CN109641832B - Azo compounds, polymers, and methods of preparation and use - Google Patents

Abstract

The invention provides an azo compound, a polymer, a preparation method and application. The azo compound has good blue light intercepting performance, and the compound is a polymerizable azo compound and is not easy to migrate and diffuse in a polymer.

Description

Azo compounds, polymers, and methods of preparation and use

Technical Field

The present invention relates to the field of ophthalmic medical devices, in particular to azo compounds, polymers, and methods of preparation and use.

Background

In recent years, studies have shown that the blue portion of visible light can cause damage to the human eye, particularly the retina, resulting in decreased vision and even blindness. Therefore, the adhesive film capable of intercepting blue light or the component capable of intercepting blue light is added in the eye medical devices such as glasses lenses, so that the blue light is prevented from damaging eyes.

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

Disclosure of Invention

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

although the current spectacle lenses with the blue light interception function are common, the blue light interception function is rare in eye medical devices such as artificial crystals and the like which are directly contacted with human eyes. The inventor finds that the blue light interception function is realized by adding yellow dye with blue light absorption function in the eye medical device. The eye medical device directly contacting with human eyes requires that the added yellow dye cannot diffuse and migrate in the eye medical device, that is, the added yellow dye needs to be ensured to be stably stored in the eye medical device and not enter human eyes, so as to ensure the safety performance of the eye medical device. The yellow dyes that can meet the above requirements are very limited, thus limiting the development of ocular medical devices with blue light interception functionality.

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

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

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

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

Drawings

FIG. 1 shows a graph of the spectral transmittance test of a polymer A-0 according to the invention;

FIG. 2 shows a graph of the spectral transmittance test of the polymer A-1 according to the invention;

FIG. 3 shows a graph of the spectral transmittance test of the polymer A-2 according to the invention;

FIG. 4 shows a graph of the spectral transmittance test of the polymer A-3 according to the invention;

FIG. 5 shows a graph of the spectral transmittance test of the polymer B-0 according to the invention;

FIG. 6 shows a graph of the spectral transmittance test of the polymer B-1 according to the invention;

FIG. 7 shows a graph of the spectral transmittance test of the polymer B-2 according to the invention.

Detailed Description

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

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

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

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

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

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

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

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

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

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

In the present invention, all numbers disclosed herein are approximate values, regardless of whether the word "about" or "approximately" is used. There may be differences below 10% in the value of each number or reasonably considered by those skilled in the art, such as differences of 1%, 2%, 3%, 4% or 5%. The term "blue light" refers to visible light with a wavelength range of 400-550nm, and the terms "intercept blue light", "absorb blue light" and the like mean that when the visible light containing blue light enters and passes through one side of the surface of a material formed by the substances such as the azo compound or the polymer and the like, the light intensity of the blue light in emergent light on the other side surface of the material is obviously reduced compared with that of the blue light in the incident light, and even the emergent light does not contain the blue light. "room temperature" in the present invention means a temperature of from about 10 degrees celsius to about 40 degrees celsius. In some embodiments, "room temperature" refers to a temperature of from about 20 degrees celsius to about 30 degrees celsius; in some other embodiments, "room temperature" refers to 20 degrees celsius, 22.5 degrees celsius, 25 degrees celsius, 27.5 degrees celsius, and the like.

In the 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 is especially intended to meanMethyl, ethyl, C of formula₃Alkyl radical, C₄Alkyl radical, C₅Alkyl and C₆An alkyl group.

The term "alkyl" or "alkyl group" denotes a saturated straight or branched chain hydrocarbon group which may be a monovalent, divalent or trivalent hydrocarbon group. 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 2 carbon atoms.

Unless otherwise specified, the term "C" is used herein_1-12Alkyl "groups contain 1-12 carbon atoms. The term "C_1-6Alkyl "having" C_1-12Alkyl "has a similar meaning, except that C_1-6The alkyl group contains up to 6 carbon atoms and will not be described in detail here.

Examples of alkyl groups include, but are not limited to, methyl (Me, -CH)₃) Ethyl group (Et, -CH)₂CH₃) N-propyl (n-Pr, -CH)₂CH₂CH₃) Isopropyl group (i-Pr, -CH (CH)₃)₂) N-butyl (n-Bu, -CH)₂CH₂CH₂CH₃) Isobutyl (i-Bu, -CH)₂CH(CH₃)₂) Sec-butyl (s-Bu, -CH (CH)₃)CH₂CH₃) Tert-butyl (t-Bu, -C (CH)₃)₃) N-pentyl (-CH)₂CH₂CH₂CH₂CH₃) 2-pentyl (-CH (CH)₃)CH₂CH₂CH₃) 3-pentyl (-CH (CH)₂CH₃)₂) 2-methyl-2-butyl (-C (CH)₃)₂CH₂CH₃) 3-methyl-2-butyl (-CH (CH)₃)CH(CH₃)₂) 3-methyl-1-butyl (-CH)₂CH₂CH(CH₃)₂) 2-methyl-1-butyl (-CH)₂CH(CH₃)CH₂CH₃) N-hexyl (-CH)₂CH₂CH₂CH₂CH₂CH₃) 2-hexyl (-CH (C)H₃)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, undecyl, and the like.

The term "alkoxy" denotes an alkyl group attached to the rest of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. In one embodiment, the alkoxy group contains 1 to 12 carbon atoms; in another embodiment, the alkoxy group contains 1 to 6 carbon atoms; in yet another embodiment, the alkoxy group contains 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group contains 1 to 2 carbon atoms.

Unless otherwise specified, the term "C" is used herein_1-12Alkoxy "groups contain 1-12 carbon atoms. The term "C_1-6Alkoxy "having" C_1-12Alkoxy "has a similar meaning, except that C_1-6The alkoxy group contains up to 6 carbon atoms and is not described in detail here.

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 terms "alkylene" and "alkylene chain" refer to a straight or branched divalent hydrocarbon chain composed of only carbon and hydrogen atoms, containing no unsaturated bonds, having 1 to 12 carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain may be attached to the remainder of the molecule through any two carbon atoms in the chain.

