Patent Application
20080064880
The invention relates to compounds of the Formula 1:
X—Y-Z Formula 1
wherein Y is an aromatic cyclic structure substituted at least once with OH and optionally with SH, H, C1-22 alkyl, C2-22 alkene, C2-22 alkyne, primary, secondary or tertiary amine, amino, nitro, nitroso, halogen, and at least one of X and Z are a carbon-containing ring structure that may also contain at least one of oxygen, nitrogen and sulfur. Preferably, X and Z are independently selected from H, nitro, nitroso, cyano, halogen, C1-22 alkyl, C1-22 alkoxy, —C(O)R9 wherein R9 is C1-8 alkyl, —O—C—O—R9 wherein R9 is C1-8 alkyl, —COOR10 wherein R10 is H or C1-8 alkyl, —C(O)NR10 wherein R10 is H or C1-8 alkyl, a primary, secondary or tertiary amine, substituted or unsubstituted carbocyclic ring, a substituted or unsubstituted aryl ring, a substituted or unsubstituted heteroaryl ring, a substituted or unsubstituted benzannulated carbocyclic ring, a substituted or unsubstituted benzannulated heterocyclic ring, a substituted or unsubstituted arylannulated carbocyclic ring or a substituted or unsubstituted arylannulated heterocyclic ring. Preferably at least one of X and Z are a substituted or unsubstituted benzoxazole, benzothiazole, or benzimidazole.
The inventive compounds absorb ultraviolet light in the 380 nm to 400 nm range but have less than 10% absorption in the 410-420 nm range.
Preferred compounds include 2-hydroxyphenyl(benzoxazol-2-yl) derivatives of Formula 2 below:
wherein R1, R2, R3 and R4 are independently selected from H, alkyl (C1-C8), alkoxy (C1-C8), acyl (—C(O)R; R=alkyl C1-C8), acetoxy (—OC(O)R; R=alkyl C1-C8), carboxylic acid and esters (—CO2R═H or alkyl of C1-C8), amine (NR2; R═H or alkyl C1-C8), nitro, nitroso, cyano, halogen (Cl, Br, I or F), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, amide (—C(O)NR2 R═H or alkyl C1-C8), or wherein
R1 and R2 or R2 and R3 or R3 and R4 together form a carbocyclic ring, substituted or unsubstituted and fused carbocyclic ring, substituted or unsubstituted benzannulated carbocyclic and substituted or unsubstituted arylannulated carbocyclic; and R5, R6, R7 and R8═H, alkyl (C1-C8), alkoxy (C1-C8), acyl (—C(O)R; R=alkyl C1-C8), acetoxy (—OC(O)R; R=alkyl C1-C8), carboxylic acid and esters (—CO2R═H or alkyl of C1-C8), amine (NR2; R═H or alkyl C1-C8), nitro, nitroso, cyano, halogen (Cl, Br, I or F), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, amide (—C(O)NR2 R═H or alkyl C1-C8), substituted or unsubstituted heterocyclic, substituted or unsubstituted benzannulatedheterocyclic and substituted or unsubstituted arylannulated heterocyclic; or
R5 and R6 or R6 and R7 or R7 and R8 together form a carbocyclic ring, substituted or unsubstituted benzannulated carbocyclic and substituted or unsubstituted arylannulated carbocyclic.
Particularly preferred compounds of the present invention preferably have the Formula 3:
wherein:
X1 and X2 are independently selected from N, S or 0, preferably 0 in some embodiments;
Y is an aromatic carbocyclic or heterocyclic moiety substituted at least once with OH and optionally substituted with, SH, H, C1-22 alkyl, C2-22 alkene, C2-22 alkyne, primary, secondary or tertiary amine, nitro, nitroso, halogen;
R2, R3, R12 and R13 are independently a substituted or unsubstituted, straight or branched C1-22 alkyl, C2-22 alkene, C2-22 alkyne, phenyl, C3-6 cycloalkyl;
wherein R2 and R3 together or R12 and R13 form an aromatic or nonaromatic 1 to 3 ring cyclic structure.
