KR20210063323A - Crystals of Bisfluorene Compounds - Google Patents

Abstract

The present invention provides a crystal 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 crystal make it a task
As a means for solving the above problem, the present invention has one or more endothermic peaks by differential scanning calorimetry in a temperature range of 158°C or higher and lower than 161°C, 9,9-bis[4-(2-heed) A crystal of oxyethoxy)-3-phenylphenyl]fluorene is provided.

Description

Crystals of Bisfluorene Compounds

The present invention relates to a crystal 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 crystal.

Conventionally, a group of compounds having a fluorene skeleton, such as 9,9-bis(4-hydroxyphenyl)fluorene, is excellent in heat resistance and optical properties. It is used as a raw material for resins, raw materials for antioxidants, raw materials for heat-sensitive recording materials, and raw materials for photosensitive resists. Among them, a resin prepared from 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene having a chemical structure represented by the following formula (1) is said to have excellent optical properties. It attracts attention (for example, patent documents 1, 2 etc.).

As a method for producing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene represented by the general formula (1), as shown in the following scheme, it is represented by the general formula (2) A method of obtaining a target product by reacting 9-fluorenone with alcohol represented by the general formula (3) is known (Patent Document 3).

Further, in a reaction solution containing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene represented by the general formula (1), aromatic hydrocarbons and methanol are added to precipitate There is known a method in which methanol is removed by making the crystals at 60°C or higher after isolating the formed crystals (Patent Document 4). The crystal obtained by crystallization is a clathrate of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene and methanol, and energy and time by heating are required to remove the inclusion methanol. indispensable

9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene and toluene represented by the formula (1) are mixed with a specific solvent without dissolving toluene. There is a known method for removing the crystals (Patent Document 5), but since most of the crystals obtained have a high melting point, a lot of energy and time are required for melting or dissolving. Also, depending on the solvent to be used, a crystal having a low melting point is obtained. Since the crystal forms an inclusion body, energy for removing the solvent from the inclusion body is not only required, but also the bulk density is low.

A method for producing a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene represented by the above formula (1) having a high bulk density is known (Patent Document 6), The obtained crystal was an inclusion body, and there was a problem that the solvent could not be removed by heating while maintaining the crystal from the inclusion body, or that energy for removing the solvent from the inclusion body was required even when it could be removed.

There is also known a production method for obtaining 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene represented by the above formula (1) instead of an clathrate (Patent Document 7), the most The crystal of the melting point requires a lot of energy when it is melted and used. In addition, in order to obtain a low-melting-point crystal, it is necessary to cool at a very high rate, so it is difficult to implement on a commercial scale, or because a special apparatus is required, application to an industrial scale is not easy. In addition, low-melting crystals have a poor color, which not only has problems in use for optical purposes, but also has a problem that the residual amount of a solvent used for crystallization is large.

A group of compounds having a fluorene skeleton such as 9,9-bis(4-hydroxyphenyl)fluorene is known to form an clathrate between a reaction solvent and a solvent used for purification, while the clathrate solvent Since it requires a high temperature and a lot of time to remove it, it is difficult to apply it on an industrial scale, and the compound having a fluorene skeleton in which a solvent is included is used as a raw material for production of epoxy resins, polyesters, etc., or for other uses. It is also known that there is a problem in industrial use.

Japanese Patent Laid-Open No. 2011-074222 Japanese Patent Laid-Open No. 2011-168722 Japanese Patent Laid-Open No. 2001-206863 Japanese Patent Laid-Open No. 2017-200900 Japanese Patent Laid-Open No. 2018-076245 Specification of Chinese Patent Application Publication No. 106349030 Japanese Patent Laid-Open No. 2017-200901

The present invention has been made against the background of the above circumstances, and a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene having a specific endothermic peak by differential scanning calorimetry analysis. and to provide a method for producing the crystal.

As a result of intensive studies for solving the above-mentioned problems, the present inventors have obtained 9,9-bis[4-(2-hydroxyethoxy)- having a specific endothermic peak by differential scanning calorimetry analysis by crystallization using a specific solvent. It was discovered that the crystal|crystallization of 3-phenylphenyl] fluorene was obtained, and this invention was completed.

The present invention is as follows.

1. 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl, characterized in that it has at least one endothermic peak according to differential scanning calorimetry in a temperature range of 158°C or more and less than 161°C ] A crystal of fluorene.

2. The crystal according to 1., characterized in that it is not an clathrate.

3. A method for producing a crystal according to 1. or 2., comprising a step of crystallization using acetonitrile.

4. The production method according to 3., further comprising a step of drying the crystal obtained by crystallization under a temperature condition of 45° C. or higher and lower than the melting point.