The terms "heteroalkylene" and "heteroalkylene" refer to alkylene and alkylene chains into which one or more heteroatoms such as O, N, S, NR may be inserted, and/or, wherein optionally one or more-CH groups₂-by-C (═ O), -S (═ O)₂And isoradical substitution, wherein alkylene and alkylene chain have the meaning as described herein. Unless otherwise specified, the heteroalkylene or heteroalkylene group contains 1 to 12 carbon atoms, in some embodiments the heteroalkylene group contains 1 to 10 carbon atoms, in other embodiments the heteroalkylene group contains 1 to 5 carbon atoms, and in yet other embodiments the heteroalkylene group contains 1 to 4 carbon atoms. Examples include, but are not limited to, -CH₂OCH₂-，-CH₂CH₂OCH₂-，-CH₂SCH₂-，-CH₂NHCH₂-，-CH₂O-，-CH₂CH₂O-，-CH₂CH₂CH₂O-，-CH₂CH₂CH₂CH₂O-，-CH₂CH₂CH₂CH₂CH₂O-，-CH₂CH₂CH₂CH₂CH₂CH₂O-，-CH₂OCH₂CH₂-，-CH₂CH₂OCH₂CH₂-，-CH₂C(＝O)CH₂-，-CH₂C(＝O)OCH₂-，-CH₂S(＝O)₂OCH₂-and the like.

The term "divalent organic group" refers to a group having two unpaired electrons, and the divalent organic group in the present invention is not particularly limited, and may include a divalent aromatic hydrocarbon group, a divalent saturated or unsaturated aliphatic hydrocarbon group, a 2-valent heterocyclic group, a divalent heteroalkyl group, and the like.

The term "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system consisting of 3 to 12 carbon atoms, having carbon atoms as ring atoms. In one embodiment, cycloalkyl consists of 3 to 10 carbon atoms; in another embodiment, cycloalkyl consists of 3 to 8 carbon atoms; in yet another embodiment, the cycloalkyl group consists of 3 to 6 carbon atoms. The cycloalkyl groups may be independently unsubstituted or substituted with one or more substituents described herein. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like.

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 12 ring atoms, wherein at least one ring atom is selected from the group consisting of nitrogen, sulfur and oxygen atoms. Unless otherwise specified, a heterocyclyl group may be carbon-or nitrogen-based, and a-CH 2-group may optionally be replaced by-C (═ O) -, a ring sulfur atom may optionally be oxidized to an S-oxide, and a ring nitrogen atom may optionally be oxidized to an N-oxide. Examples of heterocyclyl groups include, but are not limited to: oxirane, azetidinyl, oxetanyl, thietanyl, pyrrazolPyrrolidinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxolanyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1, 1-dioxo-thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thiaoxanyl, homopiperazinyl, homopiperidinyl, homomorpholinyl, oxepinyl, thiepanyl, oxazepanyl, and oxazepanyl

Radical, diaza

Radical, S-N-aza

-yl, indolinyl, 1,2,3, 4-tetrahydroquinolinyl, 1,2,3, 4-tetrahydroisoquinolinyl, 1, 3-benzodioxol, 2-oxa-5-azabicyclo [2.2.1]Hept-5-yl, benzopyrrolidinyl, dihydrobenzofuranyl, benzomorpholinyl, 3, 4-dihydro-pyridine [3,2-b ]][1,4]Oxazinyl, 1, 3-benzodioxolyl, tetrahydropyridinyl, 1, 4-benzodioxanyl, pyridin-2 (1H) -one-3-yl, pyridin-2 (1H) -one-4-yl, pyridin-2 (1H) -one-5-yl, pyridin-2 (1H) -one-6-yl, pyrazin-2 (1H) -one-3-yl, pyrazin-2 (1H) -one-5-yl, pyrazin-2 (1H) -one-6-yl. Examples of substitutions of the-CH 2-group in the heterocyclyl by-C (═ O) -include, but are not limited to: 2-oxopyrrolidinyl, oxo-1, 3-thiazolidinyl, 2-piperidinonyl, 3, 5-dioxopiperidinyl and pyrimidinedione. Examples of sulfur atoms in heterocyclic groups that are oxidized include, but are not limited to: sulfolane, 1, 1-dioxothiomorpholinyl. The heterocyclyl group may be optionally substituted with one or more substituents as described herein.

In one embodiment, heterocyclyl is a heterocyclic group of 4-7 atoms; in another embodiment, heterocyclyl is a 4 atom heterocyclyl; in another embodiment, heterocyclyl is a 5 atom heterocyclyl; in another embodiment, heterocyclyl is a 6 atom heterocyclyl; in yet another embodiment, heterocyclyl is a heterocyclic group of 7 to 12 atoms; in yet another embodiment, heterocyclyl refers to heterocycloalkyl.

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, indenyl, naphthyl and anthracene. 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., 2-triazolyl and 5-triazolyl), 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 "alkenylene" denotes a divalent alkylene radical resulting from the removal of two hydrogen atoms from a straight or branched chain alkene. Unless otherwise specified, alkenylene groups contain 1-12 carbon atoms. In one embodiment, the alkenylene group contains 1 to 8 carbon atoms; in one embodiment, the alkenylene group contains 1-6 carbon atoms; in another embodiment, the alkenylene group contains 1-4 carbon atoms; in yet another embodiment, the alkenylene group contains 1-3 carbon atoms; in yet another embodiment, the alkenylene group contains 1-2 carbon atoms. Examples include-CH-, -CH ═ CH-CH₂-，-CH＝CH-CH(CH₃)-，-CH＝CH-C(CH₃)₂-, and the like.

The term "alkynylene" denotes a divalent alkynyl group resulting from the removal of a hydrogen atom from a straight or branched chain alkyne. Unless otherwise specified, alkynylene groups contain 1-12 carbon atoms. In one embodiment, the alkynylene group contains 1 to 8 carbon atoms; in one embodiment, the alkynylene group contains 1-6 carbon atoms; in another embodiment, the alkynylene group contains 1-4 carbon atoms; in yet another embodiment, the alkynylene group contains 1-3 carbon atoms; in yet another embodiment, the alkynylene group contains 1-2 carbon atoms. Examples of such include-C.ident.C-, -C.ident.C-CH₂-，-C≡C-CH(CH₃)-，-C≡C-C(CH₃)₂-, and the like.

In one aspect of the present invention, an azo compound is provided. The azo compound has a formula shown in formula Ia, or is a stereoisomer or tautomer of the compound shown in formula Ia.

In the formula (Ia), the reaction mixture is,

R¹is H or alkyl;

x is O, NH or NR⁶；

Y¹、Y²Each independently O, S, NH or NR⁶(ii) a Wherein R is⁶Is C_1-10Alkyl groups of (a);

W¹、W²each independently is a single bond or a divalent organic group;

R²、R³、R⁴and R⁵Each independently is alkyl, alkoxy, F, Cl, Br, hydroxyl, phenoxy, benzyloxy, sulfonic group, CN, NO₂Or COOR⁷(ii) a Wherein each R⁷Independently is H or C_1-4An alkyl group;

m and n are each independently 0, 1,2,3 or 4, and p and q are each independently 0, 1,2,3,4 or 5. m is equal to n, or may not be equal; p and q may or may not be equal. The azo compound with the structure is a polymerizable yellow dye, can play a good role in blue light absorption/interception, and can form a copolymer with other materials (such as monomers or additives for forming ocular medical devices such as intraocular lenses) so as to reduce the risk of migration of the azo compound in the ocular medical devices, and thus, the azo compound can be used for preparing the ocular medical devices with the blue light interception function.

In one embodiment of the invention, R¹Is H or alkyl; in another embodiment, R¹Is H or C_1-4An alkyl group; in yet another embodiment, R¹Is H or methyl, ethyl, propyl, isopropyl, hydroxymethyl or hydroxyethyl.

In one embodiment of the invention, X is O, NH or NR⁶，R⁶Is C_1-10Alkyl groups of (a); in another embodiment, X is O, NH or NR⁶，R⁶Is C_1-6Alkyl groups of (a); in yet another embodiment, X is O or NH.

In one embodiment of the present invention, Y¹、Y²Each independently O, S, NH or NR⁶，R⁶Is C_1-10Alkyl groups of (a); in another embodiment, Y¹、Y²Each independently is O, S, NH or NR⁶，R⁶Is C_1-6Alkyl groups of (a); (ii) a In yet another embodiment, Y¹、Y²Each independently O, S.

In one embodiment of the invention, W¹、W²Each independently is a single bond or a divalent organic group; in another embodiment, W¹、W²Each independently is a single bond or a heteroalkylene or alkylene group; in yet another embodiment, W¹、W²Each independently is a single bond, C_1-12Heteroalkylidene radical, C_1-12An alkylene group of (a); in some embodiments, W¹、W²Each independently is a single bond, C_1-10Heteroalkylidene radical, C_1-10An alkylene group of (a); in some embodiments, W¹、W²Each independently is a single bond, C_1-8Heteroalkylidene radical, C_1-8An alkylene group of (a); in some embodiments, W¹、W²Each independently is a single bond, C_1-6Heteroalkylidene radical, C_1-6An alkylene group of (a); in some embodiments, W¹、W²Each independently is a single bond, C_1-4Heteroalkylidene radical, C_1-4An alkylene group of (a). Examples of such divalent organic groups include, but are not limited to, alkylene, haloalkylene, aminoalkylene, hydroxy-substituted alkylene, cyano-substituted alkylene, cycloalkyl-substituted alkylene, heterocyclyl-substituted alkylene, aryl-substituted alkylene, heteroaryl-substituted alkylene,alkylenealkenylene, alkylenealkynylene, heteroalkylene, haloheteroalkylene, aminoheteroalkylene, hydroxy-substituted heteroalkylene, cyano-substituted heteroalkylene, cycloalkyl-substituted heteroalkylene, heterocyclyl-substituted heteroalkylene, aryl-substituted heteroalkylene, heteroaryl-substituted heteroalkylene, heteroalkylenealkenyl, heteroalkylenealkynyl; the alkylene group is a divalent hydrocarbon chain composed of carbon and hydrogen atoms, having 1 to 12 carbon atoms, and examples of the alkylene group include, but are not limited to, methylene, ethylene, propylene, n-butylene, 2-methylpropylene, and the like. The heteroalkylene is an alkylene or alkylidene chain into which one or more heteroatoms such as O, N, S, NR may be inserted, and/or in which one or more-CH groups may be incorporated₂-by-C (═ O), -S (═ O)₂And isoradical substitution, wherein alkylene and alkylene chain have the meaning as described herein. Examples of heteroalkylenes include, but are not limited to, alkylene-O-, alkylene-N-, alkylene-S-, alkylene-O-alkylene, alkylene-N-alkylene, alkylene-S-alkylene, alkylene-C (═ O) -, alkylene-S (═ O)₂-, -C (═ O) alkylene-, -S (═ O)₂Alkylene-, alkylene-C (═ O) -alkylene, alkylene-S (═ O)₂Alkylene, alkylene-C (═ O) -NR-, -C (═ O) NR alkylene-, -C (═ O) -O-alkylene-, alkylene-C (═ O) -O-, -C (═ O) -O-alkylene-, -C (═ O) -alkylene-NR-, -C (═ O) -alkylene-O-, etc., wherein each R is alkyl; specific examples are-CH₂CH₂O-、-CH₂O-、-CH₂CH₂CH₂O-、-CH₂CH₂CH₂CH₂O-、-CH₂CH₂CH₂CH₂CH₂O-，-CH₂CH₂CH₂CH₂CH₂CH₂O-、-CH₂OCH₂-、-CH₂CH₂OCH₂-、-CH₂SCH₂-、-CH₂NHCH₂-、-CH₂-C(＝O)-、-CH₂-S(＝O)-、-CH₂-S(＝O)₂-、-C(＝O)-CH₂-、-S(＝O)-CH₂-、-S(＝O)₂-CH₂-、-CH₂-C(＝O)-CH₂-、-CH₂-S(＝O)-CH₂、-CH₂-S(＝O)₂-CH₂、-CH₂-C(＝O)-NR-、-C(＝O)NR-CH₂-、-C(＝O)-O-CH₂-、-CH₂-C(＝O)-O-、-C(＝O)-O-CH₂-、-C(＝O)-CH₂-NR-、-C(＝O)-CH₂-O-, etc., wherein each R is alkyl.

In one embodiment of the invention, m and n are each independently 0, 1,2,3 or 4, R²And R³Each independently is alkyl, alkoxy, hydroxyl, F, Cl, Br, phenoxy, benzyloxy, sulfonic group, CN, NO₂、COOR⁷Wherein each R⁷Is H or C_1-4An alkyl group; in another embodiment, R²And R³Are each independently C_1-12Alkyl radical, C_1-12Alkoxy, hydroxy, F, Cl, Br, phenoxy, NO₂(ii) a In yet another embodiment, R²And R³Are each independently C_1-6Alkyl radical, C_1-6Alkoxy, hydroxy, F, Cl, NO₂At least one of (a); in yet another embodiment, R²And R³Each independently is methyl, methoxy or hydroxy. In the above embodiments of the present invention, R²And R³Are independent of each other, and when m or n is greater than 1, a plurality of R in the azo compound²May be the same or different, and a plurality of R' s³Or may be the same or different.

In one embodiment of the invention, p and q are each independently 0, 1,2,3,4 or 5, R⁴And R⁵Can be respectively and independently alkyl, alkoxy, F, Cl, Br, hydroxyl, phenoxy, benzyloxy, sulfonic group, CN, NO₂Or COOR⁷Wherein each R⁷Is H or C_1-4An alkyl group; in another embodiment, R⁴And R⁵Are each independently C_1-12Alkyl, hydroxy, C_1-12Alkoxy, F, Cl, Br, phenoxy, NO₂(ii) a In yet another embodiment, R⁴And R⁵Are each independently C_1-6Alkyl, hydroxy, C_1-6Alkoxy, F, Cl, NO₂(ii) a In yet another embodiment, R⁴And R⁵Each independently is methyl, hydroxy, fluoro or methoxy. In the above embodiments of the present invention, R⁴And R⁵Are independent of each other, and when p or q is greater than 1, a plurality of R in the azo compound⁴May be the same or different, and a plurality of R' s⁵And may be the same or different.

In one embodiment of the invention, R¹Is H or methyl, m and n can be 0, p and q are each independently 0 or 1 or 2, i.e., the azo compound does not contain R²And R³May not contain R⁴Or R⁵May also contain one or two R⁴Or R⁵。R⁴、R⁵Each independently is hydroxy, methyl, fluoro or methoxy. That is, R⁴And R⁵The number and the type of the substituent groups can be the same or different, when the azo compound contains two R⁴And/or two R⁵When two R are present⁴May be the same or different, two R⁵And may be the same or different.

In another embodiment of the invention, R¹Is H or methyl, m and n are 1, i.e. the azo compound contains only one R²And a R³. Wherein R is²Is hydroxy, methyl or methoxy, R³And R²The same or different. R⁴、R⁵Each independently is hydroxy, methyl or methoxy, and p and q are 0 or 1 or 2. That is, the azo compound may not have R⁴Or R⁵It is also possible to have one or two R⁴And one or two R⁵。R⁴And R⁵The number and the kind of the substituents may be the same or different.

In another embodiment of the present invention, the azo compounds of the present invention have a compound according to the general formula shown in formula (I), or are stereoisomers or tautomers of a compound according to the general formula shown in formula (I):

in the formula (I), the compound represented by the formula (I),

R¹is H or alkyl;

R²、R³、R⁴and R⁵Each independently is alkyl, alkoxy, F, Cl, Br, hydroxyl, phenoxy, benzyloxy, sulfonic group, CN, NO₂Or COOR⁷(ii) a Wherein each R⁷Independently is H or C_1-4An alkyl group;

m and n are each independently 0, 1,2,3 or 4;

p and q are each independently 0, 1,2,3,4 or 5.

In another embodiment of the present invention, the azo compound of the present invention may be a compound satisfying the general formulae represented by the following formulae (1) to (19), or a stereoisomer or tautomer of a compound satisfying the following general formulae:

the compound satisfying the general formulas shown in the formulas (1) to (19) or the azo compound satisfying the stereoisomer or tautomer of the compound having the general formulas has a relatively ideal blue light blocking effect, can be added to raw materials for synthesizing an eye medical device as a blue light absorbent, and can be used for preparing a flexible eye medical device such as a foldable artificial crystal because the compound does not adversely affect the optical properties (refractive index, spectral transmittance and the like) and the mechanical properties (tensile strength, elongation at break, elastic modulus and the like) of the eye medical device.

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

In the present invention, the ratio of the blue-light absorber and the bulk monomer in the polymer can be adjusted according to the actual situation. The term "bulk monomer" 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 blue-light absorber during the polymerization. Since the blue-light absorber contains a polymerizable group, monomers commonly used for forming a polymer can be copolymerized with the blue-light absorber proposed in the present invention, and thus, in the present invention, the specific type of the bulk monomer is not particularly limited, and at least one of a (meth) acrylate monomer, a vinyl monomer, and an allyl monomer can be included. 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 polymer provided by the invention, at least one of a cross-linking agent, an ultraviolet absorbent and an initiator can be further included. The crosslinking agent, the ultraviolet absorber and the initiator can be mixed with the bulk monomer and the blue light absorber to form the polymer provided by the invention through polymerization. In one embodiment of the present invention, the crosslinking agent may include, but is not limited to, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1, 3-propanediol dimethacrylate, 1, 6-hexanediol dimethacrylate, 1, 3-butanediol dimethacrylate, 1, 4-butanediol diacrylate, trimethylolpropane trimethacrylate, 1, 5-bis (methacryloyloxy) -2,2,3,3,4, 4-hexafluorohexane, 1, 6-bis (acryloyloxy) -2,2,3,3,4,4,5, 5-octafluorohexane, and pentaerythritol tetraacrylate. UV absorbers may include, but are not limited to, 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 2- [3- (2H-benzotriazol-2-yl) -4-hydroxyphenyl ] ethyl 2-methacrylate, 2- (2H-benzotriazol-2-yl) -4-methyl-6- (2-propenyl) phenol, 2- (5-chloro-2H-benzo [ d ] [1,2,3] triazole) -4-methyl-6- (2-allyl) phenol, 4-allyl-2- (5-chloro-2H-benzo [ d ] [1,2,3] triazole) -6-methoxyphenol, 2- (5-chloro-2H-1, 2, 3-benzo [ d ] [1,2,3] triazole) -4-methyl-6-allylphenol, 2-hydroxy-4- (methacryloyloxy) benzophenone, and 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate. Initiators may include, but are not limited to, benzoyl peroxide, t-butyl hydroperoxide, cumyl hydroperoxide, bis (4-t-butylcyclohexyl) peroxydicarbonate, azobisisobutyronitrile, and azobis (2, 4-dimethylvaleronitrile). Thereby, the properties of the polymer can be further improved.

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

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

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

In one embodiment, the gradient heat treatment may include:

a first reaction stage:

in the first reaction stage, the raw material mixture is heated to 40-70 ℃ for reaction, and the reaction time can be 1-24 hours. The reaction at a lower temperature can prevent the reaction rate from being too fast, and is beneficial to forming a sample with uniform appearance, thereby improving the performance of the polymer.

And a second reaction stage:

in the second reaction stage, the raw material mixture after the first reaction stage is heated to 80-120 ℃ for reaction, and the reaction time can be 1-24 hours. Therefore, the method is beneficial to promoting the further reaction of the residual raw materials and the conversion rate of the raw materials, and can further improve the performance of the polymer prepared by the method.

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

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

The following shorthand words are used throughout the present invention

g

mL of

mmol millimole

h hours

min for

s second

Boc tert-butyloxycarbonyl group

EtOAc ethyl acetate

n-Hex n-hexane

EXAMPLE 1 preparation of azo Compound

The following synthetic routes describe azo compounds: preparation of 1, 3-bis (4- (4' -hydroxyazobenzene) oxy) -2-propyl methacrylate (formula below):

(1) preparation of 1, 3-bis (4-nitrophenoxy) -2-propanol:

4-nitrophenol (11.2g, 81.2m mol), potassium carbonate (11.2g, 81.2mmol) and absolute ethanol (200mL) were added in this order to a three-necked flask, and after the mixture was stirred under reflux for 1hour, 1, 3-dibromo-2-propanol (4.4g, 20.2mmol) was slowly added dropwise thereto, and stirring was continued for 24 hours. The reaction was poured into water (500mL), stirred for 0.5h, filtered, the filter cake washed with aqueous sodium hydroxide (10% wt, 200mL), water (300mL), and the collected solid was dried under vacuum at 50 ℃ for 5h to give 1, 3-bis (4' -nitrophenoxy) -2-propanol as a light-colored solid, 4.8g in total, 68% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：357[M+Na]⁺；

¹H NMR(400MHz,CDCl₃)δ(ppm):8.26(t,2H)，8.23(t,2H)，7.06(t,2H)，7.03(t,2H)，4.52-4.50(m,1H)，4.26-4.34(m,4H)，2.61-2.60(d,1H)。

(2) preparation of 1, 3-bis (4' -aminophenoxy) -2-propanol:

to a single-neck flask were added 1, 3-bis (4-nitrophenoxy) -2-propanol (4.8g, 14.4mmol) obtained in step (1), 5% palladium on carbon (3.05g, 1.4mmol), ammonium formate (18.1g, 287.3mmol), and tetrahydrofuran (50mL) in this order, and the mixture was stirred at 45 ℃ for 1 h. The reaction was filtered, the filter cake was washed with dichloromethane (100mL), the collected filtrate was diluted to 250mL with dichloromethane and washed with saturated brine (80mL × 4), the organic phase was dried over anhydrous sodium sulfate for 2H after separation, the solvent was removed by rotary evaporation after filtration to give 1, 3-bis (4-aminophenoxy) -2-propanol as a pink solid 3.3g with a yield of 96%, and the mass spectrum and nmr H spectrum data were as follows:

LC-MS(ESI,pos.ion)m/z：275[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ(ppm):6.80-6.78(m,4H)，6.67-6.66(m,4H)，4.35-4.31(m,1H)，4.11-4.05(m,4H)，3.47(s,4H)，2.66(s,1H)。

(3) preparation of 1, 3-bis (4- ((tert-butoxycarbonyl) amino) phenoxy) -2-propanol:

to a single-neck flask, 1, 3-bis (4-aminophenoxy) -2-propanol (3.3g, 12mmol) prepared in step (2), Boc anhydride (6.3g, 28.9mmol) and methanol (50mL) were added in this order, and the mixture was stirred at room temperature for 1 h. The reaction was filtered, the filter cake was rinsed with n-hexane (300mL), and the collected solid was dried under vacuum at 40 ℃ for 2h to give 5.6g of a white solid in 98% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：497[M+Na]⁺；¹H NMR(400MHz,CDCl₃)δ(ppm):7.29-7.27(m,4H)，6.89-6.87(m,4H)，6.40(s,2H)，4.40-4.33(m,1H)，4.16-4.08(m,4H)，2.65-2.64(d,1H)，1.53(s,18H)。

(4) preparation of 1, 3-bis (4- ((tert-butoxycarbonyl) amino) phenoxy) -2-propyl methacrylate:

to a single-neck flask were added 1, 3-bis (4- ((tert-butoxycarbonyl) amino) phenoxy) -2-propanol prepared in step (3) (5.6g, 11.8mmol), diisopropylethylamine (6.3g, 60.6mmol), 4-dimethylaminopyridine (0.76g, 6.2mmol) and tetrahydrofuran (70mL) in this order, and after sufficient dissolution, methacryloyl chloride (10.4g, 100mmol) was slowly added dropwise thereto and stirring was continued for 24 h. The reaction was filtered, the tetrahydrofuran removed by rotary evaporation and the product purified by column chromatography (n-Hex/EtOAc (v/v) ═ 5:1) to give 5.7g of a yellow viscous liquid in 64% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：565[M+Na]⁺；

¹H NMR(400MHz,CDCl₃)δ(ppm):7.29-7.26(m,4H)，6.89-6.87(m,4H)，6.40(s,2H)，6.16(s,1H)，5.61(s,1H)，5.53-5.48(m,1H)，4.27-4.26(m,4H)，1.97(s,3H)，1.53(s,18H)。

(5) preparation of 1, 3-bis (4-aminophenoxy) -2-propyl methacrylate:

and (3) adding the 1, 3-bis (4- ((tert-butoxycarbonyl) amino) phenoxy) -2-propyl methacrylate (5.1g, 9mmol) obtained in the step (4) and a trifluoroacetic acid/dichloromethane mixed solution (volume ratio of 3:4, 35mL) into a single-neck flask in sequence, fully dissolving, and stirring at normal temperature for 15 min. The reaction was diluted to 200mL with dichloromethane and neutralized with saturated sodium bicarbonate, separated, the organic phase dried over anhydrous sodium sulfate for 2h, filtered, the solvent removed by rotary evaporation and the product purified by column chromatography (n-Hex/EtOAc (v/v) ═ 1:1) to give 2.6g of a yellow viscous liquid in 80% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：343[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ(ppm):6.80-6.78(m,4H)，6.66-6.64(m,4H)，6.16(s,1H)，5.61-5.60(s,1H)，5.50-5.46(m,1H)，4.25-4.21(m,4H)，3.48(s,4H)，1.97(s,3H)。

