device may be an intraocular lens, an intraocular lens, a contact lens, a corneal correction, an intracorneal lens, a corneal inlay, a corneal ring or a glaucoma filter device. 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 polymerization method can be carried out in a suitable mold or container to obtain a rod-shaped, block-shaped, or plate-shaped polymer, and then processed into a desired shape by a processing method such as cutting, polishing, or laser processing. After the polymer is formed into a shape or a polymerization reaction in a mold corresponding to the desired shape, finer processing is performed as needed.

In yet another 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, medical, and the like. The benzotriazole ultraviolet absorber proposed by the present invention may be added to a material for manufacturing the above-mentioned ocular medical device, and may be added to a coating, an ink, a resin, a plastic, a rubber, an elastomer, a film, In materials such as cosmetics, optoelectronics, and medical materials, the above materials have an ultraviolet absorbing function.

General synthetic process

In general, the compounds of the present invention can be prepared by the methods described herein, unless otherwise stated, wherein each substituent has the meaning as described herein. The following reaction schemes and examples are provided to further illustrate the contents of the present invention. Those skilled in the art will recognize that the chemical reactions described herein can be used to suitably prepare a number of other compounds of the invention, and that other methods for preparing the compounds of the invention are considered to be within the scope of the invention. Inside. For example, the synthesis of those non-exemplified compounds according to the present invention can be successfully accomplished by modifications by those skilled in the art, such as appropriate protection of the interfering group, by the use of other known reagents in addition to those described herein, or The reaction conditions are subject to some conventional modifications. Additionally, the reactions or known reaction conditions disclosed herein are also recognized to be suitable for the preparation of other compounds of the invention.

The examples described below, unless otherwise indicated, all temperatures are set to degrees Celsius. The 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. The general reagents were purchased from Shantou Xiqiao Chemical Plant, Guangdong Guanghua Chemical Reagent Factory, Guangzhou Chemical Reagent Factory, Tianjin Haoyuyu Chemical Co., Ltd., Qingdao Tenglong Chemical Reagent Co., Ltd., and Qingdao Ocean Chemical Plant. Anhydrous tetrahydrofuran, dioxane, toluene and diethyl ether are obtained by refluxing with sodium metal. Anhydrous dichloromethane and chloroform were obtained by reflux drying of calcium hydride. Ethyl acetate, petroleum ether, n-hexane, N,N-dimethylacetamide and N,N-dimethylformamide were previously dried over anhydrous sodium sulfate.

The following reaction is generally carried out under a positive pressure of nitrogen or argon or on a dry solvent (unless otherwise indicated), the reaction bottle is stoppered with a suitable rubber stopper, and the substrate is driven through a syringe. The glassware is dry.

The column is a silica gel column. Silica gel (300-400 mesh) was purchased from Qingdao Ocean Chemical Plant. The nuclear magnetic resonance spectrum was determined by using CDC1 ₃ , DMSO-d ₆ , CD ₃ OD or acetone-d ₆ as a solvent (reported in ppm) using TMS (0 ppm) or chloroform (7.26 ppm) as a reference standard. When multiple peaks appear, the following abbreviations are used: s (singlet, unimodal), d (doublet, doublet), t (triplet, triplet), q (quartet, quadruple), m (multiplet, Multiple peaks), br (broadened, broad peaks), dd (doublet of doublets), dt (doublet of triplets). Coupling constant, expressed in Hertz (Hz).

Low-resolution mass spectrometry (MS) data was measured with a G1312A binary pump and a G1316A TCC (column temperature maintained at 30 °C) Agilent 6320 Series LC-MS spectrometer, G1329A autosampler and G1315B DAD detector for analysis The ESI source was applied to an LC-MS spectrometer.

Low-resolution mass spectrometry (MS) data was determined by a spectrometer equipped with a G1311A quaternary pump and a G1316A TCC (column temperature maintained at 30 °C) Agilent 6120 Series LC-MS. The G1329A autosampler and the G1315D DAD detector were used for analysis. The ESI source was applied to an LC-MS spectrometer.

