JPH0239514B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a novel compound of 4-alkyl-
1-Hydroxyalkyl-2,6,7-trioxabicyclo[2,2,2]octane, i.e. general formula,

The present invention provides a compound (hereinafter referred to as a bicyclo compound) represented by the formula: (wherein R ₁ is an alkylene group and R ₂ is a hydrogen atom or an alkyl group) and a method for producing the same. Conventionally, various bicyclo compounds have been known, for example, the general formula (However, R is a lower alkyl group) 1-alkyl-4-hydroxymethyl-2,
6,7-trioxabicyclo[2,2,2]octane is known. In addition, a general formula derived from the above general formula (A), The unsaturated carboxylic acid ester having a bicycloorthoester ring shown in the formula is attracting attention for its usefulness as a polymerizable monomer having a small volumetric shrinkage rate during polymerization and curing. However, regarding the application of the bicyclo compound represented by the above general formula (A) and its unsaturated carboxylic acid ester, conventionally known polymerization curing catalysts, such as boron trifluoride, have problems in handling.
Alternatively, due to problems in terms of harmful effects on the human body, or because the polymerization activity is low, no industrially useful use has been found at present. The present inventors have conducted extensive research on polymerizable monomers that have a small volumetric shrinkage rate during polymerization and curing. As a result, it becomes a raw material for a new unsaturated carboxylic ester, and the unsaturated carboxylic ester derived from the raw material has higher polymerization activity than the known unsaturated carboxylic ester represented by the general formula (B), For example, we have successfully synthesized a useful bicyclo compound that exhibits extremely good performance when applied as an adhesive component. The inventors have now provided the above-mentioned novel compound and a method for producing the same. That is, the present invention provides the general formula (However, R ₁ is an alkylene group and R ₂ is a hydrogen atom or an alkyl group) 4-alkyl-1-hydroxyalkyl-2,6,7-trioxabicyclo[2,2,2]octane It is. The present invention also provides a method for producing 4-alkyl-1-hydroxyalkyl-2,6,7-trioxane represented by the above general formula () by dehydrating hydroxycarboxylic acid and trimethylolalkane in the presence of an acid. A method for producing bicyclo[2,2,2]octane is also provided. The general formula () of the present invention is

In the formula, R ₁ is an alkylene group, and R ₂ is a hydrogen atom or an alkyl group. The alkylene group and alkyl group are not particularly limited, but lower alkylene groups and alkyl groups, such as those having 1 to 3 carbon atoms, are generally preferred due to economical limitations in the production of the above compounds. As mentioned above, the above compound of the present invention is somewhat similar in structure to the bicyclo compound represented by the general formula (A) among known compounds, but the bonding mode of the oxygen atom to the hydroxyl group in the bicyclo ring is different. Therefore, as mentioned above, there are significant differences in the polymerization properties of the unsaturated carboxylic acid esters of the bicyclo compounds derived from the respective compounds as raw materials.
Both have significantly different properties. Of course, their manufacturing methods are also completely different. In addition, the compound represented by the general formula () of the present invention is effectively used as a monomer with low shrinkage during polymerization and curing, for example, in medical materials or dental materials, since the unsaturated carboxylic acid ester derived from the compound is effectively used in medical materials or dental materials. It is extremely useful industrially as a raw material. The compound represented by the general formula () of the present invention can be confirmed to be the compound by the following measurements. (1) Measurement of infrared absorption spectrum (IR) Bicycloorthoester structure

[Formula] and the presence of hydroxyl group (-OH) can be confirmed. Several absorption bands originating from the former appear between 1000cm ^-1 and 1200cm ^-1 , and absorption bands originating from the latter appear between 3300cm -1 and 1200cm ^-1 .
Appears at 3400cm ^-1 . (2) Measurement of ¹ H-Nuclear Magnetic Resonance Absorption Spectrum ( ¹ H-NMR) When measured in deuterated chloroform or deuterated dimethyl sulfoxide solvent with tetramethylsilane as the standard, δ (ppm) = 3.8 to 4.2. A singlet absorption peak derived from six methylene hydrogens in the bicyclo ring appears at this position. In addition, the difference in the types of R ₁ and R ₂ in the above general formula () can be determined by observation and analysis of the position and multiplicity of absorption peaks derived from hydrogen in R ₁ and R ₂ and the relative ratio of absorption peak areas. Can be distinguished. for example
When R ₁ is a methylene group and R ₂ is an ethyl group, the singlet absorption peak derived from the methylene group hydrogen of R ₁ in deuterated chloroform solvent is δ (ppm) = 3.55
In addition, a quartet absorption peak derived from methylene hydrogen in R ₂ is observed at the position of δ (ppm) = 1.30. Furthermore, a triplet absorption peak derived from methyl hydrogen in R ₂ is observed at the position of δ (ppm) = 0.85. When the areas of the three types of absorption peaks are measured as described above and their ratios are calculated, the values match the ratios of the numbers of hydrogens bonded to each group. The most characteristic difference between the general formula () of the present invention and the known general formula (A) is the absorption peak position of hydrogen on the carbon adjacent to the bicycloorthoester ring. That is, the general formula ()
In the alkylene group sandwiched between the hydroxyl group and the bicycloorthoester ring represented by R ₁ , the hydrogen absorption peak on the carbon adjacent to the bicycloorthoester ring is lower in magnetic field than the corresponding hydrogen absorption peak in general formula (A). observed on the side. Also, the general formula ()
The absorption peak of hydrogen on the carbon adjacent to the bicycloorthoester ring of the alkyl group represented by R ₂ is observed on the higher magnetic field side than the corresponding absorption peak of hydrogen in general formula (A). For example, R ₁ is a methylene group,
When R ₂ is an ethyl group, regarding the former, δ (ppm) = 3.55 in the general formula (), and the corresponding general formula (A)
In this case, a hydrogen absorption peak is observed at δ (ppm) = 3.45. Furthermore, regarding the methylene hydrogen of the latter ethyl group, in the general formula (), δ (ppm) =
1.30, and hydrogen absorption peaks are observed at δ (ppm) = 1.60 in the corresponding general formula (A). (3) Mass spectrometry As a means of mass spectrometry, molecular weight can be determined by any of the following methods: electron impact method (abbreviated as EI), electrolytic desorption method (abbreviated as FD), or chemical ionization method (abbreviated as CI). Can be confirmed. The molecular weight of the compound is M
Then, in the EI method, a molecular ion peak is observed at the M ⁺ or (M+1) ⁺ position, in the FD method, a molecular ion peak is observed at the M ⁺ position, and in the CI method, a pseudomolecular ion peak is observed at the (M±1) ⁺ position. be done. (4) Elemental analysis This can be confirmed by comparing the analysis results of carbon and hydrogen with the theoretical values calculated from the general formula (). The compound represented by the general formula () of the present invention can be confirmed by the various measuring methods described above. Further, when confirming the compound of the present invention, it is also possible to prepare a standard chart measured for a compound whose structure has been confirmed in advance, and to confirm the compound by comparing with the standard chart. The compound represented by the general formula () is a white solid at room temperature, and has a unique melting point depending on the difference between R ₁ and R ₂ . In addition, the compound represented by the general formula () is generally methylene chloride,
It is soluble in solvents such as chloroform, acetone, dioxane, and ether, and is ring-opened with an acid catalyst while dissolved in these solvents. In addition, by selecting reaction conditions, ring-opening polymerization can be further performed to produce a polymer with almost no volumetric contraction during the ring-opening polymerization. The compound represented by the general formula () of the present invention is useful as a raw material for a novel unsaturated carboxylic acid ester, as described above. The unsaturated carboxylic acid ester can be produced by using a catalyst such as a tertiary amine that is easy to handle and has less harmful effects on the human body, as is clear from the application examples and comparative examples described below. Since it polymerizes and hardens in a short period of time, it is extremely useful as a raw material for dental or medical materials used in the mouth, for example. The method for producing the compound of the present invention represented by the general formula () is not particularly limited, and any method can be employed. Typical examples of industrially advantageous manufacturing methods are as follows. That is, by dehydrating a hydroxycarboxylic acid represented by the general formula HO-R ₁ --COOH () and a trimethylolalkane represented by the general formula (HOCH ₂ ) ₃ C-R ₂ (), the above-mentioned General formula () is synthesized. However, R ₁ and R ₂ in the above general formulas () and () are R 1 and R ₂ in the above general formula ()
and R ₂ . In this reaction, first, the raw materials hydroxycarboxylic acid and trimethylolalkane are mixed in a suitable solvent such as benzene, toluene, xylene, etc., and an acid catalyst such as P is added.
-By reacting in the presence of toluenesulfonic acid, sulfuric acid, etc., the general formula A reaction intermediate represented by is produced. The above reaction is
Generally, it is preferable to carry out the reaction under reflux of the solvent in an inert gas atmosphere such as nitrogen gas. Further, the progress of the reaction can be determined by measuring the amount of water that is azeotropically distilled off with the solvent. Next, the intermediate, that is, the compound represented by the general formula (), is treated with an acid catalyst, such as P-
In the presence of toluenesulfonic acid, sulfuric acid, etc., under reduced pressure,
By heating and performing a dehydration reaction, the compound of the present invention represented by the general formula () is obtained. As conditions for the above dehydration reaction, a temperature range of 140 to 220° C. under reduced pressure of about 1 to 0.03 mmHg is generally suitably employed. The compound of the present invention can be separated from the reaction system by vaporizing and distilling it off after the above dehydration reaction. The distilled liquid solidifies under air cooling and becomes a white crystalline solid. As mentioned above, the compounds of the present invention can be prepared, for example, by the general formula (However, R ₃ is a hydrogen atom or an alkyl group.) By reacting with an unsaturated carboxylic acid chloride represented by the formula (R 3 is a hydrogen atom or an alkyl group), a novel unsaturated carboxylic acid ester represented by the general formula () is obtained. The novel unsaturated carboxylic acid ester represented by the general formula () is an extremely useful compound that exhibits excellent performance when applied to molding materials, composite materials, adhesives, casting materials, etc. For example, when used as a dental adhesive component, results were obtained that showed higher adhesive strength than conventionally known dental adhesives, not only on the enamel of freshly extracted bovine teeth but also on the dentin. There is. Therefore, the compound of the present invention is an extremely useful compound as a raw material for the novel unsaturated carboxylic acid ester represented by the general formula (), which has many useful uses. In order to explain the present invention more specifically, Examples, Application Examples, and Comparative Examples are given below, but the present invention is not limited to these Examples. Example 1 Glycolic acid was added to a 500 c.
22.82g (0.3mol), trimethylolpropane
Add 40.25g (0.3mol) and 150c.c. of benzene,
Stirring was carried out at 95°C for 2 hours. Thereafter, 0.1 g of P-toluenesulfonic acid was added to the reaction solution, and benzene reflux was performed. 5.4 ml (about 0.3 mol) of water was distilled off in about 2 hours. After stopping the stirring of the reaction system and air cooling to room temperature, benzene was removed using an evaporator. Then, using a rectifier, 0.2mmHg/
Perform vacuum distillation under conditions of 170 to 180℃, and reduce to 116℃/
A fraction of 0.2 mmHg was obtained. This was recrystallized from methylene chloride to obtain 34.18 g of a white solid. The yield is
It was 65.5%. The physical properties and various measured values of the white solid thus obtained were as follows. (1) Melting point 60-61℃ (2) Infrared absorption spectrum (results are attached as Figure 1) 3350cm ^-1 (νOH) 1100, 1090, 1050, 1020cm ^-1

[Formula] (3) ¹ H-nuclear magnetic resonance absorption spectrum (results are attached as Figure 2) Measurement solvent: Deuterium chloroform Standard: Tetramethylsilane

[Table] (4) Mass spectrometry spectrum EI method, m/e=175 (M+1) ⁺ (5) Elemental analysis

[Table] From the above measurement results, the white solid has the structural formula It was confirmed that this was the case. Example 2 31.9 g of lactic acid was placed in a 500 c.c. eggplant-shaped flask equipped with a water metering receiver, a cooling tube, and a calcium chloride tube.
(0.35mol), trimethylolpropane 40.86g
(0.3mol) and toluene 150c.c.,
Stirring was performed at ℃ for 10 minutes. Thereafter, 0.1 g of P-toluenesulfonic acid was added to the reaction solution, and toluene was refluxed. 6.3 ml (about 0.35 mol) of water was distilled off in about 2.5 hours. After stopping the stirring of the reaction system and air cooling it to room temperature, toluene was removed using an evaporator. Then, using a rectifier, 0.13mmHg/170
Perform vacuum distillation under conditions of ~190℃, 102 ~
A fraction of 106.5°C/0.13mmHg was obtained. This fraction turned into a white solid upon cooling to room temperature. The yield of this white solid was 44.25 g, giving a yield of 78.5%. The physical properties and various measured values of the white solid thus obtained were as follows. (1) Melting point 66-68℃ (2) Infrared absorption spectrum (results are attached as Figure 3) 3400cm ^-1 (νOH) 1125, 1070, 1015, 990cm ^-1

[Formula] (3) ¹ H-nuclear magnetic resonance absorption spectrum (results are attached as Figure 4) Measurement solvent: heavy dimethyl sulfoxide Standard: tetramethylsilane

[Table] (4) Mass spectrometry CI method, m/e=189 (M+1) ⁺ (5) Elemental analysis

[Table] From the above measurement results, the white solid has the structural formula It was confirmed that this was the case. Examples 3 to 8 Same as Example 1 except that the raw materials shown in Table 1 were used as R ₁ of the hydroxycarboxylic acid represented by the general formula () and R ₂ of the trimethylolalkane represented by the general formula (). Six types of corresponding bicyclo compounds were synthesized using similar reaction conditions and operations. The elemental analysis values and mass spectrometry results of the obtained compound are shown in Table 1, and they were in good agreement with the calculated values predicted from the above general formula ().
Furthermore, the above-mentioned characteristic absorption band and hydrogen absorption peak were confirmed by measurement of infrared absorption spectrum and ¹ H-nuclear magnetic resonance spectrum.

[Table] Application example 1 and comparative example 1 4-ethyl-1- obtained in Example 1 was placed in a 500 c.c. separable flask equipped with a stirrer and a dropping funnel.
Hydroxymethyl-2,6,7-trioxabicyclo[2,2,2]octane 32.74g
(0.188mol), triethylamine 50g (0.50mol)
and benzene 200c.c. While stirring this at 0℃, 26.13g of methacrylic acid chloride
(0.25 mol) was added dropwise into the reaction solution from a dropping funnel. After completion of the dropwise addition, the reaction solution was stirred at 0° C. for about 2 hours and further stirred at room temperature for 15 hours. Thereafter, the reaction solution was filtered to remove triethylamine hydrochloride produced during the reaction. After removing benzene and excess triethylamine from the filtrate using an evaporator, hexane is added, extraction is performed, and the hexane layer is concentrated to produce a pale yellow liquid.
13.61g was obtained. The yield was 29.9%. The physical properties and various measured values of the pale yellow liquid thus obtained were as follows. (1) Boiling point 95℃/0.07mmHg (2) Specific gravity 1.1519 (20℃) (3) Infrared absorption spectrum 1720cm ^-1 (νC=O) 1635cm ^-1 (νC=C) 1280cm ^-1 (

[Formula]) 1160, 1105, 1060, 1020, 1000cm ^-1

[Formula] (4) ¹ H-Nuclear Magnetic Resonance Absorption Spectrum Measurement Solvent: Deuterochloroform Standard: Tetramethylsilane

[Table] (5) Mass spectrometry FD method, m/e=242 (M ⁺ ) (6) Elemental analysis

[Table] From the above measurement results, the pale yellow liquid has the structural formula It was confirmed that 4-ethyl-1-hydroxymethyl-2,6,7-trioxabicyclo[2,
2,2] Octane methacrylate 0.5g
(2.87×10 ^-3 mol) was placed in a glass polymerization ampoule. To this, 5 mol% of the tertiary amine shown in Table 2 was added to the above compound, and then, after sealing the tube, a polymerization reaction was carried out in an oil bath at 70°C, and the polymerization curing time and volume associated with curing were The shrinkage rates were determined and the results are summarized in Nos. 1 to 4 of Table 2. Note that the polymerization curing time was defined as the time from the start of heating until the reactant in the sealed tube stopped flowing. Further, the volume shrinkage rate was calculated based on the specific gravity of the monomer and the polymerized cured product, respectively. In addition, for comparison, the following structural formula 1-ethyl-4-hydroxymethyl-
2,6,7-trioxabicyclo[2,2,2]
All procedures were carried out in the same manner except that octane methacrylate was used in place of the 4-ethyl-1-hydroxymethyl-2,6,7-trioxabicyclo[2,2,2]octane methacrylate,
The results are shown in Nos. 5 to 8 of Table 2. However, in the case of the comparative example, the obtained polymer was agar-like and it was impossible to determine the volume shrinkage rate.

[Table] Application Example 2 Using the unsaturated carboxylic acid ester of the bicyclo compound obtained in Application Example 1, solutions A and B having the compositions shown below were prepared, and the adhesive strength to tooth structure was measured. {4-ethyl-1-hydroxymethyl-2,
6,7-trioxabicyclo[2,2,2]
Octane methacrylic acid ester 49.8 parts by weight A Ethanol 49.8 parts by weight Benzoyl peroxide 0.4 parts by weight} B {Ethanol 98.9 parts by weight Dimethyl-P-toluidine 1.1 parts by weight The adhesive strength was determined by the following method. First, the surface of a freshly extracted bovine tooth was polished with emery paper (#320) to expose the smooth dentin. Next, the polished surface was treated with a 37% orthophosphoric acid aqueous solution for one minute, washed with water for 30 seconds, and then dried by blowing nitrogen gas. Then, a plate-shaped wax with holes having an inner diameter of 6 mm and a thickness of 2 mm was attached to the dry surface with double-sided tape. Next, the above-mentioned liquids A and B were mixed at a ratio of 2:1 and applied to the tooth surface surrounded by the plate-shaped wax, and dried with nitrogen gas. Thereafter, a commercially available dental composite resin restorative material (manufactured by Johnson & Johnson, trade name: Adaptake) was filled according to the prescription. After leaving it for an hour, remove the plate-like wax and add 37
After being immersed in water at ℃ for one day and night, the tensile strength was measured. Tensilon manufactured by Toyo Baldwin Co., Ltd. was used for the measurement, and the tensile speed was 2 mm/min. The resulting adhesive strength was 27.6 Kg/cm ² . Also, for comparison, the following structural formula 1-ethyl-4-hydroxymethyl-
2,6,7-trioxabicyclo[2,2,2]
Using octane methacrylate in place of the 4-ethyl-1-hydroxymethyl-2,6,7-trioxabicyclo[2,2,2]octane methacrylate, Solution C has the composition shown below. and D solution were prepared and carried out in the same manner. The resulting adhesive strength was 17.5 Kg/cm ² . {1-ethyl-4-hydroxymethyl-2,6,
7-Trioxabicyclo[2,2,2]octane methacrylate ester 49.8 parts by weight C Ethanol 49.8 parts by weight Benzoyl peroxide 0.4 parts by weight} D {Ethanol 98.9 parts by weight Dimethyl-P-toluidine 1.1 parts by weight} Further, known Liquids E and F, which are dental adhesives, were prepared and tested in the same manner as above, and the adhesive strength obtained was 11.5 Kg/cm ² . {Bis-glycidyl methacrylate 21.5 parts by weight E-triethylene glycol dimethacrylate
28.1 parts by weight Ethanol 50.0 parts by weight Benzoyl peroxide 0.5 parts by weight} F {Ethanol 99.0 parts by weight Dimethyl-P-toluidine 1.0 parts by weight}

[Brief explanation of drawings]

FIGS. 1 and 3 show the measurement results of infrared absorption spectra of the white solids obtained in Examples 1 and 2. Furthermore, FIGS. 2 and 4 show the measurement results of ¹ H-nuclear magnetic resonance absorption spectra of the white solids obtained in Examples 1 and 2.

Claims (1)

[Claims] 1 General formula, (However, R ₁ is an alkylene group and R ₂ is a hydrogen atom or an alkyl group.) 4-alkyl-1-hydroxyalkyl-2,6,7-
Trioxabicyclo[2,2,2]octane. 2 A hydroxycarboxylic acid represented by the general formula HO―R ₁ -COOH (wherein R ₁ is an alkyl group) and a hydroxycarboxylic acid represented by the general formula (HOCH ₂ ) ₃ C―R ₂ (however, R ₂ is a hydrogen atom or is an alkyl group), the general formula is characterized by reacting with a trimethylolalkane represented by (However, R ₁ is an alkylene group and R ₂ is a hydrogen atom or an alkyl group) 4-alkyl-1-hydroxyalkyl-2,6,7-trioxabicyclo[2,2,2]octane manufacturing method.