Method for producing crystals of biphenanthrene skeleton-containing dihydroxy compound

Abstract

The present invention addresses the problem of providing a method by which a biphenanthrene skeleton-containing dihydroxy compound can be more efficiently and stably produced. To solve the problem, provided is a method for producing crystals of a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), the method comprising a crystallization step for precipitating crystals of the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) from a crystallization solution that contains the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) and at least one organic solvent selected from among C6-C9 aromatic hydrocarbon-based organic solvents and C5-C9 aliphatic ketone solvents. (In the formula, R1s each independently represent a C2-C4 alkylene group, R2s each independently represent a C1-C6 alkyl group, a C6-C18 aryl group, or a halogen atom, and ns each independently represent 0 or an integer of 1-4.)

Description

Method for producing crystals of biphenanthrene skeleton-containing dihydroxy compounds

[0001] This invention relates to a method for producing crystals of biphenanthrene skeleton-containing dihydroxy compounds.

[0002] In recent years, resins for optical lenses have been developed, and various monomers have been considered as raw materials. Initially, bisphenol A was the main monomer, but monomers with a fluorene skeleton, such as 9,9-bis{4-(2-hydroxyethoxy)phenyl}fluorene (Patent Document 1, etc.), have been used, and it has been reported that dihydroxy compounds with a binaphthalene skeleton can be used as raw material monomers to increase the refractive index (Patent Document 2). Due to the increasing need for higher refractive indices in resins for optical lenses, compounds with higher refractive indices than those used as monomer raw materials in conventional polymers have been investigated, and dihydroxy compounds with a biphenanthrene skeleton have been reported (Patent Documents 3 and 4). Patent Documents 3 and 4 describe 10,10'-bis(2-hydroxyethoxy)-9,9'-biphenanthrene (sometimes referred to as compound (1a-1)), which is one type of dihydroxy compound with a biphenanthrene skeleton. It has been described that compound (1a-1) can be synthesized by reacting 10,10'-dihydroxy-9,9'-biphenanthrene (sometimes referred to as compound (2a-1)) with ethylene carbonate in the presence of potassium carbonate using dimethylformamide as a solvent, followed by alkali treatment, and then adding the reaction solution to water to precipitate and isolate the crystals of compound (1a-1). It has also been reported that compound (1a-1) could not be obtained by reacting 10,10'-dihydroxy-9,9'-biphenanthrene with ethylene carbonate in the presence of potassium carbonate using toluene as a solvent.

[0003] International Publication No. 2007 / 142149, International Publication No. 2014 / 073496, International Publication No. 2021 / 187075, International Publication No. 2021 / 220811

[0004] When the inventors conducted a synthesis experiment of compound (1a-1) based on the description in Patent Document 3, it became clear that the reaction solution after the reaction contained residual 10,10'-dihydroxy-9,9'-biphenanthrene, as well as a large amount of by-products resulting from the excessive reaction of ethylene carbonate, indicating that the conversion rate of the raw materials and the reaction selectivity of the target compound were not high. Furthermore, dimethylformamide, which was described as a preferred reaction solvent and used, is known to decompose slowly at high temperatures above 100°C, releasing dimethylamine, which has a strong pungent odor. This raises safety and hygiene concerns, such as a rapid increase in pressure in the reactor due to the generation of volatile components. When an aqueous sodium hydroxide solution was added to the reaction solution after the reaction, the target compound (1a-1) produced in the reaction precipitated, resulting in a heterogeneous two-phase state of solid and liquid. Such a two-phase state makes post-treatment such as purification treatments prone to heterogeneity, and therefore, it was considered an unsuitable manufacturing method for industrial production where quality stability is required. In the manufacturing method described in Patent Document 3, when precipitating crystals, a treatment solution containing compound (1a-1) is added to water, and the resulting crystals are recovered. Synthesis experiments revealed that the obtained crystals contained large amounts of iron and copper from the raw material compound (2a-1), as well as bases and metals resulting from the potassium carbonate used during the reaction and the sodium hydroxide added after the reaction. When synthesizing biphenantrols (2a) such as compound (2a-1) used as a raw material, conventional methods using catalysts and equipment containing metals such as copper and iron can result in the contamination of these metals. In manufacturing methods for compounds (1a-1) that contain large amounts of bases and metals, there is a concern that the metals contained in the raw material will remain in compound (1a-1), causing similar problems. Furthermore, when the liquid after crystal precipitation was filtered, it became clear that the filtrate drained slowly and required a long time during the filtration process, yet the filtered crystals were in a paste-like state containing a large amount of solvent. This revealed that the manufacturing method described in Patent Document 3 has problems with filtration operability and handling of the filtered material, making it unsuitable for industrial production.