(6) preparation of 1, 3-bis (4- (4' -hydroxyazobenzene) oxy) -2-propyl methacrylate:

a three-necked flask was charged with a mixed solution (20mL) of 1, 3-bis (4-aminophenoxy) -2-propyl methacrylate (0.8g, 2.34mmol) obtained in step (5), potassium bromide (0.614g, 5.16mmol), concentrated hydrochloric acid (1.7g, 16.77mmol) and acetone/water (volume ratio 1:1) in this order, the mixed solution was stirred in a low temperature bath at-5 ℃ C, when the internal temperature reached 0 ℃ or less, sodium nitrite (0.32g, 4.75mmol) was dissolved in water (10mL), and slowly added dropwise to the reaction mixture, and stirring was continued for 0.5 h. Phenol (0.49g, 5.21mmol), sodium hydroxide (0.21g, 5.25mmol) were dissolved in water (15mL) and added dropwise to the above diazonium salt solution, maintaining the solution temperature at not higher than 5 ℃ during the addition. After stirring for a further 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the solid collected was passed through column chromatography to give the azo compound as an orange solid 0.6g with 47% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：554[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ(ppm):7.90-7.84(m,8H)，7.11-6.94(m,4H)，6.96-6.94(m,4H)，6.21(s,1H)，5.66(s,1H)，5.64-5.61(m,1H)，5.41(s,2H)，4.43-4.42(m,4H)，2.00(s,3H)。

EXAMPLE 2 preparation of azo Compound

The following synthetic routes describe azo compounds: preparation of 1, 3-bis (4- (2',4' -dihydroxyazobenzene) oxy) -2-propyl methacrylate (formula:

the procedure of example 1 was repeated, except that in step (6), a mixed solution (20mL) of 1, 3-bis (4-aminophenoxy) -2-propyl methacrylate (1.2g, 3.5mmol), potassium bromide (2.99g, 25.6mmol), concentrated hydrochloric acid (2.55g, 25.6mmol) and acetone/water (volume ratio 1:1) was added in this order to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, sodium nitrite (0.485g, 7.0mmol) was dissolved in water (10mL), and the mixture was slowly added dropwise to the reaction mixture and stirred for 0.5 h. Resorcinol (0.88g, 8.0mmol), sodium hydroxide (0.63g, 15.8mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution, maintaining the solution temperature not higher than 5 ℃ during the addition. After stirring for a further 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was purified by column chromatography (n-Hex/EtOAc (v/v) ═ 3:1) and recrystallised from methanol to give the azo compound as a dark red solid 0.3g with a yield of 15%. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：585[M+H]⁺；

¹H NMR(400MHz，DMSO-d₆)δ(ppm):12.28(s,2H)，10.42(s,2H)，7.86-7.84(d,4H)，7.66-7.64(d,2H)，7.18-7.15(d,4H)，6.50-6.47(d,2H)，6.35-6.34(d,2H)，6.06(s,1H)，5.72(s,1H)，5.57-5.55(m,1H)，4.49-4.41(m,4H)，1.98(s,3H)。

EXAMPLE 3 preparation of azo Compound

The preparation of the azo compound 1, 3-bis (4- (2 '-methyl-4' -hydroxyazophenyl) oxy) -2-propyl methacrylate (formula) is described below according to the synthetic route:

the procedure of example 1 was repeated, except that in step (6), a mixed solution (20mL) of 1, 3-bis (4-aminophenoxy) -2-propyl methacrylate (2.0g, 5.83mmol), potassium bromide (1.2g, 10.1mmol), concentrated hydrochloric acid (4.0g, 39.5mmol) and acetone/water (v/v ═ 1:1) was added in this order to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, sodium nitrite (0.97g, 14.0mmol) was dissolved in water (10mL), and the mixture was slowly added dropwise to the reaction mixture, and stirring was continued for 0.5 h. M-methylphenol (1.26g, 9.20mmol), sodium hydroxide (0.93g, 23.3mmol), sodium carbonate (1.23g, 11.6mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution while maintaining the solution temperature at not higher than 5 ℃. After stirring for an additional 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was purified by column chromatography (n-Hex/EtOAc (v/v) ═ 3:1) and recrystallised from methanol to give the title compound as a dark red solid (0.3g, 15%).

LC-MS(ESI,pos.ion)m/z：581[M+H]⁺；

¹H NMR(400MHz，CDCl₃))δ(ppm):7.89-7.87(d,4H)，7.66-7.64(d,2H)，7.07-7.05(d,4H)，6.79-6.79(d,2H)，6.73-6.71(t,2H)，6.21(s,1H)，5.66(s,1H)，5.64-5.62(m,1H)，5.55(s,2H)，4.43-4.42(d,4H)，2.69(s,6H)，2.00(s,3H)。

EXAMPLE 4 preparation of azo Compound

The preparation of the azo compound 1, 3-bis (4- (2 '-methoxy-4' -hydroxyazophenyl) oxy) -2-propyl methacrylate (formula) is described below according to the synthetic route:

the procedure of example 1 was repeated, except that in step (6), a mixed solution (20mL) of 1, 3-bis (4-aminophenoxy) -2-propyl methacrylate (1.0g, 2.97mmol), potassium bromide (0.61g, 5.1mmol), concentrated hydrochloric acid (2.10g, 19.8mmol) and acetone/water (v/v ═ 1:1) was added in this order to a three-necked flask, the mixed solution was stirred in a low-temperature bath at-5 ℃ and, when the internal temperature reached 0 ℃ or lower, sodium nitrite (0.50g, 7.2mmol) was dissolved in water (10mL), and the mixture was slowly added dropwise to the reaction mixture, and stirring was continued for 0.5 h. Metamethoxyphenol (0.8g, 6.4mmol), sodium hydroxide (0.51g, 12.8mmol), and sodium carbonate (0.61g, 5.8mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution while maintaining the solution temperature at not higher than 5 ℃. After stirring for an additional 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was purified by column chromatography (n-Hex/EtOAc (v/v) ═ 2:1) and recrystallised from methanol to give the title compound as a dark red solid (0.5g, 28%).