Both spectrometers are equipped with an Agilent Zorbax SB-C18 column measuring 2.1 x 30 mm, 5 μm. The injection volume was determined by sample concentration; the flow rate was 0.6 mL/min; the peak of HPLC was recorded by UV-Vis wavelengths at 210 nm and 254 nm. The mobile phase was a 0.1% formic acid acetonitrile solution (Phase A) and a 0.1% formic acid ultrapure aqueous solution (Phase B). Gradient elution conditions

As shown in Table 1:

Table 1

Time (min)	A (CH 3 CN, 0.1% HCOOH)	B(H 2 O, 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 evaluated by Agilent 1100 Series High Performance Liquid Chromatography (HPLC) with UV detection at 210 nm and 254 nm, Zorbax SB-C18 column, size 2.1 x 30 mm, 4 μm, 10 min, flow rate 0.6 mL/min 5-95% (0.1% formic acid in acetonitrile) (0.1% aqueous formic acid), the column temperature was kept at 40 °C.

The following abbreviations are used throughout the invention:

Example

Example 1

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

synthetic route:

Step 1: Synthesis of Compound (1-1)

In an ice water bath, o-nitroaniline (5.05 g, 36.2 mmol), concentrated hydrochloric acid (11 mL, 37%), sodium nitrite (3.13 g, 43.5 mmol) and water (50 mL) were added to a single-necked flask and mixed with diphenol. (3.99g, 36.2mmol) and sodium hydroxide (1.74g, 43.5mmol) were made into an aqueous solution (50mL), and then added to the above reaction solution, stirred for 3h, then added Zn powder (14.12g, 144.8mmol), room temperature The mixture was stirred for 12 hours and suction filtered to give a crude solid. The obtained crude product was purified by silica gel chromatography eluting elut elut elut elut elut elut

MS (ESI, pos.ion) m / z: 228 [M + 1] +.

¹ H-NMR (400MHz, d ₆ -DMSO) δ (ppm): 10.43 (s, 1H), 9.99 (s, 1H), 8.17 - 7.88 (m, 2H), 7.62 (d, J = 8.8 Hz, 1H) ), 7.58 - 7.44 (m, 2H), 6.55 (d, J = 2.5 Hz, 1H), 6.45 (dd, J = 8.8, 2.5 Hz, 1H).

Step 2: Synthesis of Compound (1-2)

Compound (1-1) (2.4 g, 10.57 mmol), K ₂ CO ₃ (1.61 g, 11.67 mmol), 1-chloro-3-ethoxy-2-propanol (1.61 g, 11.67 mmol) and ethanol (100 mL) was added to a single-necked flask, stirred at 80 ° C for 8 h, then the heating was stopped, extracted with dichloromethane, and evaporated to dryness. The obtained crude product was purified by silica gel column chromatography. : V) = 2:1 gave a pale-yellow solid product (1.4 g, yield 40.2%).

MS (ESI, pos.) m/z: 330 [M+1] ⁺ .

^{1 H-NMR (400MHz, CDCl} 3) 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 = 2.5 Hz, 1H), 6.67 (dd, J = 9.0, 2.4 Hz, 1H), 4.22 (d, J = 4.8 Hz, 1H), 4.11 (p, J = 9.6 Hz, 2H), 3.72 - 3.63 (m, 2H), 3.61 (dd, J = 14.6, 7.9 Hz, 2H), 2.59 (d, J = 4.9 Hz, 1H), 1.48 - 1.10 (m, 3H) .