Preferably, Y is further substituted with other groups such as hydrogen, a substituted or unsubstituted, straight or branched C1-22 alkyl, C2-22 alkene, C2-22 alkyne, phenyl, C3-6 cycloalkyl.
Preferably, at least one of the pairs R2 and R3 together or R12 and R13 form
to provide a compound such as that shown in Formula 4:
wherein X is O, N or S; and Z is OH, SH, or NH2. Preferably Z is OH or X is O.
In another preferred embodiment, Y in Formula 3 is
wherein Z1 is OH, primary or secondary amine, or SH.
An example of such a compound is shown in Formula 5 below:
wherein X1 and X2 are independently O, N or S, preferably O in some embodiments, and Z1 is as defined above.
It is preferred that the branched alkyls on the Y group of Formula 3 are C1-C10 alkyls, or more preferably C11-C22 alkyls. The alkyls may be aliphatic or branched, substituted, e.g., with halogen, or unsubstituted. C1 to C3 aliphatic or C3 to C6 branched alkyls are preferred.
It is preferred that the compounds according to the present invention have a UV light absorbance of at least 95% in the 380-405 nm range and also an absorbance of less than 5% in the 410-420 nm range. More preferably, the compounds absorb greater than 95% UV light in the 385-400 range, and more preferably in the 390-405 nm range.
Particularly preferred species are described in the examples.
Optimally, there is no absorbance in the 410-420 nm range, but less than, 10% absorbance is required, less than 5% is preferred, and 1-3% is most preferred.
The UV absorbers of the present invention can be incorporated into or onto any organic glass substrate currently used for organic ophthalmic lenses, including but not limited to thermoplastic lenses. Such incorporation can be done by mixing the UV absorbers with monomers prior to polymerizing them into an organic glass containing the absorber. Alternatively, the UV absorbers may be incorporated into a coating and deposited on a polymerized organic glass.
Polycarbonate (thermoplastic) substrates, in particular the ophthalmic lenses manufactured by the Gentex Optics company, are examples of such substrates. Among other suitable substrates are the substrates obtained by the polymerization of alkyl methacrylates such as methyl (meth)acrylate and ethyl (meth)acrylate, allyl derivatives such as the allyl carbonates of linear or branched aliphatic or aromatic polyols, thio(meth)acrylics, thiourethanes, polyethoxylated aromatic (meth)acrylates such as the polyethoxylated bisphenolate dimethacrylates.
Recommended substrates include substrates obtained by polymerization of the allyl carbonates of polyols such as ethylene glycol bis(allyl carbonate), diethylene glycol bis(2-methyl carbonate), diethylene glycol bis(allyl carbonate), ethylene glycol bis(2-chloroallyl carbonate), triethylene glycol bis(allyl carbonate), 1,3-propanediol bis(allyl carbonate), propylene glycol bis(2-ethylallyl carbonate), 1,3-butenediol bis(allyl carbonate), 1,4-butenediol bis(2-bromoallyl carbonate), dipropylene glycol bis(allyl carbonate), trimethylene glycol bis(2-ethylallyl carbonate), pentamethylene glycol bis(allyl carbonate), isopropylene bisphenol A bis(allyl carbonate).
Some substrates that are particularly recommended are substrates obtained by polymerization of ethylene glycol bis(allyl carbonate), sole under the trade name CR 39® by the company PPG Industries (lens ORMA® ESSILOR).
Among other recommended substrates are substrates obtained by polymerization of thio(meth)acrylic monomers.
The UV absorber/plastic blend will have a UV absorbance of that will be a result of the combination of the absorbance of the UW absorber and any absorbance of the plastic.
The compositions of the present invention may have one or more chiral centers and may have enantiomers and diastereoisomers that are contemplated to be within the scope of the present invention.
In a preferred embodiment, the compounds of the invention are prepared by forming an intermediate compound of Formula 6:
and reacting the formula under suitable conditions and with suitable reagents to form a compound of the formula:
wherein Y and R1—R4 are defined above.
Preferred embodiments of the invention are discussed in detail in the Examples below.