LC-MS(ESI,pos.ion)m/z：613[M+H]⁺；

¹H NMR(400MHz，CDCl₃))δ(ppm):7.87-7.85(d,4H)，7.68-7.66(d,2H)，7.03-7.01(d,2H)，6.57(s,2H)，6.49-6.46(t,4H)，6.20(s,1H)，5.65(s,1H)，5.60-5.59(m,1H)，4.39-4.38(d,4H)，3.97(s,6H)，1.98(s,3H)。

EXAMPLE 5 preparation of azo Compound

The preparation of the azo compound 1, 3-bis (4- (2',4' -dihydroxyazobenzene) oxy) -2-propyl acrylate (formula below) is described below according to the synthetic route:

(1) preparation of 1, 3-bis (4-aminophenoxy) -2-propyl acrylate

To a single-neck flask were added 1, 3-bis (4- ((tert-butoxycarbonyl) amino) phenoxy) -2-propanol (5.0g, 10.4mmol), triethylamine (4.5g, 44.6mmol), 4-dimethylaminopyridine (0.26g, 2.1mmol) and tetrahydrofuran (70mL) in this order, and after sufficient dissolution, acryloyl chloride (4.2g, 46.6mmol) was slowly added dropwise thereto, and the reaction was continued with stirring. After 24h, the tetrahydrofuran was removed by rotary evaporation, the mixture was dissolved in dichloromethane (50mL), and trifluoroacetic acid (30mL) was added to react at room temperature for 1 hour. After the reaction was complete, the reaction was diluted with dichloromethane (200mL) and neutralized with aqueous sodium bicarbonate, after which the organic phase was dried over anhydrous sodium sulfate for 2h, filtered, the solvent removed by rotary evaporation, and the product was purified by column chromatography (n-Hex/EtOAc1:1) to afford 2.0g of a pale yellow viscous liquid in 60% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：329[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ(ppm)：6.80-6.78(d,4H)，6.66-6.64(d,4H)，6.50-6.45(t,1H)，6.23-6.20(t,1H)，5.90-5.87(t,1H)，5.54-5.49(m,1H)，4.23-4.21(m,4H)，3.46(s,4H)。

(2) preparation of 1, 3-bis (4- (2',4' -dihydroxyazobenzene) oxy) -2-propyl acrylate

A three-necked flask was charged with a mixed solution (20mL) of 1, 3-bis (4-aminophenoxy) -2-propyl acrylate (2.0g, 6.1mmol) obtained in step (1), potassium bromide (6.2g, 52.1mmol), concentrated hydrochloric acid (5.1g, 50.3mmol) and acetone/water (volume ratio 1:1) in this order, the mixed solution was stirred in a low temperature bath at-5 ℃ C, when the internal temperature reached 0 ℃ or less, sodium nitrite (0.98g, 14.2mmol) was dissolved in water (10mL), and slowly added dropwise to the reaction mixture, and stirring was continued for 0.5 h. Resorcinol (1.7g, 15.5mmol), sodium hydroxide (1.3g, 32.5mmol) were dissolved in water (20mL) and added dropwise to the above diazonium solution, maintaining the solution temperature not higher than 5 ℃ during the addition. After stirring for a further 0.5h the reaction was filtered and the filter cake was washed with water (100mL) and the collected solid was purified by column chromatography (n-Hex/EtOAc (v/v) ═ 3:1) and recrystallised from methanol to give the azo compound as a dark red solid 0.3g with 8.6% yield. Mass and nuclear magnetic resonance H spectral data are as follows:

LC-MS(ESI,pos.ion)m/z：571[M+H]⁺；

¹H NMR(400MHz，DMSO-d₆)δ(ppm)：12.29(s,2H)，10.44(s,2H)，7.86-7.84(d,4H)，7.66-7.63(d,2H)，7.17-7.15(d,4H)，6.50-6.47(t,2H)，6.42-6.38(d,1H)，6.35-6.34(d,2H)，6.28-6.22(m,1H)，6.02-6.00(d,1H)，5.63-5.58(m,1H)，4.48-4.42(m,4H)。

example 6 preparation of Polymer A-1

0.3500g of acrylic acid-2-phenylethyl ester, 0.2500g of methacrylic acid-2-phenylethyl ester, 0.3500g of ethoxyethyl methacrylate, 0.0350g of 1, 4-butanediol diacrylate, 0.0100g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 0.0200g of bis (4-tert-butylcyclohexyl) peroxydicarbonate and 0.0100g of the azo compound prepared in example 1 are mixed uniformly, then transferred into a mold consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, the mold is put into an oven with the temperature of 60 ℃ for reaction for 3 hours, the temperature of the oven is raised to 100 ℃ and kept for 3 hours to obtain a transparent elastic polymer, and the obtained material is subjected to reflux cleaning by absolute ethyl alcohol to remove residual raw materials, vacuum drying at 60 deg.C for 24 hr.

Example 7 preparation of Polymer A-2

0.3500g of acrylic acid-2-phenylethyl ester, 0.2500g of methacrylic acid-2-phenylethyl ester, 0.3500g of ethoxyethyl methacrylate, 0.0350g of 1, 4-butanediol diacrylate, 0.0100g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 0.0200g of bis (4-tert-butylcyclohexyl) peroxydicarbonate and 0.0015g of the azo compound prepared in example 2 are mixed uniformly, then the mixture is transferred into a mold consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, the mold is put into an oven with the temperature of 60 ℃ for reaction for 3 hours, the temperature of the oven is raised to 100 ℃ and kept for 3 hours to obtain a transparent elastic polymer, and the obtained material is subjected to reflux cleaning by absolute ethyl alcohol to remove residual raw materials, vacuum drying at 60 deg.C for 24 hr.

Example 8 preparation of Polymer A-3

0.3500g of acrylic acid-2-phenylethyl ester, 0.2500g of methacrylic acid-2-phenylethyl ester, 0.3500g of ethoxyethyl methacrylate, 0.0350g of 1, 4-butanediol diacrylate, 0.0100g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 0.0200g of bis (4-tert-butylcyclohexyl) peroxydicarbonate and 0.0015g of the azo compound prepared in example 5 are mixed uniformly, then the mixture is transferred into a mold consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, the mold is put into an oven with the temperature of 60 ℃ for reaction for 3 hours, the temperature of the oven is raised to 100 ℃ and kept for 3 hours to obtain a transparent elastic polymer, and the obtained material is subjected to reflux cleaning by absolute ethyl alcohol to remove residual raw materials, vacuum drying at 60 deg.C for 24 hr.

Comparative example 1: preparation of Polymer A-0

0.3500g of acrylic acid-2-phenylethyl ester, 0.2500g of methacrylic acid-2-phenylethyl ester, 0.3500g of ethoxyethyl methacrylate, 0.0350g of 1, 4-butanediol diacrylate, 0.0100g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole and 0.0200g of bis (4-tert-butylcyclohexyl) peroxydicarbonate are uniformly mixed, then the mixture is transferred into a die consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, the die is put into an oven with the temperature of 60 ℃ for reaction for 3 hours, the temperature of the oven is raised to 100 ℃ and the temperature is kept for 3 hours to obtain a transparent elastic polymer, the obtained material is subjected to reflux cleaning by absolute ethyl alcohol to remove residual raw materials, vacuum drying at 60 deg.C for 24 hr.