Step 3: Synthesis of Compound (1)

Compound (1-2) (0.8 g, 2.43 mmol), p-toluenesulfonic acid (0.13 g, 0.698 mmol), acrylic acid (0.6 g, 6.98 mmol) and toluene (100 mL) were added to a single-necked bottle and refluxed for 12 h, then steamed The toluene was removed, and the obtained crude material was purified to silica gel elution elution elution

MS (ESI, pos.ion) m / z: 384 [M + 1] +.

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

Example 2

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

synthetic route:

Step 1: Synthesis of Compound (1-1)

Refer to step 1 of Example 1.

Step 2: Synthesis of Compound (2-1)

Compound (1-1) (5.20 g, 22.91 mmol), K ₂ CO ₃ (3.48 g, 25.20 mmol), 1-chloro-3-methoxy-2-propanol (3.12 g, 25.20 mmol) and ethanol (100 mL) was added to a single-necked flask, and stirred under reflux at 80 ° C for 8 h, then the heating was stopped, extracted with dichloromethane, and evaporated to dryness. The obtained crude product was purified by silica gel column chromatography. V: V) = 2:1 gave a pale yellow solid product (3.0 g, yield 41.58%).

MS (ESI, pos.ion) m / z: 316 [M + 1] +.

^{1 H-NMR (400MHz, CDCl} 3) 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 = 2.6 Hz, 1H), 6.67 (dd, J = 9.1, 2.7 Hz, 1H), 4.21 (tt, J = 13.7, 7.0 Hz, 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, 4.4 Hz, 1H).

Step 3: Synthesis of Compound (2)

Compound (2-1) (2.4 g, 7.62 mmol), p-toluenesulfonic acid (0.16 g, 0.91 mmol), acrylic acid (0.67 g, 9.14 mmol) and toluene (100 mL) were placed in a single-necked bottle and refluxed for 12 h, then steamed The toluene was removed, and the obtained crude product was purified to silica gel elute elute elute

MS (ESI, pos.) m/z: 370[M+1] ⁺ .

¹ H-NMR (400 MHz, CDCl ₃ ) δ (ppm): 11.44 (s, 1H), 8.31 (d, J = 9.1 Hz, 1H), 7.93 (dd, J = 6.5, 3.0 Hz, 2H), 7.63 - 7.36 (m, 2H), 6.89 - 6.70 (m, 1H), 6.66 (dd, J = 9.1, 2.4 Hz, 1H), 6.46 (dd, J = 27.5, 12.8 Hz, 1H), 6.19 (dt, J = 30.8, 15.4 Hz, 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

synthetic route:

Step 1: Synthesis of Compound (1-1)

Refer to step 1 of Example 1.

Step 2: Synthesis of Compound (2-1)

Refer to step 2 of Example 2.

Step 3: Synthesis of Compound (3)

Compound (2-1) (5.95 g, 18.88 mmol), p-toluenesulfonic acid (0.49 g, 0.28 mmol), methacrylic acid (4.87 g, 56.64 mmol) and toluene (100 mL) were added to a single-necked bottle and refluxed for 12 h, then The toluene was removed by rotary distillation. EtOAc (EtOAc:EtOAc)

MS (ESI, pos.ion) m / z: 384 [M + 1] +.

¹ H-NMR (400MHz, CDCl ₃ ) δ (ppm): 11.45 (s, 1H), 8.32 (d, J = 9.1 Hz, 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 = 10.6 Hz, 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) methacrylate -2-propyl ester

synthetic route:

Step 1: Synthesis of Compound (4-1)

In a ice water bath, 4-methoxy-2-nitroaniline (9.00 g, 53.6 mmol), concentrated hydrochloric acid (16 mL, 37%), sodium nitrite (4.44 g, 64.3 mmol) and water (50 mL) The flask was mixed, and an aqueous solution (50 mL) of m-diphenol (7.07 g, 64.3 mmol) and sodium hydroxide (3.08 g, 77.2 mmol) was added, stirred for 3 h, then Zn powder (17.42 g, 268 mmol) was added and stirred at room temperature. After 12 hours, the solid was obtained by EtOAc (EtOAc:EtOAc) Yield 34.1%).

