JP4859450B2 - Phosphono group-containing polymerizable compound - Google Patents

Description

  The present invention relates to a phosphono group-containing polymerizable compound, and in particular, an adhesive composition that exhibits excellent adhesive strength and excellent adhesion durability, particularly when used as a dental adhesive or dental adhesive primer. And a novel phosphono group-containing polymerizable compound.

  For the restoration of teeth damaged by caries or the like, a filling material called a composite resin is mainly used. This composite resin is generally used after being filled into a cavity of a tooth and then cured by polymerization.

  However, since this material itself does not have adhesiveness to the tooth, a dental adhesive is used in combination. This adhesive material is required to have an adhesive strength sufficient to overcome internal stress generated when the composite resin is cured, that is, tensile stress generated at the interface between the composite resin and the tooth. Otherwise, there is a possibility of not only dropping off due to long-term use in a harsh oral environment but also creating a gap at the interface between the composite resin and the tooth, from which bacteria may invade and adversely affect the dental pulp Because.

  Dental hard tissue consists of enamel and dentin, and clinically requires adhesion to both. Conventionally, for the purpose of improving adhesiveness, a method of pretreating a tooth surface prior to application of an adhesive has been used.

  As such a pretreatment material, an acid aqueous solution for decalcifying the tooth surface is generally used, and acid aqueous solutions such as phosphoric acid, citric acid and maleic acid have been used. In the case of enamel, the adhesion mechanism with the treated surface is a macro mechanical fit in which the adhesive penetrates and hardens to the rough surface by decalcification of the acid aqueous solution, whereas in the case of dentin Is said to be a micro mechanical fitting in which the adhesive penetrates into the fine voids of the sponge-like collagen fibers exposed on the tooth surface after decalcification and hardens.

  However, penetration into collagen fibers is not as easy as the enamel surface, and a penetration enhancer called a primer is generally used after treatment with an acid aqueous solution. That is, this method is a three-step system that requires two stages of pretreatment before applying a dental adhesive to obtain good adhesion strength to both enamel and dentin. There was a problem of being complicated.

  For the purpose of reducing the complexity of this operation, a two-step system for treating with a self-etching primer and a dental adhesive having both a decalcification function of an acid aqueous solution and a penetration promoting function of a dentin primer (for example, Patent Documents 1 and 2) Was proposed. In recent years, a one-step system (for example, Patent Documents 3 and 4) has been proposed in which treatment is performed with an adhesive having both a decalcification function of an acid aqueous solution, a penetration promoting function of a dentin primer, and a function as an adhesive to the dentin. Has been put to practical use.

  According to the above adhesive system, since no acid etching agent is used, a water washing step is unnecessary and it can be handled only by drying. In addition, not only enamel but also dentin provides a certain degree of adhesion and marginal sealing. However, this adhesive system uses a primer (self-etching primer), but it still has practically sufficient adhesion durability (that is, durability of adhesion) and edge sealing durability (that is, durability of edge sealing). ) Is not obtained. That is, when the durability test for adhesion is carried out, the adhesiveness and the edge blocking performance are greatly lowered with time, although the degree varies depending on the type of the acid or acidic group-containing polymerizable monomer used.

  In this self-etching type adhesive system, an acidic group-containing polymerizable monomer containing an acidic group such as a carboxylic acid group, a phosphoric acid group or a sulfonic acid group in the molecule is used in the adhesive composition. Contains multiple types. So far, as the acidic group-containing polymerizable monomer, polymerizable compounds as shown in the following compound group have been devised and some have been put into practical use.

  However, even when these acidic group-containing polymerizable compounds are blended in the adhesive, the deterioration of the adhesion durability over time is still seen, so when used as an adhesive, not only the initial adhesive strength, There is a need for new acidic group-containing polymerizable compounds that are excellent in adhesion durability.

  On the other hand, in recent years, the following compounds

Furthermore, the following compound group

[Wherein, R ₁ ′ represents a hydrogen atom or a substituted or unsubstituted C _{1 to} C ₁₈ alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted C _{5 to} C ₁₈ aryl group or a heteroaryl group, substituted or unsubstituted _C 5 _{-C 18} alkylaryl group or alkylheteroaryl group, a substituted or unsubstituted _C 7 _{-C 30} aralkyl group,; _{R 3} 'and _{R 4'} independently of one another are difunctional sex substituted or unsubstituted C ₁ -C ₁₈ carbon chain group, a difunctional substituted or unsubstituted cycloalkylene group, a difunctional substituted or unsubstituted C ₅ -C ₁₈ aryl group or a heteroaryl group, a difunctional substituted or an unsubstituted _C 5 _{-C 18} alkylaryl group or alkylheteroaryl group, a difunctional substituted or unsubstituted _C 7 _{-C 30} aralkyl group. ]
Several phosphonic acid group-containing polymerizable compounds having good hydrolysis resistance have been devised (see Patent Documents 5 and 6).

  Thus, when the above-mentioned phosphonic acid group-containing polymerizable compound is blended as a one-step type adhesive material that has been put into practical use in recent years, the initial adhesive strength to the tooth (especially to the enamel) In a state that is excellent to some extent, it is possible to obtain a considerably good adhesion durability. However, the use of the phosphonic acid group is not sufficient for the compatibility with the tooth substance, and the initial adhesive strength and the adhesive durability cannot be said to be satisfactory, and further improvement is desired. It was rare.

JP-A-06-009327 Japanese Patent Application Laid-Open No. 06-024928 Japanese Patent Laid-Open No. 10-236912 Japanese Patent Laid-Open No. 10-245525 JP 2002-12598 A JP-T-2005-514338

  The present invention has been made to meet the above-mentioned demand, and has an acidic group-containing polymerizable compound having affinity with a tooth and decalcification power and useful for a dental adhesive composition. The purpose is to develop a material that is highly superior in terms of not only initial adhesive strength but also adhesive durability.

  The inventors of the present invention have continually studied to solve the above problems. As a result, a novel phosphono group-containing polymerizable compound having a specific structure was created, and it was found that the above problem could be solved by using the phosphono group-containing polymerizable compound, and the present invention was completed.

  That is, the present invention provides the following general formula (1)

[Wherein, R ₁ represents a chain hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 10 carbon atoms, an aromatic hydrocarbon group having 6 to 15 carbon atoms, or the total of carbon and hetero atoms. A heterocyclic group having 5 to 10 atoms, R ₂ is a styryl group, vinyl group, acryloyl group, or methacryloyl group , R ₃ is a chain hydrocarbon group having 1 to 8 carbon atoms, 3 to 8 carbon atoms Or an aromatic hydrocarbon group having 6 to 8 carbon atoms. ]
It is a phosphono group containing polymeric compound represented by these.

  The present invention also provides a dental adhesive comprising the phosphono group-containing polymerizable compound and a polymerization initiator.

  The present invention also provides a dental adhesive primer comprising the phosphono group-containing polymerizable compound and a volatile organic solvent.

  Furthermore, the present invention provides a method for producing the above-described phosphono group-containing polymerizable compound as a general formula (3)

[Wherein, R ₁ represents a chain hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 10 carbon atoms, an aromatic hydrocarbon group having 6 to 15 carbon atoms, or the total of carbon and hetero atoms. A heterocyclic group having 5 to 10 atoms, R ₂ is a styryl group, vinyl group, acryloyl group, or methacryloyl group , R ₃ is a chain hydrocarbon group having 1 to 8 carbon atoms, 3 to 8 carbon atoms Or an aromatic hydrocarbon group having 6 to 8 carbon atoms. ]
Also provided is a method of reacting a compound of formula (I) with a phosphoryl halide in the presence of a tertiary amine.

  Since the phosphono group-containing polymerizable compound of the present invention is a strongly acidic group, the phosphono group-containing polymerizable compound is excellent in affinity with a tooth and has a high deashing power. Therefore, when the compound is used as an adhesive component of a dental adhesive, it can be used as a one-step type adhesive without using acid etching or primer treatment. In that case, enamel, dentin, etc. It exhibits excellent adhesive strength against hard tissues, and this is highly superior not only in initial adhesive strength but also in adhesive durability. Similarly, when used as a component of a dental adhesive primer, it can also be used as a self-etching primer that is used without acid etching, and in this case also exhibits excellent adhesiveness.

The reason why the phosphono group-containing polymerizable compound of the present invention has such excellent adhesiveness is that its molecular structure has two hydrophilic groups and two hydrophobic groups, so-called Gemini type (dimer type) interface. It has a structure similar to that of an active agent, and it is presumed that it may be related to the fact that a surface active ability can be effectively expressed in a dental adhesive with a small amount of addition. That is, the phosphono group, which is a hydrophilic part, acts on the tooth surface to decalcify the teeth, and the radically polymerizable groups of R ₃ and R ₄ which are hydrophobic parts on the opposite side aggregate to improve the polymerizability. It is expected that it will be obtained.

The phosphono group-containing polymerizable compound in the present invention (hereinafter also referred to as the compound of the present invention) has two phosphono groups in its structure, and each phosphono group is derived from R ₁ and a phosphate ester described below. It has the structure which couple | bonds with two of these groups, respectively.

Here, in the general formula (1), R ₁ is a chain hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 10 carbon atoms, an aromatic hydrocarbon group having 6 to 15 carbon atoms, Alternatively, it is a heterocyclic group having 5 to 10 total atoms of carbon and hetero atoms.

The R ₁ is not particularly limited as long as the above conditions are satisfied, but the following can be given as a preferred specific example.

  Examples of the chain hydrocarbon group having 1 to 20 carbon atoms include alkylene groups such as methylene group, ethylene group, propylene group, butylene group, pentylene group, hexylene group, octylene group, decylene group, undecylene group, pentadecylene group, and octadecylene group. An alkenylene group such as a propenylene group, an isopropenylene group, a butenylene group, an isobutenylene group, a pentenylene group, an isopentenylene group, a decenylene group, a tetradecenylene group, a hexadecenylene group, an icosenylene group; a propynylene group, a butynylene group, a pentynylene group, a pentynylene group, Group, an alkynylene group such as a pentadecynylene group and a nonadecynylene group, among which an alkylene group having 2 to 12 carbon atoms is preferable.

  Examples of the alicyclic hydrocarbon group having 3 to 10 carbon atoms include cyclopropylene group, cyclobutylene group, cyclopentylene group, cyclohexylene group, 2-methyl-cyclohexylene group, and 2,5-dimethyl-cyclohexylene group. 2-butyl-cyclohexylene group and the like, and among them, those having 5 to 8 carbon atoms such as cyclopentylene group, cyclohexylene group, 2-methyl-cyclohexylene group and the like are preferable.

  Examples of the aromatic hydrocarbon group having 6 to 15 carbon atoms include arylene groups such as a phenylene group, a methylphenylene group, and a naphthylene group; a xylylene group, a benzylidene group, and the like. Among these, a phenylene group, a methylphenylene group, and the like Are preferably those having 6 to 10 carbon atoms.

  Examples of the heterocyclic group having 5 to 10 total atoms of carbon and hetero atoms include 2,5-pyridinylene group, 2,5-furanylene group, 2,5-thiophenylene group, 2-pyridinylmethylene group, 2- And pyridinylethylene group, 3,7-quinolinylene group, etc. Among them, the total number of carbon and hetero atoms such as 2,5-pyridinylene group, 2,5-furanylene group, 2,5-thiophenylene group, etc. The thing of 5-6 is preferable.

Among the above R ₁ groups, an alkylene group having 2 to 12 carbon atoms is particularly preferred in view of the effect of the present invention.

These groups of R ₁ and R ₂ are usually the same in the same molecule, but may be different. In addition, in each group, when the upper limit of the carbon number is exceeded, the adhesive strength is remarkably lowered, which is not preferable.

Formula (1) Medium R ₂ is scan styryl group, a vinyl group, an acryloyl group or a methacryloyl group. Each group of these R ₂ may be of different within the same molecule, but typically it is common to those of the same type.

  Among these radical polymerizable group-containing groups, an acryloyl group and a methacryloyl group are particularly preferable from the viewpoint of improving adhesive strength.

In the compound of the present invention, the combination of the groups R ₁ and R ₂ has a total carbon number of both groups of 8 or more, particularly preferably 10 or more, which improves the polymerizability and the strength of the cured product. It is desirable from the viewpoint of improving the adhesion by making the thickness higher.

Further, R ₃ in the general formula (1), the chain-like hydrocarbon group having 1 to 8 carbon atoms, alicyclic hydrocarbon group having 3 to 8 carbon atoms or an aromatic hydrocarbon group having a carbon number of 6-8, It is. In each group, when the upper limit of the number of carbon atoms is exceeded, the adhesive strength is remarkably lowered, which is not preferable.

  Examples of the chain hydrocarbon group having 1 to 8 carbon atoms include alkylene groups such as a methylene group, an ethylene group, a propylene group, a butylene group, a pentylene group, a hexylene group, a heptylene group, and an octylene group; a propenylene group, an isopropenylene group, Alkenylene groups such as butenylene group, isobutenylene group, pentenylene group, isopentenylene group, etc .; alkynylene groups such as propynylene group, butynylene group, pentynylene group, etc. are mentioned, and among them, an alkylene group having 2 to 6 carbon atoms is preferable.

  Examples of the alicyclic hydrocarbon group having 3 to 8 carbon atoms include a cyclopropylene group, a cyclobutylene group, a cyclopentylene group, a cyclohexylene group, and a cycloheptylene group, and among them, a cyclopentylene group and a cyclohexylene group. The thing of carbon numbers 5-8, such as, is preferable.

  Examples of the aromatic hydrocarbon group having 6 to 8 carbon atoms include arylene groups such as 1,2-phenylene group, 1,3-phenylene group, 1,4-phenylene group, 2-methyl-1,4-phenylene group, and the like. O-xylylene group, m-xylylene group, p-xylylene group, benzylidene group, group, etc., among which 1,2-phenylene group, 1,3-phenylene group, 1,4-phenylene group, 2- Those having 6 to 7 carbon atoms such as methyl-1,4-phenylene group are preferred.

  Typical examples of such phosphono group-containing polymerizable compounds of the present invention include N, N′-dimethacryloyl-N, N′-di (undecyldihydrogen phosphate) -ethylenediamine, N, N′— Dimethacryloyl-N, N'-di (undecyl dihydrogen phosphate) -ethylenediamine, N, N'-dimethacryloyl-N, N'-di (eicosyl dihydrogen phosphate) -ethylenediamine, N, N'- Dimethacryloyl-N, N′-di (octyl dihydrogen phosphate) -ethylenediamine, N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -ethylenediamine, N, N′-diacryloyl -N, N'-di (pentadecyl dihydrogen phosphate) Ethylenediamine, N, N′-diacryloyl-N, N′-di (heptyl dihydrogen phosphate) -ethylenediamine, N, N′-dimethacryloyl-N, N′-di (nonadecyl dihydrogen phosphate) -tetra Methylenediamine, N, N′-dimethacryloyl-N, N′-di (decyl dihydrogen phosphate) -tetramethylene diamine, N, N′-dimethacryloyl-N, N′-di (heptyl dihydrogen phosphate) -Tetramethylenediamine, N, N'-dimethacryloyl-N, N'-di (propyldihydrogen phosphate) -tetramethylenediamine, N, N'-diacryloyl-N, N'-di (dodecyldihydrogen) Phosphate) -tetramethylenediamine, N, N′-diacrylo Ru-N, N′-di (propyl dihydrogen phosphate) -tetramethylene diamine, N, N′-dimethacryloyl-N, N′-di (tridecyl dihydrogen phosphate) -hexamethylene diamine, N, N '-Dimethacryloyl-N, N'-di (octyl dihydrogen phosphate) -hexamethylenediamine, N, N'-dimethacryloyl-N, N'-di (pentyl dihydrogen phosphate) -hexamethylene diamine, N , N′-Dimethacryloyl-N, N′-di (butyl dihydrogen phosphate) -hexamethylenediamine, N, N′-diacryloyl-N, N′-di (undecyl dihydrogen phosphate) -hexamethylene Diamine, N, N′-Diacryloyl-N, N′-di (ethyl dihydride) Rogen phosphate) -hexamethylenediamine, N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -p-phenylenediamine, N, N′-diacryloyl-N, N′-di (Hexyl dihydrogen phosphate) -p-phenylenediamine, N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -o-phenylenediamine, N, N′-diacryloyl-N, N′-di (hexyl dihydrogen phosphate) -o-phenylenediamine, N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -m-phenylenediamine, N, N′-di Acryloyl-N, N′-di (hexyl dihydrogen phosphate) -m-phenyle Diamine, N, N′-distyryl-N, N′-di (octyl dihydrogen phosphate) -ethylene diamine, N, N′-divinyl-N, N′-di (octyl dihydrogen phosphate) -tetramethylene diamine, N, N′-dimethacryloyl-N, N′-di (phenyldihydrogenphosphate) -ethylenediamine, N, N′-dimethacryloyl-N, N′-di (benzyldihydrogenphosphate) -tetramethylenediamine, N, N′-dimethacryloyl-N, N′-di (pyridinyl dihydrogen phosphate) -hexamethylene diamine and the like.

  Among these phosphono group-containing polymerizable compounds, compounds that are particularly prominent in the present invention are those represented by the following general formula (2).

[In formula, A is hydrogen or a methyl group, l is an integer of 2-12, m is an integer of 1-8. ]
The compound of the present invention can be confirmed by using, for example, nuclear magnetic resonance spectroscopy (NMR), infrared absorption spectroscopy (IR), elemental analysis or the like. Hereinafter, specific examples of characteristic identification sites are exemplified, and a method for identifying a target compound is shown.
In the ¹ H-NMR (nuclear magnetic resonance) spectrum method, characteristic absorption appears in the following range.

When the radical polymerizable group of R ₂ is a methacryloyl group, the proton absorption appears in the following range. _{1.90~2.20ppm (s, 3H, C H} 3 -C (CH 2) -), 4.90~5.20ppm and 5.00~5.30ppm (s respectively, 2H, _CH 2 = C) When the radical polymerizable group of R ₂ is an acryloyl group, absorption of protons appears in the following range. 6.00 to 6.50 ppm (2H and C H ₂ = C, respectively); when the radical polymerizable group of R ₂ is a vinyl group, the absorption of protons appears in the following range. 4.70 to 5.20 ppm (s, 3H, C H ₂ = C H , respectively); When the radical polymerizable group of R ₂ is a styryl group, absorption of protons appears in the following range. 4.90-5.90 (s, _{respectively, 3H, C H 2 = C} H), 6.30~7.50 (m, 4H, -C 6 H 4). Absorption of the protons of the methylene group to which PO (OH) ₂ —O— is bonded appears in the following range. 3.00 to 4.50 ppm (t, 2H, —C H ₂ —O); absorption of protons of a hydroxy group bonded to phosphorus appears in the following range. 1.00 to 6.00 ppm (s, 2H, (O H ) ₂ P = O)
In the ³¹ P-NMR spectrum method, phosphorus in the phosphono group shows absorption in the following range. : 0.10 to 30.00 ppm
In the IR (infrared absorption, single reflection ATR (total reflection method)) spectral method, characteristic absorption appears in the following range.

Absorption appears in the following range at the PO site. 980-1050 cm < ^-1 >; P = O site | part absorbs in the following range. 1250-1320 cm ^-1
In the elemental analysis method, the content ratio of elements (carbon, hydrogen, nitrogen) constituting the compound of the present invention can be quantified.

  The phosphono group-containing polymerizable compound of the present invention may be produced by any method. Examples of general synthesis methods include the methods shown below. That is, the general formula (3)

[Wherein, R ₁ represents a chain hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 20 carbon atoms, an aromatic hydrocarbon group having 6 to 15 carbon atoms, or the total of carbon and hetero atoms. A heterocyclic group having 5 to 10 atoms, R ₂ is a styryl group, vinyl group, acryloyl group, or methacryloyl group , R ₃ is a chain hydrocarbon group having 1 to 8 carbon atoms, 3 to 8 carbon atoms Or an aromatic hydrocarbon group having 6 to 8 carbon atoms. ]
Is a method in which a compound represented by the above is reacted with phosphoryl halide in the presence of a tertiary amine.

  In this method, as the phosphoryl halide, known compounds such as phosphoryl chloride and phosphoryl bromide are used without limitation, and among them, phosphoryl chloride is preferably used. It is efficient that the amount of phosphoryl chloride used is 2 to 4 equivalents, more preferably 2.0 to 2.8 equivalents, relative to 1 equivalent of the compound represented by the general formula (3).

  As the tertiary amine for promoting the reaction between the compound represented by the general formula (3) and the phosphoryl halide, known compounds such as triethylamine, tripropylamine, tributylamine and the like are used without limitation, and among these, triethylamine Is preferably used. It is efficient that the amount of the tertiary amine used is 1 equivalent or more with respect to 1 equivalent of phosphoryl halide, more preferably 1.0 to 1.2 equivalents with respect to 1 equivalent of phosphoryl halide. is there.

  The reaction of each of the above raw materials may be carried out in any way. Usually, however, phosphoryl halide is dissolved in a solvent, and then cooled as necessary at a temperature of −40 to 0 ° C. It is preferable to carry out by adding the compound represented by (3) and the tertiary amine as the same solution or separate solutions gradually by a method such as dropwise addition. Phosphoryl halide is used after being dissolved so as to have a concentration of 1 to 10% by mass, and the compound represented by the general formula (3) and the tertiary amine are added after being dissolved so as to have a concentration of 5 to 20%. Is preferred.

  The above reaction is preferably carried out with stirring, and is continued after the addition of the compound represented by the general formula (3) and the tertiary amine until the compound represented by the general formula (3) disappears. In order to generate a phosphate group in the middle, it is preferable to add 1 to 10 molar amount of distilled water to the reaction solution. After completion of the reaction, the compound of the present invention is obtained by washing the reaction solution with dilute hydrochloric acid, aqueous sodium chloride solution, distilled water, etc., adding a polymerization inhibitor as necessary, and concentrating and drying the reaction solution. .

  In the above reaction, the reaction solvent is not particularly limited as long as it can dissolve each compound of the compound represented by the general formula (3), halogenated phosphoryl, and tertiary amine, and does not inhibit the reaction. Organic solvents can be used. Specific examples include toluene, diethyl ether, methylene chloride and the like.

  The compound represented by the general formula (3) used in carrying out the above-described method for producing the compound of the present invention may be obtained by any method, but can be efficiently synthesized, for example, by the following method. That is, the general formula (4)

[Wherein, R ₁ has the same meaning as described above. X represents a halogen atom. ]
A halogenated alcohol represented by the general formula (5)

[Wherein R ₃ has the same meaning as described above. ]
Is reacted with an alkylenediamine represented by the general formula (6)

Next, the compound represented by the general formula (6) is converted into the compound represented by the general formula (7).

[Wherein R ₂ has the same meaning as described above. X represents a halogen atom. ]
It is the method of making it react with the halide shown by this.

In this method, as the halogenated alcohol represented by the general formula (4), a compound having each group described in R ₁ described above and having a halogen atom such as chlorine, bromine or iodine as X can be used without limitation. . Similarly, as the alkylene diamine represented by the general formula (5), those having each group described for R ₃ can be used without limitation.

  The reaction of the halogenated alcohol represented by the general formula (4) and the alkylene diamine represented by the general formula (5) may be carried out in any way, but these are reacted in a reaction solvent with heating and stirring. Is preferred. The heating temperature is generally 40 to 120 ° C, more preferably 50 to 100 ° C. This reaction also requires an inorganic base such as sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, calcium hydroxide. As these inorganic bases, known ones can be used without limitation, but it is more preferable to use ones that dissolve well in an alcohol solvent such as sodium hydroxide or potassium hydroxide. The amount of these bases is preferably 1.0 to 2.5 equivalents, more preferably 1.0 to 1.5 equivalents, relative to 1 equivalent of the halogenated alcohol represented by the general formula (4). These bases are gradually added as a 1 to 30% by mass solution, for example, by dropwise addition to a reaction solution in which the halogenated alcohol represented by the general formula (4) and the alkylene diamine represented by the general formula (5) are dissolved. Is preferred.

  The reaction solvent for this reaction is not particularly limited as long as it can dissolve each halogenated alcohol represented by the general formula (4) and the alkylenediamine represented by the general formula (5) and does not inhibit the reaction. Instead, a known organic solvent can be used. Specifically, water or a lower alcohol solvent such as methanol, ethanol, propanol, or butanol is used.

  After completion of the above reaction, the solvent is distilled off, and the crude product obtained as necessary is purified by recrystallization or the like to obtain the compound represented by the general formula (6).

  Further, the reaction of the compound represented by the general formula (6) thus obtained and the halide represented by the general formula (7) is not particularly limited, but the general formula (7) used is not limited. Depending on the type of halide shown (for example, halogenated methacryloyl or halogenated acryloyl), the reaction is preferably carried out in the presence of a tertiary amine. As the tertiary amine, those described in the reaction of the compound represented by the general formula (3) with the halogenated phosphoryl are also preferably used. The amount of the tertiary amine used is 1.0 equivalent or more with respect to 1 equivalent of the halide represented by the general formula (7), more preferably 1.0 to 1.5 equivalents with respect to 1 equivalent. There are efficient.

The halide represented by the general formula (7) has the groups described for R ₂ described above, and a compound having a halogen atom such as chlorine, bromine or iodine as X can be used without limitation.

  The reaction of the compound represented by the general formula (6) and the halide represented by the general formula (7) may be carried out in any way, but it is preferable to react them in a reaction solvent with stirring. . The reaction temperature is generally 0 to 80 ° C., more preferably 0 to 60 ° C. In addition, this reaction is gradually performed by dropping the halide of the general formula (7) as a 1 to 30% solution into a reaction solution in which the compound represented by the general formula (6) and the tertiary amine are dissolved. It is preferable to add to.

  The reaction solvent for this reaction is not particularly limited as long as it can dissolve the compounds represented by the general formula (6) and the starting materials of the halide represented by the general formula (7) and does not inhibit the reaction. Instead, a known organic solvent can be used. Specifically, an organic solvent such as methylene chloride, diethyl ether, toluene, N, N′-dimethyl-formamide is used.

  After completion of the above reaction, the solvent is distilled off, and the crude product obtained as necessary is purified using column chromatography or the like to obtain the general formula (3)

What is necessary is just to obtain the compound shown by these.

  In the reaction of the compound represented by the general formula (6) and the halide represented by the general formula (7), in addition to the compound represented by the general formula (3), which is the target product, during the reaction, the general formula (8)

The by-product indicated by may be generated.

  However, when the by-product represented by the general formula (8) is produced, it can be converted into the compound represented by the general formula (3) by reacting it with an inorganic base. The reaction for converting the by-product represented by the general formula (8) into the compound represented by the general formula (3) may be carried out in any manner, but these are reacted in a reaction solvent with stirring. Is preferred. The reaction temperature is generally 0 to 100 ° C., more preferably 0 to 80 ° C. Moreover, this reaction requires inorganic bases, such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and these can be used without a restriction | limiting. The amount of these bases added is preferably 1.0 to 20.0 equivalents, more preferably 1.0 to 10.0 equivalents, relative to 1 equivalent of the compound represented by the general formula (8). These bases are preferably added as a solid to a reaction solution in which the compound represented by the general formula (8) is dissolved.

  The reaction solvent for this reaction is not particularly limited as long as it can dissolve the by-product represented by the general formula (8) and does not inhibit the reaction, and a known organic solvent can be used. Specifically, water, water such as methanol, ethanol, propanol, butanol or a lower alcohol solvent is used.

  After the completion of the reaction, the solvent is distilled off, and the crude product obtained as necessary may be purified by using column chromatography to obtain the compound represented by the general formula (3).

  The phosphono group-containing polymerizable compound of the present invention can be used for various applications by taking advantage of the hydrophilicity and acidity of the phosphono group in addition to its excellent radical polymerization characteristics. Preferably, the hydrophilicity and acidity provided by the phosphono group exhibit a decalcification function of the tooth surface and a penetration promotion function of the dentin primer. It can be effectively used as a polymerizable monomer component in a dental composition. When used as such a dental adhesive or dental adhesive primer, the compounding amount of the compound is preferably in the range of 1 to 50% by mass and more preferably in the range of 5 to 40% by mass with respect to the total mass of the composition. The range of 10 to 30% by mass is most preferable.

  When used as a dental adhesive, the compound of the present invention is blended with a polymerization initiator and, if necessary, a filler. Any known polymerization initiator can be used without limitation. Among them, typical polymerization initiators include combinations of organic peroxides and amines, combinations of organic peroxides, amines, and sulfinates, acidic compounds, and combinations of aryl borates, barbituric acid. Chemical polymerization initiators such as alkylboranes; and combinations of aryl borates and photoacid generators, combinations of α-diketones and tertiary amines, combinations of acylphosphine oxides and tertiary amines, thioxanthone And photopolymerization initiators such as a combination of α-aminoacetophenones and tertiary amines. Moreover, it is also possible to use a dual cure type in which these chemical polymerization initiators and photopolymerization initiators are used in combination, and polymerization can be initiated by either chemical polymerization or photopolymerization.

  Examples of compounds that can be suitably used as the compounds used in the various chemical polymerization initiators include organic peroxides such as t-butyl hydroperoxide, cumene hydroperoxide, di-t-butyl peroxide, peroxide, and the like. Examples include dicumyl oxide, acetyl peroxide, lauroyl peroxide, and benzoyl peroxide. These can be used alone or in combination of two or more.

  As the amines, secondary or tertiary amines are preferable, and specific examples thereof include N-methylaniline, N-methyl-p-toluidine and the like as secondary amines. N, N-dimethylaniline, N, N-diethylaniline, N, N-di-n-butylaniline, N, N-dibenzylaniline, N, N-dimethyl-p-toluidine, N, N-diethyl -P-toluidine, N, N-dimethyl-m-toluidine, p-bromo-N, N-dimethylaniline, m-chloro-N, N-dimethylaniline, p-dimethylaminobenzaldehyde, p-dimethylaminoacetophenone, p -Dimethylaminobenzoic acid, p-dimethylaminobenzoic acid ethyl ester, p-dimethylaminobenzoic acid amyl ester, N, N-dimethyla Slanic acid methyl ester, N, N-dihydroxyethylaniline, N, N-dihydroxyethyl-p-toluidine, p-dimethylaminophenethyl alcohol, p-dimethylaminostilbene, N, N-dimethyl-3,5-xylidine 4-dimethylaminopyridine, N, N-dimethyl-α-naphthylamine, N, N-dimethyl-β-naphthylamine, tributylamine, tripropylamine, triethylamine, N-methyldiethanolamine, N-ethyldiethanolamine, N, N- Dimethylhexylamine, N, N-dimethyldodecylamine, N, N-dimethylstearylamine, N, N-dimethylaminoethyl methacrylate, N, N-diethylaminoethyl methacrylate, 2,2 ′-(n-butylimino) diethano And the like. These can be used individually or in mixture of 2 or more types.

  Examples of various compounds preferably used for the various photopolymerization initiators include α-diketones such as camphorquinone, benzyl, α-naphthyl, acetonaphthene, naphthoquinone, p, p′-dimethoxybenzyl, p , P′-dichlorobenzylacetyl, 1,2-phenanthrenequinone, 1,4-phenanthrenequinone, 3,4-phenanthrenequinone, 9,10-phenanthrenequinone, and the like.

  Examples of the tertiary amine include those exemplified as the components of the chemical polymerization initiator.

  Acylphosphine oxides include benzoyldiphenylphosphine oxide, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2,6-dimethoxybenzoyldiphenylphosphine oxide, 2,6-dichlorobenzoyldiphenylphosphine oxide, 2,3,5 , 6-tetramethylbenzoyldiphenylphosphine oxide and the like.

  As the blending amount of the polymerization initiator, a known addition range is employed without any particular limitation. Suitably, it is 0.01-20 mass parts (preferably 0.1-8 mass parts) with respect to 100 mass parts of compounds of this invention.

