JP2020200251A - Method for producing siloxane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a siloxane compound suitable for a medical material. SOLUTION: An epoxy compound represented by the following formula (5) is reacted with (meth) acrylic acid to produce a siloxane of the following formula (1). A is a group represented by the following formula (2) or the like. [Selection diagram] None

Description

The present invention relates to a method for producing a siloxane. Specifically, siloxane suitable for medical materials and a method for producing the same are provided.

Conventionally, a monomer having a siloxane is known as a compound used for a medical material such as an ophthalmic device. For example, 3- [Tris (trimethylsiloxy) silyl] propyl methacrylate (TRIS) is widely used as a monomer for ophthalmic devices. The polymer obtained by copolymerizing this TRIS with N, N-dimethylacrylamide or N-vinyl-2-pyrrolidone, which are hydrophilic monomers, has a beneficial feature of high oxygen permeability. However, the highly hydrophobic siloxane monomer cannot be said to have high compatibility with these hydrophilic monomers, and there is a problem that phase separation occurs when hydrogel as a medical material is produced, resulting in cloudiness. ..

該ＳｉＧＭＡは、メタクリル酸とエポキシ変性シロキサン化合物の付加反応により形成されるモノマーであり、分子内に水酸基を有するために良好な親水性を発現する。そのため、親水性モノマーである２−ヒドロキシエチルメタクリレート、Ｎ，Ｎ−ジメチルアクリルアミドやＮ−ビニル−２−ピロリドンとの相溶性に優れるという利点を有している。しかし、ＳｉＧＭＡは、カルボン酸とエポキシ変性シロキサン化合物の付加反応にて製造されるが、生成する水酸基に由来する副反応が避けられず、目的とするシロキサン化合物の純度が低下するという問題がある。 Patent Documents 1, 2 and 3 describe a siloxane compound having glycerol methacrylate represented by the following formulas (a) and (a'): methylbis (trimethylsiloxy) silylpropylglycerol methacrylate (SiGMA).

The SiGMA is a monomer formed by an addition reaction of methacrylic acid and an epoxy-modified siloxane compound, and exhibits good hydrophilicity because it has a hydroxyl group in the molecule. Therefore, it has an advantage of being excellent in compatibility with 2-hydroxyethyl methacrylate, N, N-dimethylacrylamide and N-vinyl-2-pyrrolidone, which are hydrophilic monomers. However, although SiGMA is produced by an addition reaction of a carboxylic acid and an epoxy-modified siloxane compound, there is a problem that a side reaction derived from the generated hydroxyl group is unavoidable and the purity of the target siloxane compound is lowered.

In addition, when hydrogels are prepared using the compound, there are cases where the highly reactive hydroxyl groups present in the molecule give undesired results. For example, radicals may be added to existing hydroxyl groups, causing the formation of crosslinked structures by hydroxyl radicals. As a result, an unexpected increase in hardness and a decrease in hydroxyl groups cause a decrease in hydrophilicity.

Japanese Unexamined Patent Publication No. 54-55455 Japanese Unexamined Patent Publication No. 56-22325 Japanese Unexamined Patent Publication No. 2004-182724

As described above, a siloxane having a glycerol (meth) acrylate is suitable for producing an ophthalmic device or the like because it has high oxygen permeability and compatibility with a hydrophilic monomer, and the glycerol (meth) There is a demand for a method for producing a siloxane having an acrylate with high purity. On the other hand, in the (co) polymer obtained by using SiGMA as a monomer, a crosslinked structure is formed by highly reactive hydroxyl groups existing in the molecule, resulting in an unexpected increase in hardness and a decrease in hydrophilicity due to a decrease in hydroxyl groups. May be caused. Therefore, it has been difficult for conventional siloxanes to provide medical materials having beneficial hydrophilicity and sufficient strength. Therefore, there is still a demand for compounds and compositions that overcome these drawbacks.

An object of the present invention is to provide a method for producing a siloxane having a glycerol (meth) acrylate with high purity. Furthermore, it is an object of the present invention to provide a siloxane having a purity useful as a medical material, high oxygen permeability, and sufficient compatibility with other polymerizable monomers.

The present inventors have made diligent studies to solve the above problems, and in the addition reaction between an epoxy-modified siloxane compound having a substituent on an epoxy group and a carboxylic acid, a side reaction derived from the generated hydroxyl group is suppressed, and glycerol is suppressed. It has been found that a siloxane having a (meth) acrylate can be obtained with high purity. Furthermore, it has been found that the obtained tertiary hydroxyl group-containing siloxane compound has excellent compatibility with other hydrophilic monomers and does not cause the formation of an unexpected crosslinked structure in the (co) polymer.

（式中、Ｒ^１は水素原子又はメチル基であり、Ｒ^２は炭素数１〜６の一価炭化水素基であり、Ｌは、エーテル結合を含んでよい炭素数２〜１０の二価炭化水素基であり、Ａは下記式（２）または（３）で表される基であり、

上記式（２）においてｎは１〜１００の整数であり、上記式（３）においてａは０〜１０の整数であり、ｂは０〜１０の整数であり、ｃは０〜１０の整数であり、ただしａ＋ｂ＋ｃは２以上であり、Ｒは、互いに独立に炭素数１〜１０の１価炭化水素基である）
の製造方法であって、
下記式（５）で表されるエポキシ化合物

（式中、Ｒ^２、Ｌ、及びＡは上記の通りである）と、
（メタ）アクリル酸とを反応させて、
上記式（１）で表される化合物を得る工程を含む、前記シロキサンの製造方法。 That is, it is a method for producing a siloxane represented by the following formula (1).
Siloxane represented by the following formula (1)

(In the formula, R ¹ is a hydrogen atom or a methyl group, R ² is a monovalent hydrocarbon group having 1 to 6 carbon atoms, and L is a divalent hydrocarbon having 2 to 10 carbon atoms which may contain an ether bond. It is a hydrogen group, and A is a group represented by the following formula (2) or (3).

