JPS61126052A - Fluorine-containing methacrylic acid ester - Google Patents

Abstract

NEW MATERIAL:A fluorine-containing methacrylic acid ester of formula I [A, B are F, perfluoromethyl; m, n are 0, 1; X is formula II (l is 1-8), formula III (D, E are F, perfluoromethyl; p, r are 1-7)]. EXAMPLE:The compound of formula IV. USE:A starting material for producing a fluorine-containing polymer of high oxygen permeability, therefore it is used as a starting material for oxygen- permeating material, which will be used for ophthalmologic purposes such as hard contact lenses. PREPARATION:For example, perfluoropolyether is obtained from FCO(CF2)nCOF and tetrafluoroethylene oxide in the presence of fluorine anion and the product is converted into an iodine compound. The iodine compound is allowed to react with allyl acetate to form a diepoxide, which is treated with methacryloyl halide and an alkali to give the objective fluorine-containing methacrylic acid ester of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Application] The present invention relates to a fluorine-containing methacrylic acid ester useful as a raw material for producing a fluorine-containing polymer having oxygen permeability.

Oxygen that can be used to continuously supply oxygen to biological tissues without using biological fluids (e.g. blood) that are unstable to oxygen loading that requires physical agitation etc. Although it is preferable to use a permeable body, the present invention relates to a fluorine-containing methacrylic ester useful as a raw material for producing a polymer for producing such an enzyme permeable body.

More specifically, the present invention relates to a fluorine-containing methacrylic acid ester useful as a raw material for producing a fluorine-containing polymer having oxygen permeability useful as a raw material for producing oxygen permeable materials such as ophthalmic materials such as hard contact lenses (HCL).

[Prior art]

Conventionally, polymethyl methane (PMMA) has been widely used as a material for HCL and the like due to its excellent optical properties, chemical properties, physical strength, and mechanical processability.

By the way, since the cornea is an avascular tissue, the oxygen necessary for its respiratory metabolism is obtained by diffusion from the blood vessels in the eyelid mucosa and the aqueous humor when the eyes are closed, but when the eyes are open. It is taken in from the atmosphere. Therefore, wearing HCL will form an oxygen barrier, leading to hyperemia, edema and other angles 111! May cause harm. Acid S necessary for this cornea! is 3.5 to 4.8 pJ (
STP) /d,hr.

Conventional PMMA-based HCL has very low oxygen permeability, so only small HCL devices can be used, which causes a strong foreign body sensation to the eyes.
It has been desired to develop an oxygen permeable material such as L. Under these circumstances, in recent years, noricone methacrylate-based HCL has been developed (Japanese Patent Publication No. 52-33502), which has improved oxygen permeability by introducing a nitrogen-loxane bond into the ester moiety of methacrylic acid ester.
, oxygen-permeable OC+ mainly composed of cellulose acetate butyrate (C to B), and oxygen-permeable HCL using fluorine-containing methacrylate (Japanese Patent Application Laid-Open No. 57-51705).

The silicone methacrylate-based HCL disclosed in Japanese Patent Publication No. 52-33502 is generally different from the conventional PMMA-based HC.
Although it has an oxygen permeability several tens to hundreds of times higher than that of L, it has the disadvantage that it is inferior in hardness and hydrophilicity, so it is easily contaminated with lipids and the like.

Therefore, methyl methacrylate (MMA
), but when the proportion of silicone methacrylate increases, a! ! However, the above-mentioned drawbacks become more noticeable.

In addition, soft contact lenses are also susceptible to contamination by bacteria and fungi, contamination by tear fluid components (proteins, lipids, mucin, etc.), cumbersome handling, T9 staining from cigarette smoke and cosmetics such as mascara, yellowing, and clouding. There are problems such as long life and short lifespan.

On the other hand, fluorine-containing polymers are corrosion resistant, resistant to stains, and highly permeable to oxygen and carbon dioxide.Using these properties, it is possible to produce HCL with high oxygen permeability from fluorine-containing monomer copolymers. Medical oxygen permeability, such as HCL, which has excellent oxygen permeability, ultraviolet resistance, surface hardness, hydrophilicity, and stain resistance, and does not give a foreign body feeling when worn on the eyes etc. There is a need for oxygen permeable bodies and polymers for producing such oxygen permeable bodies.

[Problem that the invention seeks to solve]

An object of the present invention is to provide a raw material polymer for producing a fluorine-containing polymer useful for producing a medical oxygen permeable material having the above-mentioned excellent properties.