  Moreover, what is necessary is just to mix | blend a filler with respect to a dental adhesive material as needed, in order to improve the intensity | strength of an adhesive material. As such fillers, known fillers such as inorganic fillers, organic fillers, and composite fillers of inorganic fillers and organic fillers can be used without limitation.

As the inorganic filler, silica; minerals based on silica such as kaolin, clay, mica, mica; silica based, Al ₂ O ₃ , B ₂ O ₃ , TiO ₂ , ZrO ₂ , BaO, La Examples thereof include ceramics and glasses containing ₂ O ₃ , SrO ₂ , CaO, P ₂ O _{5 and the} like. As the glass, lanthanum glass, barium glass, strontium glass, soda glass, lithium borosilicate glass, zinc glass, fluoroaluminosilicate glass, borosilicate glass, and bioglass are preferable. Other than these, crystalline quartz, hydroxyapatite, alumina, titanium oxide, yttrium oxide, zirconia, calcium phosphate, barium sulfate, aluminum hydroxide, sodium fluoride, potassium fluoride, sodium monofluorophosphate, lithium fluoride, ytterbium fluoride Is also preferable.

  Examples of the organic filler include polymethyl methacrylate, polyethyl methacrylate, polyfunctional methacrylate polymer, polyamide, polystyrene, polyvinyl chloride, chloroprene rubber, nitrile rubber, and styrene-butadiene rubber.

  Examples of the composite filler of an inorganic filler and an organic filler include those obtained by dispersing an inorganic filler in an organic filler and those obtained by coating an inorganic filler with various polymerizable monomers.

  In order to improve curability, mechanical strength, applicability, etc., the filler may be used after being surface-treated with a known surface treatment agent such as a silane coupling agent. As the surface treatment agent, vinyltrimethoxysilane, vinyltriethoxysilane, vinyltrichlorosilane, vinyltri (β-methoxyethoxy) silane, γ-methacryloyloxypropyltrimethoxysilane, γ-glycidoxypropyltrimethoxysilane, γ- Examples are mercaptopropyltrimethoxysilane and γ-aminopropyltriethoxysilane.

  One type of filler may be blended, or a plurality of types may be blended in combination. The blending amount varies depending on the specific bonding target of the dental adhesive. For example, when the dental adhesive is used as an adhesive for a filling composite resin, the filler content is preferably in the range of 0.1 to 30% by mass with respect to the total mass of the dental adhesive. The range of 0.5-20 mass% is more preferable. The blending amount of the filler when used as a dental cement composition is preferably in the range of 30 to 85% by mass, more preferably in the range of 40 to 80% by mass, based on the total mass of the cement composition. A range of ˜75 mass% is most preferred.

  The dental adhesive using the compound of the present invention is not subjected to pretreatment, that is, at least one of the above-described decalcification treatment of the tooth surface with the acid aqueous solution and the permeation treatment (primer treatment) to the dentin primer. In particular, when used as a one-step system type adhesive that does not perform both treatments, it is preferable to add water. In general, water promotes the decalcification action of the acidic group-containing polymerizable monomer on the tooth, and improves the permeability of the adhesive to the tooth. In use, it is necessary to use one that does not substantially contain impurities that adversely affect the adhesion. Therefore, distilled water or ion exchange water is preferable.

  The blending amount of water is preferably in the range of 0.01 to 70% by mass, more preferably in the range of 0.05 to 50% by mass, and in the range of 0.1 to 30% by mass with respect to the total mass of the composition. Most preferred. Adhesiveness may be deteriorated when the amount of water is too large or too small.

  The dental adhesive containing the compound of the present invention as an adhesive component is excellent not only for the tooth quality but also for crown restoration materials (metals, porcelain, ceramics, composite resin cured products, etc.) broken in the oral cavity. Expresses adhesive strength. When the dental adhesive according to the present invention is used for bonding a fractured crown restoration material, the dental adhesive according to the present invention may be a primer such as a commercially available metal bonding primer, porcelain bonding primer, or the like. You may use it in combination with tooth surface cleaning agents, such as chlorate and hydrogen peroxide.

  When the dental composition comprising the phosphono group-containing polymerizable compound of the present invention is used as a dental adhesive primer composition, the compound of the present invention is used after being dissolved in a volatile organic solvent. As this volatile organic solvent, a known organic solvent can be used without any limitation as long as it has volatility at room temperature. The term “volatile” as used herein means that the boiling point at 760 mmHg is 100 ° C. or lower and the vapor pressure at 20 ° C. is 1.0 KPa or higher.

  Specific examples of such volatile organic solvents include methanol, ethanol, propanol, isopropyl alcohol, acetone, methyl ethyl ketone, methylene chloride, hexane, and ethyl acetate. A plurality of these organic solvents can be mixed and used as necessary. In view of harmfulness to living organisms, ethanol, propanol or acetone is preferable.

  The compounding amount of the volatile organic solvent in the dental adhesive primer using the compound of the present invention is not limited as long as each component blended as described above is uniform, but generally the total mass of the composition. On the other hand, it is 15-60 mass%. Preferably it is 20-50 mass%.

  Moreover, it is preferable to mix | blend water with a dental adhesive primer as needed. The water used is the same as that described above. The blending amount is preferably in the range of 0.01 to 70% by mass, more preferably in the range of 0.05 to 40% by mass, and most preferably in the range of 0.1 to 15% by mass, based on the total mass of the composition. . Adhesiveness may decrease when the amount is too much or too little.

  In addition, the dental composition comprising the compound of the present invention, such as the dental adhesive and the dental adhesive primer, may optionally include other components known as compounding components of the dental composition, such as Further, other acidic group-containing radical polymerizable monomers, radical polymerizable monomers having no acidic group, ultraviolet absorbers, polymerization inhibitors, polymerization inhibitors, dyes, pigments, and the like may be blended. Moreover, a volatile water-soluble organic solvent can be suitably mix | blended with a dental adhesive material.

  The method for producing the dental composition described above is not particularly limited, and may be performed according to a known method for producing a dental composition, and is generally blended under an inert light such as red light. All the ingredients are weighed and mixed well until a homogeneous solution is obtained.

  Hereinafter, the present invention will be described in more detail with reference to examples. The present invention is not limited to the following examples. Abbreviations and abbreviations used below are as follows.

[Acid group-containing polymerizable monomer]
PM: Mixture of 2-methacryloyloxyethyl dihydrogen phosphate (PM1) and bis (2-methacryloyloxyethyl) hydrogen phosphate (PM2) MDP; 10-methacryloxydecyl phosphate MAC-10; 11-methacryloyloxy -1,1-undecanedicarboxylic acid 4-META; 4-methacryloyloxyethyl trimellitic anhydride phosphonic acid; N, N′-dimethacryloyl-N, N′-di (octyldihydroxyphosphoryl) -ethylenediamine
[Polymerizable monomer]
3G; triethylene glycol dimethacrylate HEMA; 2-hydroxyethyl methacrylate TMPT; trimethylolpropane trimethacrylate D-2,6E; bisphenol A polyethoxymethacrylate
[Polymerization initiator]
CQ; camphorquinone DMBE; 4-dimethylaminobenzoic acid ethyl ester
[Polymerization inhibitor]
HQME; Hydroquinone monomethyl ether
[Filler]
Example 1 of silica-titania particles surface-treated with a silane coupling agent
[Production of N, N′-diundecanol-ethylenediamine]
In a three-necked reaction vessel, 24.50 g (97.5 mmol) of 11-bromo-1-undecanol was dissolved in 250 ml of ethanol, and 2.83 g (47.1 mmol) of ethylenediamine and an appropriate amount of thymol blue were added as an indicator. , Stirred and refluxed. A solution prepared by dissolving 3.96 g (99.0 mmol) of sodium hydroxide in 150 ml of ethanol was dropped into the reaction solution while observing the color of the indicator. After reacting under reflux for 24 hours, the solvent was distilled off under reduced pressure. After distilling off the solvent, it was washed thoroughly with water to remove residual sodium hydroxide and the generated salt, and the resulting crude product was recrystallized from methanol.