Step 1. Preparation of 2-Methoxy-N,N′-Bis(2-hydroxy-9,9-dipropyl-2-methoxyfluoren-3-yl)-1,4-benzenedicarboxamide
A mixture of methoxyterephthalic acid (1.50 g, 7.65 mmol), thionyl chloride (1.23 mL, 2.00 g, 16.8 mmol) and N-methylpyrrolidine (1.0 mL) in tetrahydrofuran (50.0 mL) was heated under reflux for 5 hours to form methoxyterephthaloyl chloride in-situ. The formed methoxyterephthaloyl chloride solution was cooled and added drop-wise to a solution of 3-amino-9,9-dipropyl-2-hydroxyfluorene (5.00 g, 16.8 mmol), pyridine (2.65 g, 33.6 mmol) and tetrahydrofuran (150 mL) and stirred under nitrogen at room temperature for 18 hours. The resulting mixture was treated with concentrated hydrochloric acid (10.0 mL) and stirred for 15 min. The crude product was collected, washed with water and then slurried with methanol (75.0 mL), stirred for 30 min. and filtered. The collected solid was slurried for 30 min. with a mixture of methanol (100 mL) and 5% aqueous sodium bicarbonate (50.0 mL). The filtered solid was slurrried once more, for a further 30 min. with methanol (100 mL), collected, washed with methanol and dried to yield 2-methoxy-N,N′-bis(2-hydroxy-9,9-dipropyl-2-methoxyfluoren-3-yl)-1,4-benzenedicarboxamide (4.01 g, Yield 69%).
Analytical Results were as follows: Melting point, 262-266° C.
Step 2. Preparation of 1,4-Bis(9,9-dipropyl-9H-fluoreno[3,2-d]oxazol-2-yl)-2-methoxyphenyl.
A magnetically stirred mixture of 2-methoxy-N,N′-bis(2-hydroxy-9,9-dipropyl-2-methoxyfluoren-3-yl)-1,4-benzenedicarboxamide (3.75 g, 4.97 mmol), powdered boric acid (0.1 g), and diethylene glycol dibutyl ether (60.0 mL) under nitrogen was heated to reflux for 45 min. with removal of water. The resulting mixture was then concentrated with removal of solvent (40.0 mL), allowed to cool to below 60° C., poured into hexane (120 mL) and stored for 18 hours at −20° C. The mixture was filtered and dried to yield crude product (2.96 g, yield 85%). Purification by extraction from neutral alumina (3 cm3) with heptane on an Ace-Kauffman column yielded 1,4-bis(9,9-dipropyl-9H-fluoreno[3,2-d]oxazol-2-yl)-2-methoxyphenyl as yellow needles (2.10 g; yield 59%).
Analytical Results were as follows: Melting point 210-213° C.
Step 3. Preparation of 1,4-Bis(9,9-dipropyl -9H-fluoreno[3,2-d]oxazol-2-yl)-2-hydroxyphenyl.
A mixture 1,4-bis(9,9-dipropyl-9H-fluoreno[3,2-d]oxazol-2-yl)-2-methoxyphenyl (1.94 g, 2.70 mmol), anhydrous lithium iodide (0.63 g, 4.72 mmol) and 2,4,6-collidine (30.0 mL) stirred under nitrogen, was heated under reflux for 4 hours. The resulting mixture was poured into water (150 mL), treated with hydrochloric acid (20.0 mL), stirred for 15 min. and filtered. The collected solid crude product was added to 5% sodium bicarbonate (200 mL), stirred, filtered washed with water and dried under vacuum to obtain crude 1,4-bis(9,9-dipropyl-9H-fluoreno[3,2-d]oxazol-2-yl)-2-hydroxyphenyl. Purification by extraction from neutral alumina (2 cm3) on an Ace-Kauffinan column, with toluene (60.0 mL) overnight, concentration of the extract, suspension of the residue in hot heptane, then cooling gave the product as yellow solid, 1.28 g (67%). Further purification by way of soxhlet extraction using ethyl acetate afforded 1,4-bis(9,9-dipropyl-9H-fluoreno[3,2-d]oxazol-2-yl)-2-hydroxyphenyl as a yellow solid (1.15 g yield 60%).
Analytical Results were as follows: M. pt. 330-331.5°.
Step 1. Preparation of 2,7-Dibromo-3-methoxyfluorene.
A stirred solution 3-methoxyfluorene (66.3 g, 0.34 mol) and dichloromethane (650 mL) was treated drop-wise with a portion of a solution of bromine (34.3 mL, 106 g, 0.667 mol) and dichloromethane (34.3 mL) at room temperature to initiate a reaction. The reaction was then cooled to −2° C. and the reminder of the bromine-dichloromethane solution added over 2 hours. The resulting slurry was stirred for a further 30 min. then diluted with methanol (1300 mL) and stored under refrigeration for 3 days. The product was collected, washed with methanol (300 mL) and dried under vacuum to yield crude product (89 g) as an off white solid, m. pt. 169-172° C. Purification by recrystallization (1-butanol) afforded 2,7-dibromo-3-methoxyfluorene (86.4 g, yield 71%).
Analytical Results were as follows: M. pt. 171.5-172.5° C. Analytical Calculation: C, 47.50; H, 2.85; Br, 45.14%. Found: C, 47.75; H, 2.65; Br, 47.00%. 1Hnmr (200 MHz, CDCl3): □=3.78 (2H, sl br s, H9), 4.00 (3H, s, CH3O), 7.49 (1H, dd, J5,6=8.1 Hz, J6,8=1.7 Hz, H6), 7.58 (1H, dd, J5,8=0.5 Hz, H5), 7.64 (1H, dd, J8,9=0.8 Hz, H8), 7.67 (1H, sl br d, J1,9=0.9 Hz, H1).
Step 2. Preparation of 2,7-Dibromo-9,9-dipropyl-3-methoxyfluorene
To a stirred mixture of 2,7-dibromo-3-methoxyfluorene (87.7 g, 0.244 mol), potassium t-butoxide (28 g, 0.25 mol) and dry methyl sulfoxide (500 mL) was added 1-bromopropane (22.6 mL, 0.25 mol) at such a rate as to keep the reaction exotherm temperature below 45° C. A further quantity of potassium t-butoxide (39.0 g; 0.35 mol) and 1-bromopropane (31.6 mL; 0.35 mol) were added. The resulting mixture was stirred at room temperature for 1 hour and treated with 50% methanol/water (500 mL). The purple color was discharged by addition of 6.0M hydrochloric acid (2.0 mL) and the mixture cooled at 0° C. for 1 hour. The crude product was collected and washed with 50% methanol/water (250 mL) and dried to yield crude product (106 g). Purification by extraction from neutral alumina (5 cm3) with hexane on an Ace-Kauffman column with hexane afforded 2,7-dibromo-9,9-dipropyl-3-methoxyfluorene (95 g; m. pt. 127-131.5° C.). Further purification by re-crystallization (2-propanol) gave pure product (84 g, yield 78%).
Analytical Results were as follows: M. pt, 130.5-133.5° C.
Step 3. Preparation of 2,7-Dicyano-9,9-dipropyl-3-methoxyfluorene
A mixture of 2,7-dibromo-9,9-dipropyl-3-methoxyfluorene (83 g, 0.19 mol), and copper(I) cyanide (50 g, 0.56 mol) in anhydrous dimethylformamide (70.0 mL) was stirred under reflux and argon for 18 hours. The reaction was allowed to cool to 90° C. and treated with a solution of potassium cyanide (100 g) in water (350 mL). The resulting mixture was stirred rapidly for a further 4.5 hours. The granular product was collected by filtration, crushed, washed with water and dried. The tan colored solid was extracted from a soxhlet with methylcyclohexane. Cooling and seeding of the methylcyclohexane extract afforded 2,7-dicyano-9,9-dipropyl-3-methoxyfluorene upon filtration (62.6 g; yield 99%).
Analytical Results were as follows: Melting point ° C. 163-167° C. Analytical Calculation: C, 79.97; H, 6.71; N, 8.48. Found: C, 80.33; H, 6.58; N, 8.51%.
