JP4645016B2 - Method for producing silicone compound - Google Patents

Description

  The present invention relates to a method for producing a silicone compound capable of obtaining a polymer particularly suitable for ophthalmic lenses such as contact lenses, intraocular lenses and artificial corneas.

  Conventionally, compounds having a silicon group are known as monomers for ophthalmic lenses.

As one of such compounds, a compound represented by the above formula (c) or (c ′) is known (for example, Patent Document 1). Since this compound has a hydroxyl group in the molecule, it has a feature that compatibility with a hydrophilic monomer is easily obtained. When this compound is synthesized by the method described in Patent Document 1, the following formula (d) is obtained as a by-product.

Is produced. Since this by-product (d) is a crosslinkable monomer having a silicone component in the molecule, for example, compared with ethylene glycol dimethacrylate, which is one of commonly used crosslinking agents, it is ophthalmic. There is an advantage that the oxygen permeability of the lens polymer is not lowered. However, when synthesizing the compound represented by the above formula (c) or (c ′), (d) produces only about 2%, so that the polymer obtained by polymerizing the above formula (c) or (c ′) A sufficient elastic modulus could not be provided.
JP-A 56-22325 Example 4

  An object of this invention is to provide the method of manufacturing the crosslinkable silicone compound represented by general formula (z) or (z ').

In order to achieve the above object, the present invention has the following configuration.
“(1) The following general formula (z) or (z ′)

In a method for obtaining a silicone compound represented,
Under following general formula (a) or (a ')

The silicone compound represented by the following general formula (x)

A method for producing a silicone compound, characterized in that a compound represented by the formula:
(A is tris (trimethylsiloxy) silyl group, bis (trimethylsiloxy) methylsilyl group, trimethylsiloxydimethylsilyl group, polydimethylsiloxane group, polymethylsiloxane group or poly-co-methylsiloxane-dimethylsiloxane group, X is carbon number Represents a divalent group of ^{1 to} 20. R ^{1 to} R ³ each independently represents hydrogen, a substituent having 1 to 20 carbon atoms, or —XA, and R ⁴ and R ⁵ each independently represents at least one group. .L representing a substituent having 1 to 20 carbon atoms having a polymerizable group p Ka in water H-L represents a 20 following groups.)
(2) The group L is an alkoxy group having 1 to 20 carbon atoms, a hydroxyl group, fluorine, chlorine, bromine, iodine and the following general formulas (g1) to (g3)

Manufacturing method (1) silicone compounds, wherein the one in which in selected from the group consisting of groups represented. "

  According to the present invention, a crosslinkable silicone compound represented by the general formula (z) or (z ′) can be obtained.

In general formula (z) or (z ′), R ^{1 to} R ³ each independently represent hydrogen, a substituent having 1 to 20 carbon atoms, or —XA.

R ^{4, R 5} each independently represent a substituent having 1 to 20 carbon atoms and having at least one polymerizable group. Here, the polymerizable group represents a carbon-carbon double bond capable of radical polymerization. R ^4, examples of a carboxylic acid consisting of ^{R 5 R} 4 -COOH and ^R 5 -COOH are, vinyloxy acetate, allyloxy acetate, (meth) acrylic acid, crotonic acid, 2- (meth) acryloylpropanesulfonic acid, 3 -(Meth) acryloylbutanoic acid, 4-vinylbenzoic acid and the like can be mentioned. Of these, (meth) acrylic acid is preferred because it is easy to obtain any of carboxylic acid, carboxylate, and carboxylic anhydride.

X represents a C1-C20 divalent aliphatic or aromatic substituent .

A is a tris (trimethylsiloxy) silyl group, bis (trimethylsiloxy) methylsilyl group, trimethylsiloxydimethylsilyl group, polydimethylsiloxane group, polymethylsiloxane group or poly-co-methylsiloxane-dimethylsiloxane group .

In the present invention , the compound represented by the formula (x) having a polymerizable group is allowed to act on the hydroxyl group of the silicone compound represented by the general formula (a) or (a ′) to perform esterification, whereby the general formula (z ) Or (z ′) is obtained.

In the general formula (x), L represents a group having a pKa of HL of 20 or less. Examples thereof include an alkoxy group having 1 to 20 carbon atoms, a hydroxyl group, fluorine, chlorine, bromine, iodine, and the following general formulas (g1) to (g3).

Group represented by these. Among these, the alkoxy group having 1 to 20 carbon atoms, the hydroxyl group, and chlorine (g1) to (g3) are preferable from the viewpoint of availability, and chlorine and (g1) are more preferable because of high reactivity. .

  When the pKa of HL generated after the reaction is 3 or less, since the siloxanyl group is decomposed by the acidity of HL, it is preferable to add a base. Examples of bases to be added include amines such as ammonia, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, and hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide. And the like.