[0005] Patent Document 3 describes the purification of a compound (1a-1) by recrystallization using crystals obtained through the above reaction and crystallization steps, with chloroform and hexane as solvents. The inventor attempted to conduct a recrystallization experiment based on the description in Patent Document 3, but the crystals of compound (1a-1) did not dissolve in the described amounts of chloroform. In light of the results of the solubility of compound (1a-1) in chloroform measured by the inventor, it was clear that the amount was insoluble, and therefore purification by recrystallization based on the description in Patent Document 3 was not possible. As described above, it has become clear that the manufacturing method described in Patent Document 3 for producing compound (1a-1) has major problems in terms of the efficiency of the reaction step, the operability of the subsequent processing, and the handling of the crystals. In view of these issues, the object of the present invention is to provide a method for producing biphenanthrene skeleton-containing dihydroxy compounds such as compound (1a-1) more efficiently and stably.

[0006] The inventors diligently investigated methods for producing biphenanthrene skeleton-containing dihydroxy compounds such as compound (1a-1), and as a result discovered that crystals can be precipitated from a crystallization solution containing a biphenanthrene skeleton-containing dihydroxy compound when a specific solvent is used, thus completing the present invention.

[0007] The present invention is as follows: 1. A method for producing crystals of a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), comprising a crystallization step of precipitating crystals of the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) from a crystallization solution containing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) and at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms. (In the formula, R １ Each independently represents an alkylene group with 2 to 4 carbon atoms, R ２1. Each independently represents an alkyl group having 1 to 6 carbon atoms, an aryl group having 6 to 18 carbon atoms, or a halogen atom, and each independently represents 0 or an integer from 1 to 4. 2. The method for producing a compound according to 1, wherein the aliphatic ketone solvent having 5 to 9 carbon atoms is at least one selected from methyl isobutyl ketone and cyclohexanone. 3. The method for producing a compound according to 1, wherein the aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms is at least one selected from benzene, toluene, orthoxylene, metaxylene, paraxylene, mixed xylene, and mesitylene. 4. The method for producing a compound according to 1, wherein the crystallization solution is a crystallization solution obtained through a washing step with water. 5. The method for producing a compound according to 1, wherein the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) is any of the biphenanthrene skeleton-containing dihydroxy compounds represented by chemical formulas (1a-1) to (1a-3).

[0008] By performing the crystallization operation according to the manufacturing method of the present invention, crystals of biphenanthrene skeleton-containing dihydroxy compounds can be efficiently and stably produced, while also offering excellent handling properties and low content of specific organic solvents and water.

[0009] The present invention provides a method for producing crystals of a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) (hereinafter sometimes referred to as "dihydroxy compound (1a)"), characterized by comprising a crystallization step of precipitating crystals of the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) from a crystallization solution containing the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) and at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms.

