TW200934458A - Polymerizable water-soluble or alcohol-soluble UV-light absorbent - Google Patents

Abstract

The present invention relates to a polymerable water-soluble or alcohol-soluble UV-light absorbent, which is represented by the following formula (I): wherein R1 is H or C1 to 5 alkyl; R2 is H, Cl, Br or I; R3 is H or methyl; and m is an integer in the range of from 3 to 12. The above-mentioned compounds are suitable for copolymerization with one or more monomers so that the UV-light resistance of the copolymer can be efficiently promoted. For example, the polymer made by copolymerizing the above-mentioned compound with acrylate monomers could be applied in production of optical medical material, especially in contact lenses or intraocularlenses.

Description

200934458 IX. Description of the Invention: [Technical Field of the Invention] 5 10 15 ❹ 20 The present invention relates to a novel polymerizable water-soluble or alcohol-soluble ultraviolet light absorber. The present invention discloses a novel chemical thereof and a method for producing the same Its application in optical medical materials. [Prior Art] Most of the ultraviolet light in the dawn is irradiated to the surface of the earth with radiant energy having a wavelength between 290 nm and 400 nm. Ultraviolet light with a short wavelength below 175 nm is absorbed by oxygen at about 1 km latitude, while ultraviolet rays with radiation between 175 11111 and 29 〇 nm are absorbed by the ozone layer at about 15 km above sea level. It is well known that exposure to ultraviolet radiation not only damages the skin, but also causes corneal damage and visual symptoms, and is one of the main causes of cataract formation. Therefore, how to provide adequate visual protection against UV radiation, reduce the chance of cataract incidence, and protect people who are particularly vulnerable to UV rays, such as patients undergoing eye surgery or patients sensitive to light, is a matter of concern. . In general, the addition of UV absorbers in contact lenses or general glasses can reduce the harmful effects of UV radiation by absorbing UV light between 290 nm and 400 nm, which not only protects the vision system but also reduces cataracts. Incidence rate opportunities. So far, many different types of UV absorbers have been developed and effectively used in contact lens or general eyeglasses. However, it is generally preferred to prevent the UV absorber from being lost by the lens in different environments. The lens material is grafted or copolymerized with the polymerizable UV absorber of 200934458. For example, U.S. Patent No. 4,304,895, the disclosure of which is incorporated herein by reference in its entire entire entire entire entire disclosure

©5 Although the above-mentioned reactive benzophenone-based ultraviolet absorber can participate in polymerization, the UV absorber of this type is less stable. When applied to a lens, the anti-ultraviolet properties of this type of absorbent are often slowly diminished due to the period of use and shelf life of the lens. At the same time, the above-mentioned ultraviolet absorber is water-repellent' insoluble in the hydrophilic acrylic comonomer and copolymer. Even though these compounds are slightly soluble in hydrophilic comonomers and copolymers, when the copolymers hydrate, they tend to condense from microphase separation. This agglomeration causes the material to become foggy, destroying the transparency of the material. In addition, the reactive ultraviolet light absorber disclosed in U.S. Patent No. 4,528,311, the following formula:

200934458 The above-mentioned benzotriazole type ultraviolet absorber is polymerizable and has good stability, but the compound still tends to be hydrophobic, and the hydrophobic property will cause microphase separation and haze formation. The ultraviolet light absorber disclosed in U.S. Patent No. 6,036,891, makes the use of the new compound 2-( 2'-hydroxy-5'-hydroxyethoxyethylphenyl)-2H-benzotriene (2). - (2,-hydroxy-55-hydroxyethoxyethylphenyl) -2H-benzotriazole reacts with methacryloyl chloride to produce a mono-ester compound, as follows:

10 However, the above patent specification does not mention how to obtain the new compound 2-(2'-hydroxy-5'-hydroxyethoxyethylphenyl)-2H-benzotriazole, nor does it provide the synthesis of key raw materials. The method should be a major defect of the invention patent, and at the same time, the obtained reactive ultraviolet light absorber has higher hydrophilicity than the absorbent developed by the prior art, but its water solubility is still low. The ultraviolet light absorber provided by Japanese Patent JP3655061 is as follows:

CH2CH2—C_OCH2CH2—0-C—c=ch2 o ch3 also suffers from the problem that water solubility is still low. Hydrophilic and water-soluble or alcohol-soluble are different properties. Since the contact lens material must be hydrophilic, the lens can follow the eyeball, and the function of correcting vision can be improved, and hydrophilicity can increase comfort. Due to the importance of the hydrophilicity of contact lenses or artificial crystals, the raw materials for the manufacture of lenses must be hydrophilic. After synthesis, a small amount of non-polymerized components must be washed away to ensure no toxicity. In general, in the manufacturing process 5, a large amount of solvent must be used to wash away the remaining unreacted monomers, which is time consuming and laborious. Will increase costs. If a water-soluble or alcohol-soluble component is used for the reaction, not only will the material be produced after the polymerization, but no volatile organic compounds (v〇c) ® will be emitted when the remaining unreacted monomers are washed away. And environmental issues can also reduce production costs. 10 Our novel invention Π) The polymerizable UV absorber belongs to the class of double Sb (di-ester) compounds, and has excellent water solubility or alcohol solubility, and hydrophilic or water soluble monomers. By carrying out the reaction, it is possible to stably produce a copolymerized product which is excellent in transparency and good in transparency. 15

SUMMARY OF THE INVENTION The present invention provides a novel polymerizable water-soluble or alcohol-soluble ultraviolet light absorber which is represented by the following formula (1):

.〇-fCH2CH2〇VC-C=CH2 (I), gas, bromine or dish wherein Ri is hydrogen or C^-Cs alkyl, r2 is hydrogen I is hydrogen or methyl, and ^ is 3~12. The present invention also provides a copolymer obtained by polymerizing a compound represented by the formula (1) with a hydrophilic or water-soluble monomer (4). The copolymer thus obtained, 8 20 200934458*, is optically and transparent polymer and can be used in the manufacture of optical medical materials such as contact lenses or artificial crystals and the like. [Embodiment] The novel polymerizable water-soluble ultraviolet light absorber provided by the present invention is represented by the following formula (I):

Wherein R! is hydrogen or (VC5 alkyl, R2 is hydrogen, gas, bromine or iodine, R3 is hydrogen or methyl, and m is 3 to 12. 10) The preparation method of the compound of the above formula (I) is as follows By a compound of the following formula (II),

HO

Ri

CH2CH2COOH (II) reacts with polyethylene glycol (PEG; polyethylene glycol) of formula (III),

OH (III) 15 to obtain a compound of formula (IV),

HO

0-fCH2CH2〇VH 9 (IV) 200934458 Further reacting a compound of formula (IV) with an acrylic compound of formula (V),

A compound of formula (I) is obtained. Wherein the ruler is as defined above, and X is 3-12. Or, the method for preparing the compound of the above formula (I) is also via a compound of the following formula (II)

Reacting with a compound of the following formula (VI),

(VI) 10 gives the compound of the formula (1). Wherein, Ri, R2, and R3 are as defined above, and n is 3 to 12% by weight. • The water-soluble compound of the above formula (I) of the present invention also has excellent alcohol-soluble, and is suitable for use in the manufacture. Hydrophilic contact lenses or artificial crystals. 15 The compound of the formula (I) in the present invention is preferably, for example, as follows: HO R,

(I), 200934458 Compound (I)-a: ReH, R2=H, R3=H, m=6-8; Compound (I)-b. Ri=H, R2=H, R3=CH3, m=9 -ll; Compound (I)-c: R^H, R2=H, R3=CH3, m=5_7; Compound (I)-d: Κ((:Η3)3, R2=H, R3=CH3,m 5 ❹ 10 15 Compound (I)-e : Κ((:Η3)3, R2=H, R3=CH3, m=3-5. The present invention also provides a copolymer of the formula (I) The compound is formed by polymerization with a hydrophilic or water-soluble monomer. The thus obtained hydrophilic polymer having good transparency and transparency can be used for the manufacture of contact lenses or artificial crystals, and can simplify the subsequent unreacted single. The extra-equivalent step of the body. Suitable hydrophilic materials comprise so-called hydrogels or silicone hydrogels. The compounds of the formula (I) according to the invention and hydrophilic or water-soluble monomers The polymerization carried out can be carried out by any known method. The processes and conditions are carried out in a manner that is familiar to the artist. It is possible to add other additives to the desired reaction as appropriate. Additives include, but are not limited to, crosslinkers , surfactant, diluent, stabilizer, photoinitiator, dyeing ❹ For the convenience of further explanation of the first description of the body. The following examples will be described as more 20, but the person can be light unless otherwise stated. The invention is further described in detail below with reference to the following examples, which are not intended to limit the scope of the invention, and any material changes that are readily available to the skilled artisan are included in the embodiments of the invention. The percentages used are in degrees Celsius °c. 11 200934458 The structure of the compounds mentioned in the examples is as follows:

0

II 0-fCH2CH2〇Vc-c=CH2 (I), 4 Compound (I)-a : Ri=H, R2=H, R3=H, m=6-8; Compound (I)-b : R^H , R2=H, R3=CH3, m=9-ll; Compound (I)-c: Ri=H, R2=H, R3=CH3, m=5-7; Compound (I)-d: Ι^= (:((:Η3)3, R2=H, R3=CH3, m=5-7; Compound (I)-e: , R2=H, R3=CH3, m=3-5.

Ch2ch2cooh ( n ) Formula (11)-1 : Ι^=Η, R2=H ; Formula (11)-2 : Κ((:Η3)3, R2=H ;

〇a}〇H, n=6-8, purchased from Aldrich PR 15 PEG360MA:

, n=5-7, purchased from Aldrich Public 12 200934458 ο ΌΗ η=9-11, purchased from Aldrich

II h2c=c " PEG526MA : CH3 Company; Η, PEG200:

, CT /〇Η χ , χ = 3-5, purchased from Fluka Company Example 1 Preparation of Compound (I)-a @ 20 grams of the compound of formula (11)-1, 26.8 grams? £〇375 per person, 2.7 g of p-Toluenesulfonic acid and 100 g of toluene were placed in a 1 liter four-neck reaction flask; the reaction flask was equipped with a thermometer and a distilled water removal device, respectively. The reaction flask was stirred and heated to 112 ° C on a stirring heater. After collecting about 1 ml of water in a steaming 10 water removal apparatus, the reaction was observed by TLC. After cooling to 90 ° C, the temperature was slowly added. 100 ml of 1N aqueous solution of sodium hydrogencarbonate (NaHC03) was stirred for 15 minutes. The mixed solution was poured into an extraction flask and allowed to stand for separation. The lower aqueous solution was poured into a waste liquid tank, and then 100 ml of IN NaHC03 aqueous solution was added and poured into an extraction flask. The layer was allowed to stand, and the lower layer of water was discarded, and the organic layer was concentrated to give 45 g of crude product (I)-a. Purification of Compound (1)-a Approximately 300 g (15 times the amount of the sample) of the column packing (label: Waters; specification: preparative C18 125A) was uniformly stirred and mixed with 450 ml of decyl alcohol, and then slowly poured into the column. (Position: Pyrex; Specification: 25G3) 20 Filling is carried out. After the filling in the column is compacted, the methanol is replaced with an equal amount of deionized water, and then the dying solution (methanol: water) is continued at 2 liters. =1 : 1) After the replacement, weigh about 20 grams of crude product (1)-a and slowly pour it into the column. 13 200934458 5 ❹ 10 15 ❹ First rushing the bank with about 2 liters (methanol: water = i: 丨After scouring and collecting in an amount of 2 ml per bottle, the dyke solution of methanol: water = 7:3 was used to continue charging & collected and sampled for analysis by HPLC, and about 4 liters were collected and purity was started. The higher target product appeared, and the reverse TLC sheet (Merck RP-18 hwS) was used to judge the end point of the embankment. After the test result was completed, the sample which was concentrated to meet the product specifications was obtained, that is, a target product with a brown oil shape was obtained. . Compound (I)-a 囷 spectrum ^NMRCCDCls): δ: 11.18 (8,1 Η), 8.26 (S, 1H), 7.90 (q, 2H), 7.50 (q, 2H), 7.20 (d, 1H) ' 7.12 (d,1H) ' 6.41 (m,1H),6·15 (% 1H),5.82 (m, 1H) M.25(m,4H) *3.63(m,24H) >2.99(t,2H) * 2.68 (t, 2H). Examples 2 to 4 The synthesis and purification steps of Example 1 were repeated, and the preparation of the compound (I)-c and the compound (I)-d was carried out, and the relevant materials were reacted using the materials shown in Table 1. Table I

Preparation of raw material and raw material 2 Example 2 Compound (1)-b (ΪΪΗ PEG526MA Example 3 Compound (1)-C aipr-PEG360MA Example 4 Compound (1)-d (ΪΙΓ2~~ PEG360MA 20 200934458 The obtained finished compound (I)-b, compound (I)-c, and the compound (I)-d related 1H NMR spectrum are as follows. Compound (I)-b map! H NMR (CDC13): 5 δ : 11.19 ( s, 1H), 8.26 (s, lH), 7.93(q,2H), 7.52( q,2H), 7.21 ( d,1H), 7.12( d,1H), 6.12( s,1H), 5.56 (s,lH) > 4.26 ( m, 4H ), 3.63 (m, 36H), 3.00 (t, 2H), 2.69 (t, 2H), 1.94 (s, 3H) φ Compound (I)-c spectrum 10 XH NMR (CDCI3): δ: 11.17 ( s, 1H ), 8.24 (s, lH), 7.91 (q, 2H), 7.47 (q, 2H), 7.20 (d, 1H), 7.11 (d, 1H), 6.12 (s, 1H), 5.56 (s, lH) , 4.26 (m, 4H), 3.63 (m, 20H), 3. 〇〇 (t, 2H), 2.69 (t, 2H), 1.89 (s, 3H). 15 Compound (I)-d map! H NMR (CDCI3): δ : 11.81 ( s, 1H) , 8.14 (s, lH) , 7.92 (q, 2H), o ^ 7.47 ( q, 2H), 7.20 ( s, 1H), 6.12 ( s, 1H), 5.57( s,1H), 4.28 (m 4H), 3.64 (m, 20H), 3.00 (t, 2H), 2.73 (t, 2 〇 2H), 1.94 (s, 3H), 1.50 (s, 9H). Example 5 Compound (I)-e Preparation 100 grams of the compound of formula (11)-2, 590 grams of PEG200, 5.6 grams of p-butanol acid (PTSA) and 500 ml of toluene were placed in a 1 liter four-neck reaction flask; The thermometer and the distillation water removal device were installed. The reaction flask was stirred and heated to 112 ° C on a stirring heater, and about 5 ml of water was collected in a distillation water removal device, and the reaction was completely observed by TLC, and the temperature was lowered to 90 ° C. After that, slowly add 468 ml of aqueous solution at a constant temperature for 15 minutes, pour the mixed solution into the extraction flask and let it stand. Pour the lower aqueous solution into the waste liquid tank, and then add 400 ml of the aqueous solution and pour it into the extraction bottle. The layers were separated, the lower aqueous solution was discarded, and the organic layer was concentrated to give 162 g. 28.8 g of the above product, 8.8 g of Methacrylic 0 acid., 0.98 g of p-toluenesulfonic acid (PTSA) and 200 ml of stupid were placed in a 1 liter, four-liter four-neck reaction flask; It is equipped with a thermometer and a distilled water removal device. After the reaction flask was stirred and heated to 112 ° C on a stirring heater, the water was collected in a distillation water removal device to obtain about 0.8 ml of water, and the reaction was observed by TLC. After the reaction was completed, the temperature was lowered to 90 ° C, and the temperature was maintained. Slowly add 200 ml of 1N aqueous solution of sodium bicarbonate (NaHC03) and stir for 15 minutes. Pour the mixed solution into the extraction flask and let it stand. Pour the lower aqueous solution into the waste tank, then add 200 ml of 1N sodium bicarbonate. The aqueous solution was poured into an extraction flask and allowed to stand for separation. The lower aqueous solution was discarded, and the organic layer was collected to give 18 g of crude product (I)-e. Purification of Compound (I)-e 20 Approximately 225 grams (15 times the amount of sample) of the column packing (label:

Waters;Specification: preparative C18 125A) After mixing with 225 ml of sterol, mix slowly and slowly into the column (label: Pyrex; size: 25G3) for filling, after the packed material in the column is compacted The methanol was replaced with an equal amount of deionized water, and then replaced with 1 liter of methanol: water = 9:1 dyke 16 200934458 liquid, then the crude product (I)-e was slowly poured into about 17 grams. In the column, the levee solution of about 1 liter of methanol:water=9:1 is firstly collected and collected in an amount of 200 ml per bottle. Then, 1 liter of each bottle is continuously extracted and collected and sampled by HPLC. Analysis: After about 2 liters of collection, the target product with higher purity began to appear, and the reverse TLC sheet (Merck RP-18 F254S) was used to judge the end point of the bank. After the HPLC test result was completed, the sample was concentrated to meet the product specifications. 'I get a target product that looks like a brown oil. Compound (I)-e 4 NMR spectrum Q !H NMR (CDC13): 10 δ : U.81 ( s, 1H) ' 8.14 ( s, 1H), 7.92 ( q, 2H), 7.47 (q, 2H), 7_20(s,1H), 6.11( s,1H), 5.56( s,1H), 4.26 ( m, 4H), 3.63 ( m,12H), 3.00 ( t,2H), 2.74 ( t, 2H), 1.93 ( s, 3H), 1.50 ( s, 9H). 15 Example 6 Solubility test Commercially available Benzotriazole A [phenylpropionic acid, 3-( 2H-benzox 2 oxa-2-yl)-5-(1,1-didecylethyl)-4 was used in the experiment. -trans-based, 2-[(2-methyl-1_drum-2-ylpropanyl)oxy]ethyl ester; Benzenepropanoic acid, 3-20 ( 2H-benzotriazol-2-yl )-5-( 1,1-dimethylethyl )-4-hydroxy-, 2-[(2-methyl-l-oxo-2-propenyl) oxy]ethylester] with compound (I)-a, compound (I)-b, compound (I -c, compound (1)_(i and compound (i)_e, solubility test with 40% isopropanol (IPA) / 60% water alcohol water system. Test method 17 200934458 in 40% isopropanol (IPA) aqueous solution For the solubility measurement, the instrument components are as follows: Waters 717autersampler, Waters 996 PDA (photodiode array detecter), Waters 600 pump, set injection volume 20//L, analytical column: phenamex Luna Cl 8, flow rate lmL/min , 5 The mobile phase is cyanocane. In the calibration line production, the sample was prepared as a 1023 mg/L 40% IPA aqueous solution and diluted to 512.5 mg/L and 102.5 mg/L by serial dilution. With area to concentration To determine the solubility of the sample under the 40% IPA aqueous solution, firstly prepare the sample to be a saturated solution at 40% IPA at room temperature, and then dilute the sample to make the absorption peak area of the analysis result of 10 Within the calibration range, the true concentration was pushed back by the calibration curve. The results are shown in Fig. 1. As shown in Fig. 1, the solubility test was carried out with a 40% IPA/60% water alcohol water system, and the results showed the compound of the present invention. The solubility tests of (I)-a, compound (I)-b, compound (I)-c, compound (I)-d and compound (I)-e were all superior to those of Benzotriazole A, which was previously marketed. Example 7 The percentage of raw materials and composition used in the experimental experiment is shown in Table 2: 20 Table 1 * Formulation HEMA EGDMA 1907 ΤΡΟ RUVA 1 97.3 1.98 0.33 0.17 2 97.3 1.98 0.33 0.17 0.5 HEMA : methyl procyanoic acid 2. Ethyl vinegar (2,hyHroxyethyl methacrylate) EGDMA : ethylene glycol dimethacrylate 1907 : Irgacure 907 in Ciba company 18 200934458 ΤΡΟ : Darocur TPO purchased from Ciba company RUVA : compound (I) -e