Means for Solving Problem C] The present inventors have conducted extensive research in order to achieve the above object. As a result, the general formula 8% [in the formula, A and B each represent a single atom or a perfluoromethyl group, m and n each represent O or 1, and X represents the general formula (however, i represents 1 to 8). (indicates an integer), or a group represented by the general formula (where D and E each represent a fluorine atom or a perfluoromethyl group, p and " each represent an integer from 1 to 7, and l
has the same meaning as above) indicates a group represented by]
And, the fluorine-containing methacrylic ester (1) itself is polymerized, or preferably, the fluorine-containing methacrylic ester (a hydrophilic monomer, a silicon-containing monomer, a meccrylic group-containing monomer, and a monomer containing a meccrylic group) is polymerized. Medical oxygen made from a fluorine-containing polymer having a number average molecular weight of +000 to ROOOO, which is prepared by copolymerizing with at least one monomer selected from the group consisting of seven monomers having two or more possible functional groups. Transparent bodies (especially
It has been found that the above object can be easily achieved when manufacturing HCL), and the present invention has been completed.

That is, the present invention provides a novel fluorine-containing methacrylic acid ester (
Regarding 1).

In this specification, p and " each represent an integer of 1 to 7, but preferably the sum of p and " is 2 to 1O.

Fluorine-containing methacrylic acid ester (1) of the present invention The fluorine-containing methacrylic acid ester (1) of the present invention is produced, for example, as follows. Tetrafluoroethylene oxide and hexafluoropropylene oxide are diberfluoroanlufluoride, such as F CO (C
In the presence of F2)n COF, etc. and a fluorinated anion, perfluoropolyether (11) is produced, which is converted into an iodide (2) and reacted with allyl acetate to lead to a compound (3) having an epoxide group. is well known [for example, J. Org. Chew, 27
．． 3033 (1962) ) -(In the above formula, A,
L3 and X are the same as Ail! ! Furthermore, dieboxide (3) is mixed with a slightly appropriate amount of a reactive derivative of methacrylic acid,
For example, treatment with methacrylic halide ([FII, methacrylic chloride) or ethylene glycol monomethacrylate and alkali (e.g., sodium hydroxide, potassium hydroxide, triethylamine, etc.]
The desired fluorine-containing methacrylic acid ester (T) is obtained.

The fluorine-containing methacrylic acid ester (+) of the present invention can be produced by polymerizing itself, or by polymerizing the fluorine-containing methacrylate ester (+) or
By copolymerizing at least one monomer selected from a silicon-containing monomer, a methacrylic group-containing monomer, and a monomer having two or more polymerizable functional groups, a polymer having f11 anti-permeability can be obtained.

Examples of the hydrophilic seven polymers used in the copolymerization include ethylene glycol monomethacrylate, diethylene glycol monomethacrylate, triethylene glycol monomethacrylate, glycerin methacrylate, 2-hydroxyethyl methacrylate, N-vinylpyrrolidone, and dimethylacrylamide. By introducing the hydrophilic hexamer, it is possible to improve the 8M aqueous properties of the obtained polymer and suppress the interaction with body fluid components.

That is, it suppresses hemolysis and the like.

Examples of the silicon-containing monomer include 3-(methacryloxy)propyltrimethoxysilane, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane, and 3-(methacryloxy)propyldimethquinemethylsilane.

Examples of the methacrylic group-containing monomer include methyl methacrylate, ethyl methacrylate, and benzyl methacrylate.

As a hexamer having two or more polymerizable functional groups,
Ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, allyl methacrylate, diallyl phthalate,
Alternatively, trimethylolpropane trimethacrylate and the like can be mentioned.

In the case of copolymerization, the mixing ratio of each monomer is 5 to 60% by weight of the fluorine-containing methacrylic ester (I), 5 to 10% by weight of the hydrophilic monomer, and 2 to 2% of the silicon-containing monomer.
5 to 55% by weight, 1 to 10% by weight of a methacrylic group-containing monomer, and 0.0% of a monomer having two or more polymerizable functional groups.
A preferred example is a combination of 1 to 5% by weight.

Examples of the polymerization initiator used in copolymerization include radical polymerization initiators such as benzoyl peroxide, t-butyl peroxide, abisisobutyronitrile, and azobisdimethylvaleronitrile.

