阅读说明：本技术 (甲基)丙烯酰基化合物和其制造方法 ((meth) acryloyl compound and method for producing same ) 是由 冈村薰 于 2019-08-22 设计创作，主要内容包括：本发明提供具有有益的亲水性和充分的强度的、适合于医疗用材料的(甲基)丙烯酰基化合物和其制造方法。解决手段为下式(1)表示的化合物及其制造方法。(式中,R～1为氢原子或甲基,R～2为碳原子数1～6的一价烃基,R～3为氢原子或甲基,L为可以含有醚键的、碳原子数2～10的二价烃基)。(The present invention provides a (meth) acryloyl compound having beneficial hydrophilicity and sufficient strength suitable for medical materials, and a method for producing the same. The solution is a compound represented by the following formula (1) and a method for producing the same. (in the formula, R 1 Is a hydrogen atom or a methyl group, R 2 Is a C1-6 monovalent hydrocarbon group, R 3 A hydrogen atom or a methyl group, and L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may have an ether bond).)

1. A compound represented by the following formula (1),

[ solution 1]

In the formula, R¹Is a hydrogen atom or a methyl group，R²Is a C1-6 monovalent hydrocarbon group, R³Is a hydrogen atom or a methyl group, and L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may have an ether bond.

2. The compound of claim 1, wherein R¹Is methyl.

3. The compound according to claim 1 or 2, wherein L is represented by the following formula (2), n is 1 or 2,

[ solution 2]

The sites denoted by and are bonding sites.

4. A compound according to any one of claims 1 to 3, wherein R²Is methyl.

A (co) polymer comprising repeating units derived from the polymerization of (meth) acryloyl groups of a compound of any one of claims 1 to 4.

6. The (co) polymer according to claim 5, wherein the mass ratio of the repeating unit is 10% by mass or more relative to the total mass of the (co) polymer.

7. A hydrogel comprising the (co) polymer of claim 5 or 6.

8. A medical material comprising the (co) polymer of claim 5 or 6.

9. A process for producing a compound represented by the following formula (1),

[ solution 3]

In the formula (1), R¹Is a hydrogen atom or a methyl group, R²Is a C1-6 monovalent hydrocarbon group, R³Is a hydrogen atom or a methyl group, L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may have an ether bond,

which comprises a step of reacting an epoxy compound represented by the following formula (3) with (meth) acrylic acid to obtain a compound represented by the above formula (1),

[ solution 4]

R²、R³And L is as described above.

10. The manufacturing method according to claim 9, wherein R¹Is a methyl group, L is represented by the following formula (2), n is 1 or 2,

[ solution 5]

The sites denoted by and are bonding sites.

11. A process for producing an epoxy compound represented by the following formula (3),

[ solution 6]

R²、R³And L is as described above, and L is,

which comprises a step of reacting an alcohol compound represented by the following formula (4) with an epoxy compound represented by the following formula (5) to obtain an epoxy compound represented by the above formula (3),

[ solution 7]

R³As described above, L' is a single bond or a divalent hydrocarbon group having 1 to 8 carbon atoms which may have an ether bond,

[ solution 8]

R²As mentioned above, X is a halogen atom.

12. The production process according to claim 11, wherein L is represented by the following formula (2), n is 1 or 2,

[ solution 9]

The sites indicated by and are bonding sites.

Technical Field

The present invention relates to a (meth) acryloyl compound. Specifically disclosed are a (meth) acryloyl compound suitable for a medical material and a method for producing the same.

Background

Conventionally, as an acryl compound used for a medical material, a hydrophilic compound such as N, N-dimethylacrylamide and 2-hydroxyethyl methacrylate is known. These are compatible with other acryl compounds, and polymers obtained by (co) polymerizing them have high transparency, strength, and affinity with water, and thus are suitable as medical materials. Patent documents 1 and 2 describe compounds having a terminal unsaturated bond and a (meth) acryloyl group represented by the following formula (a) or (a') in order to make the strength of the material more desirable. Such a bifunctional compound can be used as a crosslinking component, and further, various functional groups and functions can be introduced by utilizing an unsaturated bond. Further, since it has a hydroxyl group, it is suitable as a hydrogel material such as a medical material.

[ solution 1]

Documents of the prior art

Patent document

Patent document 1: japanese laid-open patent publication No. 50-128740

Patent document 2: japanese patent laid-open No. 2006 and 193429.