According to the present invention, a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene having a specific endothermic peak by differential scanning calorimetry analysis, which is not an inclusion body, and a crystal thereof A manufacturing method may be provided.

When 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene contains a compound such as an organic solvent, the inclusion body and, for example, (meth)acrylic acid, etc. When reacting, a compound such as an inclusion organic solvent inhibits the reaction, resulting in a problem that the reaction does not proceed. In addition, when the inclusion body is melted and used as a resin raw material, it is not only necessary to remove from the reaction apparatus the vapor derived from the compound such as the inclusion organic solvent generated during melting, but also the remaining organic solvent by the compound. There also existed problems, such as a quality fall of the target resin. Moreover, depending on the flash point and ignition point of compounds, such as an organic solvent to be included, there also existed concerns about the disaster prevention at the time of transport or storage of the said inclusion body.

As described above, it has at least one endothermic peak by differential scanning calorimetry in a temperature range of 158°C or higher and lower than 161°C, and is not an inclusion body 9,9-bis[4-(2-hydroxyethoxy)-3- The crystals of phenylphenyl]fluorene are not yet known. Moreover, since the inclusion organic solvent can be removed with a much lower calorific value than removing the organic solvent from the conventional inclusion crystal, energy consumption in manufacturing can be suppressed.

That is, a novel crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene that has a specific endothermic peak by differential scanning calorimetry and is not an inclusion body and a method for producing the same It is very useful also in industrial use, such as a resin raw material.

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure which shows the differential thermal and thermogravimetric analysis (DTG) curve of the acetonitrile inclusion body obtained by removing the adhesion solvent in the drying process of Example 1. FIG.
FIG. 2 is a diagram showing a differential scanning calorimetry (DSC) curve of a non-clathrate crystal (crystal of the present invention) obtained by the drying process of Example 1. FIG.
3 is a diagram showing a differential scanning calorimetry (DSC) curve of the crystal obtained in Example 2 (crystal of the present invention).
It is a figure which shows the differential thermal/thermogravimetry (DTG) curve of the crystal|crystallization obtained by removing the adhesion solvent in Example 2. FIG.
5 is a diagram showing a differential thermal and thermogravimetric analysis (DTG) curve of the crystal obtained in Comparative Example 1. FIG.
6 is a diagram showing a differential scanning calorimetry (DSC) curve of a crystal obtained by Comparative Example 2. FIG.
7 is a diagram showing a differential scanning calorimetry (DSC) curve of a crystal obtained by Comparative Example 3. FIG.
8 is a diagram showing a differential scanning calorimetry (DSC) curve of the crystal obtained by Comparative Example 4. FIG.
9 is a diagram showing a differential thermal and thermogravimetric analysis (DTG) curve of the crystal obtained in Comparative Example 6.
10 is a diagram showing a differential thermal and thermogravimetric analysis (DTG) curve of the crystal before drying of Comparative Example 7.
11 is a diagram showing a differential scanning calorimetry (DSC) curve of the crystal after drying of Comparative Example 7.

The present invention will be described in detail below.

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

<About the synthesis method>

There is no restriction|limiting in particular about the synthesis|combining method of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene in this invention, For example, in patent document 3 mentioned above, The known manufacturing method described can be applied.

The reaction between 9-fluorenone represented by the formula (2) and alcohols represented by the formula (3), shown in the following scheme, will be described.

The addition molar ratio of the alcohol represented by the formula (3) to the 9-fluorenone represented by the formula (2) is not particularly limited as long as it is at least the theoretical value (2.0), but is usually in the range of 2 to 20 times the molar amount, preferably 3 to It is used in the range of 10-fold molar amount.

An acid catalyst may be used during the reaction. The acid catalyst to be used is not particularly limited, and a known acid catalyst can be used. Specific examples of the acid catalyst include inorganic acids such as hydrochloric acid, hydrogen chloride gas, 60 to 98% sulfuric acid, 85% phosphoric acid, p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, formic acid, trichloroacetic acid or trifluoroacetic acid. Solid acids, such as an organic acid and a heteropolyacid, etc. are mentioned. Preferably, they are heteropolyacids, such as phosphotungstic acid. The suitable amount of the acid catalyst used varies depending on the reaction conditions. For example, in the case of a heteropolyacid such as phosphotungstic acid, it is in the range of 1 to 70 parts by weight, preferably 5 to 40 parts by weight, based on 100 parts by weight of 9-fluorenone. It is used in the range of parts, more preferably in the range of 10 to 30 parts by weight.

