JP6241977B2 - Method for producing alcohol compound having fluorene skeleton - Google Patents

Description

  The present invention relates to a method for producing an alcohol compound having a novel fluorene skeleton, which is suitable as a monomer for forming a resin (optical resin) constituting an optical member such as an optical lens and an optical film, and has excellent processability and productivity.

  In recent years, resin materials such as polycarbonate, polyester, polyacrylate, polyurethane, and epoxy, which use an alcohol compound having a fluorene skeleton as a raw material monomer, are excellent in optical properties, heat resistance, and the like. It is attracting attention as a material. Among them, the following formula (1)

で表される構造を有するアルコール化合物は、該アルコール化合物及びその誘導体から製造される樹脂が屈折率等の光学特性、耐熱性、耐水性、耐薬品性、電気特性、機械特性、溶解性等の諸特性に優れることから、特に光学樹脂の原材料として着目されている（例えば特許文献１〜５）。

The alcohol compound having a structure represented by the above is a resin produced from the alcohol compound and derivatives thereof such as optical properties such as refractive index, heat resistance, water resistance, chemical resistance, electrical properties, mechanical properties, solubility, etc. Since it is excellent in various properties, it has attracted attention as a raw material for optical resins (for example, Patent Documents 1 to 5).

  As a method for producing the alcohol compound represented by the above formula (1), in the presence of a base catalyst, the following formula (2)

で表されるフェノール化合物とエチレンオキサイドとを反応させる方法が知られている（特許文献２）。しかしながら、該方法で得られる上記式（１）で表されるアルコール化合物はその純度が低く、エチレンオキサイドが３〜４分子付加した化合物（以下、多量体と称することもある）が多量に副生し、目的とする上記式（１）で表されるアルコール化合物を高純度で得ることは困難である。

There is known a method of reacting a phenol compound represented by the formula (II) with ethylene oxide (Patent Document 2). However, the alcohol compound represented by the above formula (1) obtained by this method has low purity, and a large amount of a compound (hereinafter sometimes referred to as a multimer) in which 3 to 4 molecules of ethylene oxide are added is by-produced. However, it is difficult to obtain the target alcohol compound represented by the formula (1) with high purity.

  On the other hand, as an improved process for producing the alcohol compound represented by the above formula (1), in the presence of an acid catalyst and thiols, the following formula (3)

で表されるアルコール化合物と９−フルオレノンとを反応させ上記式（１）で表されるアルコール化合物を得る方法が提案され（特許文献３）、また、該製法による着色の問題を改善する手法として、酸触媒及び９―フルオレノン類１００重量部に対して３重量部以上のチオール類存在下、上記式（３）で表されるアルコール化合物と９―フルオレノンとを反応させ上記式（１）で表されるアルコール化合物を得る方法が提案されている（特許文献４）。

A method for obtaining the alcohol compound represented by the above formula (1) by reacting the alcohol compound represented by formula (9) with 9-fluorenone is proposed (Patent Document 3), and as a method for improving the coloring problem caused by the production method. In the presence of 3 parts by weight or more of thiols with respect to 100 parts by weight of the acid catalyst and 9-fluorenone, the alcohol compound represented by the above formula (3) is reacted with 9-fluorenone and represented by the above formula (1). A method for obtaining the alcohol compound to be used has been proposed (Patent Document 4).

  However, the above method does not sufficiently improve the coloration, and requires a large amount of thiols during the reaction. Therefore, it is difficult to completely remove the thiols from the product. When manufacturing resin, there exists a problem that the sulfur content derived from thiols causes the further coloring of resin. Furthermore, when the inventors of the present application made additional trials on the methods described in Patent Documents 2 and 4, the resulting crystalline alcohol compound represented by the above formula (1) includes a reaction and a removal operation after the reaction ( It was found that the clathrate was incorporated with the solvent (aromatic hydrocarbons) used in the crystallization operation.

  Further, in Patent Document 5, in Synthesis Example 2, diethylene glycol is used as a solvent, the phenol compound represented by the above formula (2) is reacted with ethylene carbonate, isopropyl alcohol is added after completion of the reaction, and up to 10 ° C. It is described that the crystals of the alcohol compound represented by the above formula (1) were obtained by cooling. Therefore, the inventors of the present application re-examined the above-mentioned method and analyzed the obtained crystal. As in Patent Documents 2 and 4, it was found that a crystal with a large amount of the solvent used in the reaction and crystallization was obtained. did.

Japanese Patent Application Laid-Open No. 07-149881 JP 2001-122828 A JP 2001-206863 A JP 2009-256342 A JP 2009-173647 A

  An object of the present invention is to produce a crystal of an alcohol compound represented by the above formula (1) in which the residual amount of the solvent used in the reaction or post-treatment after the reaction is greatly reduced.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have made reaction or post-treatment after reaction by crystallizing the alcohol compound represented by the above formula (1) under specific conditions. It was found that crystals of the alcohol compound represented by the above formula (1) that do not include the solvent used in the above can be produced. Specifically, the following invention is included.

[1]
Hereinafter, the manufacturing method of the alcohol compound represented by following formula (1) including the process of (i), (ii), and (iii) in this order.

（ｉ）
上記式（１）で表されるアルコール化合物、芳香族炭化水素類及びメタノールを含む溶液を調製する工程。
（ｉｉ）
前記溶液から２５℃以上で前記アルコール化合物の結晶を析出させ、析出した結晶を分離取得する工程。
（ｉｉｉ）
６０℃以上で、前記結晶からメタノールを除去する工程。

(I)
The process of preparing the solution containing the alcohol compound represented by the said Formula (1), aromatic hydrocarbons, and methanol.
(Ii)
A step of depositing crystals of the alcohol compound from the solution at 25 ° C. or higher, and separating and acquiring the precipitated crystals.
(Iii)
Removing methanol from the crystals at 60 ° C. or higher.

[2]
The method for producing an alcohol compound represented by the above formula (1) according to claim 1, wherein the ratio of the aromatic hydrocarbons to methanol is 1: 0.3 to 1: 5 on a weight basis.

[3]
Before the step (i), in the presence of at least one compound selected from the group consisting of a glycol diether and a cyclic ketone having 5 to 12 carbon atoms, the following formula (2)

で表されるフェノール化合物とエチレンカーボネートとを反応させ、上記式（１）で表されるアルコール化合物を製造する工程を含む、［１］または［２］記載の上記式（１）で表されるアルコール化合物の製造方法。

Represented by the above formula (1) described in [1] or [2], comprising a step of reacting a phenol compound represented by the formula (1) with ethylene carbonate to produce an alcohol compound represented by the above formula (1). A method for producing an alcohol compound.

[4]
The crystal | crystallization of the alcohol compound represented by the said Formula (1) which does not have a peak of 1153 +/- 2 (cm ^<-1> ) in an infrared absorption spectrum.

[5]
The crystal | crystallization of the alcohol compound represented by the said Formula (1) whose content of the organic compound which is liquid at 25 degreeC is 1 weight% or less.

[6]
In the infrared absorption spectrum, the alcohol represented by the above formula (1) having no peak of 1153 ± 2 (cm ⁻¹ ) and having an organic compound content of 1% by weight or less at 25 ° C. Compound crystals.

[7]
The yellowness (YI value) of a solution obtained by dissolving 12 g of the alcohol compound represented by the formula (1) in 30 mL of N, N-dimethylformamide having a purity of 99% by weight or more is 10 or less, [4] Or the crystal | crystallization of the alcohol compound represented by the said Formula (1) description of [5].

  According to the present invention, since the solvent used in the reaction or post-treatment after the reaction is not included, the residual amount of the solvent in the crystal is greatly reduced. Crystals can be provided.

  Furthermore, since the crystals of the alcohol compound represented by the above formula (1) obtained by the method of the present invention have high purity and little coloration, various resin materials such as polycarbonate, polyester, polyacrylate, polyurethane, and epoxy are used. It is suitably used as a raw material.

  In particular, when the crystal is included in the solvent used in the reaction or post-treatment after the reaction, the inclusion of the solvent during melting of the crystal is released when the crystal is used as a resin raw material. It may be necessary to safely remove the used solvent out of the system, or the quality of the resulting resin may not be constant due to the influence of the encapsulated solvent. Furthermore, when storing and transporting the alcohol compound represented by the above formula (1) in which the solvent is included, more strict countermeasures for disaster prevention are required as compared with crystals not including the solvent.

  However, the crystal of the alcohol compound represented by the above formula (1) can include clathrate by inclusion of various organic compounds including aromatic hydrocarbons, while using a solvent in the reaction or after-treatment after the reaction. Without producing crystals of the alcohol compound represented by the above formula (1), it is difficult. Accordingly, when the crystal of the alcohol compound represented by the above formula (1) is produced by a general production method such as the above-described known method, the inclusion in which the solvent used in the reaction or the post-treatment after the reaction is included is included. In order to obtain a crystal of the alcohol compound represented by the above formula (1) which is an inclusion body and removes the clathrate from the inclusion body and is not an inclusion body, the crystal is once heated to a melting point or higher to be melted. It is necessary to perform complicated operations that are not easy to implement industrially, such as removal after the removal. However, according to the production method of the present invention, crystals of the alcohol compound represented by the above formula (1) that do not include the solvent used in the reaction or post-treatment after the reaction can be easily produced. Therefore, it can be said that the invention is very meaningful in producing and using a crystal of the alcohol compound represented by the above formula (1) on an industrial scale.

2 is an infrared absorption spectrum of the crystal obtained in Example 1. 2 is an infrared absorption spectrum of the crystal obtained in Comparative Example 1. 2 is an infrared absorption spectrum of the crystal obtained in Comparative Example 11. 2 is an infrared absorption spectrum of the crystal obtained in Reference Example 1. It is an infrared absorption spectrum of the crystal obtained in Comparative Example 13.

As described above, the present invention is characterized in that the steps (i), (ii) and (iii) are included in this order in the production of the alcohol compound represented by the formula (1).
(I)
A step of preparing a solution (crystallization solution) containing the alcohol compound represented by the above formula (1), aromatic hydrocarbons and methanol (hereinafter also referred to as a crystallization solution preparation step).
(Ii)
A step of depositing crystals of the alcohol compound from the solution at 25 ° C. or higher, and separating the precipitated crystals (hereinafter sometimes referred to as a crystallization step).
(Iii)
A step of removing methanol from the crystal at 60 ° C. or higher (hereinafter also referred to as a drying step).
Hereinafter, the steps (i), (ii) and (iii) will be described in detail.

As the alcohol compound represented by the above formula (1) used as a raw material of the present invention, those produced by a known method such as the above-mentioned patent document can be used. From the viewpoint of improvement, it is preferable to produce the alcohol compound represented by the above formula (1) by the method described below. In addition to the feature that the solvent used in the reaction or post-treatment after the reaction is not included by producing the alcohol compound represented by the above formula (1) by the following method, the following (a) and It becomes possible to produce an alcohol compound represented by the above formula (1) having the characteristics of // (b).
(A) The HPLC purity determined by the method described later is usually 90% or higher, preferably 95% or higher, more preferably 98% or higher.
(B) The YI value measured by the method described later is usually 10 or less, preferably 7 or less.

  The method for producing an alcohol compound represented by the above formula (1), which is a preferred embodiment of the present invention, is in the presence of at least one compound selected from the group consisting of glycol diethers and cyclic ketones having 5 to 12 carbon atoms. The phenol compound represented by the above formula (2) is reacted with ethylene carbonate.

  The phenol compound represented by the above formula (2) may be a commercially available product, or can be produced by reacting fluorenone with 2-phenylphenol in the presence of an acid catalyst.