In the above formula (2), n is an integer of 1 to 100, in the above formula (3), a is an integer of 0 to 10, b is an integer of 0 to 10, and c is an integer of 0 to 10. Yes, but a + b + c is 2 or more, and R is a monovalent hydrocarbon group having 1 to 10 carbon atoms independently of each other)
It is a manufacturing method of
Epoxy compound represented by the following formula (5)

And ^{(wherein, R} 2, L, and A are as defined above),
By reacting with (meth) acrylic acid,
The method for producing a siloxane, which comprises a step of obtaining a compound represented by the above formula (1).

According to the production method of the present invention, a siloxane having glycerol (meth) acrylate can be produced with high purity. In addition, the compound of the present invention has excellent compatibility with other hydrophilic monomers and provides preferable strength in the (co) polymer.

Hereinafter, the present invention will be described in detail.

The present invention provides a method for producing a compound represented by the above formula (1). The production method of the present invention is characterized in that an epoxy-modified siloxane compound having a substituent on an epoxy group is used as a raw material and subjected to an addition reaction with methacrylic acid or acrylic acid. That is, the compound represented by the above formula (5) is characterized by having a substituent on the carbon to which L on the epoxy group is bonded. By having a substituent, the hydroxyl group generated in the reaction with (meth) acrylic acid becomes a tertiary hydroxyl group with low reactivity, so that the side reaction is suppressed and the siloxane represented by the above formula (1) is highly purified. Can be obtained at. Furthermore, since the hydroxyl group of the siloxane represented by the above formula (1) is tertiary, side reactions during the polymerization reaction between the (poly) siloxane monomer and the hydrophilic monomer are suppressed. The (co) polymer containing a repeating unit derived from the siloxane obtained by the production method of the present invention has excellent compatibility with other hydrophilic monomers and has preferable strength.
Hereinafter, the compound of the present invention will be described in detail.

The compound of the present invention is a siloxane represented by the above formula (1). The compound has a terminal (poly) siloxane structure (portion represented by A), a terminal (meth) acryloyl group, and a tertiary hydroxyl group as a linking group between the (poly) siloxane and the (meth) acryloyl group. It is a feature. In the compound of the present invention, the hydroxyl group serving as a hydrophilic group is tertiary and can suppress side reactions. These characteristics make it possible to provide preferable strength in a (co) polymer containing a repeating unit derived from the compound of the present invention while maintaining compatibility with a hydrophilic monomer.

In the above formula (1), R ¹ is a hydrogen atom or a methyl group, preferably a methyl group.

In the above formula (1), R ² is a monovalent hydrocarbon group having 1 to 6 carbon atoms. Examples of the monovalent hydrocarbon group include an alkyl group such as a methyl group, an ethyl group, a propyl group, an n-butyl group, a t-butyl group, a pentyl group and a hexyl group; a cycloalkyl group such as a cyclopentyl group and a cyclohexyl group; and a phenyl group. Examples include an aryl group such as a group. R ² is preferably an alkyl group having 1 to 4 carbon atoms, more preferably a methyl group.

In the above formula (1), L is a divalent hydrocarbon group having 2 to 10 carbon atoms, which may contain an ether bond, and is preferably a divalent hydrocarbon group having 4 to 10 carbon atoms. Examples of the divalent hydrocarbon group include ethylene, 1,3-propylene, 1-methylpropylene, 1,1-dimethylpropylene, 2-methylpropylene, 1,2-dimethylpropylene, and 1,1,2-trimethyl. Propylene, 1,4-butylene, 2-methyl-1,4-butylene, 2,2-dimethyl-1,4-butylene, 3-methyl-1,4-butylene, 2,2-dimethyl-1,4- Butylene, 2,3-dimethyl-1,4-butylene, 2,2,3-trimethyl-1,4-butylene, 1,5-pentylene, 1,6-hexanylene, 1,7-heptanylene, 1,8- Examples thereof include octanylene, 1,9-nonanilen, and 1,10-decanilen.

（式（４）において、ｐは１〜２の整数であり、ｑは１〜４の整数であり、好ましくはｑは２〜４の整数であり、より好ましくはｑは２である。＊は式（１）における炭素原子との結合箇所であり、＊＊は式（１）におけるＡとの結合箇所である）
該式（４）で表される基として、好ましくは−ＣＨ_２ＯＣ_３Ｈ_６−、または−ＣＨ_２ＯＣ_２Ｈ_４ＯＣ_３Ｈ_６−である。 Examples of the divalent hydrocarbon group having 2 to 10 carbon atoms, preferably 4 to 10 carbon atoms, containing an ether bond include polyalkylene oxides such as polyethylene oxide, polypropylene oxide, and polyethylene-propylene oxide. .. It is preferably a group represented by the following formula (4).

(In equation (4), p is an integer of 1 to 2, q is an integer of 1 to 4, preferably q is an integer of 2 to 4, and more preferably q is 2. * Is The bond point with the carbon atom in the formula (1), ** is the bond point with A in the formula (1))
The group represented by the formula (4) is preferably −CH ₂ OC ₃ H ₆ − or −CH ₂ OC ₂ H ₄ OC ₃ H ₆ −.

A is a polysiloxane represented by the above formula (2) or (3), n is an integer of 1 to 100, a is an integer of 0 to 10, and b is an integer of 0 to 10. c is an integer from 0 to 10, where a + b + c is 2 or more. Preferably, n is an integer of 2-20. Further, in the formula (3), it is preferable that a is 1, b is 1, and c is 0.

R is a monovalent hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, independently of each other. Examples of the monovalent hydrocarbon group include an alkyl group such as a methyl group, an ethyl group, a propyl group, an n-butyl group, a t-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group and a decyl group; Cycloalkyl groups such as groups and cyclohexyl groups; aryl groups such as phenyl groups and tolyl groups can be mentioned. R is preferably an alkyl group or a phenyl group having 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and further preferably R is a methyl group, an n-butyl group, or a t-butyl group.