MS (ESI, pos.ion) m / z: 258 [M + 1] +.

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

Step 2: Synthesis of Compound (4-2)

Compound (4-1) (4.7 g, 18.3 mmol), K ₂ CO ₃ (3.03 g, 21.9 mmol), 1-chloro-3-methoxy-2-propanol (3.03 g, 21.9 mmol) and ethanol (100 mL) was added to a single-necked flask, and stirred under reflux at 80 ° C for 8 h, then the heating was stopped, extracted with dichloromethane, and evaporated to dryness. The obtained crude product was purified by silica gel column chromatography. V: V) = 2: 1 gave a pale yellow solid product (2.2 g, yield: 33.5%).

MS (ESI, pos.) m/z: 360 [M + 1] ⁺ .

¹ H-NMR (400 MHz, CDCl ₃ ) δ (ppm): 11.39 (s, 1H), 8.33 (t, J = 53.3 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.22 - 7.15 ( m, 1H), 7.15 (s, 1H), 6.73 (d, J = 2.6 Hz, 1H), 6.65 (dd, J = 9.1, 2.7 Hz, 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 = 15.1 Hz, 1H), 1.49 - 1.10 (m, 3H).

Step 3: Synthesis of Compound (4)

Compound (4-2) (2.2 g, 6.13 mmol), p-toluenesulfonic acid (0.13 g, 0.74 mmol), methacrylic acid (0.63 g, 7.32 mmol) and toluene (100 mL) were placed in a single-necked bottle and refluxed for 12 h, then The toluene was removed by rotary evaporation. EtOAc (EtOAc:EtOAc)

MS (ESI, pos.) m/z: 428[M+1] ⁺ .

^{1 H-NMR (400MHz, CDCl} 3) 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, 2.0 Hz, 1H), 7.13 (d, J=2.2 Hz, 1H), 6.85–6.70 (m, 1H), 6.70–6.58 (m, 1H), 5.65 (tt, J=13.7, 6.8 Hz) , 2H), 5.39 (p, J = 5.1 Hz, 1H), 4.44 - 4.13 (m, 2H), 3.93 (s, 3H), 3.74 (dd, J = 12.4, 5.2 Hz, 2H), 3.69 - 3.46 ( m, 2H), 2.17 - 1.81 (m, 3H), 1.24 (dt, J = 14.0, 7.0 Hz, 3H).

Example 5

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

synthetic route:

Step 1: Synthesis of Compound (5-1)

In an ice water bath, 4-chloro-2-nitroaniline (7.84 g, 45.6 mmol), concentrated hydrochloric acid (14 mL, 37%), sodium nitrite (3.94 g, 54.7 mmol) and water (50 mL) were added to a single-necked bottle. An aqueous solution (50 mL) of m-diphenol (9.97 g, 91.2 mmol) and sodium hydroxide (2.34 g, 54.7 mmol) was added and stirred for 3 h, then Zn powder (14.82 g, 228 mmol) was added and stirred at room temperature for 12 hours. After suction filtration, the crude solid was obtained, and the obtained crude product was purified by silica gel column chromatography, eluting with ethyl ether (V:V)=20:1 to obtain a pale yellow solid product (1.4 g, yield 11.8%).

MS (ESI, pos.) m/z: 262[M+1] ⁺ .

¹ H-NMR (400MHz, CDCl ₃ ) δ (ppm): 11.17 (s, 1H), 8.24 (d, J = 8.9 Hz, 1H), 7.93 (d, J = 1.1 Hz, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.43 (dd, J=9.0, 1.8 Hz, 1H), 7.21–7.10 (m, 1H), 6.67 (t, J=4.8 Hz, 1H), 6.58 (dd, J=9.0) , 2.6 Hz, 1H).