Step 4. Preparation of 9,9-Dipropyl-3-methoxyfluorene-2,7-dicarboxylic Acid
To a stirred solution of potassium hydroxide (61 g, 0.95 mol, 87% purity) in water (1400 mL) was added 2,7-dicyano-9,9-dipropyl-3-methoxyfluorene (62.6 g, 0.19 mol) and 1-propanol (350 mL). The mixture was heated under reflux for 70 h and then allowed to cool to room temperature. The mixture was treated with 6.0M HCl (180 mL), stirred for 1 h and the resulting solid collected, washed with water and dried to afford 9,9-dipropyl-3-methoxyfluorene-2,7-dicarboxylic acid (66.5 g; yield 95%).
Analytical Results were as follows: Melting point 282-285° C. dec. Analytical Calculation: C, 71.72; H, 6.57; N, 0.00%. Found: C, 70.81; H, 6.42; N, 0.19%. FTIR (KBr): 3300 br (OH), 3060 br sh, 2930 s, 2875 (Me), 2640 br, 2540 br, 1720 s & 1675 vs (C═O), 1605 (C═C), 1578, 1430 s, 1270 s, 1222 s, 1210 s, 1170 (Ar—O), 1026 (Me—O), 910 w, 840 w, 780 w, 725 w. 1H NMR (60 MHz, 10% in pyridine-d5): 0.75 (1 OH, br s, CH3CH2CH2), 2.1 (4H, br s, CH3CH2CH2), 4.05 (3H, s, OCH3), 7.87 (1H, d, J1-4=2 Hz, H4), 8.15 (1H, d, J5=6=8 Hz, H5), 8.51 (1H, dd, J6-8=3 Hz, H6), 8.70 (2H, br s, H1, H8), 14.29 (2H, s, COOH).
Step 5. Preparation of N,N′-Bis(2-hydroxy-5-methylphenyl)-9,9-dipropyl-3-methoxyfluorene-2,7-dicarboxamide
A solution of 9,9-dipropyl-3-methoxyfluorene-2,7-dicarboxylic acid (43 g, 0.117 mol), thionyl chloride (30.0 mL, 48.9 g, 0.41 mol), p-dioxane (430 mL) and N-methylpyrrolidinone (2.0 mL), under argon, was stirred and heated under reflux for 3 h. Concentration of the reaction mixture by distillation of p-dioxane (50.0 mL) precipitated the diacid dichloride intermediate. The dark diacid dichloride solution, over a period of 20 min., was added to a cooled (0° C.) stirred solution of 2-amino-4-methylphenol (30.8 g, 0.25 mol), anhydrous piperidine (21.0 mL) and p-dioxane (200 mL) under argon. The resulting mixture was stirred at room temperature for 18 h then treated with water (50.0 mL) to dissolve the pyridinium chloride. The mixture was then added to 1.8 L of water, with stirring, to form the crude product as a granular solid, which was collected, washed with 50% methanol/water (500 mL), and dried to afford N,N′-bis(2-hydroxy-5-methylphenyl)-9,9-dipropyl-3-methoxyfluorene-2,7-dicarboxamide (77.2 g).
Analytical Results were as follows: M. pt. 150-170° C. dec.
Step 6. Preparation of 2,7-Bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-methoxyfluorene.
A mixture N,N′-bis(2-hydroxy-5-methylphenyl)-9,9-dipropyl-3-methoxyfluorene-2,7-dicarboxamide (76.7 g, 0.133 mol), powdered boric acid (1.8 g) and (750 mL) stirred under argon was slowly heated to reflux allowing water to be distilled. After cooling overnight the resulting mixture was further distilled to remove diethylene glycol dibutyl ether (600 mL). The residual mixture was added to methanol (500 mL) causing precipitation of crude product. The mixture was diluted with water (100 mL) and cooled to −20° C. for 18 h. The mixture was filtered and the solid washed with methanol to afford crude product (51.4 g; m. pt. 205-230° C.). Purification by soxhlet extraction with hexane yielded 2,7-Bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-methoxyfluorene (34.6 g; yield 48%).
Analytical Results were as follows: M. pt. 240-248° C.