Hereinafter, a method for producing the compound represented by the above formula (1) will be described.
The production method of the present invention is characterized by using an epoxy-modified siloxane compound having a substituent on the epoxy group. Since the hydroxyl group contained in the compound produced in the production method of the present invention is tertiary, side reactions caused by the hydroxyl group can be suppressed. Thereby, the compound of the present invention can be obtained with high purity.

（式中、Ｒ^２は炭素数１〜６の一価炭化水素基であり、Ｌは、エーテル結合を含んでよい炭素数２〜１０の二価炭化水素基であり、Ａは上記式（２）または（３）で表されるポリシロキサンである）
（メタ）アクリル酸とを反応させて、
上記式（１）で表される化合物を得る工程（以下、工程Ｉという）を含む。 The production method of the present invention comprises an epoxy compound represented by the following formula (5) and an epoxy compound.

(In the formula, R ² is a monovalent hydrocarbon group having 1 to 6 carbon atoms, L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may contain an ether bond, and A is the above formula (2). ) Or (polysiloxane represented by (3))
By reacting with (meth) acrylic acid,
The step (hereinafter, referred to as step I) for obtaining the compound represented by the above formula (1) is included.

（ｎ、ａ、ｂ、ｃ、Ｒは上記の通りである。）
下記式（８）で表される不飽和化合物とをヒドロシリル化反応させて

（Ｒ^２は上記の通りであり、Ｒ^３は水素原子またはメチル基であり、Ｌ’は、単結合又はエーテル結合を含んでよい、炭素数１〜８の二価炭化水素基である）
上記式（５）で表されるエポキシ化合物を得る工程（以下、工程ＩＩという）を含む。
以下、各工程について詳細に説明する。 The production method of the present invention further comprises a hydrogen siloxane compound represented by the following formula (6) or (7).

(N, a, b, c, R are as described above.)
Hydrosilylation reaction with unsaturated compound represented by the following formula (8)

(R ² is as described above, R ³ is a hydrogen atom or a methyl group, and L'is a divalent hydrocarbon group having 1 to 8 carbon atoms, which may contain a single bond or an ether bond.)
The step of obtaining the epoxy compound represented by the above formula (5) (hereinafter, referred to as step II) is included.
Hereinafter, each step will be described in detail.

（式中、Ｒ^２は炭素数１〜６の一価炭化水素基であり、Ｌは、エーテル結合を含んでよい炭素数２〜１０の二価炭化水素基であり、Ａは上記式（２）または（３）で表されるポリシロキサンである）
（メタ）アクリル酸とを反応させて、
上記式（１）で表される化合物を得る工程である。 ・ Process I
In the step I, the epoxy compound represented by the following formula (5) and the epoxy compound

(In the formula, R ² is a monovalent hydrocarbon group having 1 to 6 carbon atoms, L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may contain an ether bond, and A is the above formula (2). ) Or (polysiloxane represented by (3))
By reacting with (meth) acrylic acid,
This is a step of obtaining the compound represented by the above formula (1).

The reaction can be carried out according to a conventionally known method. For example, the reaction may be carried out by adding 1 mol equivalent or more of (meth) acrylic acid to the epoxy compound represented by the formula (5). The reaction temperature is not particularly limited, but is preferably a temperature that does not exceed the boiling point of the solvent used. For example, it is preferably carried out at a temperature of 0 to 120 ° C. The reaction may be carried out in the presence of a solvent, a catalyst or a stabilizer. The solvent, catalyst, and stabilizer are not particularly limited as long as they are conventionally known. The above-mentioned solvents and stabilizers can be used.

The amount of methacrylic acid or acrylic acid added may typically be an amount ratio of 1 molar equivalent or more with respect to compound (5). If it is less than the above value, the epoxy group remains, which is not preferable. The upper limit is not limited, but is preferably an amount ratio of 1 to 5 molar equivalents, more preferably 1.2 to 3 molar equivalents. If the amount of methacrylic acid or acrylic acid added is large, it is not preferable from the viewpoint of yield and economy.

The catalyst in the above step I may be any conventionally known epoxy curing catalyst. Examples thereof include acid catalysts, base catalysts, organometallic catalysts, amine catalysts and the like, and are selected from alkali metal salts of (meth) acrylic acid, amine compounds, phosphorus compounds, or aluminum, titanium, iron, zinc and tin. It is preferably carried out in the presence of any one or more metal catalysts. The acid catalyst is not particularly limited, but for example, hydrochloric acid, sulfuric acid, boron trifluoride, boron trichloride, magnesium chloride, magnesium bromide, aluminum trichloride, aluminum bromide, zinc chloride, tin chloride (IV). , Iron (III) Chloride, Antimon Fluoride (V), Antimon Chloride (V), Phosphorus Trichloride, Phosphorus Dichloride, Phosphorus Oxychloride, Titanium Tetrachloride, Titanium Trichloride, Zirconium Chloride, Tetraisopropoxytitanium. To. The base catalyst is not particularly limited, but for example, metal hydroxide compounds such as lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, and calcium hydroxide, lithium (meth) acrylate, and (meth). Examples thereof include neutralizing salts such as sodium acrylate and potassium (meth) acrylate. The organic metal catalyst is not particularly limited, but for example, stanas diacetate, stanas dioctate, stanas dioleate, stanas dilaurate, dibutyltin oxide, dibutyltin diacetate, dibutyltin dilaurate, dibutyltin dichloride, etc. Organic tin catalysts such as dioctyl tin dilaurate, acetylacetone aluminum, acetylacetone iron, acetylacetone copper, acetylacetone zinc, acetylacetone beryllium, acetylacetone chromium, acetylacetone indium, acetylacetone manganese, acetylacetone molybdenum, acetylacetone titanium, acetylacetone cobalt, acetylacetone vanadium, acetylacetone zirconium, etc. Acetylacetone metal salts are exemplified. Examples of the amine catalyst include pentamethyldiethylenetriamine, triethylamine, N-methylmorpholinbis (2-dimethylaminoethyl) ether, N, N, N', N ", N" -pentamethyldiethylenetriamine, N, N, N'. -Trimethylaminoethyl-ethanolamine, bis (2-dimethylaminoethyl) ether, N-methyl-N'N'-dimethylaminoethyl piperazine, N, N-dimethylcyclohexylamine, diazabicycloundecene, triethylenediamine, tetra Examples thereof include methylhexamethylenediamine, N-methylimidazole, trimethylaminoethylpiperazin, tripropylamine, tetramethylammonium salt, tetraethylammonium salt, triphenylammonium salt and the like.