Step 2: Synthesis of Compound (5-2)

Compound (5-1) (1.75 g, 6.70 mmol), K ₂ CO ₃ (1.11 g, 8.05 mmol), 1-chloro-3-ethoxy-2-propanol (1.11 g, 8.05 mmol) and ethanol (100 mL) was added to a single-necked flask, and stirred under reflux at 80 ° C for 8 h, then the heating was stopped, extracted with dichloromethane, and evaporated to dryness. The obtained crude product was purified by silica gel column chromatography. V: V) = 2: 1 gave a pale yellow solid product (0.8 g, yield 32.7%).

MS (ESI, pos.) m/z: 364[M+1] ⁺ .

¹ H-NMR (400 MHz, CDCl ₃ ) δ (ppm): 11.21 (s, 1H), 8.29 (d, J = 9.1 Hz, 1H), 7.94 (d, J = 1.2 Hz, 1H), 7.88 (d, J=9.0 Hz, 1H), 7.44 (dd, J=9.0, 1.8 Hz, 1H), 6.74 (d, J=2.6 Hz, 1H), 6.67 (dd, J=9.1, 2.7 Hz, 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, 4.4 Hz, 1H), 1.32 - 1.21 (m, 3H).

Step 3: Synthesis of Compound (5)

Compound (5-2) (0.8 g, 2.20 mmol), p-toluenesulfonic acid (0.05 g, 0.26 mmol), methacrylic acid (0.23 g, 2.64 mmol) and toluene (100 mL) were added to a single-neck bottle and refluxed for 12 h, then The toluene was removed by rotary evaporation. EtOAc (EtOAc:EtOAc)

MS (ESI, pos.ion) m / z: 432 [M + 1] +.

^{1 H-NMR (400MHz, CDCl} 3) δ (ppm): 11.19 (s, 1H), 8.28 (d, J = 9.1Hz, 1H), 7.92 (t, J = 5.9Hz, 1H), 7.88 (d, J=9.0 Hz, 1H), 7.44 (dd, J=9.0, 1.7 Hz, 1H), 6.74 (d, J=2.6 Hz, 1H), 6.66 (dd, J=9.2, 2.6 Hz, 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 = 5.2 Hz, 2H), 3.63 - 3.50 ( m, 2H), 1.97 (d, J = 13.6 Hz, 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

synthetic route:

Step 1: Synthesis of Compound (1-1)

Refer to step 1 of Example 1.

Step 2: Synthesis of Compound (1-2)

Refer to step 2 of Example 1.

Step 3: Synthesis of Compound (6)

Compound (1-2) (2.83 g, 8.6 mmol), p-toluenesulfonic acid (0.25 g, 1.5 mmol), methacrylic acid (2.43 g, 28.3 mmol) and toluene (100 mL) were placed in a single-neck bottle and refluxed for 12 h, then The toluene was removed by rotary evaporation. EtOAc (EtOAc:EtOAc)

LC-MS (ESI, pos.ion) m / z: 397 [M + Na] +.

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

Example 7 Preparation of Polymer A1

2-Phenylethyl acrylate (0.60 g), 2-phenylethyl methacrylate (0.35 g), 1,4-butanediol diacrylate (0.05 g), bis(4-tert-butyl ring) The hexyl peroxydicarbonate (0.02 g) and the ultraviolet absorber (0.02 g) prepared in Example 1 were uniformly mixed, and then transferred to a mold consisting of two layers of glass and a sheet of polytetrafluoroethylene, and then the mold was The mixture was placed in an oven at 60 ° C for 3 hours, then the oven was elevated to 100 ° C and maintained for 3 hours to obtain a transparent and elastic polymer. The obtained material was ultrasonically washed in absolute ethanol and vacuum dried at 60 ° C for 24 hours. That is, the polymer A1 was obtained.