In the reaction, a cocatalyst such as thiols may be used along with the acid catalyst as needed. The reaction rate can be accelerated by use. Examples of such thiols include alkyl mercaptans and mercaptocarboxylic acids, and preferably alkyl mercaptans having 1 to 12 carbon atoms and mercaptocarboxylic acids having 1 to 12 carbon atoms. Examples of the alkyl mercaptans having 1 to 12 carbon atoms include alkali metal salts such as methyl mercaptan, ethyl mercaptan, n-octyl mercaptan, n-dodecyl mercaptan, and their sodium salts. Examples of the mercaptocarboxylic acids of 1 to 12 include thioacetic acid and β-mercaptopropionic acid. In addition, these can be used individually or in combination of 2 or more types. The amount of the thiol used as the co-catalyst is usually in the range of 1 to 30 mol%, preferably in the range of 2 to 10 mol%, based on the raw material 9-fluorenone.

Although it is not necessary to use a reaction solvent during the reaction, it may be used for reasons such as operability in industrial production or improvement of reaction rate. The reaction solvent is not particularly limited as long as it does not flow out of the reactor at the reaction temperature and is inert to the reaction. For example, aromatic hydrocarbons such as toluene and xylene, methanol, ethanol, 1-propanol, 2-propanol, etc. lower aliphatic and organic solvents such as saturated aliphatic hydrocarbons such as alcohol, hexane, heptane and cyclohexane, water, and mixtures thereof. Of these, aromatic hydrocarbons are preferably used.

The reaction temperature varies depending on the type of acid catalyst used, but when a heteropoly acid such as phosphotungstic acid is used as the acid catalyst, it is usually 20 to 200°C, preferably 40 to 170°C, more preferably 50 to 120°C. is the range Depending on the boiling point of the organic solvent to be used, the reaction pressure may be carried out under pressure or reduced pressure so that the reaction temperature is within the above range, or the reaction may be carried out while removing the water produced.

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

The endpoint of the reaction can be confirmed by liquid chromatography or gas chromatography analysis. It is preferable to make the time point when unreacted 9-fluorenone lose|disappears and no increase of the target substance is confirmed as the end point of reaction.

<About post-processing of the reaction>

After completion of this reaction, a known post-treatment method can be applied. For example, an aqueous alkali solution such as an aqueous sodium hydroxide solution or an aqueous ammonia solution is added to the reaction completion solution to neutralize the acid catalyst. The neutralized reaction mixture is allowed to stand, and if necessary, a solvent to be separated from water is added, and the aqueous layer is separated and removed. If necessary, distilled water is added to the obtained oil layer, stirred and washed with water, and the operation of separating and removing the water layer is repeated one to several times to remove the neutralization salt, and the obtained oil layer is cooled as it is to precipitate crystals. Crude crystals can be obtained by separating the crystals. Further, from the obtained oil layer, the solvent or excess alcohols represented by the above formula (3) are removed by distillation, a solvent such as an aromatic hydrocarbon is added to the obtained residue to make a uniform solution, cooled, and the precipitated crystals are separated and crude You can get a decision. This crude crystal or the residue has one or more endothermic peaks by differential scanning calorimetry in a temperature range of 158°C or higher and lower than 161°C by going through the crystallization step of the present invention, and is not an inclusion body 9,9-bis[4- A crystal of (2-hydroxyethoxy)-3-phenylphenyl]fluorene can be obtained.

<About the process of crystallization>

The manufacturing method of the present invention is characterized in that it includes a step of crystallizing using acetonitrile (hereinafter also referred to as a crystallization step). Here, it does not specifically limit as acetonitrile which can be used, A commercially available acetonitrile can be used generally.

The amount of acetonitrile used in the crystallization step is 100 parts by weight of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene contained in the residue or crude crystal obtained by post-treatment of the reaction. , 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 there is much quantity of acetonitrile to be used, the amount of crystals obtained will fall, and when it is small, the purity of a target substance will fall and it is unpreferable. In addition, when the amount of acetonitrile to be used is small, the residue obtained by the reaction post-treatment step used in the crystallization step or a solvent contained in the crude crystal, for example, 9,9-bis [ Since 4-(2-hydroxyethoxy)-3-phenylphenyl] fluorene increases, it is unpreferable.

In the crystallization process of the present invention, when a solvent other than acetonitrile is used, one or more endothermic peaks by differential scanning calorimetry are in the temperature range of 158°C or higher and lower than 161°C, and 9,9-bis[4] that is not an inclusion body Since crystals of -(2-hydroxyethoxy)-3-phenylphenyl]fluorene cannot be obtained, it is not preferable.