The amount of the catalyst added may be any amount as long as it is the amount of the catalyst for advancing the addition reaction. Further, the catalyst may be used alone or in combination of two or more. The temperature of the addition reaction is not particularly limited and may be adjusted as appropriate. In particular, 20 ° C. to 150 ° C., more preferably 50 ° C. to 120 ° C. The reaction time is, for example, 1 to 30 hours, preferably 5 to 20 hours.

・ Process II
In this step, the hydrogen siloxane compound represented by the above formula (6) or (7) and the epoxy group-containing unsaturated compound represented by the above formula (8) are hydrosilylated and represented by the above formula (5). This is a step of obtaining an epoxy compound to be produced.

In the above formula (8), R ³ is a hydrogen atom or a methyl group. It is preferably a hydrogen atom. In the above formula (8), L'is a divalent hydrocarbon group having 1 to 8 carbon atoms which may contain a single bond or an ether bond, and is preferably a divalent hydrocarbon group having 2 to 8 carbon atoms including an ether bond. It is a hydrocarbon group.

Examples of the divalent hydrocarbon group having 1 to 8 carbon atoms include methylene, ethylene, 1,3-propylene, 1-methylpropylene, 1,1-dimethylpropylene, 2-methylpropylene, 1,2-dimethylpropylene, and the like. 1,1,2-trimethylpropylene, 1,4-butylene, 2-methyl-1,4-butylene, 2,2-dimethyl-1,4-butylene, 3-methyl-1,4-butylene, 2,2 -Dimethyl-1,4-butylene, 2,3-dimethyl-1,4-butylene, 2,2,3-trimethyl-1,4-butylene, 1,5-pentylene, 1,6-hexanylene, 1,7 -Heptanilen, 1,8-octanilen and the like can be mentioned.

（式（４’）において、ｐは１〜２の整数であり、ｑ’は０〜２の整数であり、好ましくはｑ’は０又は１であり、より好ましくはｑ’は０である。式（４’）及び（４’’）において、＊および＊＊で示される部位は結合手であり、＊＊は式（８）中にある不飽和結合との結合箇所である）
好ましくは−ＣＨ_２ＯＣＨ_２−、または−ＣＨ_２ＯＣ_２Ｈ_４ＯＣＨ_２−である。 Examples of the group containing an ether bond include polyalkylene oxides such as polyethylene oxide, polypropylene oxide, and polyethylene-propylene oxide. Particularly preferably, it is a group represented by the following formula (4') or (4 ″).

(In equation (4'), p is an integer of 1-2, q'is an integer of 0-2, preferably q'is 0 or 1, and more preferably q'is 0. In formulas (4') and (4 ″), the sites represented by * and ** are the binding hands, and ** is the binding site with the unsaturated bond in formula (8)).
It is preferably −CH ₂ OCH ₂ − or −CH ₂ OC ₂ H ₄ OCH ₂ −.

The reaction between the alcohol compound and the epoxy compound can be carried out according to a conventionally known method. For example, an epoxy compound having an equivalent amount of 1 mol or more may be added to the alcohol compound and reacted. The reaction temperature is not particularly limited, but is preferably a temperature that does not exceed the boiling point of the solvent used. For example, it is preferably carried out at a temperature of about 0 ° C to about 120 ° C. The reaction may be carried out in the presence of a solvent or a catalyst. The solvent and catalyst may be conventionally known ones and are not particularly limited.

Further, the reaction of the hydrogen siloxane compound represented by the above formula (6) or (7) with the epoxy group-containing unsaturated compound represented by the above formula (8) may also be carried out according to a conventionally known method. For example, it is preferable to add 1 molar equivalent or more of the epoxy group-containing unsaturated compound represented by the formula (8) to the hydrogen siloxane compound represented by the formula (6) or (7) for reaction. The reaction temperature is not particularly limited, but is preferably a temperature that does not exceed the boiling point of the solvent used. For example, it is preferably carried out at a temperature of 0 to 120 ° C. The reaction may be carried out in the presence of a solvent, a hydrosilylation catalyst or a stabilizer. The solvent, hydrosilylation catalyst and stabilizer may be any conventionally known one and are not particularly limited.

In the reaction, it is preferable to add 1 molar equivalent or more of the unsaturated compound to the hydrogen siloxane compound. If it is less than the above value, a hydrosilyl group remains, which is not preferable. The upper limit is not limited, but is preferably 1 molar equivalent to 3 molar equivalents, more preferably 1.1 to 2.0 molar equivalents, and particularly preferably 1.2 to 1.5 molar equivalents. It is a quantity ratio. If the amount of the unsaturated compound added is large, it is not preferable from the viewpoint of yield and economy.

The hydrosilylation catalyst is preferably, for example, a noble metal catalyst, particularly a platinum catalyst derived from chloroplatinic acid. In particular, it is preferable to completely neutralize the chlorine ions of platinum chloride acid with baking soda to improve the stability of the platinum catalyst. For example, a complex (calstead catalyst) of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane and a sodium bicarbonate neutralized product of chloroplatinic acid is more preferable.

The amount of the hydrosilylation catalyst added may be any amount as long as it is a catalyst amount for advancing the above reaction. For example, a complex of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane and a layered neutralized product of chloroplatinic acid is 1 ppm to 80 ppm in terms of platinum with respect to the mass of the hydrogen siloxane compound. It may be used in the amount that becomes.