Examples 8 to 12 Preparation of Polymers A2 to A6

The procedure is the same as that of the above-mentioned Embodiment 1, except that the ultraviolet absorber prepared in Example 2, Example 3, Example 4, Example 5 and Example 6 is used instead of the UV absorber in Example 1, respectively. The polymers A2 to A6 were obtained.

Comparative Example Preparation of Polymer A0

2-Phenylethyl acrylate (0.60 g), 2-phenylethyl methacrylate (0.35 g), 1,4-butanediol diacrylate (0.05 g), and bis(4-tert-butylcyclohexane) The hexyl peroxide percarbonate (0.02 g) was uniformly mixed, then transferred to a mold consisting of two layers of glass and a sheet of polytetrafluoroethylene, and the mold was placed in an oven at 60 ° C for 3 hours, then oven The temperature was raised to 100 ° C and continued for 3 hours to obtain a transparent and elastic polymer. The obtained material was ultrasonically washed in absolute ethanol and vacuum dried at 60 ° C for 24 hours to obtain a polymer A0.

Spectral transmittance measurement

(1) Test method: The spectral transmittance of each polymer material in the range of 200 nm to 800 nm light wave was measured by an Agilent Cary 60 ultraviolet-visible spectrophotometer at room temperature.

(2) Test results:

1 to 6 show the results of spectral transmittance of the polymers A1 to A6 prepared in Examples 7 to 12. Figure 7 shows the results of the spectral transmittance of the polymer A0 prepared in the comparative example. It can be seen from the drawing that the polymer A0 prepared by the comparative example without the addition of the ultraviolet absorber of the present invention has a strong transmittance at 300 nm and a weak absorption of ultraviolet light or The polymers A1 to A6 prepared in Examples 1 to 6 which were not absorbed, and which were added to the ultraviolet absorbers of the present invention, had a spectral transmittance at 400 nm and below which was almost zero, indicating the benzotriene proposed by the present invention. The azole ultraviolet absorber has a strong ultraviolet absorption capacity.

It is obvious to those skilled in the art that the present invention is not limited to the foregoing illustrative embodiments, and may be embodied in other specific forms without departing from the essential characteristics. The present embodiments are to be considered in all respects as illustrative and not restrict All changes within the scope are included in this article.

In the description of the present specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example" or "some examples" and the like means a specific feature described in connection with the embodiment or example, A structure, material or feature is included in at least one embodiment or example of the invention. In the present specification, the schematic representation of the above terms does not necessarily mean the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in a suitable manner in any one or more embodiments or examples.

Although the embodiments of the present invention have been shown and described, it is understood that the foregoing embodiments are illustrative and not restrictive The scope of the present invention is defined by the appended claims and their equivalents.

Claims (18)

1. A benzotriazole ultraviolet absorber characterized in that the benzotriazole ultraviolet absorber is a compound represented by the formula (I) or a stereoisomer and a mutual mutation of the compound represented by the formula (I) Structure, nitrogen oxides, hydrates, solvates,

   

   among them:

   R ¹ is H or C _1-12 alkyl;

   R ² is O or S;

   A ₁ is a bond or a C _1-12 alkylene group; A ₂ is H or a C _1-12 alkyl group;

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

   R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or C _1-4 alkyl;

   Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , A ₂ , R ³ , R ⁴ and R ⁵ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.
2. The benzotriazole ultraviolet absorber according to claim 1, wherein the benzotriazole ultraviolet absorber is a compound represented by the formula (Ia) or a stereoisomer of the compound represented by the formula (Ia) , tautomers, nitrogen oxides, hydrates, solvates,

   
3. The benzotriazole ultraviolet absorber according to claim 1, wherein the benzotriazole ultraviolet absorber is a compound represented by the formula (Ib) or a stereoisomer of the compound represented by the formula (Ib) , tautomers, nitrogen oxides, hydrates, solvates,

   

   among them:

   R ¹ is H or C _1-8 alkyl;

   R ⁶ is H or C _1-12 alkyl;