Disclosure of Invention

Problems to be solved by the invention

However, when the compound represented by the above formula (a) or (a') is a compound having an unsaturated bond into which another functional group is introduced or a compound having a 2-fold cross-linked structure is formed, an undesirable side reaction may occur because the reactivity of a hydroxyl group present in the molecule is high. For example, when a crosslinked structure is formed by radical addition to an unsaturated bond, a radical is added to a hydroxyl group to form a crosslinked structure using a hydroxyl radical, and thus unexpected hardness (e.g., increase in elastic modulus) and decrease in hydrophilicity due to decrease in hydroxyl groups may occur. Therefore, the above-mentioned acryl compound cannot provide a medical material having a favorable hydrophilicity and a sufficient strength.

In view of the above circumstances, the present invention provides a (meth) acryloyl compound having advantageous hydrophilicity and sufficient strength, which is suitable for a medical material, and a method for producing the same.

Means for solving the problems

The present inventors have conducted intensive studies to solve the above problems and have found that a (meth) acryl compound having a tertiary hydroxyl group does not react with a tertiary hydroxyl group during polymerization, and thus can provide a (co) polymer having excellent hydrophilicity and sufficient strength, and have completed the present invention.

Namely, the present invention provides a (meth) acryloyl compound represented by the following formula (1).

[ solution 2]

(in the formula, R¹Is a hydrogen atom or a methyl group, R²Is a C1-6 monovalent hydrocarbon group, R³A hydrogen atom or a methyl group, and L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may have an ether bond).

Further, the present invention provides a method for producing the (meth) acryloyl compound, a (co) polymer comprising a repeating unit derived from the compound, and a hydrogel and a medical material, particularly a contact lens, each containing the (co) polymer.

Effects of the invention

The (meth) acryloyl compound of the present invention has a terminal unsaturated bond in addition to a (meth) acryloyl group in a molecule, and therefore forms a crosslinked structure by polymerization of an unsaturated bond in addition to polymerization of a (meth) acryloyl group, and provides a (co) polymer having preferable strength. In addition, since it has a tertiary hydroxyl group, the compatibility with a hydrophilic monomer is excellent. Further, since the tertiary hydroxyl group does not undergo a side reaction, a (co) polymer having excellent hydrophilicity and sufficient strength can be provided.

Detailed Description

The (meth) acryloyl compound of the present invention is described in detail below.

The compound of the present invention is a (meth) acryloyl compound represented by the above formula (1). The compound is characterized by having a (meth) acryloyl group, a terminal unsaturated bond, and a tertiary hydroxyl group. The compound has excellent compatibility with a hydrophilic monomer, and the (co) polymer can have preferable strength by using the compound as a monomer or a crosslinking agent. In addition, since the hydroxyl group as a hydrophilic group is tertiary, side reactions can be suppressed. By these features, the strength of the (co) polymer can be improved while maintaining compatibility with other hydrophilic monomers.

In the above formula (1), R¹Is a hydrogen atom or a methyl group, preferably a methyl group.

In the above formula (1), R²Is a monovalent hydrocarbon group having 1 to 6 carbon atoms. Examples of the monovalent hydrocarbon group include alkyl groups such as methyl, ethyl, propyl, butyl, pentyl and hexyl; cycloalkyl groups such as cyclopentyl and cyclohexyl; aryl groups such as phenyl and the like. R²Preferably an alkyl group having 1 to 4 carbon atoms, and more preferably a methyl group.

In the above formula (1), R³Is a hydrogen atom or a methyl group. Preferably a hydrogen atom.

In the formula (1), L is a divalent hydrocarbon group having 2 to 10 carbon atoms which may contain an ether bond. Preferably a group represented by the following formula (2), and n is 1 or 2.

[ solution 3]

(sites indicated by and are bonding sites).