Step 7. Preparation of 2,7-Bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-hydroxyfluorene
A mixture of a solution of 2,7-bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-methoxyfluorene] (34.6 g, 0.0638 mol) and 2,4,6-collidine (250 mL) that was prepared under argon by stirring and heating to 95° C. To this solution, dry lithium iodide (14.9 grams, 0.111 mol) was added and the resulting mixture was heated to reflux for 30 minutes and then allowed to cool to room temperature. The reaction was quenched with a mixture of concentrated HCl (167 mL ), water (300 mL) and ice (500 g). The product was collected and washed with a minimum of water and methanol to afford upon drying crude product (40 g). Purification by extraction from of acidic alumina (3 cm3) on Ace-Kauffman column with methylcyclohexane gave 2,7-bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-hydroxyfluorene (24.93 g, yield 74%).
Analytical Results were as follows: M. pt. 291-293° C. 1H NMR (300 MHz, CDCl3): 0.71 (10H, br s, CH3CH2CH2), 2.1 (4H, br s, CH3CH2CH2), 2.5 (6H, br s, ArCH3), 7.17-8.28 (11H, m, ArH. 13C NMR (300 MHz, CDCl3): 14.80 (CH3CH2CH2), 17.6.9 (CH3CH2CH2), 21.97 (CH3Ar), 43.24 (CH3CH2CH2), 55.61 (ArCAr) and 109.12-163.90 (aromatic C).
Two 1.65 mm polycarbonate test articles (UV400 #1 and UV400 #2) comprising polycarbonate blended with an absorber of the invention were prepared. More specifically polymer blend containing FCR2407 polycarbonate (commercially available from Bayer) and the UV absorber 2,7-Bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-hydroxyfluorene (prepared in as set forth in Example 2) was prepared by admixing the polycarbonate and the UV absorber in a concentration of 0.22% (w/w). Optical flats were prepared by charging an injection molding apparatus with the polymer blend.
The UV400 #1 and UV400 #2 articles exhibited an integrated absorbence of >99.9% between 370-400 nm (99.9% at 400 nm), with a yellow index of 2.7-2.8. These values compared to two control Essilor Tan lens (#1 and #2),. The Essilor Tan lenses are a UV380 product, which as a 1.8 mm flat gave 90-92% absorbance with a yellow index of 2.6-2.8. Generally, a yellow index of 2.6 to 2.8 is an acceptable minimum for commercial products.
Results of the comparison of the articles according to the invention with TAN #1 and TAN #2 are summarized in Tables 1-3 below, and the corresponding figures.
The data in Table 4 show the advantages of FCR2407 polycarbonate commercially available from Bayer doped with 2,7-Bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-hydroxyfluorene of the present invention (UV400 #1) compared to the undoped commercially available polycarbonate, with regard to UV blocking in the 370-400 nm region.
Data in Table 5 show how UV400 #1 compares with a commercially available heavily doped UV blocking polycarbonate (OQ4620) (commercially available from General Electric) with regard to transmission at 400 nm and the yellow index.
Comparative extinction coefficient studies were conducted to determine the extinction coefficient of UV absorbers made according to the invention with SEESORB 701 (2-(2-hydroxy-5-methylphenyl)-2H-benzotriazole) and SEESORB 102 (2-hydroxy-4-octyloxybenzophenone) which are commercially available UV absorbers sold by, for example, Shipro Kasei Kaisha. These compounds are well known to those of skill. The optical density measurements of 1,4-Bis(9,9-dipropyl-9H-fluoreno[3,2-d]oxazol-2-yl)-2-hydroxyphenyl, 2,7-Bis(5-methylbenzoxazol-2-yl)-9,9-dipropyl-3-hydroxyfluorene, SEESORB 702, and SEESORB 102 was taken in solution on a common UV/is spectrophotometer. Extinction coefficients are a common measure of absorbers and dyes to indicate their strength at a chosen wavelength. In the context of measuring the benefits of the invention, extinction coefficients determine the prominent and relevant absorbance maxima in the UV region. The table shows the claimed materials to be both significantly shifted towards the 400 nm mark and also to be significantly stronger absorbers at those wavelengths, when compared to the two SEESORB products
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP05/14202 | 12/30/2005 | WO | 00 | 1/23/2006 |
| Number | Date | Country | |
|---|---|---|---|
| 60640506 | Dec 2004 | US |