   R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, nitro, cyano, C _1-8 alkyl, C _1-8 alkoxy, C _2-6 alkenyl , C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl, sulfonic acid or COOR ⁵ ; R ⁵ is H Or C _1-4 alkyl;

   Wherein C _{1 1-4} alkyl, C _1-8 alkyl, C _1-12 alkyl, C _1-8 alkoxy, C _{2 - in} R ¹ , R ³ , R ⁴ , R ⁵ and R ⁶ ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 heterocyclyl, C _6-10 aryl, C _1-9 heteroaryl or amino are optionally independently 2, 3 or 4 selected from the group consisting of hydrogen, hydrazine, hydroxy, amino, fluoro, chloro, bromo, iodo, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _2-6 olefin Substituted by a substituent of a C _2-6 alkynyl group, a C _1-4 alkylamino group or a C _6-10 aryl group.
4. The benzotriazole ultraviolet absorber according to claim 3, wherein the benzotriazole ultraviolet absorber is a compound represented by the formula (Ic) or a stereoisomer of the compound represented by the formula (Ic) , tautomers, nitrogen oxides, hydrates, solvates,

   
5. The benzotriazole ultraviolet absorber according to any one of claims 1 to 4, wherein the R ¹ is H or a methyl group.
6. The benzotriazole ultraviolet absorber according to claim 3 or 4, wherein the R ⁶ is H or a C _1-8 alkyl group.
7. The benzotriazole ultraviolet absorber according to any one of claims 1 to 6, wherein each of R ³ and R ^{4 is} independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, and nitrate. Base, cyano, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl, C _6-10 aryl or C _1-6 alkylamino.
8. The benzotriazole ultraviolet absorber according to any one of claims 1 to 7, wherein each of R ³ and R ^{4 is} independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, amino, and nitrate. Base, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, trifluoroethyl Base, phenyl, methylamino or ethylamino.
9. The benzotriazole ultraviolet absorber according to any one of claims 1 to 8, wherein the benzotriazole ultraviolet absorber has a structure of one of the following:

   

   

   

   

   

   Their stereoisomers, tautomers, nitrogen oxides, hydrates and solvates.
10. A method for preparing a benzotriazole ultraviolet absorber according to claim 3, which comprises: subjecting a compound of the formula (II) to a condensation reaction with a compound of the formula (III) to obtain the benzene And triazole ultraviolet absorber:

    

    Wherein R ⁷ is hydroxy, chloro, bromo or C _1-6 alkoxy.
11. The process according to claim 10, wherein the compound of the formula (II) is obtained by a substitution reaction of a compound of the formula (IV) with a compound of the formula (V):

    

    Wherein R ⁸ is chlorine, bromine,

    
12. The process according to claim 11, wherein the compound of the formula (IV) is obtained by a coupling reaction of a compound of the formula (VI) with a compound of the formula (VII):

    
13. A polymer comprising the benzotriazole ultraviolet absorber according to any one of claims 1 to 9, wherein the monomer constituting the polymer comprises the polymer.
14. The polymer according to claim 13, wherein the monomer constituting the polymer further comprises a bulk monomer comprising a (meth) acrylate monomer, a vinyl monomer, and At least one of the allyl monomers.
15. The polymer according to any one of claims 13 to 14, wherein the polymer further comprises at least one of a crosslinking agent, a blue light absorber, and an initiator.
16. An ocular medical device, characterized in that the ocular medical device comprises the polymer of any one of claims 13-15.
17. The ocular medical device according to claim 16, wherein the ocular medical device is an intraocular lens, an intraocular lens, a contact lens, a corneal correction, an intracorneal lens, a corneal insert, a corneal ring, or a glaucoma filter. Optical device.
18. Use of the ultraviolet absorber according to any one of claims 1 to 9 in paints, inks, resins, plastics, rubbers, elastomers, films, cosmetics, optoelectronics or medical materials.

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