In the present invention , a catalyst may be used. In particular, when the pKa of HL is 7 or less, the reactivity of the compound (x) decreases, so it is better to use it. Examples of the catalyst used include pyridine, N, N-dimethylaminopyridine, N, N-dicyclohexylcarbodiimide, iron (III) chloride, titanium (IV) isopropoxide, zirconium (IV) butoxide and the like .

  The silicone compound obtained by the method for producing a silicone compound of the present invention may be further purified by silica gel column purification, distillation purification or the like, if necessary.

  The polymer obtained by polymerizing the silicone compound obtained by the production method of the present invention is particularly suitable as an ophthalmic lens such as a contact lens, an intraocular lens, and an artificial cornea.

  Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited thereto.

<Measurement method>
For the gas chromatograph (GC) measurement, GC-18A (FID detector) manufactured by Shimadzu Corporation was used for the main body, and DB-5 (0.25 mm × 30 m × 1 μm) for J & W was used for the capillary column. The carrier gas was helium (138 kPa), the inlet temperature was 280 ° C., the detector temperature was 280 ° C., and the temperature raising program was 60 ° C. (5 minutes) → 10 ° C./minute→325° C. (19 minutes). A sample was prepared by dissolving 100 μL of a measurement sample in 1 mL of isopropyl alcohol, and 1 μL was injected.

Comparative Example 1
In a 300 mL eggplant flask, the following formula (c1)

30 g (89 mmol) of epoxysilane represented by the following formula: 30.66 g (356 mmol) of methacrylic acid, 2.89 g (27 mmol) of sodium methacrylate, 0.14 g (1 mmol) of p-methoxyphenol, 16.49 g (107 mmol) of methacrylic anhydride And heated to 100 ° C. in an air atmosphere and stirred. After confirming that the area percentage of the epoxysilane (c1) was 0.1% or less by GC, the reaction solution was cooled to room temperature. Add 50 mL of hexane to the reaction solution, wash 7 times with 50 mL of 0.5N aqueous sodium hydroxide solution and 3 times with 35 mL of 2.6% brine, dry the organic layer by adding sodium sulfate, filter and remove the solvent with an evaporator. Was distilled off to obtain a crosslinkable silicone compound (d). When the purity was measured by GC, the results shown in Table 1 were obtained.

Synthesis example 1
Except without added methacrylic anhydride experimented in the same manner as in Comparative Example 1,

The silicone compound represented by these was obtained. The following synthesis was performed using this compound as a raw material.

Example 1
To a 200 mL eggplant flask, 30 g (71 mmol) of the silicone compound (c) or (c ′) obtained in Example 2 above, 8.62 g (85 mmol) of triethylamine, and 30 mL of ethyl acetate were added and stirred for 10 minutes in an ice bath. From the dropping funnel, 8.90 g (85 mmol) of methacrylic acid chloride was added dropwise. The mixture was stirred for 6 hours while returning to room temperature, then washed 3 times with 50 mL of 0.5N aqueous sodium hydroxide solution and 3 times with 35 mL of 2.6% brine, dried by adding sodium sulfate to the organic layer, filtered and evaporated. The solvent was distilled off. When the GC purity of the obtained liquid was measured, the results shown in Table 1 were obtained.

Comparative Example 2
Synthesis Example 1 in the resulting silicone compound (c) or (c ') 30g (71mmol) , was added methacrylic anhydride 16.41 g (106 mmol) was heated to 100 ° C., and stirred for 16 hours. Add 50 mL of hexane to the reaction solution, wash 5 times with 50 mL of 0.5N aqueous sodium hydroxide solution and 3 times with 35 mL of 2.6% brine, dry the organic layer by adding sodium sulfate, filter and remove the solvent with an evaporator. Was distilled off to obtain a crosslinkable silicone compound (d). The GC purity was as shown in Table 1.

Comparative Example 3
To 30 g (71 mmol) of the compound (c) or (c ′) obtained in Synthesis Example 1 above, 71.05 g (710 mmol) of methyl methacrylate and 6 g (21 mmol) of titanium (IV) isopropoxide were added. The mixture was stirred for a time to obtain a crosslinkable silicone compound (d). The GC purity was as shown in Table 1.

Comparative Example 4
A 100 mL three-necked flask was equipped with a reflux condenser, a mechanical stirrer, and a drying tube filled with calcium chloride, and N-nitrosophenylhydroxylamine was added to 30 g (71 mmol) of the compound (c) or (c ′) obtained in Synthesis Example 1 above. 0.3 g (1% by weight) of aluminum was added and heated at 150 ° C. for 20 hours to obtain a crosslinkable silicone compound (d). The GC purity was as shown in Table 1.

