JPS58192891A - Novel polymerizable phosphoric acid monoester and its preparation - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R is H or CH3; n is 2-4). EXAMPLE:2-{m-[2-(Methacryloyloxy)ethoxy]phenoxy}ethyl dihydrogen phosphate of formula II. USE:Adhesive for dental use. It has excellent adhesivity to metals and hard tissue of human body (especially the teeth) and high water resistance. PROCESS:The diol of formula II is made to react with (meth)acrylic acid, and the resultant mixture of the monoester and diester of said diol is further made to react with more than equimolar amount of phosphorus oxychloride based on said monoester. The P-Cl bond of the reaction product is hydrolyzed, the OH group of the monoester is converted to phosphoric acid ester, and the phosphoric acid ester is separated from the mixture of said phosphoric acid ester and the above diester.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel phosphoric acid monoester compound represented by the general formula (wherein 8 represents H or CjHs and n represents an integer from 2 to 4) and a method for producing the same. Such compounds exhibit very good adhesion to metals and human hard tissue (particularly teeth), and have a high degree of water resistance.

Conventionally, it has been known that when a polymerizable composition containing 2-(meth)acryloyloxyethyl dihydrogen phosphate is applied to the surface of iron or stainless steel and polymerized and cured, a film that adheres to the metal can be obtained. Patent applications have been filed for various compositions for industrial use (for example, JP-A-50-100120). Phosphate ester compounds (
It is generally known that monoesters (monoesters, diesters) have adhesive properties to metals, but phosphate ester compounds have significantly superior adhesive strength than 2-(meth)acryloyloxyethyl dihydrogen phosphate. There are no cases where the chemical structure or chemical name has been clearly specified.

With the aim of developing dental adhesives, the present inventors conducted a detailed study on the adhesive strength of (meth)acrylic acid esters having phosphoric residues (-PO(OH), ) to metals and tooth structure. In the process, I discovered a surprising fact. That is, the water resistance of the adhesive composition containing 0.5 to 5 tji% of 2-methacryloyloxyethyl dihydrodiene phosphate to Ni-0r alloy and stainless steel is disclosed in JP-A-54-1255B. This was significantly inferior to that of 4-methacryloxyethyltrimellitic acid, which has an adhesive effect on metals and tooth structure, and also showed no adhesive effect on teeth. It has been revealed that the above-mentioned new compound synthesized for adhesive strength evaluation exhibits metal and tooth adhesive strength several times higher than that of 4-methacryloxyethyl trimellitic acid.

Although it is known that phosphate ester compounds adhere to metals, we believe that this is due solely to the presence of 2-methacryloyloxyethyl dihydrogen phosphate saturated bonds. This is probably because it was not possible to systematically synthesize and evaluate the adhesive strength. As a result of keenly pursuing the adhesive force expression mechanism of phosphate ester compounds, the present inventors found that not only the presence of phosphoric acid groups and polymerizable type 2 packing, but also the structure of the organic residue that connects both groups exerts adhesive force. We have discovered a new fact that this has a decisive effect, and have now synthesized the compound of the present invention.

That is, the first invention of the present application is a novel polymerizable phosphoric acid monoester compound represented by the above general formula (g). Its chemical name is 2-(m-(2-(methacryloyloxy)ethoxy)phenoxy]ethyl dihydrogen phosphate, 3-(m7(3-(methacryloyloxy)propoxy)phenoxy]propyl dihydrogenphosph ate, 4-(m-(4-(methacryloyloxy)butoxy)phenoxy]butyl dihydrodiene sulfate, 2-(m-(2-(acryloyloxy)ethoxy)phenoxy]ethyl dihydrodiene phosphate, 3-(m-(5-(acryloyloxy)propoxy)phenoxy]propyl dinoλ hydrodiene phosphate, 4-(m-(4-(
Acryloyloxy)butoxy)phenoxycobutyl
Dihydrogen phosphate.

The synthesis of these compounds is as follows: (1) (meth)acrylic acid and no+aH2
= integer from 2 to 4) (monoester,
The reaction is carried out in a two-stage process consisting of (a diester mixture is produced) and (II) a reaction of converting the monoester in the ester mixture into a phosphoric acid ester. In the first step, the esterification reaction of (meth)acrylic acid and diol, it is difficult to selectively synthesize only the monoester necessary for the present invention, but if both components are reacted in equimolar amounts, The monoester whose structure is shown below is
Middle) RR H2C=C-COOfCH2kO-◎-0+0HxkSaki-C=CH2(C) (In the formula, R is H or OHs, In
(represents an integer from 2 to 4) and a mixed system of (meth)acrylic acid and diol, which are the raw materials thereof.

If only monoester (6) is to be isolated from this, chromatography must be used and the purification cost becomes extremely high.

Therefore, the inventors of the present application first removed the raw material components that are easy to separate from the mixed system [diol and (meth)acrylic acid, and left the monoester (6) and diester 0, which are difficult to separate, in the mixed system, and added the next phosphor to the mixed system. By subjecting the monoester (2) to an acid esterification reaction, converting the hydroxyl group of the monoester (2) into a phosphoric acid ester, and then isolating it, the above-mentioned problem of isolating the monoester and Jesdel was avoided. That is, the invention of fH2 of the present application is based on a monoester and diester mixture of a diol represented by the general formula % (n represents an integer of 2 to 4) obtained by reacting the diol with (meth)acrylic acid; The monoester is reacted with phosphorus oxychloride in an amount equal to or more than the same mole, and then the P-C1l bond of the resulting reaction product is hydrolyzed to convert the hydroxyl group of the monoester into a phosphoric acid ester, and then the phosphoric acid Polymerizability represented by the general formula (wherein 8 represents ■ or cH, and n represents all integers from 2 to 4), characterized in that the phosphoric ester is isolated from a mixture of an ester and the above-mentioned diester. This is a method for producing a phosphoric acid monoester compound.

Specifically, it is desirable to do the following. Charge 0.5 to 1.5 moles of (meth)acrylic acid per mole of diol into a reaction vessel and esterify in a batch manner at 120°C or lower in the presence of an acid catalyst with no solvent or with the addition of an appropriate amount of a solvent such as benzene. Perform a reaction. If the amount of (meth)acrylic acid charged per mole of diol is less than 0.5 mole or more than 1.5 mole, the yield of monoester will be greatly reduced, which is not preferred. As an esterification catalyst, a non-volatile strong acid such as sulfuric acid, sulfonic acid, or phosphoric acid is used at a concentration of 0.0% based on the total amount charged.
Add 1-10% by weight.

In addition, hydroquinone monomethyl ether, hydroquinone, 2.2'-
A polymerization inhibitor such as methylenebis(4-ethyl-6-tart-butylphenol) is added in an amount of 100 to 10,000 PPm based on (meth)acrylic acid. Air or oxygen is blown into the reaction solution to suppress polymerization, but if the reaction temperature is 1.
If the temperature exceeds 20'C, there is still a risk of polymerization. Therefore 1
201: Hereinafter, the reaction is preferably carried out at 100° C. or lower under reduced pressure while distilling produced water, or while water is azeotropically distilled off together with benzene. When water no longer distills out after several hours, the reaction is stopped and the reaction solution is diluted 1.5 times with an aromatic solvent, preferably toluene.

As a result of the dilution, almost all of the unreacted diol precipitates out as a solid, which is then removed separately. The P solution was washed with an alkaline aqueous solution to remove meth)acrylic acid and the acid added as a catalyst, and after repeated washing with neutral water, Na28
By dehydrating with a drying agent such as 04, Mg80s, and distilling off the solvent under reduced pressure, a mixture of monoester and diester (B) (Q) can be obtained.
Abbreviated as C. ), the mixing ratio is easily determined, and the mixture is used as the raw material for the next reaction.

Next, the phosphoric acid esterification reaction will be described.

Phosphorus oxychloride, tetrahydrofuran, ethyl ether, ethyl acetate, halogenated hydrocarbons, etc.! The mixture is diluted with a medium or nitrogen to the extent that the concentration does not fall below 511% by weight, placed in a dehumidified reaction vessel, and cooled to -10° to -60°C. The amount of phosphorus oxychloride used is 1.0 to 2.0 mol per 1 mol of the monoester, while the initial mixture of phosphorus (in the monoester) and diester is used in an equimolar amount or slightly in excess of the monoester. The mixture is mixed with an amount of a tertiary amine such as triethylamine, tributylamine, pyridine, N-methylmorpholine, etc., and the mixture is added dropwise into a cooled reaction vessel either as is or after diluting with a solvent such as tetrahydrofuran. During the dropwise addition, stir the reaction solution vigorously.
The reaction temperature is maintained between -10°C and -60°C. When the temperature is -10℃ or higher, the phosphoric acid diester (6) shown below tends to be produced as a by-product (wherein, B is H or cH, and n represents a natural number from 2 to 4). However, problems such as a decrease in the reaction rate and solidification of the solution occur. -10 for at least 30 minutes after completion of instillation
Stirring is continued while maintaining the temperature at ~-60°C, and then the reaction temperature is raised to 0°C, water and the above-mentioned tertiary amine are added dropwise, and unreacted P-α bonds are hydrolyzed. At this time, water is added in a molar amount in excess of the remaining P-α bond, and the tertiary amine is added dropwise in such a manner that the total amount of water added is five times that of phosphorus oxychloride. After completion of the dropwise addition, the reaction is continued at 0° C. to room temperature until hydrolysis of the P-α bond is completed. At the end of the reaction, phosphoric acid monoester (a) is present as a product in the reaction vessel.
, by-product nophosphoric acid diester @, triethylammonium chloride, phosphoric acid, diester (Q
, water, and an organic solvent (eg, tetrahydrofuran) are present. Among these methods, several methods can be considered to isolate only the target product, phosphoric acid monoester (A). For example, a method may be used in which the mixture is extracted into an aqueous phase with phosphoric acid monoester (t)Kaneshima salt, made acidic again, and re-extracted from the aqueous phase into an organic phase with an appropriate organic solvent. However, the most efficient and high-yield method that the present inventors have tried is as follows.

First, after carrying out a phosphoric acid esterification reaction in tetrahydrofuran, triethylammonium chloride precipitated in the reaction solution is separated using a filter, an appropriate amount of the polymerization inhibitor is added to the P solution, and the solvent is distilled off under reduced pressure. The resulting residue is dissolved in ethyl acetate and the solution is washed several times with dilute aqueous hydrochloric acid. Thereafter, it is washed with neutral water, dehydrated and dried, and the solvent is distilled off to obtain a liquid residue. The residue is washed repeatedly with toluene to remove toluene-soluble diester (Q) and phosphoric acid diester (b).

The toluene-insoluble portion solidifies when the solvent is distilled off under reduced pressure, and the solid contains 9596 or more phosphoric acid monoester (4).

The crude phosphoric acid monoester is dissolved in a suitable organic solvent such as tetrohydro7ran, ethyl acetate, acetone, ethanol, etc., and after separating the insoluble matter, recrystallization is performed by adding a precipitant such as n-hexanetoluene. Purification and high purity can be achieved easily.

The structure of the obtained crystal was identified by analytical means such as island 1, infrared, mass spectrometry, and elemental analysis, and the chemical structure was determined by the formula (A
) was confirmed.

Next, the uses and usage of the compound of the present invention will be described. The compound can be applied alone or mixed with other copolymerizable vinyl compounds, and cured by polymerization to form various metals (Fe
%Ni, Cr, Cu, Zn.

M, etc.) as well as 2-methacryloyloxyethyl
Because dihydrogen phosphate strongly adheres to teeth that have shown little adhesive effect, it is used as a dental adhesive (adhesive applied to teeth during tooth restoration, inlays, etc.).
It is extremely useful as a component of adhesives for bonding crowns etc. to teeth, orthodontic adhesives, adhesives for holding bridge posts etc., dental composite filling materials, etc.). It also adheres well to bones as well as teeth, so it is expected to be used as bone cement. Furthermore, by taking advantage of its adhesive strength to metals, it can also be applied to industrial applications such as structural adhesives, paints, and metal surface treatment agents.

In particular, when the compound of the present invention is used in dental adhesives,
It is preferable to use a composition comprising (1) the compound as an adhesive monomer, (2) a copolymerizable vinyl compound, and (3) a curing agent. The content of the adhesive compound in the composition is 0.65% by weight or more based on the total monomers from the viewpoint of adhesiveness, and is usually used in the range of 1.5 to 50% by weight.

As copolymerizable vinyl compounds, those conventionally used in dental adhesives can be used, including styrene, vinyl acetate, (meth)acrylate monomers [methyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-methacryloyloxyethyl phenylhydrodiene phosphate, tetraethylene glycol di(meth)acrylate, neopentyl glycol di(meth)acrylate, Bis-GMA, trimethylolpropane tri(meth)acrylate, bisphenol-mushi (Meth) acrylate, etc., JP-A-52-
11!1089]. These are appropriately selected to adjust the viscosity, wetting characteristics, curing characteristics, mechanical properties, etc. of the adhesive. Hardening agents include benzoyl peroxide, azobisisobutyronitrile, tributylborane, aromatic sulfinic acid (or salt), aromatic sulfinate/diacyl peroxide/aromatic A tertiary amine type or the like is used. A photosensitizer (such as benzoin methyl ether) is also used. Regarding curing agents, see JP-A-53-11
Reference is made to the description in No. 0657, 54-111494+. Furthermore, a volatile organic solvent (such as ethanol), an inorganic filler such as aluminum oxide or quartz, and an organic filler such as polymethyl methacrylate powder may be added to the above composition.

Hereinafter, the present invention will be explained in more detail with reference to Examples and Comparative Examples.

Example 1 Methacrylic acid 2509 (2.9 mol), 1,3-bis(2-hydroxyethoxy)benzene 4130f (2°4 mol), P-toluenesulfonic acid 35f1, hydroquinone monomethyl ether 0.6f, 11 The mixture was placed in a flask and heated to 85°C. After the whole has dissolved to become a homogeneous solution, use an aspirator to reduce the pressure (20 to 100
(Hg) and while blowing oxygen, raise the internal temperature to 85°~
Produced water was distilled off at 90°C. After about 4 hours, when no more water is distilled out, stop the reaction and add 1. while the reaction solution is still hot.
The unreacted diol that had precipitated was separated by P using a No. 4 filter. P solution is 5% Na2CO3
500 cc of aqueous solution was washed with water twice, then washed with neutral water five times, dried over a glass cup, added with 0.12 g of hydroquinone monomethyl ether, and toluene was distilled off under reduced pressure at 80° C. or below. By the above operation, monoester (6)
A mixture of 460% and diester (Q) was obtained. As a result of HLC analysis, the monoester content in the mixture was 641% by weight, and the remaining amount of diol as a raw material was only a trace of primary phosphorus oxychloride (55.2%). i' (0,56wd) to 1
The mixture was dissolved in 50 cc of tetrahydrofuran, placed in a 11 reaction vessel, and cooled to -50°C. The previously synthesized monoester/diester mixture 125f (0.5 mol of monoester) and triethylamine 55.47 (043
mol) in 150 CC of tetrahydrofuran, 50
It was placed in a 0 cc dropping funnel and connected to a reaction vessel. Dry N
After blowing in two gases, the phosphorus oxychloride solution was vigorously stirred, and the monoester solution was slowly added dropwise. The internal temperature was maintained at -45 to -50°C during the dropping, and kept at -45°C for 1 hour after the completion of the dropping. After that, the temperature was raised to 0℃, and the water was heated to 50m
A solution of t and triethylamine 75.91 dissolved in 100 cc of tetrahydrofuran was slowly added dropwise. For 15 hours after the completion of the dropwise addition, the reaction solution was continuously stirred on a water-cooled plate until P-α
Hydrolysis of the bond was completed. Thereafter, the precipitated triethylammonium chloride was separated using a No. 4 glass filter, 60 drops of hydroquinone monomethyl ether was added to the r solution, and then tetrahydrofuran was distilled off under reduced pressure at a temperature below 50°C. The obtained residue was dissolved in 800 cc of ethyl acetate, transferred to a separating funnel, and 300 cc of 2
Washed 5 times with N-hydrochloric acid aqueous solution and 2 times with 300 cc of neutral water. The mixture was dehydrated and dried overnight with glass salt, and 50 g of hydroquinone monomethyl ether was added thereto, and ethyl acetate was distilled off under reduced pressure to obtain a liquid residue. This was washed repeatedly with toluene, and then the volatile components in the residue were distilled off under reduced pressure. Due to the above operations? ) 679 crude phosphoric acid monoester was obtained as a solid.

Furthermore, the phosphoric acid monoester was dissolved in 150 cc of acetone, and after separating the insoluble matter, a 1:1 (volume ratio) mixed solvent of toluene and n-hexane was added to recrystallize to obtain crystals of 582. .

The melting point of the crystals was 64-67°C. Make a d6-acetone solution and perform 90 DNMR measurements at room temperature.
= ethylenic proton signals at 6.0s and 5.5s, 8 methylene proton multiple signals at δ = 4.0 to 4.5, methyl proton signal at δ = 1.8s, δ = Four proton signals of the phenylene group were observed at 6.3 to 6.5 and 7.0 to 7.2, and a proton signal of the phosphate group was observed at δ=9.2.

The results of elemental analysis were C:=49.0%, P:8.
6% [calculated value, C: 48.6%, p: 8.9%], and it was confirmed that the compound was.

Example 2 In Example 1, methacrylic acid was replaced with acrylic acid 2169
An experiment was conducted under exactly the same conditions as in Example 1, except that (5.0 mol) was used, and a mixture of diol monoester and diester was obtained. After determining the monoester content by HLC, a phosphoric esterification reaction was carried out using an amount of the mixture corresponding to 0.5 mol of monoester, followed by isolation in exactly the same manner as in Example 1. A boy solid was obtained. NMK measurement and elemental analysis of the compound [C: 47.5%
(47,0)P: 8.9% (9,5), where the values in parentheses are calculated values) It was confirmed that the compound was HO III. Further, the purity as a result of llLC analysis was 95% or more.

Examples 5-6 1. with methacrylic acid or acrylic acid, diol and L.
The 48m compound listed in Table 1 was synthesized using 3-bis(5-hydroxypropoxy)benzene or 1,5-bis(4-hydroxybutoxy)benzene and according to the method of Examples 1 and 2, and the NMR1 The structure was confirmed by elemental analysis and the purity was determined by HLO. In addition, among the elemental analysis values, the values of C, H, and P are shown in Table 1. All compounds had a purity of 95% or more.

+"<1' 2.ζ2j Example 7.8 and Comparative Example 1 Two compounds of the present invention (Example 7.8) and 2-methacryloyloxyethyl dihydrodiene phosphate (Comparative Example) were used as adhesive monomers. Adhesives of syl containing each of 1) were prepared according to the following formulations, and a water resistance test for adhesion to metal was conducted.

Adhesive composition ■ Packaging adhesive monomer 5 parts by weight Methyl methacrylate 95 I benzoyl peroxy) 1 I packaging polymethyl methacrylate powder 100 parts by weight Sodium benzenesulfinate 5 〃N, N
-Jetanol-P-Toluidine 1 evening (however,
■The packaging is made by uniformly mixing and dispersing benzenesulfinic acid and amine powders in PMMA powder. ) 10X10)l■ Ni-Cr alloy (Nt: 92,
7%) The chips were polished with 41000 abrasive paper and ultrasonically cleaned in water and methyl ethyl ketone. 5■ for this chip
Cellotape with a hole of φ was attached so that the hole coincided with the center of the polished surface. Separately 7■φ)C' 35. A stainless steel rod and a Ni-Or alloy chip were prepared for several days, and one end surface of the stainless steel rod was polished and cleaned in the same manner. The above adhesive packaging and (1) packaging were mixed in equal weights and applied with a brush to the alloy chip (the hole in the cellophane tape) and the stainless steel rod, and then butt-bonded. Adhesive samples of 20 g per adhesive were immersed in 37°C water after 1 hour of adhesion. After 24 hours and after 10 days, 1011 samples of each of the 1C samples were taken out and the tensile adhesive strength was measured using an Instron tensile tester, and the average values are shown in Table 2. Note that when the tensile strength was 400 bycj or more, the interfacial fracture occurred mainly on the Ni-Cr alloy surface.

As is clear from Table 2 @ Table 2, when the adhesive monomer of the present invention was used, the initial adhesive strength was extremely high at 400 bg7cj or more, and no decrease in adhesive strength was observed even after 10 days of immersion in water. However, when 2-methacryloyloxyethyl dihydrogen phosphate, which is a known phosphate ester monomer, was used, the adhesive strength was significantly reduced by immersion in water.

Example 9.10 and Comparative Example 2 Two-component adhesives were prepared using the monomers of Example 1.2 and Comparative Example 1 according to the following formulations, and a commercially available composite resin was acid-etched with the adhesives. It adhered to both denture treated with acid etching and dentin that was not acid etched, and its performance was evaluated.

■Liquid phenyl propane 2-hydroxyethyl methacrylate 50 diethylene glyco-7 dimethacrylate 23
Adhesive monomer 7 Penzoyl peroxide 1.5Y liquid 95% ethanol 100 Sodium pensene sulfinate 4 N,N-getanol-P-toluidine 1 An denture molar was shaved into a prismatic shape so that the dentin was exposed in the adhesive direction. Prepare an ivory square rod (10 x 10 x 30 m). Store these refrigerated in water until just before use. When dentin is bonded after acid etching, immediately before use, wipe water from the dentin surface of the denture to be bonded, and etch the dentin surface for 1 minute with a 40% orthophosphoric acid aqueous solution. Next, wash thoroughly with running water, evaporate moisture by blowing clean air or nitrogen, and wrap aluminum strips around the sides. On the other hand, wipe off moisture from the adhesive surface of the ivory stick. Apply an equal volume mixture of liquids ■ and ■ to both the denture and the ivory frame, and dry by blowing clean air or nitrogen. Commercially available composite resin “cIearfil”
FJ (manufactured by Kuraray) was kneaded, and this paste was sandwiched between the denture and the ivory bonding surface and bonded. When adhesion was performed without acid etching, only the etching and subsequent washing with water were omitted from the above steps, and the other steps were the same. After 30 minutes, the sample piece was immersed in water at 37°C, and after 18 minutes, the tensile adhesive strength was measured using an Instron tensile tester (crosshead speed 2/blood n).
)L, the results are shown in Table 3. In addition, 7 dentures were used for the evaluation of the 181 adhesive, and the average value of the adhesive strength of the 7 pieces is shown.

Table 6 As is clear from Table 3, the compound (A) of the present invention exhibited significantly higher adhesive strength than 2-methacryloyloxyethyl dino-1 hydrodiene phos7ate, which is a known phosphoric acid monoester monomer.

The patent shows that it has a high adhesive strength that can be used in dental practice even without acid etching of dentin, making it possible to simplify treatment methods that would have been unimaginable with conventional technology.

Patent applicant: Kuraray Co., Ltd. Agent Bento Attorney Ken Honda

Claims (4)

[Claims] (1) A polymerizable phosphoric acid monoester compound represented by the general formula (wherein R is H or CHs, and n represents a teno integer from 2 to 4). (2) The polymerizable phosphoric acid monoester compound according to claim 1, wherein n is 2. (3) The polymerizable phosphoric acid monoester compound according to claim 2, wherein R is CH. (4) Monoester and diester a&
The product is reacted with phosphorus oxychloride in an amount equivalent to or more than the monoester, and then the P-α bond of the reaction product obtained in step 0 is hydrolyzed to convert the hydroxyl group of the monoester into a phosphate ester, and then and then isolating the phosphoric ester from the mixture of the phosphoric ester and the diester, according to the general formula (wherein B is H or (H, %n represents an integer from 2 to 4) A method for producing a polymerizable phosphoric acid monoester compound shown in