In the crystallization process of the present invention, acetonitrile is added to the residue or crude crystal after the reaction post-treatment to be used, heated to below the boiling point of acetonitrile under normal pressure or under pressure to completely dissolve to obtain a uniform solution, and then cooled to precipitate decision can be obtained. In the case of cooling after heating to form a homogeneous solution, crystals are precipitated by cooling at 1 to 10°C per hour, preferably 3 to 7°C per hour. The temperature for precipitating crystals is preferably in the range of 40 to 58°C, more preferably in the range of 45 to 55°C, and among them, a temperature of about 50°C is suitable as the crystal precipitation temperature. In addition, when precipitating a crystal, you may use a seed crystal. After the start of precipitation of the tablet, it is maintained at the same temperature for 0 to 5 hours, and cooled to 0 to 40 ° C., preferably 10 to 35 ° C., more preferably 20 to 30 ° C. at the above cooling rate, for 0 to 3 hours. After maintaining the temperature, it is preferable to separate the precipitated crystals by filtration or the like.

<About drying process>

The acetonitrile used in the crystallization process of this invention can be completely removed by implementing the process of drying (henceforth a drying process.). In the drying step of the present invention, the crystal obtained by the crystallization step can be carried out under a temperature condition 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. . Moreover, since there is a possibility that the color of a crystal may deteriorate by heat depending on other conditions etc., 150 degrees C or less is preferable, and 130 degrees C or less is more preferable. At a temperature lower than 45°C, the acetonitrile used in the crystallization step cannot be removed, or even if it can be removed, a very large amount of time is required, which is not preferable.

When performing a drying process, normal pressure or pressure_reduction|reduced_pressure may be sufficient, but when carrying out industrially, it is more efficient to carry out under reduced pressure, and it is suitable also from what can remove the acetonitrile used in a crystallization process. In addition, it is more preferable to perform a drying process in inert gas atmosphere, such as nitrogen.

<Crystal of the present invention>

The crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene of the present invention has an endothermic peak by differential scanning calorimetry in a temperature range of 158°C or more and less than 161°C. It is characterized by having more than one. As for the endothermic peak by differential scanning calorimetry, the temperature range of 159 degreeC or more and less than 161 degreeC is more preferable, and the temperature range of 160 degreeC or more and less than 161 degreeC is still more preferable. Further, the crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene of the present invention is not an inclusion body, that is, a crystal that does not include a compound such as an organic solvent.

In the present invention, as the crystal not containing a compound such as an organic solvent, a crystal having a residual organic solvent content of 1 wt% or less is preferable, a crystal having a content of 0.5 wt% or less is more preferable, and a crystal having 0.3 wt% or less is preferable. More preferably, 0.1 wt% or less is particularly preferable. Moreover, it is preferable that the loose bulk density of the crystal|crystallization which does not contain compounds, such as an organic solvent in this invention, is the range of 0.35-0.45 g/cm<3>.

Example

The present invention will be specifically described below by way of examples, but the present invention is not limited to these examples.

The analysis method is as follows.

<Analysis method>

1. Differential Scanning Calorimetry (DSC)

5 mg of the crystals were weighed in an aluminum pan, and using a differential scanning calorimeter (manufactured by Shimadzu Corporation: DSC-60), aluminum oxide was used as a control and measured under the following operating conditions.

(Operating conditions)

Temperature increase rate: 10℃/min

Measurement temperature range: 30-200℃

Measurement atmosphere: open, nitrogen 50 mL/min

2. Differential Thermal and Thermogravimetric Analysis (DTG)

8 mg of crystals were weighed in an aluminum pan, and measured under the following operating conditions using a differential thermal and thermogravimetric analyzer (manufactured by Shimadzu Corporation: DTG-60A).

(Operating conditions)

Temperature increase rate: 10℃/min

Measurement temperature range: 30-300℃

Measurement atmosphere: open, nitrogen 50 mL/min

3. HS-GC (residual solvent analysis)

"HS-GC" is a method of introducing and analyzing a gaseous phase portion (headspace, HS) into a gas chromatograph (GC). The amount of solvent remaining in the crystal was measured by heating the sample enclosed in the vial for a certain period of time, equilibrating the gas phase and the sample, and analyzing the gas phase portion. Specifically, 0.5 g of crystals are weighed, and N-methylpyrrolidone is added thereto while precisely weighing, so that the total is 10 g. About 3 g of this solution was weighed into a vial for HS, clamped so as not to leak, and measured under the following conditions.