Examples of the divalent hydrocarbon group having 1 to 10 carbon atoms include methylene, ethylene, 1, 3-propylene, 1-methylpropylene, 1-dimethylpropylene, 2-methylpropylene, 1, 2-dimethylpropylene, 1, 2-trimethylpropylene, 1, 4-butylene, 2-methyl-1, 4-butylene, 2-dimethyl-1, 4-butylene, 3-methyl-1, 4-butylene, 2-dimethyl-1, 4-butylene, 2, 3-dimethyl-1, 4-butylene, 2, 3-trimethyl-1, 4-butylene, 1, 5-pentylene, 1, 6-hexylene, 1, 4-hexylene, and the like, 1, 7-heptylene, 1, 8-octylene, 1,9-Nonylene and 1, 10-decylene, and the like. Examples of the ether bond-containing group include polyoxyalkylenes such as polyoxyethylene, polyoxypropylene, and polyethylene-propylene oxide. Is preferably-CH₂OCH₂-or-CH₂OC₂H₄OCH₂-。

The following describes a method for producing the compound represented by the above formula (1).

The production method of the present invention includes a step (hereinafter referred to as step II) of reacting an epoxy compound represented by the following formula (3) with (meth) acrylic acid to obtain a compound represented by the above formula (1).

[ solution 4]

(R²、R³L as described above)

The production method of the present invention further includes a step (hereinafter referred to as step I) of reacting the alcohol compound represented by the following formula (4) with the epoxy compound represented by the following formula (5) to obtain the epoxy compound represented by the above formula (3).

[ solution 5]

(R³As described above, L' is a single bond or a C1-8 divalent hydrocarbon group which may have an ether bond)

[ solution 6]

(R²As mentioned above, X is a halogen atom)

The respective steps will be described in detail below.

And (I).

This step is a step of reacting an alcohol compound represented by the following formula (4) with an epoxy compound represented by the following formula (5) to obtain an epoxy compound represented by the above formula (3).

[ solution 7]

(R³As described above, L' is a single bond or a divalent hydrocarbon group having 1 to 8 carbon atoms which may have an ether bond)

[ solution 8]

(R²As mentioned above, X is a halogen atom)

In the above formula (4), L^’As described above, the divalent hydrocarbon group may contain an ether bond and has 1 to 8 carbon atoms. Preferably a group represented by the following formula (2 '), n' is 0 or 1. n 'is 0 means that L' in the above formula (4) is a single bond.

[ solution 9]

(the sites indicated by and are bonding sites)

That is, the group represented by the formula (4) is preferably represented by the following (2 ' ') or (2 ' ' ').

[ solution 10]

In the above formula (5), X is a halogen atom as described above. Examples of the halogen atom include fluorine, chlorine, bromine, and iodine.

The reaction of the alcohol compound with the epoxy compound can be carried out according to a conventionally known method. For example, 1 molar equivalent or more of an epoxy compound may be added to the alcohol compound to carry out the reaction. The reaction temperature is not particularly limited, and a temperature not exceeding the boiling point of the solvent used is preferred. For example, it may be carried out at a temperature of about 0 ℃ to about 120 ℃. The reaction may be carried out in the presence of a solvent or a catalyst. The solvent and the catalyst may be those conventionally known, and are not particularly limited.

Examples of the catalyst include basic compounds, organophosphorus compounds, tertiary amines, and Lewis acids. Examples of the basic compound include hydroxides of alkali metals and alkaline earth metals such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide. Examples of the organophosphorus compound include tricyclohexylphosphine, tributylphosphine, trioctylphosphine, cyclohexyldiphenylphosphine, dicyclohexylphenylphosphine, butyldiphenylphosphine, dibutylphenylphosphine, octyldiphenylphosphine, dioctylphenylphosphine, and triphenylphosphine. Examples of the tertiary amine include trimethylamine, triethylamine, tripropylamine, tributylamine, diazabicycloundecene, diazabicyclononene, and 1-methylimidazole. Examples of the lewis acid include boron trifluoride, aluminum chloride, methylaluminum dichloride, dimethylaluminum chloride, trimethylaluminum, magnesium chloride, magnesium bromide, titanium tetrachloride, titanium dichloride bistrifluoromethanesulfonate, dicyclopentadiene titanium bistrifluoromethanesulfonate, titanium dichloride bistrifluoromethanesulfonate, tin tetrachloride, tin (II) bistrifluoromethanesulfonate, and the like. The catalyst can be used alone in 1, also can be used in 2 or more combination.

Examples of the solvent include glycol ether solvents such as 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 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; alicyclic hydrocarbon solvents such as cyclohexane and 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. The solvent can be used alone in 1, also can be used in 2 or more combination.

And II, performing step II.

This step is a step of reacting an epoxy compound represented by the following formula (3) with (meth) acrylic acid to obtain a compound represented by the above formula (1).

[ solution 11]

(R²、R³L as described above)

This reaction can be carried out according to a conventionally known method. For example, 1 molar equivalent or more of (meth) acrylic acid may be added to the epoxy compound represented by the formula (3) to carry out the reaction. The reaction temperature is not particularly limited, and a temperature not exceeding the boiling point of the solvent used is preferred. For example, it may be carried out at a temperature of from about 0 ℃ to about 110 ℃. The reaction can be carried out in the presence of a solvent, a catalyst, and a stabilizer. The solvent, catalyst and stabilizer may be any conventionally known ones, and are not particularly limited. The solvent may be the aforementioned solvent.

Examples of the catalyst include organometallic catalysts, basic compounds, organophosphorus compounds, amine catalysts, and Lewis acids. Examples of the basic compound include the basic compounds described above. The organic metal catalyst is not particularly limited, and examples thereof include organic tin catalysts such as sodium (meth) acrylate, potassium (meth) acrylate salts, stannous diacetate, stannous dioctoate, stannous dioleate, stannous dilaurate, dibutyltin oxide, dibutyltin diacetate, dibutyltin dilaurate, dibutyltin dichloride, and dioctyltin dilaurate, and acetylacetonato metal salts such as aluminum acetylacetonate, iron acetylacetonate, copper acetylacetonate, zinc acetylacetonate, beryllium acetylacetonate, chromium acetylacetonate, indium acetylacetonate, manganese acetylacetonate, molybdenum acetylacetonate, titanium acetylacetonate, cobalt acetylacetonate, vanadium acetylacetonate, and zirconium acetylacetonate. Examples of the amine catalyst include pentamethyldiethylenetriamine, triethylamine, N-methylmorpholine bis (2-dimethylaminoethyl) ether, N ', N "-pentamethyldiethylenetriamine, N ' -trimethylaminoethyl-ethanolamine, bis (2-dimethylaminoethyl) ether, N-methyl-N ' -dimethylaminoethylpiperazine, N-dimethylcyclohexylamine, diazabicycloundecene, triethylenediamine, tetramethylhexamethylenediamine, N-methylimidazole, trimethylaminoethylpiperazine, tripropylamine, tetramethylammonium salt, tetraethylammonium salt, and triphenylammonium salt, in addition to the tertiary amine and the like. The catalyst can be used alone in 1, also can be used in 2 or more combination.

Examples of the stabilizer include a phenol-based antioxidant, a phosphorus-based antioxidant, an amine-based antioxidant, and a sulfur-based antioxidant. The phenol-based antioxidant is not particularly limited, and examples thereof include compounds selected from the group consisting of p-methoxyphenol, di-t-butyl-p-cresol, pyrogallol, t-butylcatechol, 4-thiobis (3-methyl-6-t-butylphenol), 2' -methylenebis (4-methyl-6-t-butylphenol), phenol resins, and cresol resins. The phosphorus-based antioxidant is not particularly limited, and examples thereof include tris [2- [ [2,4,8, 10-tetrakis (1, 1-dimethylethyl) dibenzo [ d, f ] [1,3,2] dioxaphosphepin-6-yl ] oxy ] ethyl ] amine, tris [2- [ (4,6,9, 11-tetra-tert-butyldibenzo [ d, f ] [1,3,2] dioxaphosphepin-2-yl) oxy ] ethyl ] amine, and ethylbis (2, 4-di-tert-butyl-6-methylphenyl) phosphite. The amine-based antioxidant is not particularly limited, and examples thereof include tri-or tetra-C1-3 alkylpiperidines or derivatives thereof, bis (2,2,6, 6-tetramethyl-4-piperidyl) oxalate, 1, 2-bis (2,2,6, 6-tetramethyl-4-piperidyloxy) ethane, phenylnaphthylamine, 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 dilauryl thiodipropionate and distearyl thiodipropionate. The stabilizer may be used alone in 1 kind, or may be used in combination of 2 or more kinds.

In any of the above reactions, the end point of the reaction can be confirmed by confirming the disappearance of the peak of the raw material compound by a conventionally known method, for example, Thin Layer Chromatography (TLC), High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), or the like. After the reaction is completed, purification may be carried out by a conventionally known method. For example, the product can be isolated by washing the organic layer with water and removing the solvent. Further, distillation under reduced pressure, activated carbon treatment, or the like may be used.

As an example of the production method of the present invention, 1 molar equivalent of the alcohol compound represented by the above formula (4), 1 molar equivalent of the epoxy compound represented by the above formula (5), 1 molar equivalent of potassium hydroxide, and 100 mass equivalents of n-hexane may be added and stirred at 20 ℃. The reaction was completed by allowing the reaction to proceed for about 4 hours. In addition, the progress of the reaction can be confirmed by monitoring the epoxy compound or the compound produced by the reaction by GC measurement or the like. After the completion of the reaction, the organic layer was washed with water, and the solvent and unreacted raw materials present in the organic layer were distilled off under reduced pressure, whereby an epoxy compound represented by the above formula (3) was obtained.

Then, 1 molar equivalent of the epoxy compound represented by the above formula (3), 2 molar equivalents of methacrylic acid, and 0.3 molar equivalent of sodium methacrylate were added. After the addition, the mixture was stirred with heating at 100 ℃. The reaction was completed by allowing the reaction to proceed for about 10 hours. In addition, the progress of the reaction can be confirmed by monitoring the epoxy compound or the compound produced by the reaction by GC measurement or the like. After the reaction, 100 mass equivalents of toluene was added, the organic layer was washed with water, and the solvent and unreacted raw materials present in the organic layer were distilled off under reduced pressure to obtain an acryloyl compound represented by formula (1) above.

The compound of the present invention can provide a polymer having a repeating unit derived from addition polymerization of a (meth) acryloyl group. The compound of the present invention has good compatibility with other compounds having a polymerizable group such as a (meth) acryloyl group (hereinafter referred to as polymerizable monomers or hydrophilic monomers). Therefore, by copolymerizing with a polymerizable monomer, a colorless and transparent copolymer can be obtained. In addition, the polymerization can be carried out alone.

Further, since the compound of the present invention has a terminal unsaturated bond in addition to the (meth) acryloyl group, the terminal unsaturated bond can be polymerized to form a crosslinked structure after the copolymerization reaction with the other polymerizable monomer. In this case, since the tertiary hydroxyl groups present in the molecule do not react, a decrease in equilibrium water content and an unexpected increase in elastic modulus can be suppressed, and a hydrogel having high strength can be provided. The reaction for forming a crosslinked structure by polymerizing the terminal unsaturated bond can be carried out in the same step as the copolymerization reaction of the (meth) acryloyl group, if a sufficient amount of the initiator is present. Even in the case of this same step, polymerization of the terminal unsaturated bond occurs after the copolymerization of the (meth) acryloyl group due to the difference in reactivity.

In the production of a copolymer containing a repeating unit derived from polymerization of the compound of the present invention and another polymerizable (hydrophilic) monomer, the proportion of the compound of the present invention may be 10% or more by mass of the repeating unit derived from the compound of the present invention relative to the mass of the entire polymer. 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, based on 100 parts by mass of the total of the compound of the present invention and the polymerizable (hydrophilic) monomer. The weight average molecular weight of the (co) polymer is not particularly limited, and may be 1,000 to 1,000,000, preferably 1,000 to 100,000, as a value measured by Gel Permeation Chromatography (GPC).

Examples of the other polymerizable (hydrophilic) monomer include acrylic monomers such as (meth) acrylic acid, methyl (meth) acrylate, ethyl (meth) acrylate, poly (ethylene glycol dimethacrylate), polyalkylene glycol mono (meth) acrylate, polyalkylene glycol monoalkyl ether (meth) acrylate, trifluoroethyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, and 2, 3-dihydroxypropyl (meth) acrylate; acrylic acid derivatives such as N, N-dimethylacrylamide, N-diethylacrylamide, N-acryloylmorpholine and N-methyl (meth) acrylamide; n-vinylpyrrolidone and the like, other unsaturated aliphatic or aromatic compounds such as crotonic acid, cinnamic acid, vinylbenzoic acid; and a siloxane monomer having a polymerizable group such as a (meth) acryloyl group. These can be used alone in 1 kind, also can be used in 2 or more.