Solvents include, for example, methyl cellosolve, ethyl cellosolve, isopropyl cellosolve, butyl cellosolve, propylene glycol monomethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, polyethylene glycol monomethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether and polyethylene glycol. Glycol ether solvents such as dimethyl ether; ester solvents such as ethyl acetate, butyl acetate, amyl acetate, ethyl lactate and methyl benzoate; aliphatic hydrocarbon solvents such as linear hexane, linear heptane and linear octane; cyclohexane and Alicyclic hydrocarbon solvents such as ethylcyclohexane; ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone; aromatic hydrocarbon solvents such as benzene, toluene and xylene; and petroleum solvents; and methyl alcohol, ethyl. Examples thereof include alcohol solvents such as alcohol, linear propyl alcohol, isopropyl alcohol, linear butyl alcohol, isobutyl alcohol, tert-butyl alcohol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol and polyethylene glycol. The solvent may be used alone or in combination of two or more.

Examples of the stabilizer include a phenol-based antioxidant, a phosphorus-based antioxidant, an amine-based antioxidant, and a sulfur-based antioxidant. The phenolic antioxidant is not particularly limited, but for example, p-methoxyphenol, di-tert-butyl-p-cresol, pyrogallol, tert-butylcatechol, 4,4-thiobis (3-methyl-). 6-tert-butylphenol), 2,2'-methylenebis (4-methyl-6-t-butylphenol), phenolic resins, compounds selected from the group consisting of cresol resins and the like. The phosphorus-based antioxidant is not particularly limited, but for example, Tris [2-[[2,4,8,10-tetrakis (1,1-dimethylethyl) dibenzo [d, f] [1, 3,2] Dioxaphosfepine-6-yl] oxy] ethyl] amine, tris [2-[(4,6,9,11-tetra-tert-butyldibenzo [d, f] [1,3] 2] Dioxaphosfepin-2-yl) oxy] ethyl] amine, ethylbis phosphite (2,4-ditert-butyl-6-methylphenyl) and the like can be mentioned. The amine-based antioxidant is not particularly limited, but is, for example, tri or tetra C1-3 alkylpiperidin or a derivative thereof, bis (2,2,6,6-tetramethyl-4-piperidyl) oxalate, 1 , 2-Bis (2,2,6,6-tetramethyl-4-piperidyloxy) ethane, phenylnaphthylamine, N, N'-diphenyl-1,4-phenylenediamine, N-phenyl-N'-cyclohexyl-1 , 4-Phenylenediamine and the like. The sulfur-based antioxidant is not particularly limited, and examples thereof include dilaurylthiodipropionate and distearylthiodipropionate. The stabilizer may be used alone or in combination of two or more.

（Ｒ^３は上記の通りであり、Ｙは単結合、又はエーテル結合を含んでよい、炭素数１〜６の二価炭化水素基である）
下記式（１０）で表されるエポキシ化合物とを反応させて得ることができる。

（Ｒ^２は上記の通りであり、Ｘはハロゲン原子である） The method for producing the epoxy group-containing unsaturated compound represented by the above formula (8) is not particularly limited. For example, the epoxy compound represented by the above formula (8) and having L'containing an ether bond and having 2 to 8 carbon atoms is the alcohol compound represented by the following formula (9).

(R ³ is as described above, and Y is a divalent hydrocarbon group having 1 to 6 carbon atoms, which may contain a single bond or an ether bond.)
It can be obtained by reacting with an epoxy compound represented by the following formula (10).

(R ² is as above, X is a halogen atom)

The reaction between the alcohol compound and the epoxy compound can be carried out according to a conventionally known method. For example, an epoxy compound having an equivalent amount of 1 mol or more may be added to the alcohol compound and reacted. The reaction temperature is not particularly limited, but is preferably a temperature that does not exceed the boiling point of the solvent used. For example, it is preferably carried out at a temperature of about 0 ° C to about 120 ° C. The reaction may be carried out in the presence of a solvent or a catalyst. The solvent and catalyst may be conventionally known ones and are not particularly limited.

In any of the above reactions, the peak of the raw material compound disappeared at the reaction end point according to a conventionally known method, for example, by thin layer chromatography (TCL), high performance liquid chromatography (HPLC), gas chromatography (GC), or the like. You can confirm that. After completion of the reaction, purification may be performed according to a conventionally known method. For example, the product can be isolated by washing the organic layer with water and then removing the solvent. Further, vacuum distillation, activated carbon treatment, or the like may be used.

As an example of the production method of the present invention, 1 molar equivalent of a hydrogen siloxane compound represented by the formula (6) or (7) and 1.1 molar equivalent of an epoxy group-containing unsaturated compound represented by the above formula (8). , Toluene solution (platinum content 0.5 wt%) of chloroplatinate sodium bicarbonate complex and vinylsiloxane complex was 10 ppm in terms of platinum relative to the mass of hydrogensiloxane compound, and toluene was 0. Add 1% by mass and heat and stir at 80 ° C. under a nitrogen atmosphere. The reaction is completed by reacting for about 2 hours. At that time, the progress of the reaction can be confirmed by monitoring the unsaturated compound or the compound to be produced by GC measurement or the like. After the reaction is completed, the unreacted raw material and solvent are distilled off under reduced pressure to obtain an epoxy compound represented by the above formula (5).

Next, 1 molar equivalent of the epoxy compound represented by the above formula (5), 2 molar equivalents of methacrylic acid, and 0.3 molar equivalents of sodium methacrylate are added. After the addition, the mixture is heated and stirred at 100 ° C. The reaction is completed by reacting for about 20 hours. At that time, the progress of the reaction can be confirmed by monitoring the epoxy compound or the compound to be produced by GC measurement or the like. After completion of the reaction, 100% by mass of n-hexane was added to the hydrogen siloxane compound, the organic layer was washed with water, and the solvent existing in the organic layer and the unreacted raw material were distilled off under reduced pressure. A siloxane compound represented by the formula (1) can be obtained.