(GC analysis conditions)

Apparatus: Shimadzu Corporation Manufacturing: GC-2010 plus

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

Detector: FID

INJ temperature: 300℃, FID temperature: 310℃

Temperature rising conditions: 40℃ (25 minutes) → 20℃/min → 300℃ (5 minutes)

Column linear velocity: 19.9 cm/sec

(HS analysis conditions)

Device: TurboMatrix HS 40 (Perkin Elmer)

Carrier gas pressure: 154 kPa

Vial heating temperature: 100℃

Injection time: 0.05 minutes

4. Loose bulk density

Using a multi-function type powder physical property measuring instrument multi-tester (MT-1001 type/manufactured by Seishin Co., Ltd.), the crystals are quietly injected by passing through a sieve so that there is no air gap in the measuring cell with a capacity of 20 cm 3 , The weight a (g) of the crystals in the cell for measurement when the cell for measurement was filled with crystals was measured, and the loose bulk density was calculated from the formula below.

[formula]

Loose bulk density (g/cm 3 ) = Weight of crystal a(g) ÷ 20 cm 3

5. Powder X-ray diffraction (XRD) analysis

0.1 g of crystals were filled in the sample packing part of a glass test plate, and the following powder X-ray diffractometer was used, and measurement was carried out under the following conditions.

Device: Rigaku Co., Ltd.: SmartLab

X-ray source: CuKα

Scan axis: 2θ/θ

Mode: Continuous

Measurement range: 2θ = 5° to 70°

Step: 0.01°

Speed measurement time: 2θ = 2°/min

IS：1/2

RS: 20.00mm

The output: 40kV-30mA

6. Particle size distribution

To 0.1 g of crystals, 0.1 g of water as a dispersion solvent and one drop of a dispersing agent (neutral detergent) were added and mixed, and this was put into an apparatus, followed by sonication (3 minutes), followed by measurement.

Apparatus: Shimadzu Corporation Manufacturing: SALD-2200

Measurement method: laser diffraction method

7. YI value (yellowness)

2.0 g of crystals were dissolved in 18.0 g of 1,4-dioxane having a purity of 99% by weight or more, and the YI value (yellowness) of the 1,4-dioxane solution obtained under the following conditions was measured.

Apparatus: Color-difference meter (made by Nippon Denshoku Kogyo, ZE6000)

A use cell: Glass test tube (24mm in diameter)

Moreover, the hue of 1, 4- dioxane was measured and corrected beforehand so that the coloration of 1, 4- dioxane itself used for a measurement might not affect a measured value (blank measurement). This blank measurement was performed, and the value which measured the sample was made into YI value (yellowness degree) in this invention.

<Synthesis example>

Synthesis of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorene

The inside of a 1-liter four-neck flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 9-fluorenone 76.3 g (0.423 mol), 907.0 g (4.24 mol) of alcohols represented by Formula 3, 13.7 g of tungstic acid phosphorus , 388.7 g of toluene was added, and the reaction was carried out while removing the reaction product water at a reaction temperature of 100°C and a pressure of 42 kPa. Disappearance of the raw material was confirmed by liquid chromatography analysis, and it was set as the completion|finish of reaction. The reaction solution was cooled to 80°C, 339.1 g of toluene, 26.69 g of a 15% aqueous sodium hydroxide solution, and 250 g of distilled water were added, the reaction solution was neutralized and left still, and the aqueous layer was removed. To the obtained oil layer, 250 g of distilled water was added, stirred and then left still, followed by washing with water to remove the water layer 4 times. From the obtained oil layer, low boiling point substances such as solvents and unreacted alcohols represented by the formula (3) were removed by distillation, and then the residue was dissolved in 1,500 g of toluene. The toluene solution was cooled to 25°C, and the precipitated crystals were filtered to obtain 232.0 g of a target product, a toluene inclusion body (98.0% purity by high-performance liquid chromatography analysis, 5 wt% inclusion of toluene).

<Example 1>

(Crystalization process)

In a 200 milliliter four-neck flask equipped with a thermometer, a stirrer, and a cooling tube, 10 g of the white crystals obtained in the above "Synthesis Example" and 30 g of acetonitrile were put, dissolved at 60 ° C, and cooled at a rate of 5 ° C per hour. , crystals were precipitated at around 50 °C. Thereafter, it was further cooled to 25° C. at the same cooling rate, and the precipitated crystals were filtered.

(Drying process)

The crystal obtained by the crystallization process was dried at a temperature of 20°C and a pressure of 1.2 kPa for 2 hours. In the obtained crystal, the residual solvent was 0.05% by weight of toluene and 3.6% by weight of acetonitrile by HS-GC analysis. In addition, although this crystal was dried for 4 hours under the same conditions, there was no change in the content of the residual solvent. From this fact, it became clear that the crystal obtained in the crystallization process was an acetonitrile inclusion body. As a result of performing differential thermal and thermogravimetric analysis (DTG) on this acetonitrile inclusion body, it was confirmed that the amount of heat to remove the inclusion acetonitrile was about 40 J/g. Fig. 1 shows a diagram showing a differential thermal and thermogravimetric analysis (DTG) curve of this acetonitrile inclusion body.

This acetonitrile inclusion body was dried in an environment of a temperature of 100°C and a pressure of 1.2 kPa for 4 hours to obtain 9.0 g of crystals that were not inclusion bodies.

(Analysis)

The crystal obtained by the drying step had a purity of 98.7% by high performance liquid chromatography analysis, and it was confirmed by HS-GC analysis that the residual solvent was 0.05% by weight of toluene and 0.2% by weight of acetonitrile.

Fig. 2 shows a diagram showing a differential scanning calorimetry (DSC) curve of a non-clathrate crystal, which was analyzed above.

<Example 2>

(Crystalization process)

In a 1 liter four-neck flask equipped with a thermometer, a stirrer, and a cooling tube, 208.7 g of the white crystals obtained in the above "Synthesis Example" and 626.1 g of acetonitrile were put, dissolved at 60 ° C, and cooled at a cooling rate of 5 ° C per hour, , When approximately 0.1 g of the seed crystal obtained in Example 1 was added at 55° C., an increase in precipitation crystals was confirmed at 50° C. It was cooled to 25°C at the same cooling rate and maintained at 25°C for 2 hours, and the precipitated crystals were separated by filtration.

(Drying process)

The crystals obtained by the crystallization process were dried in an environment of a temperature of 20°C and a pressure of 1.2 kPa for 2 hours. In the obtained crystal, the residual solvent was 0.08 wt% toluene and 3.7 wt% acetonitrile by HS-GC analysis. In addition, although this crystal was dried for 2 hours under the same conditions, there was no change in the content of the residual solvent. From this fact, it became clear that the crystal obtained by the crystallization process was an acetonitrile inclusion body. As a result of performing differential thermal and thermogravimetric analysis (DTG) on this acetonitrile inclusion body, it was confirmed that the amount of heat to remove acetonitrile inclusion was about 94 J/g.

By drying the acetonitrile inclusion body in an environment of a temperature of 100°C and a pressure of 1.2 kPa for 14 hours, 156.6 g of crystals that were not inclusion bodies were obtained.

(Analysis)

The crystals obtained by the drying step have a purity of 98.8% by high performance liquid chromatography analysis, and the residual solvent is 0.08% by weight of toluene and 0.003% by weight of acetonitrile by HS-GC analysis, and that by differential scanning calorimetry It has confirmed that the endothermic peak top temperature is 160°C, the YI value (yellowness) is 0.47, and the loose bulk density is 0.4 g/cm 3 . Moreover, the median diameter (D50) of the obtained crystal|crystallization was 34.0 micrometers, and the mode diameter was 39.6 micrometers.

Fig. 3 shows a diagram showing a differential scanning calorimetry (DSC) curve of a non-clathrate crystal that was analyzed above. In addition, a diagram showing a differential thermal and thermogravimetric analysis (DTG) curve of the crystal obtained by removing the adhesion solvent is shown in FIG. 4, and the main peak of the powder X-ray (those having a relative specific intensity exceeding 5%) is shown in the table. listed in 1.

From these analyzes, it was clarified that the obtained crystals were crystals having one or more endothermic peaks in the temperature range of 158°C or higher and lower than 161°C by differential scanning calorimetry, and further, were not inclusion bodies.

<Comparative Example 1>

An additional test was performed on the manufacturing method described in Example 1 of Patent Document 4 above.

Specifically, the inside of a 1 liter four-neck flask equipped with a stirrer, a cooling tube, and a thermometer was replaced with nitrogen, and 9,9'-bis (4-hydroxy-3-phenylphenyl) fluorene 75 g (0.149 mol), Potassium carbonate 1.7 g, ethylene carbonate 30.05 g (0.341 mol), toluene 112.5 g and methyl triglyme 7.5 g were added, the temperature was raised to 110° C., stirred at the same temperature for 16 hours, and high performance liquid chromatography (hereinafter referred to as HPLC) measurement It was confirmed that the raw material was lost.

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

After cooling the obtained reaction liquid to 90 degreeC, 113 g of water was added, it stirred at 80-85 degreeC for 30 minutes, and the water layer was isolate|separated after standing still. After repeating the same water washing operation three times, the solvent was removed from the obtained organic solvent layer to obtain a concentrate. To the obtained concentrate, 92 g of toluene and 348 g of methanol were added to obtain a crystallization solution. The obtained crystallization solution was heated to 65° C., stirred at the same temperature for 1 hour to completely dissolve the crystals, and then cooled at 0.1° C. per minute to precipitate crystals at 50° C., followed by stirring at the same temperature for 2 hours. Furthermore, after cooling to 22 degreeC, it filtered and obtained crystal|crystallization.

The obtained crystals were dried under a reduced pressure of 1.3 kPa at 55°C for 3 hours, and then a part of the crystals was analyzed by HS-GC. As a result, it was confirmed that the solvent used in the crystallization step contained 3.5 wt% of methanol. Furthermore, even if the analysis was continued for 3 hours under the same conditions, the methanol content did not decrease to 4 wt%. The amount of heat required to remove the inclusion solvent from this crystal was measured by DTG, and as a result, it was about 875 J/g. Under reduced pressure of 1.3 kPa, the internal temperature of this crystal|crystallization was raised to 90 degreeC, and it dried for 3 hours further. Since content of methanol became 0.02 weight%, it was set as the completion|finish of drying.

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

Weight of the obtained crystal: 77.9 g (yield: 88%)

HPLC purity: 98.6%

Toluene content: 0.01 wt%

Methanol content: 0.02 wt%

From the result of Comparative Example 1, it was confirmed that about 900 J/g of energy was required to remove methanol from the methanol inclusion body.

Moreover, the median diameter (D50) of the obtained crystal|crystallization was 18.5 micrometers, and the mode diameter was 21.2 micrometers.

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

<Reference Example 1>

(Comparative Example 1 of Patent Document 5)

The inside of a 1 liter four-necked flask equipped with a stirrer, an annealer and a thermometer was replaced with nitrogen, and 9,9'-bis(4-hydroxy-3-phenylphenyl) fluorene 60 g (0.119 mol), potassium carbonate 1.2 g , ethylene carbonate 24.15 g (0.274 mol) and toluene 60 g were added, followed by stirring at 110° C. for 34 hours. Then, 4.86 g of water was added, and reaction (hydrolysis) was performed at 100°C for 11 hours. After cooling the obtained reaction liquid to 85 degreeC, 30 g of toluene and 102 g of water were added, and it stirred at 80-85 degreeC for 30 minutes, and the water layer was isolate|separated after standing still. After repeating the same water washing operation three times, water was removed from the obtained organic solvent layer under reflux using a Dean-Stark apparatus, and by cooling, crystals were precipitated at 75° C., followed by stirring at the same temperature for 2 hours. Furthermore, after cooling to 26 degreeC, it filtered and obtained crystal|crystallization. The obtained crystal|crystallization was dried at 110 degreeC - 112 degreeC under reduced pressure of 1.1 kPa internal pressure for 12 hours.

As a result of analyzing the obtained crystal by the method described above, it was confirmed that it was a toluene inclusion body.

The results of analysis of the obtained crystals are shown below.

The weight of the obtained crystal: 68.5 g

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 crystals of the toluene inclusion body obtained in Reference Example 2 and 25 g of diisobutyl ketone were placed in a test tube containing a stirrer, stirred at 100° C. for 5 hours, and filtered without cooling as it was. Then, it dried in nitrogen stream for 2 hours.

A diagram showing a 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 degrees Celsius

Loose bulk density: 0.31 g/cm3

In addition, the said loose bulk density is data by the 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 had a melting point of 192°C and was a high melting point crystal, and that the loose bulk density was as low as 0.31 g/cm 3 .

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

5 g of the crystals of the toluene inclusion body obtained in Reference Example 2 and 25 g of heptane were placed in a test tube containing a stirrer, stirred at 100° C. for 2 hours, and filtered without cooling as it was. Then, it dried in nitrogen stream for 2 hours.

A diagram showing a 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 degrees Celsius

Loose bulk density: 0.38 g/cm3

In addition, the said loose bulk density is data by the 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 had a melting point of 191°C and was a high melting point crystal.

<Comparative Example 4>

(Example 17 of Patent Document 5: dibutyl ether)

5 g of the crystals of the toluene inclusion body obtained in Reference Example 2 and 25 g of dibutyl ether were placed in a test tube containing a stirrer, stirred at 100° C. for 5 hours, and filtered without cooling as it is. Then, it dried in nitrogen stream for 2 hours.

A diagram showing a 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 degrees Celsius

Loose bulk density: 0.35 g/cm3

In addition, the said loose bulk density is data by the simple test in a test tube.

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

<Comparative example 5>

A 500-milliliter four-neck 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 body obtained in the "Synthesis Example" above, 60 g of methyl isobutyl ketone, and 24 g of heptane were added thereto. The mixture was heated to 100°C and stirred for 30 minutes to dissolve all the crystals. Crystals were precipitated at 65°C by cooling the obtained solution at a rate of 0.8°C per minute. After stirring at the same temperature for 2 hours, the mixture was cooled to 20°C and filtered. The obtained crystal was dried under a reduced pressure of 1.3 kPa at 90 DEG C for 3 hours to obtain 10.6 g of the crystal of the following quality.

HPLC purity: 99.3%

Residual toluene: 112 ppm

Residual methyl isobutyl ketone: 1,680 ppm

Residual heptane: 321 ppm

YI value: 1.26 (10% dioxane 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 above.

<Comparative Example 6>

(Example 1 of Patent Document 6)

The inside of a 1 liter 4-neck flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 9-fluorenone 18.0 g (0.1 mol), 2-[(2-phenyl) phenoxy] ethanol 53.5 g (0.25 mol), After adding 1 g of 3-mercaptopropionic acid and 60 mL of toluene, and dissolving it at 65 degreeC, 25 mL of 98% sulfuric acid was dripped over 1 hour. Thereafter, the reaction was stirred at 65°C for 6 hours. After completion of the reaction, sodium hydroxide solution was added for neutralization, and further, 100 g of toluene and 50 g of water were added and stirred, and the aqueous layer was removed after standing still. After adding and stirring 60 g of water to the obtained organic layer, and leaving still, operation which removes the water layer was performed 4 times.

The washed organic layer was cooled to 10°C/hour for crystallization, stirred at 25°C for 15 hours, filtered, and 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene was prepared The product was obtained.

20.2 g of this crude product was dissolved in 60.6 g of toluene, cooled and crystallized, filtered at 25°C, and 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl]fluorene was got a decision Then, it dried at 80 degreeC and 1.3 kPa for 6 hours, and 11 g of crystals were obtained. (yield 19.0%)

As a result of analyzing the crystals by HPLC, the purity was 92.8%.

Fig. 9 is a diagram showing a differential thermal and thermogravimetric analysis (DTG) curve of the obtained crystal.

From FIG. 9, it became clear that the crystal|crystallization obtained by Example 1 of the said patent document 6 is a toluene inclusion body from the crystal weight decreasing in the temperature above melting|fusing point.

<Comparative Example 7>

(Example 2 of Patent Document 6)

After dissolving 10 g of the crystals of Comparative Example 6 with 60 g of ethanol, cooling was performed to perform crystallization, followed by filtration at 25°C to obtain crystals. After drying at 25°C and 1.3 kPa for 3 hours, analysis by HS-GC showed that the content of ethanol was 6.0% by weight. As a result of performing differential thermal and thermogravimetric analysis (DTG) on this crystal, it was confirmed that the amount of heat for removing the inclusion ethanol was about 147 J/g. A diagram showing a differential thermal/thermogravimetric analysis (DTG) curve of this crystal is shown in FIG. 10 .

Further, as a result of drying this crystal at 80 DEG C and 1.3 kPa for 6 hours, 6.9 g of a crystal having an ethanol content of 0.14 wt% was obtained. (yield 69%)

A diagram showing a 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 degrees Celsius

Loose bulk density: 0.33 g/cm3

In addition, the said loose bulk density is data by the simple test in a test tube. In addition, since details, such as a sulfuric acid dripping temperature, are not demonstrated in Example 6 that HPLC purity is lower than the numerical value described in patent document 6, it is also considered as a reason that reaction conditions do not agree completely.

Moreover, the median diameter (D50) of the obtained crystal|crystallization was 20.7 micrometers, and the mode diameter was 26.1 micrometers. The obtained crystals had a very small particle size compared to the crystals of the present invention, and no improvement in fluidity was observed compared to the crystals obtained from the methanol inclusion body of "Comparative Example 2".

From the results of Comparative Example 7, it was confirmed that approximately 150 J/g of energy was required to remove ethanol from the ethanol inclusion body, and that the melting point of the crystal obtained by removing ethanol from the inclusion body was 132°C.

Claims (4)

9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]flu, characterized in that it has one or more endothermic peaks by differential scanning calorimetry in a temperature range of 158°C or higher and lower than 161°C Oren's crystal. The method of claim 1,
A crystal, characterized in that it is not an inclusion body. A method for producing the crystal according to claim 1 or 2, comprising a step of crystallizing using acetonitrile. The method of claim 3,
Furthermore, the manufacturing method characterized by including the process of drying the crystal|crystallization obtained by crystallization under temperature conditions 45 degreeC or more and lower than melting|fusing point.

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