The glycol diether used in the present invention has the following formula (4):
_{R 1 -O (CH 2 CH 2} O) n -R 2 (4)
(Wherein, R ₁ and R ₂ are the same or different, branched represent also an alkyl group having 1 to 4 carbon atoms a, n is an integer of 1-4.)
It has the structure represented by these. Such glycol diethers include ethylene glycol dimethyl ether, propylene glycol dimethyl ether, diethylene glycol dimethyl ether, dipropylene glycol dimethyl ether, diethylene glycol ethyl methyl ether, diethylene glycol isopropyl methyl ether, diethylene glycol diethyl ether, diethylene glycol butyl methyl ether, tripropylene glycol dimethyl ether, tripropylene glycol Examples include ethylene glycol dimethyl ether, diethylene glycol dibutyl ether, triethylene glycol butyl methyl ether, and tetraethylene glycol dimethyl ether.

  Examples of the cyclic ketone having 5 to 12 carbon atoms used in the present invention include cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclodecanone, cycloundecanone and the like, and availability and handling among these cyclic ketones. Cyclopentanone and cyclohexanone are preferably used because of their good properties.

  Each of the glycol diether and the cyclic ketone may be used alone or in admixture of two or more if necessary, and the amount used is represented by the above formula (2) from the viewpoint of suppression of multimer formation. The amount is usually 0.05 to 3 times, preferably 0.08 to 1 times the weight of the phenol compound.

  The usage-amount of ethylene carbonate is 2-10 mol normally with respect to 1 mol of phenolic compounds represented by the said Formula (2), Preferably it is 2-4 mol.

  When the phenol compound represented by the above formula (2) is reacted with ethylene carbonate, the reaction is performed in the presence of a basic compound as necessary. Examples of such basic compounds include carbonates, bicarbonates, hydroxides, organic bases and the like. More specifically, potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, etc. as carbonates, potassium bicarbonate, sodium bicarbonate, lithium bicarbonate, cesium bicarbonate, etc. as hydroxides, as hydroxides Examples of the organic bases include sodium hydroxide, potassium hydroxide, lithium hydroxide and the like, and triethylamine, dimethylaminopyridine, triphenylphosphine, tetramethylammonium bromide, tetramethylammonium chloride and the like. Among these basic compounds, potassium carbonate, sodium carbonate, and triphenylphosphine are preferably used from the viewpoint of good handleability. The amount used when these basic compounds are used is usually 0.01 to 1.0 mol, preferably 0.03 to 0.2 mol per mol of the phenol compound represented by the above formula (2). It is.

  In the present invention, an inert organic solvent can be used in combination with the glycol diether and the cyclic ketone having 5 to 12 carbon atoms, if necessary. Such inert organic solvents include ketones, aromatic hydrocarbons, halogenated aromatic hydrocarbons, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, ethers, esters, and aliphatic nitriles. Amides, sulfoxides and the like. More specifically, acetone, methyl ethyl ketone, butyl methyl ketone, diisobutyl ketone, methyl isobutyl ketone, methyl isoamyl ketone, 2-heptanone, 2-octanone, cyclohexanone and the like as ketones, and toluene, xylene, Mesitylene, etc., chlorobenzene, dichlorobenzene, etc. as halogenated aromatic hydrocarbons, pentane, hexane, heptane, etc. as aliphatic hydrocarbons, dichloromethane, 1,2-dichloroethane, etc. as halogenated aliphatic hydrocarbons, ether Diethyl ether, di-iso-propyl ether, methyl tertiary butyl ether, cyclopentyl methyl ether, diphenyl ether and the like as esters, ethyl acetate, butyl acetate and the like as aliphatic nitrates Acetonitrile or the like as Le compound is dimethyl formamide as amides, dimethyl acetamide and the like, dimethyl sulfoxide, and the like as sulfoxides. Among these inert organic solvents, aromatic hydrocarbons, ketones or ethers having a boiling point of 110 ° C. or higher are preferably used because of their availability and ease of handling. These organic solvents may be used alone or as a mixture of two or more if necessary. The amount of the organic solvent used in combination is usually 0.1 to 5 times, preferably 0.5 to 3 times the weight of the phenol compound represented by the above formula (2).

  The reaction between the phenol compound represented by the above formula (2) and ethylene carbonate is usually carried out at 30 to 150 ° C, preferably 100 to 130 ° C.

  The reaction solution containing the alcohol compound represented by the above formula (1) thus obtained may be concentrated and dried as it is, and then subjected to a crystallization solution preparation step. Analysis and column purification may be performed. Moreover, after implementing the water washing process and / or concentration process which are mentioned below, it uses for the crystallization solution preparation process of this invention, and improves the purity of the alcohol compound represented by the said Formula (1) made into the objective more. Is preferable in that it is possible. Hereinafter, the water washing step and the concentration step will be described in detail.

  In the water washing step, 0.1 to 10 times by weight, preferably 0.5 to 5 times by weight of water is used for the obtained reaction solution to 1 time by weight of the phenol compound represented by the above formula (2) used in the reaction. Is added and stirred at 60 to 95 ° C., preferably 75 to 90 ° C., followed by standing and separation of the aqueous layer. In addition, by setting the washing temperature to 60 ° C. or higher, the liquid separation speed at the time of standing is faster, and by setting it to 95 ° C. or lower, the alcohol compound represented by the above formula (1) at the time of washing is decomposed. It becomes possible to suppress.

  You may implement a water-washing process in multiple times as needed. Moreover, when carrying out the water washing step, by-products can be decomposed and removed into an aqueous layer by adding a base or an acid together with water.

  Subsequently, the concentration step will be described in detail. In the concentration step, after completion of the water washing step, or the reaction solution that has not been subjected to the water washing step under normal pressure or reduced pressure, the glycol diether used in the reaction step or a cyclic ketone having 5 to 12 carbon atoms, or Furthermore, it is carried out by removing a part or all of the inert organic solvent out of the system.

<Crystallizing solution preparation process>
In the present invention, it is necessary to use an aromatic hydrocarbon and methanol in combination. When aromatic hydrocarbons are not used, crystals of the alcohol compound represented by the above formula (1) cannot be completely dissolved, and methanol is not used and crystals are formed using only aromatic hydrocarbons. When the analysis is performed, crystals of the alcohol compound represented by the above formula (1) including the aromatic hydrocarbons are obtained. In addition, when crystallization is carried out using alcohol other than methanol or other organic compounds and aromatic hydrocarbons without using methanol, the effects of the present invention are not exhibited, and aromatic hydrocarbons The crystal | crystallization of the alcohol compound represented by the said Formula (1) which included was obtained.