A hydrogel film was synthesized in the ratio of the respective components of the polymerizable mixture in Table 2. The film thickness was between 0.18 mm and 0.20 mm. The transmission spectrum of the film can be measured by a UV spectrophotomer, and each UV map (UV sepctrum) is shown in Fig. 2. Among them, the solid line (1) is the formula 1 * the dotted line (-) is the formula 2. In the application experiment results, the ultraviolet-transmission map of the present invention shows that the novel polymerizable water-soluble or alcohol-soluble ultraviolet light absorber monomer of the present invention has excellent ultraviolet light shielding effect in contact lenses. In summary, the present invention can indeed achieve the purpose of the invention through the disclosed technical ideas, and is novel, progressive and available for industrial use, and is in conformity with the patent requirements of the invention 15 . It is to be understood that the above-described embodiments, which are susceptible to variations and modifications, are derived from the technical idea of the present invention and are readily inferred by those skilled in the art. The above-described embodiments are merely examples for the convenience of the description, and the scope of the claims is intended to be limited to the above embodiments. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a commercially available Benzotriazole A and a compound (I)-a, a compound (I)-b, a compound (I)-c, and a compound (I:) in the sixth embodiment of the present invention. d and the results of the compound 25 (I)-e resolution test. 19 200934458 # Figure 2 is a UV-transfer map of Formulation 1 containing no compound of the present invention, and Formulation 2 containing Compound (I)-e of the present invention, in Example 7 of the present invention. [Main component symbol description] 5 None 〇 20

Claims (1)

200934458 X. Patent application scope: ^ A polymerizable water-soluble or alcohol-soluble ultraviolet light absorber monomer' is as shown in formula (I): 5 wherein ' Ri is hydrogen or CVC5 alkyl, r2 is hydrogen, gas, bromine, or iodine, 〇 R3 is hydrogen or methyl, and m is 3 to 12. 2. The ultraviolet light absorber monomer according to claim 1, wherein the formula (I) is HO CH2, Γ 10 3. The ultraviolet light absorber monomer according to claim 1, wherein formula (I) is 4. The ultraviolet light absorber monomer according to claim 1, wherein the formula (I) is 21 200934458 HO CH2 O o II 0-4CH2CH20^rn-C-C=CH2 CH3 5. A polymer having ultraviolet light absorbing properties, comprising: a polymerizable monomer, which is represented by the following formula (I): (I) wherein, Ri is hydrogen or CVC5 alkyl, R2 is hydrogen, gas, bromine or iodine, R3 is hydrogen or sulfhydryl, and m is from 3 to 12; and at least one polymerizable comonomer. 6. A process for producing a polymerizable water-soluble ultraviolet light absorber monomer comprising: 10 a compound of the following formula (II), (II) reacting with polyethylene glycol (PEG; polyethylene glycol) of formula (III), Η OH (III) to obtain a compound of formula (IV), 22 (iv) 200934458 Further, a compound of the formula (IV) is reacted with an acrylic compound of the formula (V), 0 II ho-c-c=ch2 R3 (v) to obtain a compound represented by the following formula (I), Wherein Ri is hydrogen or C^-Cs alkyl, R2 is hydrogen, gas, bromine or iodine, R3 is hydrogen or methyl, and X and m are from 3 to 12. 7. A process for producing a polymerizable water-soluble ultraviolet light absorber monomer comprising: 10 a compound of the following formula (II), (Π) reacting with a compound of the following formula (VI), And a compound of the following formula (I) is obtained, 23 (VI) (I) 200934458 Or 峨, wherein Ri is hydrogen or CVCs alkyl, R2 is hydrogen, gas, bromine R3 is hydrogen or methyl, and η, m are from 3 to 12. 8. A contact lens capable of preventing ultraviolet rays, which is produced by dissolving in a hydrophilic material as the monomer described in the first item of Patent Application 5 〇 10 . 9. The contact lens of claim 8, wherein the hydrophilic material comprises a hydrogel or a siiicone hydrogel.可1〇·—A UV-resistant artificial crystal, which is produced by dissolving in a hydrophilic material as the monomer described in the first application of the patent application. The artificial crystal according to the water-supply patent application, wherein the hydrogel or the silicone hydrogel 0 〇 24