During polymerization, for example, the radical polymerization initiator may be added in an amount of 0.01 to 1% by weight based on 100% by weight of the total amount of the monomers for polymerization.
They are mixed and used at a ratio of 5% by weight. After several repetitions of freezing in a dry ice-acetone bath, freezing, degassing at about 1 ssllF for several minutes, thawing under vacuum, freezing and degassing several times, ~1
Polymerization treatment was carried out several times at 10°C for 12 to 98 hours, specifically, first at 50°C for 6 hours, then at 70°C for 8 hours, further at 90°C for 5 hours, and finally under reduced pressure (approximately 1 mg).
Polymerization can be carried out by heating at 110° C. for 3 hours.

The polymer thus obtained has a highly cross-linked structure and is highly oxygen permeable.The properties of this polymer include a molecular weight of 1000 to eoooo and an oxygen permeability coefficient of 3 to 8.
0 x 10-” cc, cs/c+J, sec4s
Hg, refractive index 1.35-1.52, Vickers hardness 4
~25 are shown.

The polymer made of the fluorine-containing methacrylic acid ester (1) of the present invention is a polymer with excellent oxygen permeability, hydrophilicity, and wettability, and is easily molded and mechanically processed.

The polymers are useful as medical oxygen permeators (eg, oxygen permeators in the ophthalmology field, such as HLC).

A medical oxygen permeable material, especially HLC, is produced from the polymer by processing and molding using known means.

Reference Example 1 In a hard glass sealed test tube (20 mm φ x 10 cm), 1.5 g of Nanatsuma-3 (p+r=8>), 0.6 g of 3-(methacryloxy)propylbis(trinotyloxy)methylsilane, and methyl Methacrylate 1.5g, benzyl methacrylate 014g
, 0.2 g of allyl methacrylate, and 20+*g of azobisisobutyronitrile were added, mixed thoroughly, placed in a dry ice-acetone bath, frozen, degassed using a vacuum pump for 5 minutes at approximately 1 mm/1 g, and tested. While the inside of the tube was under vacuum, it was returned to room temperature and melted. Bubbles formed, then refrozen and degassed for 5 minutes. After repeating this operation 5 times, it was melt-sealed under vacuum, heated to 50℃ for 24 hours, and then heated to 70℃ for 5VF.
The mixture was heated at 90° C. for 8 hours. Approximately 1 liter of the produced polymer
It was dried under reduced pressure at mHg and about 100° C. for 24 hours to obtain a slightly yellow transparent material. Visocas hardness is 1k12, oxygen permeability coefficient is 5 x 10” cc, cm/c+J, sec
, mmHg. This equipment was processed into HCL.

Example a 1 Seven Tsuma-1 [General formula (+1, X is 4Cr21-
H.

1-4, m=n=Q, A, B are CF3) That is, synthesis of a compound represented by the formula: 10.89 g of fluorine-containing epoxide represented by the following formula (2 (1 mM), potassium hydroxide 33
7mg (6,0mM) and 40mg of hydroquinone ~
A person was placed in a 50 ml three-necked flask equipped with a magnetic cooler, a temperature needle, a nitrogen gas inlet tube, a sevcum, and a reflux cooling bag Wt (Dimroth) that could be heated at any time in an oil bath, and was heated under a nitrogen stream with methacrylic aft 8. 6g
(100+sM) was added dropwise using a syringe, and the reaction solution was heated to 100° C. over 3 hours, and further heated at the same temperature for 8 hours. After cooling, it was filtered to remove potassium methacrylate, chloroform was added to the filtrate and dissolved, and the mixture was washed several times with 0.5N aqueous sodium hydroxide solution until the aqueous layer was no longer colored.Then, the mixture was washed several times with saturated saline solution. After washing and drying, a polymerization inhibitor was added and the solvent was distilled off. Also, use a vacuum pump (
The solvent was distilled off. The obtained reaction solution was a non-viscous liquid, and when purified by flash column chromatography, it was a colorless, transparent, and viscous liquid. 10.
20 g (yield 71.0%).

IR (film, cs+-”): 3400 (0
11), 1730 (C proverb 0), 1590
(C-C)F-NMR (CCffi4/CFCI13
．． pp ■): 82 (CF3, 6F), 93~
94 (OCF?, 4F).

105-118 (CF2, 4F), 134
(CFo, 2F) MS (El, ■/2): Actual value (M”, 720.13) Calculated value C22H2408Fl (, Near 20.12+4
Example 2 Monomer 2 [General formula (in the mouth, X is 4 cr 2 inches.