The compounds of the present invention can provide polymers with repeating units derived from addition polymerization of (meth) acrylic groups. The compound of the present invention has good compatibility with other compounds having a polymerizable group such as a (meth) acrylic group (hereinafter, referred to as a polymerizable monomer or a hydrophilic monomer). Therefore, a colorless and transparent copolymer can be provided by copolymerizing with the polymerizable monomer. It is also possible to polymerize alone.

In the production of a copolymer containing a repeating unit derived from the polymerization of the compound of the present invention and another polymerizable (hydrophilic) monomer, the compounding ratio of the compound of the present invention is the weight of the entire polymer of the present invention. The mass ratio of the repeating unit derived from the compound may be 10% or more. More specifically, the amount of the compound of the present invention is preferably 10 to 80 parts by mass, more preferably 10 to 60 parts by mass with respect to 100 parts by mass in total of the compound of the present invention and the polymerizable (hydrophilic) monomer. Is good. If the mass ratio of the repeating unit is less than 10%, the characteristics of the compound of the present invention are unlikely to appear.

Examples of the polymerizable monomer include (meth) acrylic acid, methyl (meth) acrylate, ethyl (meth) acrylate, (poly) ethylene glycol dimethacrylate, polyalkylene glycol mono (meth) acrylate, and polyalkylene glycol monoalkyl ether (. Acrylic monomers such as meta) acrylate, trifluoroethyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2,3-dihydroxypropyl (meth) acrylate; N, N-dimethylacrylamide, N, N-diethylacrylamide , N-acryloylmorpholine, acrylic acid derivatives such as N-methyl (meth) acrylamide; other unsaturated aliphatic or aromatic compounds such as N-vinylpyrrolidone, such as crotonic acid, cinnamic acid, vinyl benzoic acid; and (meth). ) Examples thereof include a siloxane monomer having a polymerizable group such as an acrylic group. These may be used alone or in combination of two or more.

The copolymerization of the compound of the present invention with the above-mentioned other polymerizable monomer may be carried out by a conventionally known method. For example, it can be carried out using a known polymerization initiator such as a thermal polymerization initiator or a photopolymerization initiator. Examples of the polymerization initiator include 2-hydroxy-2-methyl-1-phenyl-propan-1-one, azobisisobutyronitrile, azobisdimethylvaleronitrile, benzoyl peroxide, tert-butyl hydroperoxide, and cumene. Examples thereof include hydroperoxide and 2,2'-azobis (2-methylpropionamidine) dihydrochloride. These polymerization initiators can be used alone or in combination of two or more. The blending amount of the polymerization initiator is preferably 0.001 to 2 parts by mass, preferably 0.01 to 1 part by mass, based on 100 parts by mass of the total polymerization components.

The polymer containing a repeating unit derived from the compound of the present invention is excellent in hydrophilicity. In addition, the hydrogel obtained from the polymer has high transparency and strength. Therefore, the compounds of the present invention are suitable for producing medical materials such as ophthalmic devices, contact lenses, intraocular lenses and artificial corneas. The method for producing a medical material using the polymer is not particularly limited, and a conventionally known method for producing a medical material may be followed. For example, when molding into the shape of a lens such as a contact lens or an intraocular lens, a cutting method or a mold method can be used.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples, ^{1 1} H-NMR analysis was carried out using ECS400 manufactured by JEOL and deuterated chloroform as a measurement solvent. All gas chromatograph (GC) measurements were performed under the following conditions.
Measuring device: Agilent gas chromatography (FID detector)
Capillary column: J & W HP-5MS (0.25 mm x 30 m x 0.25 μm)
Heating program: 50 ° C (5 minutes) → 10 ° C / min → 250 ° C (holding)
Inlet temperature 250 ° C, detector temperature FID 300 ° C
Carrier gas: Helium (1.0 ml / min)
Split ratio: 50: 1 Injection volume: 1 μL

ＧＰＳｉ：（３−グリシドキシプロピル）ビス（トリメチルシロキシ）メチルシラン

The compounds used in the following examples and comparative examples are as follows.
MeAGE: 2-Methyl-2-[(2-propene-1-loxy) methyl] oxylan

GPSi: (3-glycidoxypropyl) bis (trimethylsiloxy) methylsilane

以下に^１Ｈ−ＮＭＲデータを示す。
０．０−０．１ｐｐｍ（２１Ｈ）、０．４ｐｐｍ（２Ｈ）、１．４ｐｐｍ（３Ｈ）、１．６ｐｐｍ（２Ｈ）、２．６−２．８ｐｐｍ（２Ｈ）、３．３−３．４ｐｐｍ（２Ｈ）、３．４−３．６ｐｐｍ（２Ｈ）。 Example 1
[Step 1]
In a 300 mL three-necked eggplant flask equipped with a Dimroth condenser and a thermometer, 1,1,1,1,3,5,5,5-heptamethyltrisiloxane 95.0 g, MeAGE 50.0 g, and sodium chloroplatinate sodium bicarbonate neutralized under a nitrogen atmosphere. Toluene solution of vinyl siloxane complex (platinum content 0.5 wt%) 0.04 g was added, heated to 100 ° C., and aged for 2 hours. After the reaction, the solvent and unreacted raw materials were distilled off under reduced pressure at an internal temperature of 100 ° C. to obtain a colorless transparent liquid. Yield 123.0 g. ^{1 From 1} H-NMR, it was confirmed that the compound was represented by the formula (9A).

^{1 1} H-NMR data is shown below.
0.0-0.1ppm (21H), 0.4ppm (2H), 1.4ppm (3H), 1.6ppm (2H), 2.6-2.8ppm (2H), 3.3-3.4ppm (2H), 3.4-3.6 ppm (2H).