The copolymerization of the compound of the present invention and the other polymerizable monomer can be carried out by a conventionally known method. For example, the polymerization 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, t-butyl hydroperoxide, cumene hydroperoxide, 2' -azobis (2-methylpropionamidine) 2 hydrochloride, and the like. These polymerization initiators may be used alone or in combination of 2 or more. The amount of the polymerization initiator is 0.001 to 2 parts by mass, preferably 0.01 to 1 part by mass, based on 100 parts by mass of the total of the polymerization components.

The polymer comprising a repeating unit derived from the compound of the present invention is excellent in hydrophilicity. In addition, the hydrogel obtained from the polymer is excellent in strength and wettability. Thus, the compounds of the present invention are useful in the manufacture of materials for medical use, such as ophthalmic instruments, contact lenses, intraocular lenses, 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 used. For example, when the shape of a lens such as a contact lens or an intraocular lens is molded, a cutting method, a mold (mold) method, or the like can be used.

Examples

The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples. In the embodiment described below, it is preferred that,¹H-NMR analysis was performed using ECS400 manufactured by JEOL, and the solvent was measured using deuterated chloroform.

Example 1

[ step I ]

To a 1L three-necked flask equipped with a serpentine condenser and a thermometer were added 225.0g of 2- (chloromethyl) -2-methyloxirane, 125.0g of allyl alcohol, 225.0g of n-hexane, and 68.2g of potassium hydroxide, and the mixture was stirred at 20 ℃ for 10 hours. After the reaction, the mixture was washed with deionized water 3 times, and then distilled under reduced pressure to obtain a colorless transparent liquid. Yield 176.6 g. The compound represented by the following formula (6A) was confirmed by 1H-NMR.

[ solution 12]

[ step II ]

50.0g of the compound represented by the formula (6A) obtained in the above-mentioned [ step I ], 70.0g of methacrylic acid and 5.0g of sodium methacrylate were charged into a 300mL three-necked flask equipped with a serpentine condenser, a thermometer and a dropping funnel, heated to 100 ℃ and aged for 4 hours. After the reaction, 100.0g of toluene was added, and the mixture was washed with 2M aqueous sodium hydroxide solution 3 times, washed with deionized water 2 times, and the solvent, unreacted raw materials, and the like were distilled off under reduced pressure at an internal temperature of 80 ℃ to obtain a colorless transparent liquid. Yield 67.3 g. The compound represented by the formula (6B) was confirmed by 1H-NMR.

[ solution 13]

The following shows 1H-NMR data.

1.1ppm(3H)、2.0ppm(3H)、3.4ppm(2H)、4.1ppm(2H)、4.3ppm(2H)、5.3ppm(2H)、5.6ppm(1H)、5.9ppm(1H)、6.1ppm(1H)。

Example 2

[ step I ]

Step I of example 1 was repeated except that allyl alcohol was replaced with 220.0g of allyl glycol in step I of example 1 to obtain a colorless transparent liquid. Yield 180.0 g. The compound represented by the following formula (7A) was confirmed by 1H-NMR.

[ solution 14]

[ step II ]

Step II of example 1 was repeated except for replacing 67.2g of the compound represented by formula (7A) with the compound represented by formula (6A) in step II of example 1 to obtain a colorless transparent liquid. Yield 67.3 g. The compound represented by the formula (7B) was confirmed by 1H-NMR.

[ solution 15]

The following shows 1H-NMR data.

1.1ppm(3H)、2.0ppm(3H)、3.4ppm(6H)、4.1ppm(2H)、4.3ppm(2H)、5.3ppm(2H)、5.6ppm(1H)、5.9ppm(1H)、6.1ppm(1H)。

Comparative example 1

The comparative compound used in comparative example 1 was a compound having a secondary hydroxyl group represented by the following formula (a), and contained an isomer having a primary hydroxyl group represented by the following formula (a').

[ solution 16]

Comparative example 2

The comparative compound used in comparative example 2 was Allyl Methacrylate (AMA) and had no hydroxyl group.