When the crystal | crystallization obtained by the above was identified by < ¹ > H-NMR, the following absorption was confirmed and it was confirmed that N, N'- diundecanol- ethylenediamine was manufactured. The yield was 6.784 g, and the yield was 40.0%.
¹ H-NMR (500 MHz, d ₁ -CDCl ₃ , ppm):
_{1.20~1.35 (m, 17H, -CH 2} -CH 2 -CH 2, -NH -), 1.44~1.49 (m, 2H, -NH-C H 2 -), 1. _{53~1.59 (m, 2H, -C H} 2 -CH 2 -OH), 2.57~2.60 (t, 2H, -NH-C H 2 -), 2.71 (s, 1H, -OH), 3.62 ~3.64 (t, 2H, -C H 2 -OH)
[Production of N, N′-dimethacryloyl-N, N′-diundecanol-ethylenediamine]
In a three-necked reaction vessel, 8.50 g (21.2 mmol) of N, N′-diundecanol-ethylenediamine prepared in the previous step was added to 200 ml of toluene, stirred, and triethylamine 5. 50 g (54.4 mmol) was added. In the same ice bath, a solution prepared by dissolving 4.76 g (45.5 mmol) of methacryloyl chloride in 100 ml of toluene was slowly added dropwise. After stirring as it is for 12 hours, the solvent of the reaction solution is distilled off under reduced pressure and dried in vacuum. The obtained product was dissolved in methanol, 6.00 g (43.4 mmol) of potassium carbonate was added, and the mixture was stirred at room temperature. After stirring for 5 hours, potassium carbonate was removed by filtration, and the solvent of the reaction solution was distilled off under reduced pressure. This crude product was dissolved in methylene chloride and washed 5 times with 0.1N HCl aqueous solution. The organic phase was taken out and the solution was dried over silica gel, and then the silica gel was filtered off. The solvent was distilled off under reduced pressure and dried in vacuo.

The white crystals obtained above were identified by ¹ H-NMR. The following absorption was confirmed, and it was confirmed that N, N′-dimethacryloyl-N, N′-diundecanol-ethylenediamine was produced. It was. The yield was 8.08 g, and the yield was 71.0%.
¹ H-NMR (500 MHz, d ₁ -CDCl ₃ , ppm):
_{1.27~1.34 (m, 14H, -CH 2} -CH 2 -CH 2 -), 1.53~1.59 (m, 4H, -C H 2 -CH 2 -OH, -C H 2 —CH ₂ —N—), 1.95 (s, 3H, C H ₃ —C (CH ₂ ) —), 3.32 to 3.38 (m, 2H, N—CH ₂ ), 3.52 _{3.56 (m, 2H, N-} CH 2), 3.62~3.64 (t, 2H, -C H 2 -OH), 5.00 and 5.15 (s each, 2H, _CH 2 = C).
[Production of N, N′-dimethacryloyl-N, N′-di (undecyl dihydrogen phosphate) -ethylenediamine; Compound 1)]
Under stirring with a mechanical stirrer in a four-necked reaction vessel, 5.66 g (36.9 mmol) of phosphoryl chloride was dissolved in 200 ml of toluene. At −40 ° C., 7.48 g (13.9 mmol) of N, N′-dimethacryloyl-N, N′-diundecanol-ethylenediamine prepared in the previous step and 4.42 g (43.7 mmol) of triethylamine were prepared. Was dissolved in phosphoryl chloride solution slowly over 1 hour, and then stirred at -20 ° C for 1 hour.

  The temperature was further raised to 0 ° C., 30 ml (1.67 mol) of distilled water was added, and the mixture was stirred for a time. After completion of the reaction, the reaction solution was washed 3 times with 0.4N aqueous hydrochloric acid, 3 times with 0.2% saline and 5 times with distilled water, and separated. The reaction solution was dried using silica gel. After removing the silica gel by filtration, 1000 ppm of HQME as a stabilizer (polymerization inhibitor) was added to the product, and the solution was concentrated under reduced pressure. Thereafter, vacuum drying was performed to obtain a pale yellow highly viscous liquid in a yield of 3.53 g and a yield of 36.3%.

  The isolated product was analyzed by the following structural analysis means, which was N, N'-dimethacryloyl-N, N'-di (undecyl dihydrogen phosphate) -ethylenediamine.

It was confirmed that.
Elemental analysis:
The elemental analysis of this product is C54.04%, H8.78%, N4.13%, the calculated value for this compound is C55.16%, H8.97% N 4.02%.
IR (single reflection ATR, cm ⁻¹ ):
1018 (b), 1260 (b), 1619 (s), 1644 (s), 2854 (s), 2924 (s)
¹ H-NMR (500 MHz, d ₁ -CDCl ₃ , ppm):
_{1.24~1.28 (m, 14H, -CH 2} -CH 2 -CH 2 -), 1.54~1.58 (m, 2H, -C H 2 -CH 2 -N -), 1. _{64~1.69 (m, 2H, -C H} 2 -CH 2 -O), 1.95 (s, 3H, C H 3 -C (CH 2) -), 2.35 (s, 2H, ( O H ) ₂ P═O), 3.33 to 3.37 (m, 2H, N—CH ₂ ), 3.51 to 3.55 (m, 2H, N—CH ₂ ), 4.01 to 4 _{.05 (t, 2H, -C H} 2 -O), 5.00 and 5.15 (each _{s, 2H, CH 2 = C} ).
³¹ P-NMR (202.35 MHz, d ₁ -CDCl ₃ , ppm):
1.12 (s, (OH) ₂ P ═O)
Examples 2-24
In Example 1, alkylenediamine and halogenated alcohol in the [production of N, N′-diundecanol-ethylenediamine] step, and [N, N′-dimethacryloyl-N, N′-di (undecyldihydrogen) Phosphate) -Ethylenediamine Production] In the same manner as in Example 1 except that the compounds shown in Tables 1 to 5 were used as halides for introducing R _{2 in the} step, and a phosphono group-containing polymerizable compound [ Compounds 2) to 24)] were prepared. Tables 1 to 5 show the overall yields of the obtained phosphono group-containing polymerizable compound as the final product.

Further, as a result of structural analysis of the obtained final product using the same structure confirmation means as in Example 1, it was confirmed that it was the following compound. Table 6-7, elemental analysis for each compound, values calculated from the structural formulas, and showed characteristic peaks of ^{1 H-NMR} spectrum.
2); N, N′-dimethacryloyl-N, N′-di (octyl dihydrogen phosphate) -ethylenediamine,
3); N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -ethylenediamine,
4); N, N′-diacryloyl-N, N′-di (pentadecyl dihydrogen phosphate) -ethylenediamine,
5); N, N′-diacryloyl-N, N′-di (heptyl dihydrogen phosphate) -ethylenediamine,
6); N, N′-dimethacryloyl-N, N′-di (octadecyl dihydrogen phosphate) -tetramethylenediamine,
7); N, N′-dimethacryloyl-N, N′-di (decyl dihydrogen phosphate) -tetramethylene diamine,
8); N, N′-dimethacryloyl-N, N′-di (heptyl dihydrogen phosphate) -tetramethylenediamine,
9); N, N′-dimethacryloyl-N, N′-di (propyldihydrogen phosphate) -tetramethylenediamine,
10); N, N′-Diacryloyl-N, N′-di (propyldihydrogen phosphate) -tetramethylenediamine 11); N, N′-dimethacryloyl-N, N′-di (octyl dihydrogen) Phosphate) -hexamethylenediamine,
12); N, N′-dimethacryloyl-N, N′-di (pentyl dihydrogen phosphate) -hexamethylenediamine,
13); N, N′-dimethacryloyl-N, N′-di (butyldihydrogen phosphate) -hexamethylenediamine,
14); N, N′-diacryloyl-N, N′-di (nonyl dihydrogen phosphate) -hexamethylenediamine,
15); N, N′-diacryloyl-N, N′-di (ethyldihydrogen phosphate) -hexamethylenediamine,
16); N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -p-phenylenediamine,
17); N, N′-diacryloyl-N, N′-di (hexyl dihydrogen phosphate) -p-phenylenediamine,
18); N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -o-phenylenediamine,
19); N, N′-diacryloyl-N, N′-di (hexyl dihydrogen phosphate) -o-phenylenediamine,
20); N, N′-dimethacryloyl-N, N′-di (hexyl dihydrogen phosphate) -m-phenylenediamine,
21); N, N′-diacryloyl-N, N′-di (hexyl dihydrogen phosphate) -m-phenylenediamine,
22); N, N′-dimethacryloyl-N, N′-di (phenyldihydrogen phosphate) -ethylenediamine,
23); N, N′-dimethacryloyl-N, N′-di (benzyldihydrogen phosphate) -tetramethylenediamine,
24); N, N′-dimethacryloyl-N, N′-di (pyridinyldihydrogen phosphate) -hexamethylenediamine

Example 25
[Production of N, N′-distyryl-N, N′-di (octyl dihydrogen phosphate) -ethylenediamine; Compound 25)]
N, N′-Dioctanol-ethylenediamine synthesized by a method according to the [Production of N, N′-diundecanol-ethylenediamine] step in Example 1 using 8-bromo-1-octanol as the halogenated alcohol 5.30 g (16.7 mmol) was dissolved in 250 ml of absolute ethanol. While heating to 65 ° C. and stirring vigorously, 5.62 g (36.7 mmol) of 4-chlorostyrene was added over 10 minutes. The system was kept at 65 ° C. and heated and stirred for 5 hours. Thereafter, the reaction solution was cooled to room temperature, and the reaction solution was concentrated under reduced pressure. The obtained solid was washed with a small amount of absolute ethanol and dried. This was washed with a small amount of anhydrous benzene and dried under vacuum to obtain a white solid in a yield of 6.15 g and a yield of 66.9%.

  6.15 g (11.2 mmol) of this solid was synthesized according to the [production of N, N′-dimethacryloyl-N, N′-di (undecyldihydrogen phosphate) -ethylenediamine] step in Example 1. To give a pale yellow highly viscous liquid in a yield of 3.54 g and a yield of 42.9%.

  This isolated product was analyzed by the following structural analysis means, which was N, N'-distyryl-N, N'-di (octyl dihydrogen phosphate) -ethylenediamine.

It was confirmed that.
Elemental analysis:
The elemental analysis values of this product are C60.48%, H8.04%, N4.14%, the calculated value of this compound is C59.99%, and H8.00%. , N 4.12%.
¹ H-NMR (500 MHz, d ₁ -CDCl ₃ , ppm):
_{1.20~1.28 (b, 14H, -CH 2} -CH 2 -CH 2 -, N-CH 2), 1.65~1.69 (m, 2H, -C H 2 -CH 2 -O ), 2.05 to 2.10 (b, 2H, Ph—C H ₂ ), 2.38 (s, 2H, (O H ) ₂ P═O), 4.01 to 4.06 (t, 2H _{, -C H 2 -O), 5.09~5.78} (s , _{respectively, 3H, C H 2 = C} H), 6.46~7.39 (m, 4H, -C 6 H 4)
³¹ P-NMR (202.35 MHz, d ₁ -CDCl ₃ , ppm): 1.64 (s, (O H ) ₂ P = O)
Example 26
In Example 25, tetramethylene diamine was used as the alkylene diamine, N, N′-dioctanol-tetramethylene diamine was produced as an intermediate product, and this was reacted with vinyl chloride instead of 4-chlorostyrene. In the same manner as in Example 25, N, N′-divinyl-N, N′-di (octyl dihydrogen phosphate) -tetramethylenediamine was produced. The overall yield was 14.8% as shown in Table 8.

Further, as a result of structural analysis of the obtained final product using the same structure confirmation means as in Example 1, it was confirmed to be the above compound. Table 9 shows elemental analysis values of each compound, calculated values obtained from the structural formula, and characteristic peaks of ¹ H-NMR spectrum.

Reference example 1
For comparison, N, N′-dimethacryloyl-N, N′-di (octyldihydroxyphosphoryl) -ethylenediamine (hereinafter referred to as phosphonic acid) was synthesized by the following method.
[Production of N- [8- (diethoxyphosphoryl) -octyl] methacryloylamide]
6.15 g (43.1 mmol) methacryloyl chloride in 150 ml methylene chloride solution of (8-aminooctyl) phosphonic acid diethyl ester in 8.15 g (43.1 mmol) of methacryloyl chloride so that the temperature is kept at 0-5 ° C. Of 50 ml of methylene chloride and 2.41 g (60.3 mmol) of 50 ml aqueous solution of sodium hydroxide were added simultaneously with stirring. The mixture was then stirred at room temperature for a further 2 hours. The reaction was terminated by the addition of 100 ml water.

An appropriate amount of sodium chloride was added to separate the layers. The organic phase was separated and extracted twice from the aqueous phase with methylene chloride. The organic phase was washed 5 times with 1N aqueous HCl, 5 times with 1N aqueous NaHCO ₃ and 5 times with water. After drying over silica gel, filtering, and adding 1000 ppm of HQME to the product, the solvent was distilled off to obtain a yellow highly viscous liquid as a crude product. As final purification, silica gel column chromatography of this material was performed using ethyl acetate as eluent (R _f = 0.31). As a result, 7.33 g (yield: 51%) of a yellow highly viscous liquid was obtained.
[Production of N- [8- (dihydroxyphosphoryl) -octyl] methacryloylamide]
8.08 g (52.8 mmol) of trimethylsilyl bromide in 50 ml of methylene chloride solution of 7.33 g (22.0 mmol) of N- [8- (diethoxyphosphoryl) -octyl] methacryloylamide obtained in the previous step. The solution was added dropwise at room temperature with stirring. Subsequently, the reaction solution was stirred for 4 hours under reflux. Thereafter, the solvent was distilled off, and the residue was dissolved in methanol. The solution was stirred at room temperature for 16 hours. Next, the solvent was distilled off, and the remaining highly viscous liquid was dissolved in toluene. The toluene solution was washed twice with methylene chloride, and then 1000 ppm of HQME was added to the product, followed by concentration under reduced pressure. This material was dried under vacuum to obtain 5.49 g (yield: 90%) of a highly viscous liquid colored deep yellow.
[Production of N, N′-dimethacryloyl-N, N′-di (octyldihydroxyphosphoryl) -ethylenediamine (phosphonic acid)]
5.49 g (19.8 mmol) of N- [8- (dihydroxyphosphoryl) -octyl] methacryloylamide obtained in the previous step was dissolved in 50 ml of ethanol in a 300 ml reaction vessel, and 1.69 g of dibromoethane was dissolved in the solution. (9.0 mmol) was added to reflux the reaction solution. To this reaction solution, a solution prepared by dissolving 0.76 g (18.9 mmol) of sodium hydroxide in 50 ml of ethanol was added dropwise over 8 hours. Stirring was continued for 20 hours under reflux, and then heating and stirring were stopped. The reaction solution was evaporated and concentrated, and the resulting yellow highly viscous liquid was dissolved in diethyl ether. The solution was washed 3 times with concentrated hydrochloric acid, 5 times with 2% aqueous sodium chloride solution and 5 times with water. After washing with hexane five times, the organic phase was dried over silica gel, then the silica gel was filtered, and the organic phase was evaporated and concentrated. This was vacuum-dried to obtain 1.14 g (yield 10.0%) of a highly viscous liquid colored deep yellow.

  This isolated product was analyzed by the following structural analysis means, which was N, N′-dimethacryloyl-N, N′-di (octyldihydroxyphosphoryl) -ethylenediamine.

It was confirmed that.
IR (single reflection ATR, cm ⁻¹ ):
1308cm-1 (b), 1677cm-1 (s)
¹ H-NMR (500 MHz, d ₁ -CDCl ₃ , ppm):
_{1.25~1.29 (m, 10H, -CH 2} -CH 2 -CH 2 -), 1.53~1.57 (m, 2H, -C H 2 -CH 2 -N -), 1. _{77~1.99 (m, 2H, C H} 2 -P), 1.98 (s, 3H, C H 3 -C (CH 2) -), 2.41 (s, 2H, (O H) 2 _{P = O), 3.31~3.35 (m} , 2H, N-CH 2), 3.50~3.55 (m, 2H, N-CH 2), 5.05 and 5.20 (each s, 2H, CH ₂ = C)
_{^{· 31 P-NMR (202.35MHz,}} d 1 -CDCl 3, ppm): 11.30 (s, (OH) 2 P = O)
Example 27
2 g of N, N′-dimethacryloyl-N, N′-di (undecyl dihydrogen phosphate) -ethylenediamine (compound 1) prepared in Example 1, 1 g of MAC-10, 1 of D-2,6E A dental adhesive was prepared by mixing 1.5 g of 3 g, 3 g of 3G, 3 g of HEMA, 1 g of water, 50 mg of CQ, 50 mg of DMBE, and 2 g of filler.
About this dental adhesive, the adhesiveness with respect to a tooth substance was evaluated by the following method. The results show that the initial tensile strength is 17.3 MPa for enamel and 17.5 MPa for dentin, and the tensile strength after the adhesion durability test is 17.2 MPa for enamel. It showed 17.0 MPa for dentin.

[Adhesion test of dental adhesive to tooth]
Within 24 hours after slaughter, the front teeth of the cow were removed, and the enamel and dentin planes were cut out in parallel with the labial surface using # 600 emery paper in the water. Next, air is blown onto these surfaces for about 10 seconds to dry, and then a double-sided tape with a hole having a diameter of 3 mm is fixed to the flat surface, followed by paraffin wax having a hole with a thickness of 0.5 mm and a diameter of 8 mm. A simulated cavity was formed by fixing to the same center on the circular hole. The dental adhesive of the present invention was rubbed into the simulated cavity for 10 seconds and dried by blowing compressed air for about 10 seconds. Next, the adhesive was cured by irradiating with a visible light irradiator (Powerlight, manufactured by Tokuyama Dental Co., Ltd.) for 10 seconds. Furthermore, a dental composite resin (Palfique Estelite Co., Ltd. Tokuyama Dental Co., Ltd.) was filled thereon, and irradiated with a visible light irradiator for 30 seconds to produce an adhesion test piece.

After immersing the above-mentioned adhesion test piece in water at 37 ° C. for 24 hours, using a tensile tester (Autograph, manufactured by Shimadzu Corp.), it is pulled at a crosshead speed of 2 mm / min to measure the tensile bond strength between the tooth and the composite resin. did. Four tensile bond strengths per test were measured by the above method, and the average value was taken as the initial bond strength.
Further, the above-mentioned adhesion test piece immersed in water at 37 ° C. for 24 hours was reciprocated 3000 times, 4 degrees of cold water and 60 degrees of hot water with a thermal cycle tester (thermal shock tester, manufactured by Thomas), and then pulled. Using a testing machine (Autograph, manufactured by Shimadzu Corporation), the tensile strength was measured between the tooth and the composite resin by pulling at a crosshead speed of 2 mm / min. For each test, four tensile bond strengths were measured by the above method, and the average value was defined as the bond strength indicating bond durability.

Moreover, the fracture surface after the tensile test of the test piece which performed the said adhesive durability test was observed visually, and the presence or absence of coloring of a tooth surface was investigated.
Examples 28-52, Comparative Examples 1-3
A dental adhesive having the same composition (Table 10) in the same manner as in Example 27 using the phosphono group-containing polymerizable compound of Compounds 2) to 26) produced in Examples 2 to 26. Part) was prepared.

  Moreover, in order to show the comparison with the adhesive using the phosphono group-containing polymerizable compound of the present invention, the dental adhesive having the same composition using phosphonic acid synthesized in Reference Example 1, MDP and PM as other comparison targets Materials were prepared and used for comparison (Comparative Examples 1-3).

  The result of having evaluated the adhesiveness with respect to a tooth | gear about each dental adhesive material was shown to Tables 11-12. In any of the dental adhesives using the phosphono group-containing polymerizable compound of the present invention, excellent adhesion durability was obtained in addition to high initial adhesive strength.

Example 53
Dental adhesive prepared by mixing 2 g of N, N′-dimethacryloyl-N, N′-di (undecyl dihydrogen phosphate) -ethylenediamine (compound 1) prepared in Example 1, 3 g of water and 5 g of acetone Primers were produced.

About this dental adhesion primer, the adhesiveness with respect to a tooth substance was evaluated by the following method. As a result, the tensile strength at the initial stage of adhesion was 17.1 MPa, and the tensile strength after the adhesion durability test was 17.0 MPa.

[Adhesion test for dental adhesive primer]
Within 24 hours after slaughter, the front teeth of the cow were removed, and the enamel plane was cut out with # 600 emery paper so that it was parallel to the labial surface. Next, air is blown onto these surfaces for about 10 seconds to dry, and then a double-sided tape with a hole having a diameter of 3 mm is fixed to the flat surface, followed by paraffin wax having a hole with a thickness of 0.5 mm and a diameter of 8 mm. A simulated cavity was formed by fixing to the same center on the circular hole. A dental adhesive primer composition having the composition shown in Table 13 was applied to the simulated cavity using a sponge for 10 seconds, left standing for 30 seconds, and then compressed air was sprayed for about 10 seconds. Thereafter, methyl methacrylate (80 parts by mass), 2-hydroxyethyl methacrylate (20 parts by mass), N, N-dimethyl-p-toluidine (3 parts by mass), polymethyl methacrylate (130 parts by mass), benzoyl peroxide (2 Adhesive resin cement consisting of (part by mass) is filled into the simulated cavity, and then a stainless steel attachment with a diameter of 8 mmφ treated with “MR bond (manufactured by Tokuyama)” is pressed from above to produce an adhesion test piece. did.

After immersing the above-mentioned adhesion test piece in water at 37 ° C. for 24 hours, using a tensile tester (Autograph, manufactured by Shimadzu Corp.), it is pulled at a crosshead speed of 2 mm / min to measure the tensile bond strength between the tooth and the composite resin. did. Four tensile bond strengths per test were measured by the above method, and the average value was defined as the bond strength.
Examples 54-66
Dental adhesive primer having the same composition (Table 13) in the same manner as in Example 53 using the phosphono group-containing polymerizable compounds shown in Tables 14 to 15 produced in the above Examples (amount is parts by mass) Was prepared.

  Moreover, in order to show the comparison with the dental adhesive primer using the phosphono group-containing polymerizable compound of the present invention, the same composition was used using phosphonic acid synthesized in Reference Example 1 and MDP and PM as other comparison targets. A dental adhesive primer was prepared and used for comparison (Comparative Examples 4-6).

  Table 14 shows the results of evaluating the adhesiveness to the tooth for each dental adhesive primer. In any of the dental adhesive primers using the phosphono group-containing polymerizable compound of the present invention, excellent adhesion durability was obtained in addition to high adhesive strength.

Claims (5)

The following general formula (1)

[Wherein, R ₁ represents a chain hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 10 carbon atoms, an aromatic hydrocarbon group having 6 to 15 carbon atoms, or the total of carbon and hetero atoms. A heterocyclic group having 5 to 10 atoms, R ₂ is a styryl group, vinyl group, acryloyl group, or methacryloyl group , R ₃ is a chain hydrocarbon group having 1 to 8 carbon atoms, 3 to 8 carbon atoms Or an aromatic hydrocarbon group having 6 to 8 carbon atoms. ]
The phosphono group containing polymeric compound represented by these. General formula (2)

[In formula, A is hydrogen or a methyl group, l is an integer of 2-12, m is an integer of 1-8. ]
The phosphono group containing polymeric compound of Claim 1 shown by these. A dental adhesive comprising the phosphono group-containing polymerizable compound according to claim 1 or 2 and a polymerization initiator. A dental adhesive primer comprising the phosphono group-containing polymerizable compound according to claim 1 or 2 and a volatile organic solvent. General formula (3)

[In the formula, R ₁ Is a chain hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 10 carbon atoms, an aromatic hydrocarbon group having 6 to 15 carbon atoms, or a total of 5 to 10 atoms of carbon and heteroatoms. A heterocyclic group, R ₂ Is a styryl group, vinyl group, acryloyl group, or methacryloyl group, and R ₃ Is a chain hydrocarbon group having 1 to 8 carbon atoms, an alicyclic hydrocarbon group having 3 to 8 carbon atoms, or an aromatic hydrocarbon group having 6 to 8 carbon atoms. ]
The method for producing a phosphono group-containing polymerizable compound according to claim 1, wherein the compound represented by the above is reacted with phosphoryl halide in the presence of a tertiary amine.