  Examples of aromatic hydrocarbons that can be used in the present invention include toluene and xylene. The ratio of aromatic hydrocarbons to methanol in the crystallization solution is, for example, on a weight basis, aromatic hydrocarbons: methanol = 1: 0.3 to 1: 5, preferably 1: 0.5 to 1: 3. By making the ratio of methanol 0.3 times by weight or more with respect to the aromatic hydrocarbons, it becomes possible to more reliably suppress the inclusion body containing the aromatic hydrocarbons and 5 times by weight or less. Therefore, the alcohol compound represented by the above formula (1) can be easily dissolved, so that the crystallization operation becomes easier, and the purity and hue of the alcohol compound represented by the above formula (1) are improved. It is preferable because it can be easily made. Prior to the crystallization solution preparation step, these ratios are adjusted by appropriately adding aromatic hydrocarbons and methanol to the above ratio after quantitatively determining the contents of aromatic hydrocarbons and methanol by gas chromatography. can do.

  The crystallization solution may contain other organic compounds in addition to the aromatic hydrocarbons and methanol. Other organic compounds that may be included include, for example, glycol diethers used in the above-described reaction and / or cyclic ketones having 5 to 12 carbon atoms, aliphatic hydrocarbons (eg, pentane, hexane, heptane, etc.), Examples include chain ketones (for example, acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.). When other organic compounds are contained, the content is usually 0.5 times or less, preferably 0.3 times or less, based on the total amount of aromatic hydrocarbons and methanol in the crystallization solution. Although the reason why the inclusion compound containing other organic compounds is not included even if other organic compounds are contained is not clear, by crystallization in the presence of aromatic hydrocarbons and methanol, It is presumed that the alcohol compound represented by the above formula (1) is inhibited from being incorporated into the alcohol compound represented by the above formula (1), resulting in an alcohol compound represented by the above formula (1) that is not an inclusion body.

  The total amount of solvent (aromatic hydrocarbons + methanol + the above-mentioned other organic compounds) contained in the crystallization solution is usually based on 1 weight times the alcohol compound represented by the above formula (1) contained in the crystallization solution. 0.5 to 20 times by weight, preferably 1 to 10 times by weight.

  Depending on the amount of water in the crystallization solution, although depending on the content of impurities contained in the crystallization solution, the crystalline alcohol compound represented by the above formula (1) may not be obtained. Further, even when a crystalline alcohol compound represented by the above formula (1) is obtained, the purity and hue may not be sufficiently improved, so the water in the crystallization solution is usually 5% by weight or less. Preferably, the content is 1% by weight or less. As a method for reducing the water content in the crystallization solution to 5% by weight or less, for example, before adding methanol, an aromatic hydrocarbon solvent is added in advance, and azeotropic dehydration with an aromatic hydrocarbon solvent is performed under normal pressure or reduced pressure. After performing operation, the method of adding the methanol which does not contain a water | moisture content is mentioned.

<Crystal crystallization process>
Next, the crystallization process will be described in detail. The crystallization solution prepared by the above method is usually heated to a temperature not lower than 40 ° C. and not higher than the boiling point of the crystallization solution to completely dissolve the crystal and then cooled to 25 ° C. or higher, preferably 25 to 60 ° C. Preferably, crystals are precipitated at 40 to 50 ° C. When crystals are precipitated at a temperature lower than 25 ° C., the effect of the present invention is not exhibited, and a clathrate partially or entirely clathrates aromatic hydrocarbons. Further, when the crystal is precipitated at a temperature higher than 60 ° C., it may be a safety problem because it is close to the boiling point of the solvent. Examples of the method for precipitating crystals in the above-described temperature range include a method for maintaining the temperature of the crystallization solution so that the above temperature range is maintained until crystals are precipitated, and a method for inoculating seed crystals within the above temperature range. In addition, after crystal precipitation, an operation of growing the crystal by holding it at the same temperature for a certain time may be performed. After crystal precipitation, further cooling is performed as necessary to separate the precipitated crystals.

  The crystals thus separated contain methanol, but unlike the case of inclusion of aromatic hydrocarbons, methanol can be removed by setting the temperature to 60 ° C. or higher, even if not higher than the crystal melting temperature (melting point). Therefore, it is possible to easily produce crystals that do not contain the solvent used in the reaction or post-treatment after the reaction and are not an inclusion body.

<Drying process>
The drying step is performed at 60 ° C. or higher and below the melting point of the crystal, preferably 60 ° C. to 110 ° C. When the temperature is lower than 60 ° C., it is difficult to remove methanol. When carrying out the drying step, normal pressure or reduced pressure may be used. However, when industrially carried out, it is preferable to use reduced pressure because methanol can be more efficiently removed.

  The crystals of the alcohol compound represented by the above formula (1) of the present invention thus obtained can be further purified by carrying out ordinary purification operations such as adsorption, steam distillation, recrystallization and the like, if necessary. The crystals of the alcohol compound represented by the above formula (1) obtained by the method of the present invention have sufficiently high purity without performing such an operation. In addition, since the solvent used in the reaction or post-treatment after the reaction is not included in the crystal, it can be suitably used as a raw material for resin materials such as polycarbonate, polyester, polyacrylate, polyurethane, and epoxy. Also, it can be suitably used as a raw material (intermediate) for medical and agricultural chemicals, for example, in fields where the encapsulated solvent (organic compound) is a problem.

<Crystal obtained by the method of the present invention>
The crystal of the alcohol compound represented by the above formula (1) of the present invention produced by the above method is a solvent used in the reaction or post-treatment after the reaction (normal operating temperature, liquid at 25 ° C.). It is characterized by not including a certain organic compound). Therefore, the content of the organic compound which is liquid at 25 ° C. contained in the alcohol compound crystal represented by the above formula (1) obtained by the above-described method of the present invention is usually 1% by weight or less, preferably 0.5%. % By weight or less, more preferably 0.1% by weight or less.

Whether the crystal of the alcohol compound represented by the above formula (1) includes the solvent (organic compound) used in the reaction or post-treatment after the reaction, that is, the alcohol compound represented by the above formula (1) Whether or not the crystal is an inclusion body can be determined by whether or not it has 1153 ± 2 (cm ⁻¹ ), which is a peak characteristic of the inclusion body in the infrared absorption spectrum. If it does not substantially have a peak of 1153 ± 2 (cm ⁻¹ ), it can be determined that the organic compound is not an inclusion body. In the present invention, “substantially does not contain” means that little or no peak is detected in the range of 1151-1155 (cm ⁻¹ ). On the other hand, if it is not the inclusion body which includes an organic compound, it has a peak in the range of 1148 ± 2 (cm ⁻¹ ) instead of the peak in the range described above. The infrared absorption spectrum can be measured using a Fourier transform infrared spectrophotometer under the conditions described later.

  Furthermore, TG-DTA (differential thermal / thermogravimetric measurement) analysis, X-ray analysis, NMR analysis, or weight change under conditions that exceed the boiling point of the organic compound that seems to have included the obtained crystals. After sufficiently drying to such an extent that the resulting crystals are analyzed using gas chromatography or high performance liquid chromatography, it is confirmed whether or not there is a peak corresponding to the organic compound being included. Thus, it is possible to determine whether or not the crystal of the alcohol compound represented by the formula (1) includes an organic compound.

  EXAMPLES The present invention will be specifically described below with reference to examples and the like, but the present invention is not limited at all. In the examples, various measurements were performed by the following methods. In addition, the production rate (residual rate) and purity of each component described in the following examples, comparative examples, and reference examples are HPLC area percentage values (solvents in the reaction solution and organic compounds included). The peak is the corrected area percentage value), and the yield is apparent when it is assumed that the alcohol represented by the above formula (1) is an inclusion body, but not an inclusion body. Yield. The “multimer” in Examples and Comparative Examples refers to compounds obtained by further reacting one or more molecules of ethylene carbonate with the alcohol compound represented by the above formula (1).

(1) HPLC purity apparatus: LC-2010A manufactured by Shimadzu Corporation,
Column: SUMPAX ODS A-211 (5 μm, 4.6 mmφ × 250 mm),
Mobile phase: pure water / acetonitrile (acetonitrile 30% → 100%),
Flow rate: 1.0 ml / min, column temperature: 40 ° C., detection wavelength: UV 254 nm.

(2) Analysis of residual solvent amount and clathrate content The residual amount of solvent or the content of the organic compound clathrated with the alcohol compound represented by the above formula (1) is determined by gas chromatography based on the following conditions. Quantification was performed.
Apparatus: GC-2014 manufactured by Shimadzu Corporation
Column: DB-1 (0.25 μm, 0.25 mm ID × 30 m),
Temperature rise: 40 ° C. (5 minutes hold) → 20 ° C./min→250° C. (10 minutes hold)
Inj temperature: 250 ° C., Det temperature: 300 ° C., split ratio 1:10,
Carrier: nitrogen 54.4 kPa (constant),
Sample preparation method: 100 mg of a sufficiently dried alcohol compound crystal represented by the above formula (1) was weighed into a 10 ml volumetric flask, and a previously prepared acetonitrile solution of 1,2-dimethoxyethane (1,1, 5 ml of 2-dimethoxyethane (400 mg dissolved in 200 ml of acetonitrile) was added with a whole pipette, and the sample solution was dissolved in acetonitrile to prepare a sample solution.
On the other hand, 10 mg of the compound whose residual amount (inclusion amount) is to be measured is weighed into a 10 ml volumetric flask, and the same amount of 1,2-dimethoxyethane in acetonitrile as above is added, and the solution is made up with acetonitrile and dissolved. It was.
The sample solution and the standard solution were analyzed under the above-mentioned conditions, the peak areas of the obtained components were obtained with a data processor, and the content (%) of each component was calculated (internal standard method).
In addition, about the sample containing isopropanol, the solvent used for preparation of a sample solution and a standard solution was changed from acetonitrile to triglyme, and it implemented.

(3) Infrared absorption spectrum measurement A Fourier transform infrared spectrophotometer equipped with a one-time reflection type total reflection measuring device (Shimadzu Corporation Dura Sampler II) for an alcohol compound crystal represented by the above formula (1). (Shimadzu Corporation IRtracer-100) was used and measured under the following conditions.
(conditions)
Resolution: 4cm ^-1
Integration count: 16 times

(4) YI value 12 g of an alcohol compound crystal represented by the above formula (1) was dissolved in 30 ml of N, N-dimethylformamide having a purity of 99% by weight or more, and N, N-dimethyl obtained under the following conditions: The YI value (yellowness) of the formamide solution was measured.
Apparatus: Color difference meter (Nippon Denshoku Industries Co., Ltd. SE6000),
Cell used: Optical path length 33 mm Quartz cell.
In addition, the hue of N, N-dimethylformamide was measured and corrected in advance so that the coloration of N, N-dimethylformamide itself used for the measurement did not affect the measurement value. (Blank measurement).
A value obtained by measuring the sample after performing the above-described blank measurement is defined as a YI value in the present invention.

(5) Moisture value The moisture value in the crystallization solution was measured by a method (Karl Fischer volumetric titration method) based on JIS-K0068.