以下に^１Ｈ−ＮＭＲデータを示す。
０．０−０．１ｐｐｍ（２１Ｈ）、０．４ｐｐｍ（２Ｈ）、１．２ｐｐｍ（３Ｈ）、１．６ｐｐｍ（２Ｈ）、２．０ｐｐｍ（３Ｈ）、３．３−３．４ｐｐｍ（４Ｈ）、４．１ｐｐｍ（２Ｈ）、５．６ｐｐｍ（１Ｈ）、６．１ｐｐｍ（１Ｈ）。 [Step 2]
In a 300 mL three-necked eggplant flask equipped with a gym funnel, a thermometer, and a dropping funnel, 70.0 g of the compound represented by the formula (9A) obtained in the above [Step I], 70.0 g of methacrylic acid, and 6.5 g of sodium methacrylate. Was added, the mixture was heated to 100 ° C., and aged for 16 hours. After the reaction, 70.0 g of n-hexane was added, washed 4 times with 2M aqueous sodium hydroxide solution and 2 times with deionized water, and the solvent and unreacted raw materials were distilled off under reduced pressure at an internal temperature of 80 ° C. to make it colorless. A clear liquid was obtained. Yield 73.3g. ^{1 From 1} H-NMR, it was confirmed that the compound was represented by the formula (9B).

^{1 1} H-NMR data is shown below.
0.0-0.1ppm (21H), 0.4ppm (2H), 1.2ppm (3H), 1.6ppm (2H), 2.0ppm (3H), 3.3-3.4ppm (4H), 4.1 ppm (2H), 5.6 ppm (1H), 6.1 ppm (1H).

以下に^１Ｈ−ＮＭＲデータを示す。
０．０−０．１ｐｐｍ（１５Ｈ）、０．４ｐｐｍ（２Ｈ）、０．９ｐｐｍ（１８Ｈ）、１．４ｐｐｍ（３Ｈ）、１．６ｐｐｍ（２Ｈ）、２．６−２．８ｐｐｍ（２Ｈ）、３．３−３．４ｐｐｍ（２Ｈ）、３．４−３．６ｐｐｍ（２Ｈ）。
［工程ＩＩ］
実施例１の工程２において式（９Ａ）で表される化合物を式（１０Ａ）で表される化合物８７．０ｇに替えた他は実施例１を繰り返して無色透明液体を得た。収量７７．１ｇ。^１Ｈ−ＮＭＲにより下記式（１０Ｂ）で表される化合物であることを確認した。

以下に^１Ｈ−ＮＭＲデータを示す。
０．０−０．１ｐｐｍ（１５Ｈ）、０．４ｐｐｍ（２Ｈ）、０．９ｐｐｍ（１８Ｈ）、１．２ｐｐｍ（３Ｈ）、１．６ｐｐｍ（２Ｈ）、２．０ｐｐｍ（３Ｈ）、３．３−３．４ｐｐｍ（４Ｈ）、４．１ｐｐｍ（２Ｈ）、５．６ｐｐｍ（１Ｈ）、６．１ｐｐｍ（１Ｈ）。 Example 2
[Step 1]
Example 1 was repeated except that 1,1,1,3,5,5,5-heptamethyltrisiloxane was replaced with 131.9 g of (bis (t-butyldimethylsiloxy) methylsilane) in step 1 of Example 1. A colorless transparent liquid was obtained. Yield 135.1 g. ¹ It was confirmed by H-NMR that the compound was represented by the following formula (10A).

^{1 1} H-NMR data is shown below.
0.0-0.1ppm (15H), 0.4ppm (2H), 0.9ppm (18H), 1.4ppm (3H), 1.6ppm (2H), 2.6-2.8ppm (2H), 3.3-3.4 ppm (2H), 3.4-3.6 ppm (2H).
[Step II]
A colorless transparent liquid was obtained by repeating Example 1 except that the compound represented by the formula (9A) was replaced with 87.0 g of the compound represented by the formula (10A) in step 2 of Example 1. Yield 77.1 g. ¹ It was confirmed by ¹ H-NMR that the compound was represented by the following formula (10B).

^{1 1} H-NMR data is shown below.
0.0-0.1ppm (15H), 0.4ppm (2H), 0.9ppm (18H), 1.2ppm (3H), 1.6ppm (2H), 2.0ppm (3H), 3.3- 3.4 ppm (4H), 4.1 ppm (2H), 5.6 ppm (1H), 6.1 ppm (1H).

Examples 3 to 6, Comparative Example 1
In step 2 of Example 1 above, an epoxy compound represented by the formula (9A) or (10A), GPSi, methacrylic acid or acrylic acid was added to the three-necked eggplant flask so as to have the composition shown in Table 1 below. The molar ratio and catalyst concentration of each component are as in step 2 of Example 1. Then, it was heated to 100 degreeC and aged for 16 hours. After the reaction, n-hexane is added, washed 4 times with 2M aqueous sodium hydroxide solution and 2 times with deionized water, and the solvent and unreacted raw materials are distilled off under reduced pressure at an internal temperature of 80 ° C. to obtain a colorless transparent liquid. Obtained.

In each of the production methods of Examples 1 to 6 and Comparative Example 1, GC measurement was performed after the reaction, and the purity of each product was calculated from the area%. The results are shown in Table 1.

As shown in Table 1, according to the production method of the present invention, side reactions during the addition reaction of (meth) acrylic acid and the epoxy group are suppressed, and therefore, the purity is higher than that of the production method of Comparative Example 1. It is possible to produce a siloxane compound. Further, according to the production method of the present invention, a siloxane compound having glycerol (meth) acrylate can be obtained with a high purity of more than 90% even if the type of carboxylic acid or the type of catalyst is changed.

ＴＲＩＳ：３−［トリス（トリメチルシロキシ）シリル］プロピルメタクリレート

[Examples 7 to 10 and Comparative Examples 2 to 4]
Examples of Hydrogel Production Examples Compounds (9B) and (10B) obtained in Examples 1 and 2, SiGMA represented by the following formula, 3- [Tris (trimethylsiloxy) silyl] propyl methacrylate represented by the following formula ( TRIS), 2-hydroxyethyl methacrylate (HEMA), N, N-dimethylacrylamide (DMA), ethylene glycol dimethacrylate (EGDMA), Irgacure 1173 (Irg1173), the composition and compounding ratio (parts by mass) shown in Table 2 or 3. ), And stirred until a uniform solution was obtained. After stirring, bubbling with N ₂ was performed for 5 minutes to sufficiently degas, and then the mixture was sealed in a polypropylene mold. UV irradiation was performed using a high-pressure mercury lamp and the mixture was cured. After curing, it was washed by immersing it in the order of isopropanol, 50% isopropanol aqueous solution, and deionized water for several seconds to obtain a hydrogel film. Each physical property value of the obtained film was measured according to the method shown below. The results are shown in Tables 2 and 3.
SiGMA: Methylbis (trimethylsiloxy) Cyrilpropylglycerol methacrylate

TRIS: 3- [Tris (trimethylsiloxy) Cyril] Propyl Methacrylate

[Equilibrium moisture content]
After immersing the film in deionized water at 25 ° C. for 48 hours, the water on the surface was wiped off, and the mass of the hydrated film was measured. Next, the hydrated film was dried in an oven at 50 ° C. for 48 hours and in an oven at 25 ° C. for 24 hours, and the mass of the dried film was measured. The equilibrium water content was calculated by the following formula.
Equilibrium moisture content (%) = 100 x (mass of hydrated film-mass of dried film) / mass of hydrated film

[transparency]
After immersing the film in deionized water at 25 ° C. for 48 hours, the water on the surface was wiped off to prepare a hydrated film. The appearance was visually observed and evaluated by the following indexes.
A: Uniform and transparent
B: Non-uniform or cloudy

[Elastic modulus]
After immersing the film in deionized water at 25 ° C. for 48 hours, the water on the surface was wiped off to prepare a hydrated film. The Young elastic modulus of the hydrated film was measured using an Instron 5943. A film cut into 0.8 cm x 4.0 cm was measured with a 50 N load cell and a head speed of 1 cm / min, and the stress obtained on the vertical axis and the strain on the horizontal axis were taken as the initial stress-strain curve ( The slope of the straight part) was calculated and used as the Young elastic modulus (MPa).

As shown in Table 2 above, the hydrogel using TRIS as the comparative compound has difficulty in transparency, and the hydrogel using SiGMA as the comparative compound has an excessively high elastic modulus. On the other hand, the hydrogel using the siloxane compound of the present invention has excellent transparency and an appropriate elastic modulus. That is, hydrogels using the compounds of the present invention provide materials with beneficial hydrophilicity and sufficient strength.

According to the production method of the present invention, a siloxane compound that gives a hydrogel having excellent hydrophilicity and strength can be obtained. The siloxane compound is useful as a medical material, for example, a monomer for manufacturing ophthalmic devices, contact lenses, intraocular lenses, artificial corneas, and spectacle lenses.

Claims (10)

Siloxane represented by the following formula (1)

(In the formula, R ¹ is a hydrogen atom or a methyl group, R ² is a monovalent hydrocarbon group having 1 to 6 carbon atoms, and L is a divalent hydrocarbon having 2 to 10 carbon atoms which may contain an ether bond. It is a hydrogen group, and A is a group represented by the following formula (2) or (3).

In the above formula (2), n is an integer of 1 to 100, in the above formula (3), a is an integer of 0 to 10, b is an integer of 0 to 10, and c is an integer of 0 to 10. Yes, but a + b + c is 2 or more, and R is a monovalent hydrocarbon group having 1 to 10 carbon atoms independently of each other)
It is a manufacturing method of
Epoxy compound represented by the following formula (5)

And ^{(wherein, R} 2, L, and A are as defined above),
By reacting with (meth) acrylic acid,
The method for producing a siloxane, which comprises a step of obtaining a compound represented by the above formula (1). The production method according to claim 1, wherein L in the formula (1) is a divalent group represented by the following formula (4).

(In equation (4), p is an integer of 1 to 2, q is an integer of 1 to 4, * is a bond with a carbon atom in equation (1), and ** is equation (1). It is a connection point with A in). The production method according to claim 1 or 2, wherein A is represented by the above formula (3) in the formula (1), a is 1, b is 1, and c is 0. The production method according to any one of claims 1 to 3, wherein R ² is a methyl group in the formula (1). The production method according to any one of claims 1 to 4, wherein in the formulas (2) and (3), R is an alkyl group or a phenyl group having 1 to 6 carbon atoms independently of each other. The production method according to claim 5, wherein R is a methyl group, an n-butyl group, or a t-butyl group independently of each other. The reaction between the compound of the above formula (5) and (meth) acrylic acid is selected from alkali metal salts of (meth) acrylic acid, amine compounds, phosphorus compounds, or aluminum, titanium, iron, zinc and tin. The production method according to any one of claims 1 to 6, which is carried out in the presence of any one of a metal catalyst containing one or more. Hydrogen siloxane represented by the following formula (6) or (7)

(N, a, b, c, and R are as described above) and the unsaturated compound represented by the following formula (8).

(R ² is as described above, R ³ is a hydrogen atom or a methyl group, and L'is a divalent hydrocarbon group having 1 to 8 carbon atoms, which may contain a single bond or an ether bond.)
The production method according to any one of claims 1 to 7, further comprising a step of hydrosilylating with and to obtain an epoxy compound represented by the above formula (5). The production method according to claim 8, wherein L'is a group represented by the following formula (4') or (4 ″).

(In equation (4'), p is an integer of 1-2, q'is an integer of 0-2, and in equations (4') and (4''), the part represented by * and **. Is the bond site, of which ** is the bond site with the unsaturated bond in equation (8)) The production method according to claim 8 or 9, wherein R is an alkyl group or a phenyl group having 1 to 6 carbon atoms independently of each other.