Comparative Example 5
After adding 8.20 g (178 mmol) of formic acid and 0.53 g (13 mmol) of sodium hydroxide to 30 g (89 mmol) of the epoxysilane represented by (c1) and stirring at 100 ° C. for 5 hours, 0.5N aqueous sodium hydroxide solution And washed with saturated brine. After drying with sodium sulfate, the solvent was distilled off. 1 equivalent of potassium carbonate and methanol were added as solvents to the obtained liquid, and the mixture was allowed to stand at room temperature for 1 hour, and then washed with saturated brine. After drying with sodium sulfate, the solvent was distilled off to obtain a diol represented by the following formula (c2).

The obtained diol was used after purification on a silica gel column, and the target crosslinkable silicone compound was obtained in the same manner as in Example 1 except that methacrylic acid chloride and triethylamine were added in a 2-fold molar amount with respect to the diol. The GC purity was as shown in Table 1.

Comparative Example 6
Synthesis was carried out in the same manner as in Comparative Example 1 except that allyl glycidyl ether was used instead of epoxy silane to obtain a compound represented by the following formula (c3).

Comparative Example 7
To a 2 L eggplant flask was added 214 g (1 mol) of (c3), 220 mg (1 mmol) of 2,6-di-tert-butyl-4-methylphenol, 500 mL of toluene, and 518 mg (1 mmol) of platinum chloride (IV) acid hexahydrate. Then, 135.5 g (1 mol) of trichlorosilane was added dropwise. The mixture was stirred at room temperature for 8 hours and purified by distillation under reduced pressure to obtain a compound represented by the following formula (c4).

Comparative Example 8
A mixed solution of 152 g (0.43 mol) of (c4) and 272 g (2.6 mol) of methoxytrimethylsilane was added dropwise to a mixed solvent of 160 mL of water, 80 mL of methanol, and 80 mL of hexane in a 1 L eggplant flask. After stirring at room temperature for 8 hours, stirring was stopped, the aqueous layer was discarded, and the organic layer was washed 3 times with saturated aqueous sodium hydrogen carbonate solution and 3 times with saturated brine. After drying with sodium sulfate, the solvent was distilled off to obtain a crosslinkable silicone compound represented by the following formula (c5). The GC purity was as shown in Table 1.

Comparative Example 9
Synthesis was carried out in the same manner as in Comparative Example 7 except that tris (trimethylsiloxy) silane was used instead of trichlorosilane to obtain a crosslinkable silicone compound represented by (c5).

Comparative Example 10
Synthesis was carried out using 2-bromoisobutyryl bromide instead of methacrylic acid chloride to obtain a compound represented by the following formula (c6).

Comparative Example 11
To a 500 mL three-necked flask equipped with a reflux condenser and a dropping funnel, 72.5 g (0.10 mol) of (c6) and 200 mL of diethyl ether were added and stirred while refluxing, and 24.3 g (0.24 mol) of triethylamine was added from the dropping funnel. Of diethyl ether (30 mL) was added dropwise. After stirring for 24 hours while refluxing, the precipitate was filtered and the solvent was distilled off to obtain a crosslinkable silicone compound represented by (c5). The GC purity was as shown in Table 1.

Comparative Example 12
To a 300 mL benzene solution of 39.4 g (0.1 mol) of 3-allyloxypropyltris (trimethylsiloxy) silane, 38.6 g (0.2 mol) of silver methacrylate and 25.4 g (0.1 mol) of iodine were added for 16 hours. Refluxed. After completion of the reaction, the precipitate was removed by filtration, and the filtrate was washed 5 times with a saturated aqueous sodium carbonate solution and 3 times with a saturated saline solution. It dried with sodium sulfate, the solvent was distilled off, and the crosslinkable silicone compound represented by (c5) was obtained. The GC purity was as shown in Table 1.

Claims (2)

The following general formula (z) or (z ′)

A silicone compound represented by the formula:
The following general formula (a) or (a ′)

The following general formula (x)

A method for producing a silicone compound, characterized in that a compound represented by the formula:
(A is tris (trimethylsiloxy) silyl group, bis (trimethylsiloxy) methylsilyl group, trimethylsiloxydimethylsilyl group, polydimethylsiloxane group, polymethylsiloxane group or poly-co-methylsiloxane-dimethylsiloxane group, X is carbon number Represents a divalent group of ^{1 to} 20. R ^{1 to} R ³ each independently represents hydrogen, a substituent having 1 to 20 carbon atoms, or —XA, and R ⁴ and R ⁵ each independently represents at least one group. .L representing a substituent having 1 to 20 carbon atoms having a polymerizable group p Ka in water H-L represents a 20 following groups.) The group L is an alkoxy group having 1 to 20 carbon atoms, a hydroxyl group, fluorine, chlorine, bromine, iodine, and the following general formulas (g1) to (g3)

The method for producing a silicone compound according to claim 1, wherein the method is selected from the group consisting of groups represented by the formula: