TW202031630A - Crystalline of bisfluorene compound - Google Patents

Abstract

An objective of the present invention is to provide a crystalline of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] fluorene having a specific endothermic peak by differential scanning calorimetry, and a method for producing the crystalline. As a solving means, the present invention provides a crystalline of 9,9-bis [4-(2-hydroxyethoxy)-3-phenylphenyl] fluorine, the crystalline has at least one endothermic peak by differential scanning calorimetry in a temperature range of 158 DEG C or higher and less than 161 DEG C.

Description

Crystals of bismuth compound

The present invention relates to a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyrene having a specific endothermic peak measured by differential scanning calorimetry and the production of the crystal method.

In the past, 9,9-bis(4-hydroxyphenyl) pyrene and other compounds with a pyrene skeleton have been used in thermoplastic synthetic resin materials such as polycarbonate resins and epoxy resins due to their excellent heat resistance and optical properties. Uses such as thermosetting resin raw materials, antioxidant raw materials, thermal recording material raw materials, photosensitive resist raw materials, etc. Among them, the resin system made of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] 茀 having the chemical structure shown in the following chemical formula (1) has excellent optical properties And it has attracted attention (for example, Patent Documents 1, 2, etc.).

Regarding the production method of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonium represented by the above chemical formula (1), it is known to use as shown in the following reaction formula A method for obtaining the target product by reacting the 9-tendone represented by the chemical formula (2) with the alcohol represented by the chemical formula (3) (Patent Document 3).

In addition, it is known that aromatic hydrocarbons and methanol are added to a reaction solution containing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonate represented by the above chemical formula (1) In the process, after separating the precipitated crystals, the crystals are brought to 60°C or higher to remove methanol (Patent Document 4). The crystal obtained by crystallization is the inclusion compound of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyruvate and methanol. It can also be called clathrate compound ), in order to remove the included methanol, the energy and time caused by heating are indispensable.

A method for removing toluene is known by not combining the 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonate represented by the above chemical formula (1) with toluene. The compound and a specific solvent are dissolved and mixed to remove toluene (Patent Document 5). However, since almost all of the obtained crystals are those with high melting points, it takes a lot of energy and time to melt or dissolve the crystals. . In addition, although low-melting crystals can be obtained by the solvent used, since the crystal system forms clathrates, it not only requires energy to remove the solvent from the clathrates, but also the bulk density. low.

Known is a method for producing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyruvate crystals represented by the above chemical formula (1) with high overall density (Patent Document 6) , But the obtained crystals are clathrates, and it is impossible to remove the solvent from the clathrates by heating while maintaining the original crystal state, or even when the solvent can be removed, energy is required To remove the solvent from the clathrate.

There is also known a method for producing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonium represented by the above chemical formula (1) which is not an inclusion compound (Patent Document 7 ), but the crystal with the highest melting point needs to consume a lot of energy when it is melted and used. In addition, in order to obtain crystals with a low melting point, it needs to be cooled at an extremely fast rate, which is difficult to implement on a commercial scale or requires the use of special equipment, so it is not easy to apply to an industrial scale. In addition, in addition to the hue difference of low-melting crystals and the use of optical applications, there are also problems with the residual amount of solvents used for crystallization.

It is known that 9,9-bis(4-hydroxyphenyl) pyridium and other compounds with a pyridium skeleton form clathrates with the reaction solvent or the solvent used for purification, and it is necessary to remove the clathrated solvent High temperature and time-consuming, therefore, it is difficult to apply on an industrial scale. In addition, it is also known that compounds with a sulphur skeleton containing a solvent are used in the production of epoxy resins, polyesters and other raw materials and other applications. There are problems with industrial use.

[Prior Technical Literature] [Patent Literature]

Patent Document 1: Japanese Patent Application Publication No. 2001-074222

Patent Document 2: Japanese Patent Application Publication No. 2011-168722

Patent Document 3: Japanese Patent Application Publication No. 2001-206863

Patent Document 4: Japanese Patent Application Publication No. 2017-200900

Patent Document 5: Japanese Patent Application Publication No. 2018-076245

Patent Document 6: Chinese Patent Application Publication No. 106349030 Specification

Patent Document 7: Japanese Patent Application Publication No. 2017-200901

The present invention was made in view of the above-mentioned background, and its subject is to provide a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonate and a method for producing the crystal The aforementioned crystals have specific endothermic peaks determined by differential scanning calorimetry.

In order to solve the above-mentioned problems, the inventors carefully studied, and found that by using a specific solvent for crystallization, it is possible to obtain 9,9-bis[4-() with a specific endothermic peak measured by differential scanning calorimetry. The crystalline form of 2-hydroxyethoxy)-3-phenylphenyl]茀 has completed the present invention.

The present invention is as described below.

1. A crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyridium, which has at least one basis in the temperature range above 158℃ and below 161℃ The endothermic peak measured by differential scanning calorimetry.

2. The crystal as described in 1., which is not an inclusion compound.

3. A method for producing the crystal as described in 1. or 2., comprising: using acetonitrile for crystallization.

4. The manufacturing method as described in 3., further comprising: drying the crystals obtained by crystallization at a temperature of 45° C. or higher and lower than the melting point.

According to the present invention, it is possible to provide a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyridium and a method for producing the crystal. The crystal has a method based on differential scanning calorimetry. The measured specific endothermic peak, and non-inclusion compound.

In the case of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyruvate containing an organic solvent and other compounds, when the inclusion compound is combined with (meth)acrylic acid When the reaction is carried out, the inclusion of organic solvents and other compounds hinders the reaction and prevents the reaction from proceeding. In addition, when the clathrate is melted and used as a resin raw material, in addition to the vapor generated during the melting, which is derived from the "compounds such as the included organic solvent" must be removed from the reaction device, there is also The remaining organic solvents and other compounds cause problems such as degradation of the quality of the target resin. In addition, depending on the flash point and ignition point of the compound such as the contained organic solvent, there may be concerns about disaster prevention during the transportation and storage of the clathrate.

As mentioned above, the so-called "a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyridium, which has a temperature of 158°C or higher and less than 161°C There is at least one endothermic peak in the range determined by differential scanning calorimetry, and the crystal is not a clathrate." Moreover, compared with the conventional removal of the organic solvent from the clathrate crystals, since the included organic solvent can be removed with a heat much lower than this, the energy consumed during manufacturing can be suppressed.

That is, "a type of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyruvate that has a specific endothermic peak determined by differential scanning calorimetry and is not an inclusion compound The provision of "the novel crystal" and its manufacturing method is very useful for industrial use such as resin raw materials.

Figure 1 is a graph showing the differential thermal/thermogravimetry (DTG: Differential Thermogravimetry) curve of the acetonitrile clathrate obtained by removing the attached solvent in the drying step of Example 1.

Figure 2 is a graph showing the differential scanning calorimetry (DSC: Differential Scanning Calorimetry) curve of the crystals (crystals of the present invention) that are not clathrates obtained by the drying step of Example 1.

Figure 3 is a graph showing the differential scanning calorimetry (DSC) curve of the crystal obtained in Example 2 (the crystal of the present invention).

Figure 4 is a graph showing the differential thermal/thermogravimetric (DTG) curve of the crystal obtained by removing the attached solvent in Example 2.

Figure 5 is a graph showing the differential thermal/thermogravimetric (DTG) curve of the crystal obtained in Comparative Example 1.

Figure 6 is a graph showing the differential scanning calorimetry (DSC) curve of the crystal obtained in Comparative Example 2.

Figure 7 is a graph showing the differential scanning calorimetry (DSC) curve of the crystal obtained in Comparative Example 3.

Figure 8 is a graph showing the differential scanning calorimetry (DSC) curve of the crystal obtained in Comparative Example 4.

Figure 9 is a graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the crystal obtained in Comparative Example 6.

Figure 10 is a graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the crystal before drying in Comparative Example 7.

Figure 11 is a graph showing the differential scanning calorimetry (DSC) curve of the dried crystal of Comparative Example 7.

The present invention will be described in detail below.

The 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]pyridium of the present invention is a compound represented by the following chemical formula (1).

<resolve resolution>

The method for synthesizing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] sulfide of the present invention is not particularly limited. For example, the well-known manufacturing method described in the aforementioned Patent Document 3 can be applied .

The reaction between the 9-tulone represented by the chemical formula (2) shown in the following reaction formula and the alcohol represented by the chemical formula (3) is described.

The molar ratio of the alcohol represented by the chemical formula (3) to the 9- ketone represented by the chemical formula (2) is not particularly limited if it is above the theoretical value (2.0), and usually 2 to 20 times the molar ratio is used The range of the amount is preferably in the range of 3 to 10 times the molar amount.

An acid catalyst can be used in the reaction. The acid catalyst used is not particularly limited, and known acid catalysts can be used. Specific acid catalyst systems include, for example, inorganic acids such as hydrochloric acid, hydrogen chloride gas, 60 to 98% sulfuric acid, and 85% phosphoric acid; p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, formic acid, trichloroacetic acid, or Organic acids such as trifluoroacetic acid; solid acids such as heteropoly acid, etc. Preferably, they are heterogeneous polymeric acids such as phosphotungstic acid. The appropriate amount of such an acid catalyst will vary depending on the reaction conditions. For example, in the case of heterogeneous polymeric acids such as phosphotungstic acid, it can be 1 to 70 parts by weight relative to 100 parts by weight of 9-ketone The range is preferably in the range of 5 to 40 parts by weight, and more preferably used in the range of 10 to 30 parts by weight.

During the reaction, catalyst accelerators such as acid catalysts and mercaptans can also be used at the same time as needed. Through such use, the reaction speed can be accelerated. Examples of such mercaptans include alkyl mercaptans and mercaptocarboxylic acids, and alkyl mercaptans having 1 to 12 carbon atoms and mercaptocarboxylic acids having 1 to 12 carbon atoms are preferred. Alkyl mercaptans having 1 to 12 carbon atoms include, for example, bases such as methyl mercaptan, ethyl mercaptan, n-octyl mercaptan, n-dodecyl mercaptan and these sodium salts. Metal salt; Mercaptocarboxylic acids having 1 to 12 carbon atoms include, for example, thioacetic acid and β-mercaptopropionic acid. Moreover, these can be used individually or in combination of 2 or more types. The amount of mercaptan used as a catalyst accelerator is generally in the range of 1 to 30 mol%, and preferably in the range of 2 to 10 mol%, relative to the 9- ketone of the raw material.

During the reaction, the reaction solvent may not be used, and it may also be used for reasons such as increase in operability and reaction speed during industrial production. The reaction solvent is not particularly limited as long as it does not distill from the reactor at the reaction temperature and is inactive for the reaction. Examples include aromatic hydrocarbons such as toluene and xylene; methanol, ethanol, Lower aliphatic alcohols such as 1-propanol and 2-propanol; organic solvents such as saturated aliphatic hydrocarbons such as hexane, heptane, and cyclohexane, and water or mixtures of these. Among these, aromatic hydrocarbons are preferably used.

The reaction temperature varies depending on the type of acid catalyst used. In the case of using heterogeneous polymeric acids such as phosphotungstic acid as the acid catalyst, the reaction temperature is usually 20 to 200°C, preferably 40 to 170 °C, more preferably in the range of 50 to 120 °C. The reaction pressure can be carried out under increased pressure or reduced pressure according to the boiling point of the organic solvent used and the reaction temperature within the aforementioned range, or the reaction can be carried out while removing the generated water.

The reaction time varies depending on the type of acid catalyst used and the reaction conditions such as the reaction temperature, and usually ends in about 1 to 30 hours.

The end point of the reaction can be confirmed by liquid chromatography or gas chromatography analysis. It is preferable to set the time point at which unreacted 9- ketone has disappeared and no increase in the target substance is observed as the end of the reaction.

<About post-processing of reaction>

After the reaction is completed, a known post-treatment method can be applied. For example, in order to neutralize the acid catalyst, an alkaline aqueous solution such as a sodium hydroxide aqueous solution and an ammonia aqueous solution is added to the reaction-finished liquid. The neutralized reaction mixture is allowed to stand, and if necessary, a solvent separated from water is added to separate and remove the water layer. If necessary, the operation of "adding distilled water to the obtained oil layer, stirring and washing, and separating and removing the water layer" is performed once or repeated several times to remove the neutralizing salt, and the obtained oil layer is directly cooled and The precipitated crystals can be separated to obtain crude crystals. In addition, the solvent and the remaining alcohol represented by the above chemical formula (3) can be removed from the obtained oil layer by distillation, and a solvent such as aromatic hydrocarbon can be added to the obtained residue to make a uniform solution , Separate the crystals precipitated by cooling to obtain crude crystals. This crude crystal and the aforementioned residue can be passed through the crystallization step of the present invention to obtain a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonate, which is There is at least one endothermic peak measured by differential scanning calorimetry in the temperature range above 158°C and below 161°C, and it is not an inclusion compound.

<About the crystallization step>

The production method of the present invention includes a step of crystallization using acetonitrile (hereinafter also referred to as a crystallization step). Among them, the acetonitrile that can be used is not particularly limited, and generally commercially available acetonitrile can be used.

With respect to 100 parts by weight of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfide contained in the residue or crude crystals obtained by the post-treatment of the reaction, in the crystallization step The amount of acetonitrile used is preferably 150 to 600 parts by weight, more preferably 200 to 500 parts by weight, still more preferably 250 to 400 parts by weight, and most preferably 300 to 350 parts by weight. When the amount of acetonitrile used is large, the amount of crystals obtained will decrease, and when the amount of acetonitrile used is small, the purity of the target substance will decrease, which is not good. Furthermore, when the amount of acetonitrile used is small, the residues or crude crystals obtained from the post-reaction treatment step used in the crystallization step contain solvents (for example, aromatic hydrocarbons such as toluene). Bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyruvate will increase, so it is not good.

In the crystallization step of the present invention, when a solvent other than acetonitrile is used, it is impossible to obtain "at least one endothermic peak measured by differential scanning calorimetry in a temperature range above 158°C and less than 161°C. Moreover, it is not a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] pyridium, which is an inclusion compound," so it is not good.

In the crystallization step of the present invention, acetonitrile can be added to the residue or crude crystals after the reaction post-treatment step used, and heated to below the boiling point of acetonitrile under normal pressure or under pressure to make it completely dissolved. After it becomes a homogeneous solution, it is cooled to obtain precipitated crystals. After heating to form a uniform solution, in the case of cooling, cooling is performed at 1 to 10°C per hour, preferably at 3 to 7°C, to precipitate crystals. The temperature at which the crystals are precipitated is preferably in the temperature range of 40°C to 58°C, more preferably in the temperature range of 45°C to 55°C, and among them, a temperature of about 50°C is suitable as the crystal precipitation temperature. In addition, seed crystals can be used when crystals are precipitated. After the crystals begin to precipitate, it is better to keep at the same temperature for 0 to 5 hours and cool at the aforementioned cooling rate After keeping the temperature to 0 to 40°C, preferably 10 to 35°C, more preferably 20 to 30°C, and maintaining the same temperature for 0 to 3 hours, the precipitated crystals are separated by filtration operation or the like.

<About drying steps>

By implementing the drying step (hereinafter also referred to as the drying step), the acetonitrile used in the crystallization step of the present invention can be completely removed. The drying step of the present invention can be carried out for the crystals obtained from the crystallization step at a temperature of 45°C or higher and lower than the melting point, preferably 70°C or higher, more preferably 90°C or higher, and particularly preferably 100°C or higher . Furthermore, depending on other conditions, etc., since the hue of the crystal may also be deteriorated due to heat, it is preferably 150°C or less, more preferably 130°C or less. At a temperature lower than 45°C, the acetonitrile used in the crystallization step cannot be removed, or even if it can be removed, it takes a lot of time, which is not good.

The drying step can be carried out at normal pressure or under reduced pressure. However, when it is carried out industrially, the acetonitrile used in the crystallization step can be removed more efficiently when carried out under reduced pressure. For appropriate. In addition, the drying step is preferably performed in an inert gas environment such as nitrogen.

<Crystal of the present invention>

The 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] crystalline system of the present invention has at least one basis difference in the temperature range above 158℃ and below 161℃ Scan the endothermic peak determined by calorimetric analysis. The temperature range of the endothermic spectrum measured by differential scanning calorimetry is more preferably 159°C or more and less than 161°C, and more preferably 160°C or more and less than 161°C. Furthermore, the 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] crystalline form of the present invention is not an inclusion compound, that is, it does not include organic solvents and other compounds. Crystals.

In the present invention, the so-called crystals that do not include organic solvents and other compounds are preferably crystals with a residual organic solvent content of 1% by weight or less, more preferably crystals with a content of 0.5% by weight or less, and even more preferably the crystal Crystals with a content of 0.3% by weight or less are particularly preferred for crystals with a content of 0.1% by weight or less. In addition, in the present invention, the crystals that do not include compounds such as organic solvents preferably have aerated bulk density in the range of 0.35 to 0.45 g/cm ³ .

[Example]

The following examples illustrate the present invention more specifically, but the present invention is not limited to these examples.

The analysis method is as follows.

<Analytical method>

1. Differential Scanning Calorimetry (DSC)

5 mg of crystals were weighed in an aluminum pan, a differential scanning calorimetry device (manufactured by Shimadzu Corporation: DSC-60) was used, and alumina was used as a control, and the measurement was performed under the following operating conditions.

(Operating conditions)

Heating rate: 10℃/min

Measuring temperature range: 30 to 200℃

Measurement of ambient gas: open, nitrogen 50mL/min

2. Differential calorimetry/thermogravimetric analysis (DTG)

8 mg of crystals were weighed into an aluminum pan, and a differential calorimetry/thermogravimetric analyzer (manufactured by Shimadzu Corporation: TG-60A) was used to measure under the following operating conditions.

(Operating conditions)

Heating rate: 10℃/min

Measuring temperature range: 30 to 300°C

Measurement of ambient gas: open, nitrogen 50mL/min

3. HS-GC (residual solvent analysis)

The so-called "HS-GC" refers to the method of introducing the gas phase (headspace, HS (headspace)) into gas chromatography (GC) for analysis. The sample enclosed in a vial is kept warm for a certain period of time, the gas phase and the sample are in an equilibrium state, and the gas phase part is analyzed, thereby measuring the amount of solvent remaining in the crystal. Specifically, 0.5 g of the crystal was weighed, and N-methylpyrrolidone was added to the crystal while being finely weighed so that the whole was 10 g. Weigh about 3g of this solution into the HS vial, clamp it tightly so that it does not leak, and perform the measurement under the following conditions.

(GC analysis conditions)

Device: Manufactured by Shimadzu Corporation: GC-2010plus

Column: TC-1 60m×0.25mmΦ, film thickness 0.25μm

Detector: FID

INJ temperature: 300℃, FID temperature: 310℃

Heating conditions: 40°C (25 minutes)→20°C/minute→300°C (5 minutes)

String linear velocity: 19.9cm/sec

(HS analysis conditions)

Machine: TurboMatrix HS 40 (Perkin Elmer)

Carrier gas pressure: 154kPa

Heating temperature of vial: 100℃

Injection time: 0.05 minutes

4. Loose overall density

Use the Multi Tester (Model MT-1001/manufactured by Seishin Enterprise Co., Ltd.) which is a multifunctional powder physical property tester, and gently pass the crystals through the sieve without air gaps. The capacity is In a measuring tank of 20 cm ³ , the weight a (g) of crystals in the tank when the aforementioned measuring tank is filled with crystals is measured, and the bulk density of the bulk is calculated by the following calculation formula.

[Calculation formula] Overall density of loose packing (g/cm ³⁾ = weight of crystal a(g)÷20cm ³

5. Powder X-ray diffraction (XRD: X-ray Diffraction) analysis

0.1 g of the crystal was filled in the sample filling part of the glass test plate, and the measurement was performed under the following conditions using the powder X-ray diffraction apparatus described below.

Device: Rigaku Co., Ltd. product: SmartLab

X-ray source: Cu-Kα

Scan axis: 2θ/θ

Mode: Continuous

Measuring range: 2θ=5° to 70°

Step: 0.01°

Speed measurement time: 2θ=2°/min

IS: 1/2

RS: 20.00mm

Output: 40kV-30mA

6. Particle size distribution

0.1 g of crystals were added and mixed with 0.1 g of water as a dispersing solvent and a drop of a dispersant (neutral lotion), and the result was put into the device and subjected to ultrasonic treatment (3 minutes) and then measured.

Device: manufactured by Shimadzu Corporation: SALD-2200

Measurement method: laser diffraction method

7. YI value (yellowness)

烷18.0g，並藉由以下條件測定所得到之1,4-二

烷溶液的YI值(黃色度)。 Dissolve 2.0 g of crystals in 1,4-bis

18.0g of alkane, and 1,4-bis

YI value (yellowness) of alkane solution.

Device: Colorimeter (Nippon Denshoku Kogyo Co., Ltd., ZE6000)

Use tank: glass test tube (diameter 24mm)

烷本身的著色不會對測定值造成影響之方式，於事前測定1,4-二

烷的色相並進行校正(空白測定)。於實施此空白測定後，將樣本的測定值設為本發明之YI值(黃色度)。 In addition, it is to measure the 1,4-di

The coloring of the alkane itself will not affect the measured value. It is measured beforehand.

The hue of the alkane is corrected (blank measurement). After performing this blank measurement, the measured value of the sample is set as the YI value (yellowness) of the present invention.

<Synthesis example>

Synthesis of 9,9-Bis[4-(2-hydroxyethoxy)-3-phenylphenyl]sulfonate

Replace with nitrogen in a 1 liter four-necked flask equipped with thermometer, stirrer, and cooling tube, and add 76.3g (0.423mol) of 9-Fructus ketone, 907.0g (4.24mol) of alcohol represented by chemical formula (3), and phosphorus 13.7 g of tungstic acid and 388.7 g of toluene were reacted at a reaction temperature of 100°C and a pressure of 42 kPa while removing the water produced by the reaction. The disappearance of the raw materials was confirmed by liquid chromatography analysis, and it was assumed that the reaction was completed. The reaction liquid was cooled to 80° C., 339.1 g of toluene, 26.69 g of 15% sodium hydroxide aqueous solution, and 250 g of distilled water were added to neutralize the reaction liquid, and the water layer was removed after standing. Carry out the water washing operation of "add 250g of distilled water to the obtained oil layer and leave it to stand after stirring to remove the water layer" 4 times. Removal of solvents and other low-boiling substances and unreacted chemical formulas from the obtained oil layer by distillation (3) After the alcohol shown in (3), the residue was dissolved with 1500 g of toluene. This toluene solution was cooled to 25°C, and the precipitated crystals were filtered to obtain the target toluene clathrate (purity 98.0% measured by high-speed liquid chromatography analysis, 5 wt% toluene inclusion) .

<Example 1>

(Crystallization step)

Add 10g of the white crystals obtained in the above "Synthesis Example" and 30g of acetonitrile to a 200ml four-necked flask equipped with a thermometer, agitator, and cooling tube. Crystals precipitated near ℃. Thereafter, it was cooled to 25°C at the same cooling rate, and the precipitated crystals were filtered out.

(Drying step)

The crystals obtained by the crystallization step were dried for 2 hours in an environment at a temperature of 20° C. and a pressure of 1.2 kPa. According to HS-GC analysis of the obtained crystals, the remaining solvents were 0.05% by weight of toluene and 3.6% by weight of acetonitrile. Furthermore, the crystals were dried under the same conditions for 4 hours, but the residual solvent content did not change. This shows that the crystals obtained in the crystallization step are acetonitrile clathrates. By performing differential thermal/thermogravimetric analysis (DTG) on the acetonitrile inclusion compound, it was confirmed that the amount of heat to remove the acetonitrile included was about 40 J/g. The graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the acetonitrile inclusion compound is shown in Figure 1.

The acetonitrile clathrate was dried for 4 hours in an environment at a temperature of 100°C and a pressure of 1.2 kPa to obtain 9.0 g of crystals that were not clathrates.

(Analysis result)

Regarding the crystals obtained from the drying step, it was confirmed that the purity measured by high-speed liquid chromatography analysis was 98.7%, and the remaining solvents measured by HS-GC analysis were 0.05% by weight of toluene and 0.2% by weight of acetonitrile. %.

The graph showing the differential scanning calorimetry (DSC) curve of the crystals that are not clathrates after the above analysis is shown in Figure 2.

<Example 2>

(Crystallization step)

Add 208.7g of the white crystals obtained in the "Synthesis Example" and 626.1g of acetonitrile to a 1 liter four-necked flask equipped with a thermometer, a stirrer, and a cooling tube. After dissolving at 60°C, it is cooled at a cooling rate of 5°C per hour. When about 0.1 g of the seed crystal obtained in Example 1 was added at 55°C, an increase in the precipitated crystals at 50°C was confirmed. Cool to 25°C at the same cooling rate, keep at 25°C for 2 hours, and filter the precipitated crystals.

(Drying step)

The crystals obtained by the crystallization step were dried for 2 hours in an environment at a temperature of 20° C. and a pressure of 1.2 kPa. According to HS-GC analysis of the obtained crystals, the remaining solvents were 0.08% by weight of toluene and 3.7% by weight of acetonitrile. Furthermore, the crystals were dried under the same conditions for 2 hours, but the residual solvent content did not change. This shows that the crystals obtained in the crystallization step are acetonitrile clathrates. By performing differential thermal/thermogravimetric analysis (DTG) on the acetonitrile inclusion compound, it was confirmed that the amount of heat to remove the acetonitrile included was about 94 J/g.

The acetonitrile clathrate was dried for 14 hours in an environment at a temperature of 100°C and a pressure of 1.2 kPa, and 156.6 g of crystals that were not clathrates were obtained.

(Analysis result)

Regarding the crystals obtained from the drying step, it was confirmed that the purity measured by high-speed liquid chromatography analysis was 98.8%, and the remaining solvents measured by HS-GC analysis were 0.08% by weight of toluene and 0.003% by weight of acetonitrile. %. Furthermore, the temperature at the top of the endothermic peak measured by differential scanning calorimetry is 160°C, the YI value (yellowness) is 0.47, and the bulk density of the loose package is 0.4g/cm ³ . In addition, the median diameter (D50) of the obtained crystal was 34.0 μm, and the mode diameter (mode diameter) was 39.6 μm.

The graph showing the differential scanning calorimetry (DSC) curve of the crystals that are not clathrates after the above analysis is shown in Figure 3. In addition, the graph showing the differential thermal/thermogravimetric (DTG) curve of the crystal obtained by removing the above-mentioned attached solvent is shown in Figure 4, the main peak of powder X-ray (with a relative integrated intensity of more than 5%) Department as listed in Table 1.

[Table 1]

According to these analyses, it is obvious that the obtained crystalline system has at least one endothermic peak measured by differential scanning calorimetry in the temperature range above 158°C and below 161°C, and it is not a crystalline body of clathrate. .

<Comparative Example 1>

Additional tests were performed on the manufacturing method described in Example 1 of Patent Document 4 above.

In detail, a 1-liter four-necked flask equipped with a stirrer, a cooling tube, and a thermometer was replaced with nitrogen, and 75 g (0.149 mol) of 9,9'-bis(4-hydroxy-3-phenylphenyl) pyridium was added , Potassium carbonate 1.7g, ethylene carbonate 30.05g (0.341mol), toluene 112.5g and methyl triglyme 7.5g, heated to 110 ℃, and stirred at the same temperature for 16 hours, by high-speed liquid Phase chromatography (hereinafter referred to as HPLC) was measured to confirm the disappearance of the raw materials.

Then, 3.07 g of water was added, and hydrolysis was performed at 100°C for 5 hours.

After the obtained reaction liquid was cooled to 90°C, 113 g of water was added, and the mixture was stirred at 80 to 85°C for 30 minutes. After standing, the water layer was separated. After repeating the same water washing operation three times, the solvent was removed from the obtained organic solvent layer to obtain a concentrate. 92 g of toluene and 348 g of methanol were added to the obtained concentrate to obtain a crystallization solution. The resulting crystallization solution was heated to 65°C and stirred at the same temperature for 1 hour to completely dissolve the crystals, then cooled at 0.1°C per minute to precipitate crystals at 50°C and kept at the same temperature Stir for 2 hours. After further cooling to 22°C, filtration was performed to obtain crystals.

After drying the obtained crystals at 55°C for 3 hours under a reduced pressure of 1.3 kPa, a part of the crystals was analyzed by HS-GC. As a result, it was confirmed that the crystal contained 3.5% by weight of methanol which was the solvent used in the crystallization step. Even if the drying was continued for 3 hours and analyzed under the same conditions, the content of methanol was 4% by weight, which did not decrease. Measured by DTG The amount of heat required to remove the included solvent from the crystal was determined to be about 875 J/g. Under a reduced pressure of an internal pressure of 1.3 kPa, the internal temperature of the crystal was increased to 90°C, and further dried for 3 hours. Since the content of methanol became 0.02% by weight, the drying was completed.

The graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the obtained crystal is shown in Fig. 5, and each analysis value is shown below.

The weight of the obtained crystals: 77.9 g (yield: 88%)

HPLC purity: 98.6%

Toluene content: 0.01% by weight

Methanol content: 0.02% by weight

From the results of Comparative Example 1, it can be confirmed that approximately 900 J/g of energy is consumed in order to remove methanol from the methanol clathrate.

In addition, the median diameter (D50) of the obtained crystal was 18.5 μm, and the mode diameter was 21.2 μm.

Additional tests were performed on the manufacturing methods described in Comparative Example 1, Examples 8, 12, 17, 19, and 20 of Patent Document 5 above.

<Reference example 1>

(Comparative Example 1 of Patent Document 5)

Replace with nitrogen in a 1 liter four-necked flask equipped with a stirrer, a heating cooler and a thermometer, and add 60g (0.119mol) of 9,9'-bis(4-hydroxy-3-phenylphenyl)pyridium and 1.2g of potassium carbonate , 24.15g (0.274mol) of ethylene carbonate and 60g of toluene, stirred at 110°C for 34 hours. Next, 4.86 g of water was added, and the reaction (hydrolysis) was performed at 100°C for 11 hours. After the obtained reaction liquid was cooled to 85°C, 30 g of toluene and 102 g of water were added, and the mixture was stirred at 80 to 85°C for 30 minutes. After standing, the aqueous layer was separated. After repeating the same washing operation 3 times, use Dean-Stark The device was used to remove water from the obtained organic solvent layer under reflux, and the crystals were precipitated at 75° C. by cooling, and the mixture was stirred at the same temperature for 2 hours. After further cooling to 26°C, filtration was performed to obtain crystals. The obtained crystals were dried at 110 to 112°C for 12 hours under reduced pressure with an internal pressure of 1.1 kPa.

The obtained crystals were analyzed by the above method, and as a result, it was confirmed that the obtained crystals belonged to the toluene clathrate.

The analysis results of the obtained crystals are shown below.

The weight of the obtained crystals: 68.5g

HPLC purity: 97.5%

Toluene (guest molecule) content: 4.46 wt%

<Comparative Example 2>

(Example 8 of Patent Document 5: Isobutyl ketone)

5 g of the toluene clathrate crystals obtained in Reference Example 1 and 25 g of diisobutyl ketone were added to a test tube with a stir bar, stirred at 100°C for 5 hours, and filtered without cooling. Then, it was dried in a nitrogen stream for 2 hours.

The graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Fig. 6, and each analysis value is shown below.

HPLC purity: 98.40%

Toluene (guest molecule) content: below the detection limit (HS-GC)

Melting point: 192°C

Overall density of loose packing: 0.31g/cm ³

In addition, the above-mentioned bulk density of loose packing is based on data measured in a simple test in a test tube.

From the results of Comparative Example 2, it was confirmed that the crystal obtained in Example 8 of Patent Document 5 was a high melting point crystal with a melting point of 192°C, and the bulk density was also a relatively low 0.31 g/cm ³ .

<Comparative Example 3> (Example 12 of Patent Document 5: Heptane)

5 g of the toluene clathrate crystals obtained in Reference Example 1 and 25 g of heptane were added to a test tube with a stir bar, stirred at 100°C for 2 hours, and filtered without cooling. Then, it was dried in a nitrogen stream for 2 hours.

The graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Fig. 7, and each analysis value is shown below.

HPLC purity: 98.74%

Toluene (guest molecule) content: below the detection limit (HS-GC)

Melting point: 191°C

Overall density of loose packing: 0.38g/cm ³

In addition, the above-mentioned bulk density of loose packing is based on data measured in a simple test in a test tube.

From the results of Comparative Example 3, it was confirmed that the crystal obtained in Example 12 of Patent Document 5 was a high melting point crystal with a melting point of 191°C.

<Comparative Example 4>

(Example 17 of Patent Document 5: Dibutyl ether)

Add 5 g of the toluene clathrate crystals obtained in Reference Example 1 and 25 g of dibutyl ether into a test tube with a stir bar, stir at 100°C for 5 hours, and filter directly without cooling. Then, it was dried in a nitrogen stream for 2 hours.

The graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Fig. 8, and each analysis value is shown below.

HPLC purity: 97.88%

Toluene (guest molecule) content: below the detection limit (HS-GC)

Melting point: 192°C

Overall density of loose packing: 0.35g/cm ³

In addition, the above-mentioned bulk density of loose packing is based on data measured in a simple test in a test tube.

From the results of Comparative Example 4, it was confirmed that the crystal obtained in Example 17 of Patent Document 5 was a high melting point crystal with a melting point of 192°C.

<Comparative Example 5>

A 500 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 14.1 g (YI value 0.80) of the toluene inclusion compound obtained in the above "Synthesis Example" was added, 60 g of methyl isobutyl ketone, and heptane 24 g of alkane was heated to 100°C and stirred for 30 minutes to dissolve all the crystals. The obtained solution was cooled at a rate of 0.8°C per minute to thereby precipitate crystals at 65°C. After stirring for 2 hours at the same temperature, it was cooled to 20°C and filtered. The obtained crystals were dried at 90°C for 3 hours under a reduced pressure of 1.3 kPa to obtain 10.6 g of crystals of the following quality.

HPLC purity: 99.3%

Residual toluene: 112ppm

Residual methyl isobutyl ketone: 1680ppm

Residual heptane: 321ppm

烷溶液) YI value: 1.26 (10%

Alkane solution)

DSC melting endothermic maximum temperature: 171℃

Additional tests were performed on the manufacturing methods described in Examples 1 and 2 of Patent Document 6.

<Comparative Example 6>

(Example 1 of Patent Document 6)

Replace with nitrogen in a 1 liter four-necked flask equipped with thermometer, stirrer, and cooling tube. Add 18.0g (0.1 mol) of 9-Fructus ketone and 53.5g (0.25) of 2-[(2-phenyl)phenoxy]ethanol. Mol), 1 g of 3-mercaptopropionic acid, 60 mL of toluene, and dissolved at 65°C, 25 mL of 98% sulfuric acid was added dropwise for 1 hour. Then, it was stirred at 65°C for 6 hours for reaction. After the completion of the reaction, sodium hydroxide solution was added to neutralize, and then 100 g of toluene and 50 g of water were added and stirred. After standing still, the water layer was removed. The operation of "adding 60 g of water to the obtained organic layer, stirring and allowing it to stand, then removing the water layer" was implemented 4 times.

The washed organic layer was cooled at 10°C/hour and crystallized. After stirring at 25°C for 15 hours, it was filtered to obtain 9,9-bis[3-phenyl-4-(2-hydroxyethoxy) A crude product of phenyl] sulfide.

After dissolving 20.2 g of this crude product with 60.6 g of toluene, it was cooled and crystallized, and filtered at 25°C to obtain 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl ] The crystallization of 茀. Then, it was dried at 80° C. and 1.3 kPa for 6 hours to obtain 11 g of crystals (19.0% yield).

The crystals were analyzed by HPLC and the purity was 92.8%.

The graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the obtained crystal is shown in Figure 9.

According to Fig. 9, it can be seen that the weight of the crystal decreases at a temperature higher than the melting point, so the crystal obtained in Example 1 of Patent Document 6 mentioned above is a toluene clathrate.

<Comparative Example 7>

(Example 2 of Patent Document 6)

After dissolving 10 g of the above-mentioned crystal of Comparative Example 6 with 60 g of ethanol, it was cooled and crystallized, and filtered at 25° C. to obtain a crystal. After drying for 3 hours at 25°C and 1.3 kPa, analysis by HS-GC showed that the ethanol content was 6.0% by weight. Differential calorimetry/thermogravimetric analysis (DTG) was performed on this crystal. As a result, it was confirmed that the amount of heat to remove the included ethanol was about 147 J/g. The graph showing the differential thermal/thermogravimetric analysis (DTG) curve of this crystal is shown in Figure 10.

Furthermore, the crystals were dried at 80° C. and 1.3 kPa for 6 hours. As a result, 6.9 g (69% yield) of crystals with an ethanol content of 0.14% by weight were obtained. The graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Fig. 11, and each analysis value is shown below.

HPLC purity: 94.5%

Ethanol content: 0.14% by weight (HS-GC)

Toluene content: below the detection limit (HS-GC)

Melting point: 132°C

Overall density of loose packing: 0.33g/cm ³

In addition, the above-mentioned bulk density of loose packing is based on data measured in a simple test in a test tube. In addition, the fact that the HPLC purity is lower than the value described in Patent Document 6 is believed to be due to the fact that the sulfuric acid dropping temperature and other details were not explained in Example 6, so the reaction conditions were not completely consistent.

In addition, the median diameter (D50) of the obtained crystal was 20.7 μm, and the mode diameter was 26.1 μm. Compared with the crystal of the present invention, the particle size of the obtained crystal is extremely fine, and compared with the above In the crystals obtained from the methanol clathrate of "Comparative Example 1", no improvement in fluidity was confirmed.

From the results of Comparative Example 9, it was confirmed that approximately 150 J/g of energy was required to remove ethanol from the ethanol clathrate. In addition, the melting point of the crystal after ethanol was removed from the clathrate was 132°C.

Claims (4)

A 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] crystalline body, which has at least 1 basis differential scan in the temperature range above 158℃ and below 161℃ The endothermic peak measured by calorimetric analysis. Such as the crystal body described in item 1 of the scope of patent application, the crystal body is not an inclusion compound. A method for producing the crystals described in item 1 or 2 of the scope of patent application includes the step of crystallization using acetonitrile. The manufacturing method described in item 3 of the scope of the patent application further includes the step of drying the crystals obtained by crystallization at a temperature above 45° C. and below the melting point.

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