Production examples of hydrogels (examples 1 to 2 and comparative examples 1 to 2)

[ first polymerization ]

The compounds or comparative compounds obtained in the above examples, Methyl Methacrylate (MMA), N, N-Dimethylacrylamide (DMA), N, N' -Methylenebisacrylamide (MBA), and Azobisisobutyronitrile (AIBN) were mixed at the mixing ratios shown in table 1, and stirred until a uniform solution was obtained. After stirring N₂After bubbling for 5 minutes and sufficiently degassing, the mixture was sealed in a polypropylene mold (thickness: 200 μm). The mold in which the solution was enclosed was left to stand in an oven at 70 ℃ under a nitrogen atmosphere for 4 hours to be cured. After curing, the resin was taken out of the mold and washed with deionized water to obtain a hydrogel film. The physical property values of the obtained film were measured by the following methods. The results are shown in Table 1.

[ second polymerization ]

The hydrogel film obtained in the above-described first polymerization step was immersed in a 1% aqueous solution of 2,2' -azobis (2-methylpropionamidine) 2 hydrochloride (V-50) for 4 hours, and further polymerized (cured) by standing in an oven at 70 ℃ for 6 hours in a nitrogen atmosphere. The hydrogel obtained was washed with 2-propanol and deionized water. The physical property values of the obtained film were measured by the following methods. The results are shown in Table 1.

Production examples of hydrogels (examples 3 to 4 and comparative examples 3 to 4)

The respective compounds or comparative compounds obtained in the above examples, Methyl Methacrylate (MMA), N, N-Dimethylacrylamide (DMA), N, N' -Methylenebisacrylamide (MBA), and Azobisisobutyronitrile (AIBN) were mixed at the mixing ratios shown in table 2, and stirred until a uniform solution was formed. After stirring N₂After bubbling for 5 minutes and sufficiently degassing, the mixture was sealed in a polypropylene mold (thickness: 200 μm). The mold in which the solution was enclosed was left to stand in an oven at 70 ℃ under a nitrogen atmosphere for 8 hours to be cured. After curing, the resin was removed from the mold and washed with 2-propanol and deionized water to obtain a hydrogel film. The physical property values of the obtained film were measured by the following methods. The results are shown in Table 2.

[ equilibrium moisture content ]

After the film was soaked in deionized water at 25 ℃ for 48 hours, the surface was wiped off to measure the mass of the hydrated film. The hydrated film was then dried in an oven at 50 ℃ for 48 hours and in an oven at 25 ℃ for 24 hours, and the mass of the dried film was measured. The equilibrium water content was calculated by the following equation.

Equilibrium water content (%) =100 × { (mass of hydrated membrane-mass of dried membrane)/mass of hydrated membrane }

[ modulus of elasticity ]

The film was immersed in deionized water at 25 ℃ for 48 hours, and then the surface was wiped off to prepare a hydrated film. The Young's modulus of elasticity of the hydrated film was measured by instron 5943. The film cut to 0.8cm × 4.0cm was measured with a 50N load cell at a head speed of 1 cm/min, and the slope of the initial phase (straight line portion) of the stress-strain curve with the obtained stress on the vertical axis and strain on the horizontal axis was calculated as the young's modulus (MPa).

TABLE 1

TABLE 2

As shown in table 1, the hydrogel using the comparative compound having secondary and primary hydroxyl groups greatly decreased the equilibrium water content after the second polymerization, and the elastic modulus also significantly increased. In addition, the hydrogel using the comparative compound having no hydroxyl group had a low equilibrium water content and insufficient hydrophilicity. On the other hand, the hydrogel using the compound of the present invention having a tertiary hydroxyl group has a high equilibrium water content, and the decrease in the equilibrium water content after the second polymerization is small.

This is because in the case of polymerization of unsaturated bonds, secondary or primary hydroxyl groups in the compound of comparative example 1 are also reacted, while tertiary hydroxyl groups are not reacted. The compound of the present invention does not undergo crosslinking reaction of unnecessary hydroxyl groups, and therefore can provide a hydrogel in which lowering of the water content and unexpected increase in elastic modulus are suppressed in equilibrium.

As shown in table 2, the same results were obtained also in the case where polymerization of a (meth) acryloyl group and reaction of an unsaturated bond were carried out in the same step.

Therefore, hydrogels using the compounds of the present invention can have beneficial hydrophilicity with sufficient strength.

Industrial applicability

The compound of the present invention improves the hydrophilicity and strength of the resulting hydrogel. The compounds of the present invention are useful as medical materials, for example, ophthalmic instruments, contact lenses, intraocular lenses, artificial corneas, and monomers for the production of spectacle lenses.