Example 9 preparation of Polymer B-1

0.6500g of 2-phenylethyl acrylate, 0.3000g of 2-phenylethyl methacrylate, 0.0500g of 1, 4-butanediol diacrylate, 0.0180g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 0.0180g of bis (4-tert-butylcyclohexyl) peroxydicarbonate and 0.0015g of the azo compound prepared in example 3 were mixed uniformly, then transferring the mixture into a mold consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, putting the mold into a drying oven with the temperature of 60 ℃ for reaction for 3 hours, the postoven was raised to 100 ℃ and held for 3 hours to give a transparent elastic polymer, the material was washed with absolute ethanol under reflux to remove residual material and dried under vacuum at 60 ℃ for 24 hours.

EXAMPLE 10 preparation of Polymer B-2

0.6500g of 2-phenylethyl acrylate, 0.3000g of 2-phenylethyl methacrylate, 0.0500g of 1, 4-butanediol diacrylate, 0.0180g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole, 0.0180g of bis (4-tert-butylcyclohexyl) peroxydicarbonate and 0.0015g of the azo compound prepared in example 4 were mixed uniformly, then transferring the mixture into a mold consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, putting the mold into a drying oven with the temperature of 60 ℃ for reaction for 3 hours, the postoven was raised to 100 ℃ and held for 3 hours to give a transparent elastic polymer, the material was washed with absolute ethanol under reflux to remove residual material and dried under vacuum at 60 ℃ for 24 hours.

Comparative example 2: preparation of Polymer B-0

0.6500g of acrylic acid-2-phenylethyl ester, 0.3000g of methacrylic acid-2-phenylethyl ester, 0.0500g of 1, 4-butanediol diacrylate, 0.0180g of 2- (2' -hydroxy-3 ' -methallyl-5 ' -methylphenyl) benzotriazole and 0.0180g of bis (4-tert-butylcyclohexyl) peroxydicarbonate are uniformly mixed, then the mixture is transferred to a mould consisting of two layers of glass and a polytetrafluoroethylene sheet with the thickness of 0.4mm, the mould is placed in an oven with the temperature of 60 ℃ for reaction for 3 hours, the temperature of the oven is raised to 100 ℃ and the mould is kept for 3 hours to obtain a transparent and elastic polymer, the obtained material is cleaned by refluxing of absolute ethyl alcohol to remove residual raw materials, and the obtained material is dried in vacuum at the temperature of 60 ℃ for 24 hours.

Measurement of spectral transmittance

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

(2) And (3) testing results: FIGS. 1-7 show the spectral transmittance results for the polymers prepared in examples 6-10 and comparative examples 1 and 2. As can be seen from the figure, comparative example materials A-0 and B-0, to which the yellow dye (azo compound) of the present invention was not added, began to have a strong transmittance at 400nm and hardly absorbed blue light. The polymers A-1 to A-3, B-1 and B-2 added with yellow dye can obviously reduce the spectral transmission at the wavelength of 400-550 nm.

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

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

Claims (14)

1. An azo compound, which is a compound represented by formula (I) or a stereoisomer or tautomer of a compound represented by formula (I):

wherein the content of the first and second substances,

R¹is H or alkyl;

R²、R³、R⁴and R⁵Each independently is alkyl, alkoxy, F, Cl, Br, hydroxyl, phenoxy, benzyloxy, sulfonic group, CN, NO₂Or COOR⁷(ii) a Wherein each R⁷Independently is H or C_1-4An alkyl group;

m and n are each independently 0, 1,2,3 or 4;

p and q are each independently 0, 1,2,3,4 or 5,

the alkyl group contains 1 to 12 carbon atoms and the alkoxy group contains 1 to 12 carbon atoms.

2. The azo compound of claim 1, wherein R is¹Is H or methyl.

3. The azo compound of claim 1, wherein R is²、R³、R⁴And R⁵Are each independently C_1-6Alkyl radical, C_1-6Alkoxy, hydroxy, CN, NO₂F, Cl or Br.

4. The azo compound of claim 3, wherein R is²、R³、R⁴And R⁵Are each independently C_1-4Alkyl radical, C_1-4Alkoxy, hydroxy, NO₂F or Cl.

5. The azo compound of claim 4, wherein R is²、R³、R⁴And R⁵Each independently is a methyl group, a hydroxyl group, a fluorine atom or a methoxy group.

6. The azo compound of claim 1, wherein R is¹Is H or methyl, m and n are 0, p and q are each independently 0 or 1 or 2, R⁴And R⁵Each independently is hydroxyl, methyl, fluorine atom or methoxy;

or, said R¹Is H or methyl, m and n are 1, R²Is methyl, methoxy or hydroxy, the R³And R²P and q are each independently 0 or 1, and R⁴And R⁵Each independently is a hydroxyl group, a methyl group, a fluorine atom or a methoxy group.

7. The azo compound of claim 1, wherein the azo compound is a compound represented by the formula:

8. a polymer, characterized in that the monomers constituting the polymer comprise a bulk monomer and a blue light absorber, wherein the blue light absorber is the azo compound of any one of claims 1 to 7.

9. The polymer of claim 8, wherein the bulk monomer comprises at least one of a (meth) acrylate monomer, a vinyl monomer, and an allyl monomer.

10. The polymer of claim 8, wherein the polymer further comprises at least one of a crosslinking agent, an ultraviolet absorber, and an initiator.

11. An ophthalmic medical device comprising the polymer of any one of claims 8-10.

12. The ocular medical device of claim 11 wherein the ocular medical device is an intraocular lens, contact lens, corneal modifier, intracorneal lens, corneal inlay, corneal ring, or glaucoma filter.

13. A method of making the polymer of any of claims 8-10, comprising:

subjecting the raw mixture to a gradient heating treatment so as to obtain said polymer,

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

14. The method of claim 13, wherein the gradient heat treatment comprises:

a first reaction stage, wherein the temperature of the first reaction stage is 40-70 ℃, and the reaction time is 1-24 hours; and

and in the second reaction stage, the temperature of the second reaction stage is 80-120 ℃, and the reaction time is 1-24 hours.

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