<Example 1>
In a glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer, 150 g of 9,9′-bis (4-hydroxy-3-phenylphenyl) fluorene (phenol compound represented by the above formula (2)) (0.298 mol), 3.4 g (0.025 mol) of potassium carbonate, 60.1 g (0.682 mol) of ethylene carbonate, 225 g of toluene, and 15 g of triethylene glycol dimethyl ether, heated to 115 ° C., and at the same temperature After stirring for 8 hours, it was confirmed by HPLC that the raw material peak had disappeared. The production rate of multimers at the end of the reaction was about 1%.
After cooling the obtained reaction liquid to 90 degreeC, 225g of water was added, it stirred at 80-85 degreeC for 30 minutes, and the water layer was isolate | separated after standing. After the same operation was repeated three times, the solvent was removed by concentrating the obtained organic solvent layer to obtain a concentrate. To the obtained concentrate, 49 g of toluene and 188 g of methanol were added to obtain a crystallization solution. The water content in the obtained crystallization solution was 0.1% by weight.
The obtained crystallization solution was heated to 65 ° C. and stirred at the same temperature for 1 hour to completely dissolve the crystals, and then cooled at 0.1 ° C./min to precipitate crystals at 45 ° C. Stir at temperature for 2 hours. After further cooling to 22 ° C., filtration was performed to obtain crystals.
The obtained crystals were dried for 3 hours at an internal temperature of 55-59 ° C. under a reduced pressure of 1.3 kPa, and a part of the crystals was analyzed by gas chromatography. As a result, it was confirmed that the crystals contained 4% by weight of methanol. did. Furthermore, even if drying was continued under the same conditions for 3 hours and analyzed, the content of methanol was not changed to 4% by weight. Subsequently, the internal temperature was raised to 68 ° C. to 73 ° C. under reduced pressure of 1.3 kPa, and further dried for 3 hours, whereby the methanol content was 0.2% by weight.

Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.
Weight of crystals obtained: 139 g (yield: 79%)
HPLC purity: 98.5% (multimer content: 1.1%)
Toluene content: 0.03% by weight
Methanol content: 0.2% by weight
Content of organic compound which is liquid at 25 ° C .: 0.25% by weight
YI value: 0.7

The infrared absorption spectrum is shown in FIG. As shown in FIG. 1, it had a peak at 1148 (cm ⁻¹ ), but did not have a peak at 1153 ± 2 (cm ⁻¹ ).

<Example 2>
In a glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer, 150 g (0.298 mol) of 9,9′-bis (4-hydroxy-3-phenylphenyl) fluorene and 3.4 g of potassium carbonate (0. 025 mol), 60.1 g (0.682 mol) of ethylene carbonate, 225 g of toluene, and 150 g of diethylene glycol dimethyl ether, heated to 115 ° C., stirred for 13 hours at the same temperature, and the raw material peak disappeared by HPLC It was confirmed. The production rate of multimers at the end of the reaction was about 0.5%.
After cooling the obtained reaction liquid to 85 degreeC, 225 g of water was added, it stirred at 80-85 degreeC for 30 minutes, and after standing still, the water layer was isolate | separated. After repeating the same operation three times, the obtained organic solvent layer was partially concentrated to obtain a solution containing the alcohol compound represented by the above formula (1), toluene and diethylene glycol dimethyl ether.
To this solution, 54 g of toluene and 84 g of methanol were added to obtain a crystallization solution. The water in the obtained crystallization solution was 0.1% by weight, and 173 g of toluene, 84 g of methanol and 61 g of diethylene glycol dimethyl ether were contained in the 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 to 0.1 ° C./min to 50 ° C. When 0.01 g of the obtained crystal was added as a seed crystal, a crystal was precipitated. Then, it stirred at the same temperature for 1 hour. After further cooling to 25 ° C., filtration was performed to obtain crystals.
The obtained crystal was dried at an internal temperature of 68 ° C. to 73 ° C. for 3 hours under a reduced pressure of 1.1 kPa, and the methanol content was 0.2% by weight.

Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.
Weight of the obtained crystal: 123 g (yield: 70%)
HPLC purity: 98.0% (multimer content: 0.10%)
Toluene content: 0.05% by weight
Content of organic compound which is liquid at 25 ° C .: 0.26% by weight
YI value: 0.7
Infrared absorption spectrum: While it had a peak at 1148 (cm ⁻¹ ), it did not have a peak at 1153 ± 2 (cm ⁻¹ ).

<Example 3-6>
Reaction and post-treatment were performed in the same manner as in Example 1 to obtain a concentrate. The obtained concentrate was divided into four equal parts, toluene and methanol were added to give the ratios shown in Table 1 below, and crystallization and drying operations were carried out in the same manner as in the method described in Example 1 to obtain the above formula (1). The crystal | crystallization of the alcohol compound represented by these was obtained. Each analysis value of each crystal is shown in Table 1 below. In Table 1, the amount of toluene / methanol added is the ratio (times by weight) to the alcohol compound represented by the above formula (1) contained in each concentrate.

<Example 7>
In a glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer, 9,9′-bis (4-hydroxy-3-phenylphenyl) fluorene 30.0 g (0.060 mol), ethylene carbonate 13.1 g ( 0.149 mol), 0.7 g (0.005 mol) of potassium carbonate, 45.0 g of toluene and 15.0 g of cyclohexanone, stirred for 6 hours at 115 ° C., and confirmed by HPLC that the raw material peak was 1% or less. did. The production rate of multimers at the end of the reaction was about 1.0%.
After cooling the obtained reaction liquid to 85 degreeC, 23 g of water was added, it stirred at 80-85 degreeC for 30 minutes, and after standing still, the water layer was isolate | separated. After repeating the same operation three times, the obtained organic solvent layer was partially concentrated to obtain a solution containing the alcohol compound represented by the above formula (1), toluene and cyclohexanone.
To this solution, 21 g of toluene and 38 g of methanol were added to obtain a crystallization solution. The water in the obtained crystallization solution was 0.1% by weight, 38 g of toluene, 38 g of methanol and 11 g of cyclohexanone contained in the 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 to 0.1 ° C./min to 50 ° C. When 0.01 g of the obtained crystal was added as a seed crystal, a crystal was precipitated. Then, it stirred at the same temperature for 1 hour. After further cooling to 20 ° C., the crystals were filtered off by filtration, and the obtained crystals were dried at an internal temperature of 68 ° C. to 73 ° C. under a reduced pressure of 1.3 kPa for 3 hours to obtain the above formula ( A crystal containing the alcohol compound represented by 1) was obtained.

Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.
Weight of the obtained crystal: 26 g (yield: 73%)
HPLC purity: 98.6% (multimer content: 0.8%)
Toluene content: 0.02% by weight
Methanol content: 0.1% by weight
Content of organic compound which is liquid at 25 ° C .: 0.15% by weight
YI value: 1.2
Infrared absorption spectrum: While it had a peak at 1148 (cm ⁻¹ ), it did not have a peak at 1153 ± 2 (cm ⁻¹ ).

<Comparative Example 1>
In a glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer, 9,9′-bis (4-hydroxy-3-phenylphenyl) fluorene 40.0 g (0.080 mol), ethylene carbonate 16.1 g (0.183 mol), 0.8 g (0.006 mol) of potassium carbonate and 40.0 g of toluene were added, and the mixture was stirred at 110 ° C. for 11 hours, and it was confirmed by HPLC that the raw material peak was 1% or less. In addition, it was confirmed that about 3% of multimers were by-produced in the reaction solution.
After cooling the obtained reaction liquid to 85 degreeC, 68 g of water was added, it stirred at 80-85 degreeC for 30 minutes, and after standing still, the water layer was isolate | separated. After repeating the same operation three times, the obtained organic solvent layer was dehydrated under reflux using a Dean-Stark apparatus to obtain a crystallization solution in which the alcohol compound represented by the above formula (1) was dissolved. The water in the crystallization solution was 0.1% by weight.
When the obtained crystallization solution was cooled at 0.3 ° C./min, crystals were precipitated at 65 ° C. and stirred at the same temperature for 2 hours. After further cooling to 26 ° C., filtration was performed to obtain crystals.
The obtained crystal was dried at an internal temperature of 68 ° C. to 73 ° C. for 3 hours under a reduced pressure of 1.1 kPa, and contained 4% by weight of toluene. The internal temperature was raised to 110 ° C. and drying was continued for 3 hours at the same temperature, but the toluene content remained at 4% by weight.

Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.
Weight of the obtained crystal: 39.3 g (yield: 84%)
HPLC purity: 97.5% (multimer content: 2.6%)
Toluene content: 4.1% by weight

The infrared absorption spectrum is shown in FIG. As shown in FIG. 2, it did not have a peak at 1148 ± 2 (cm ⁻¹ ), but had a peak at 1153 (cm ⁻¹ ).

<Comparative example 2>
In the crystallization step, ethanol was used in place of methanol, and the same operation as in Example 1 was performed except that the final drying temperature was 90 ° C., to obtain crystals of the alcohol compound represented by the above formula (1). Each analysis value of the obtained crystal is as follows.
Weight of the obtained crystal: 127 g (yield: 72%)
HPLC purity: 98.0% (multimer content: 0.8%)
Toluene content: 4.1% by weight
Infrared absorption spectrum: no peak at 1148 ± 2 (cm ⁻¹ ), but a peak at 1153 (cm ⁻¹ ).

<Comparative Examples 3-6>
Reaction and post-treatment were performed in the same manner as in Example 1 to obtain a concentrate. The obtained concentrate is divided into four equal parts, each solvent is added so as to have the ratio shown in Table 2 below, and crystallization and drying are performed in the same manner as in Example 1 except that the final drying temperature is 90 ° C. The operation was carried out to obtain crystals of the alcohol compound represented by the above formula (1). Each analysis value of each crystal is shown in Table 2 below. In addition, the addition amount of each solvent in Table 2 is the ratio (weight times) with respect to the alcohol compound represented by the said Formula (1) contained in each concentrate.

  As shown in Table 2 above, the alcohol compound represented by the above formula (1) forms an clathrate with aromatic hydrocarbons, and when xylene is used alone or mixed with a solvent other than methanol for crystallization. It has been found that an inclusion body including an aromatic hydrocarbon can be obtained even if it is used.

<Comparative Example 7>
After carrying out the reaction and post-treatment in the same manner as in Example 2, 171 g of concentrate was obtained by removing the solvent. After adding 228 g of toluene and 114 g of methanol to the obtained concentrate, the temperature was raised to 65 ° C., and the mixture was stirred at the same temperature for 1 hour to completely dissolve the crystals. Then, the crystal | crystallization was deposited at 21 degreeC by cooling at 1.5 degreeC / min, and it stirred at the same temperature for 2 hours. Then, it filtered and the crystal | crystallization containing the alcohol compound represented by the said Formula (1) was obtained.
The obtained crystal was dried at an internal temperature of 68 ° C. to 73 ° C. for 3 hours under a reduced pressure of 1.1 kPa, and contained 4% by weight of toluene. The internal temperature was raised to 110 ° C. and drying was continued for 3 hours at the same temperature, but the toluene content remained at 4% by weight.

<Comparative Example 8>
The reaction solution was charged and reacted by the method described in Example 6 of JP-A-2001-206863 except that the reaction scale was reduced to 1/10, and the reaction solution was stirred at 65 ° C. for 1 hour. As a result, almost no alcohol compound represented by the above formula (1) was produced, and 98% of the starting 9-fluorenone remained. Therefore, stirring was further continued at the same temperature for 7 hours, and the reaction solution was analyzed by high performance liquid chromatography. Similarly, the reaction hardly proceeded and 97% of the starting material 9-fluorenone remained.
Therefore, based on the description of JP 2001-206863 [0019], when the reaction temperature was changed from 65 ° C. to 100 ° C. and stirring was continued at the same temperature, 73 hours were required until the disappearance of 9-fluorenone as a raw material. there were.
In order to carry out the post-treatment based on the literature description, the obtained reaction solution was divided into two, 10 g of methanol was added to one side and 10 g of isopropyl alcohol was added to the other side and heated to 60 ° C. In each case, 30 g of pure water was added and cooled to 30 ° C., but in both cases, crystals did not precipitate, and tar-like liquids separated from water were obtained.

<Comparative Example 9>
When the amount of 9-fluorenone used was 18 g and the method described in Example 1 of JP-A-2009-256342 was further tested, 34.2 g of the alcohol compound represented by the above formula (1) (yield: 58%, purity: 85.1). %). Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.

Xylene content: 4.8% by weight
YI value: 51
Infrared absorption spectrum: no peak at 1148 ± 2 (cm ⁻¹ ), but a peak at 1153 (cm ⁻¹ ).

<Comparative Example 10>
When the amount of 9-fluorenone used was 9 g and the method described in Example 2 of JP-A-2009-256342 was further tested, 13.5 g of alcohol compound represented by the above formula (1) (yield 46%, purity 74.7). %). Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.

Toluene content: 3.0% by weight
YI value: 83
Infrared absorption spectrum: no peak at 1148 ± 2 (cm ⁻¹ ), but a peak at 1153 (cm ⁻¹ ).

<Comparative Example 11>
When the amount of 9-fluorenone used was 18 g and the method described in Example 3 of JP-A-2009-256342 was further tested, 23.6 g of an alcohol compound represented by the above formula (1) (yield: 40%, purity: 91.2) %). Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.

Xylene content: 5.0% by weight
YI value: 18

The infrared absorption spectrum is shown in FIG. As shown in FIG. 3, it did not have a peak at 1148 ± 2 (cm ⁻¹ ), but had a peak at 1153 (cm ⁻¹ ).

<Comparative Example 12>
When the amount of 9-fluorenone used was 18 g and the method described in Example 4 of JP-A-2009-256342 was further tested, 20.7 g of the alcohol compound represented by the above formula (1) (yield 35%, purity 88.6). %). Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.

Xylene content: 5.2% by weight
YI value: 46
Infrared absorption spectrum: While it had no peak at 1148 ± 2 (cm ⁻¹ ), it had a peak at 1152 (cm ⁻¹ ).

<Reference example>
After about 2 mg of toluene was sprinkled on about 5 mg of the crystals obtained in Example 1 using a Pasteur pipette, FT-IR analysis of the crystals was carried out immediately. The infrared absorption spectrum is shown in FIG. As shown in FIG. 4, in the case where the alcohol compound crystal represented by the above formula (1) which is not an inclusion body has aromatic hydrocarbons as a solvent residue rather than as a guest molecule of the inclusion compound, It was found that 1153 ± 2 (cm ⁻¹ ), a peak peculiar to the body, has no peak and has a peak at 1148 (cm ⁻¹ ).

<Comparative Example 13>
Except for the amount of 9,9-bis (4-hydroxy-3-phenylphenyl) fluorene used being 50.2 g, the method described in JP-A-2009-173647, Synthesis Example 2 was re-examined and represented by the above formula (1). 45.1 g (purity 93.8%) of the alcohol compound obtained was obtained. Each analysis value of the crystal | crystallization of the alcohol compound represented by the said Formula (1) obtained is as follows.

Diethylene glycol content: 24.6% by weight
Isopropyl alcohol content: 42.0% by weight
Infrared absorption spectrum: no peak at 1148 ± 2 (cm ⁻¹ ), but a peak at 1153 (cm ⁻¹ ).

  Since the crystal obtained in the additional test was wet with a solvent, the crystal was further dried by drying at 90 ° C. for 8 hours under a reduced pressure of 1.1 kPa of internal pressure, whereby the above formula (1) 26.2 g (purity 94.2%) of the alcohol compound represented by the formula (1) was obtained. Each analysis value of the obtained crystal is as follows.

Diethylene glycol content: 42.4% by weight
Isopropyl alcohol content: 0.3% by weight

Further, FIG. 5 shows an infrared absorption spectrum of the obtained crystal. As shown in FIG. 5, it had no peak at 1148 ± 2 (cm ⁻¹ ), while it had a peak at 1153 (cm ⁻¹ ).

  As described above, since the content of diethylene glycol was hardly reduced, the drying operation was terminated when the drying temperature was gradually increased under a reduced pressure of 1.1 kPa, and the crystals began to melt at about 100 ° C. .

<Comparative example 14>
In a glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer, 9,9′-bis (4-hydroxy-3-phenylphenyl) fluorene 30.0 g (0.060 mol), ethylene carbonate 12.0 g (0.136 mol), 0.7 g (0.005 mol) of potassium carbonate, and 30.0 g of cyclohexanone were added and stirred at 140 ° C. for 7 hours, and the raw material peak was confirmed to be 1% or less by HPLC. The production rate of multimers at the end of the reaction was about 1.2%.
After cooling the obtained reaction liquid to 90 ° C., 23 g of cyclohexanone and 27 g of normal heptane were added, and the organic solvent layer was kept at 90 ° C. and washed with water until the washing water became neutral. After washing with water, the obtained organic solvent layer was dehydrated under reflux using a Dean-Stark apparatus to obtain a crystallization solution in which the alcohol having a fluorene skeleton represented by the above formula (1) was dissolved. The water in the crystallization solution was 0.1% by weight.
Then, after cooling to 70 degreeC and keeping at 70 degreeC for 1 hour, the crystal | crystallization was deposited, Then, it stirred at the same temperature for 2 hours. After stirring, the mixture was further cooled to 19 ° C. and filtered to obtain crystals.
The obtained crystals were dried under an internal pressure of 1.1 kPa at an internal temperature of 110 ° C. for 5 hours. Since 14 wt% of cyclohexanone was contained, the drying temperature was gradually increased under an internal pressure of 1.1 kPa. As a result, the crystal started to melt at about 115 ° C., and thus the drying operation was finished.

Claims (3)

Hereinafter, the manufacturing method of the alcohol compound represented by following formula (1) including the process of (i), (ii), and (iii) in this order.

(I)
The process of preparing the solution containing the alcohol compound represented by the said Formula (1), aromatic hydrocarbons, and methanol.
(Ii)
A step of depositing crystals of the alcohol compound from the solution at 25 ° C. or higher, and separating and acquiring the precipitated crystals.
(Iii)
Removing methanol from the crystals at 60 ° C. or higher.   The method for producing an alcohol compound represented by the above formula (1) according to claim 1, wherein the ratio of the aromatic hydrocarbons to methanol is 1: 0.3 to 1: 5 on a weight basis. Before the step (i), in the presence of at least one compound selected from the group consisting of a glycol diether and a cyclic ketone having 5 to 12 carbon atoms, the following formula (2)

The alcohol compound represented by the said Formula (1) of Claim 1 or 2 including the process of making the phenol compound represented by these, and ethylene carbonate react, and manufacturing the alcohol compound represented by the said Formula (1). Manufacturing method.

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