! -6, m=n=1)) That is, synthesis of the compound represented by the formula: 13.02 g of ethylene glycol monomethacrylate
(100a+M),) ethylamine 0.35g
(35 sM) and 40 mg of hydroquinone were placed in the same apparatus as above, and under nitrogen flow, 12.93 g (20 mM) of fluorine-containing epoxide represented by the following formula was added dropwise using a syringe.
The mixture was gradually heated to 5°C and further heated at the same temperature overnight.

After cooling, chloroform 200+wl was added and the organic layer was reduced to 0.
The mixture was washed several times with 5N sodium hydroxide solution until the aqueous layer was no longer colored, and then several times with saturated brine. An appropriate amount of polymerization inhibitor was added to the organic layer, and after drying over anhydrous magnesium sulfate, the solvent was distilled off, and further under reduced pressure (approximately 1 m + wHg)
Solvent was removed. The residue was purified by flash column chromatography to obtain viscous, slightly yellow, transparent IIi.

This gave only a single spot on TLC. 1
1.94 g (yield 66.0%), melting point approximately 15°C.

IR (film, (J-'): 3350 (OH), 1745 (C-0),
1620 (C=C)F-NMR (CIJ4/CPC
It3. ppm) Near 5-80 (CF3)
, 90-93 (CF20) 105-123 (C
F2) Elemental analysis: Experimental value C; 38.42%, F, 42.4% calculated value C28H3oO engineering. F2o:C; 37.08%H
; 3.34%, F, 41.93% Example 3 Nanatsumer-3 [A, B in general formula (1).

D and E are CF31! -5, p+r-81, that is, synthesis of the compound represented by the formula: Fluorine-containing epoxide +p+q8) represented by the following formula 3.2 g (1.5 sM), potassium hydroxide 56...
Example 1
Into a reaction vessel similar to that described in , add 690 m of methacrylic acid.
g (approximately 8mM) and benzene 20 steel! was added and refluxed for 15 hours. It was treated in the same manner as in Example 1 to obtain 2.4 g of a slightly yellowish solid. At a melting point of about 50° C. and 1R, no absorption of epoxide was observed, but absorption of hydroxyl groups, carbonyl groups, and weak absorption due to double bonds was observed.

Elemental analysis: Experimental value C: 28.5%, F: 57.0% Calculated value (C
47H22016F56) C; 29.01%H;
1.14%, F; 56.68% procedure
Correct -3 (spontaneous) January 26, 1985 Patent Application No. 246439 of 1988 2, Title of invention Fluorine-containing methacrylic acid ester 3, Relationship with the person making the amendment Case Name of patent applicant Stocks Company Midori Juji 4, Agent 541 Address No. 406, Nie Life Hirano-cho, 4-53FK, Higashi-ku, Higashi-ku, Osaka Tht (06) 227-1158 6. Correction details Molecular weight = 720 Monomer 1 molecule 11
-866 Monomer 2 molecular weight -718
Monomer 1 Molecular weight = 906 Nanatsuma-2 (2) On page 8 of the same book, in line 1θ, "27" is corrected to "Ryu".

(3) On page 8 of the police station Correct to.

(4) Add ``Mixture'' before ``Dora'' on page 11, line 19 of the interlude.

(5) On page 12 of the same book, lines 4-5, “6 hours” is replaced with “6-
Corrected to 48 hours.

(6) On page 12 of the same book, line 5, “8 hours” was replaced with “8 to 24 hours.”
Correct to "Time".

(7) On page 12 of the police station, lines 5-6, “5 hours” is replaced with “5-5 hours”.
Corrected to ``12 hours''.

(8) On page 12 of the same book, line 6, “3 hours” is replaced with “3 to 12 hours.”
Correct to "Time".

(9) Same book, page 13 Correct to.

(10) "Cylinder" in line 9 on page 15 of the same book is corrected to "pump."

(11) On page 17 of the same book, line 4, "Franyu Kalam" is corrected to "Flash Column".

(12) The 18th true formula of the same book %formula% Correct to.

that's all

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, A and B each represent a fluorine atom or a perfluoromethyl group, m and n each represent 0 or 1, and X represents the general formula - (CF_2)-_l (where l is an integer from 1 to 8) or general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (However, D and E are each a fluorine atom or a perfluoromethyl group) , p and r each represent an integer from 1 to 7, l
has the same meaning as above) represents a group represented by the following:] A fluorine-containing methacrylic acid ester represented by the following.