[0010] <Biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a)> R in general formula (1a) １Each independently represents an alkylene group having 2 to 4 carbon atoms. Among them, each is independently preferably a 1,2-ethylene group, a 1-methyl-1,2-ethylene group or a 2-methyl-1,2-ethylene group, and both are particularly preferably 1,2-ethylene groups. R in the general formula (1a) １ As for, two Rs １ are preferably both the same substituent. R in the general formula (1a) ２ Each independently represents an alkyl group having 1 to 6 carbon atoms, an aryl group having 6 to 18 carbon atoms or a halogen atom. When R ２ is an alkyl group, it is preferably an alkyl group having 1 to 4 carbon atoms, more preferably a methyl group or an ethyl group, and particularly preferably a methyl group. When R ２ is an aryl group, it is preferably an aryl group having 6 to 12 carbon atoms, more preferably a phenyl group or a naphthyl group, and particularly preferably a phenyl group. Examples of the halogen atom in R ２ include, for example, a chlorine atom, a bromine atom and an iodine atom, and a bromine atom is preferred. R in the general formula (1a) ２ is preferably each independently an alkyl group having 1 to 4 carbon atoms, a naphthyl group, a phenyl group or a bromine atom, more preferably each independently a methyl group, an ethyl group, a naphthyl group, a phenyl group or a bromine atom, still more preferably each independently a phenyl group, a naphthyl group or a bromine atom, and particularly preferably each independently a phenyl group or a bromine atom. In the general formula (1a), n each independently represents 0 or an integer of 1 to 4. Among them, each independently being 0, 1, or 2 is preferred, each independently being 0 or 1 is more preferred, and 0 is particularly preferred. Among the dihydroxy compounds (1a), the compounds represented by the chemical formulas (1a-1) to (1a-3), which are suitable compounds, are shown below. Among these, the compound represented by the chemical formula (1a-1) or the chemical formula (1a-2) is more preferred, and 10,10'-bis(2-hydroxyethoxy)-9,9'-biphenanthryl, which is the compound represented by the chemical formula (1a-1), is particularly preferred.

[0011] <Method for synthesizing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a)> There are no particular restrictions on the method for obtaining the dihydroxy compound (1a) according to the present invention, but for example, it can be obtained by synthesizing the dihydroxy compound (1a) by a reaction step in which biphenantrols (2a) and a hydroxyalkylene oxidizing agent are reacted in the presence of a basic compound.

[0012] <Biphenantrols represented by general formula (2a) (2a)> R in general formula (2a) ２ And n have the same definition as in general formula (1a), and the preferred embodiment is also the same. Biphenantrols (2a) can be produced, for example, by the manufacturing method described in Japanese Patent Publication No. 2001-039898. Examples of biphenantrols (2a) include 10,10'-dihydroxy-9,9'-biphenanthryl represented by chemical formula (2a-1) (hereinafter sometimes referred to as "compound (2a-1)"). This compound can be produced, for example, by the method described in Japanese Patent Publication No. 60-181043 or the Journal of American Chemical Society, 2008, 130, 6840. Other examples include 10,10'-dihydroxy-6,6'-diphenyl-9,9'-biphenanthryl represented by chemical formula (2a-2) (CAS registration number: 1564249-14-4) and 10,10'-dihydroxy-6,6'-dibromo-9,9'-biphenanthryl represented by chemical formula (2a-3) (CAS registration number: 1564249-12-2), which are described in Tetrahedron, 70, 1786-1793 (2014).

[0013] <Hydroxyalkylene Oxidizing Agent> In the present invention, the hydroxyalkylene oxidizing agent can be glycols containing alkylene groups having 2 to 4 carbon atoms, such as ethylene glycol and propylene glycol; carbonates represented by general formula (3), such as ethylene carbonate and propylene carbonate (hereinafter sometimes referred to as "carbonates (3)"); monohalogenated alcohols having 2 to 4 carbon atoms, such as 2-chloroethanol and 3-chloro-1-propanol; or alkylene oxides having 2 to 4 carbon atoms, such as ethylene oxide. Among these, it is preferable to use carbonates (3). R in general formula (3) １ This is the same as the definition of general formula (1a), and the preferred embodiment is also the same. (In the formula, R １ This is the same as the definition in general formula (1a).

[0014] The amount of carbonates (3) used in the reaction step is usually in the range of 2.0 to 5.0 moles, preferably in the range of 2.0 to 4.5 moles, more preferably in the range of 2.0 to 4.0 moles, and particularly preferably in the range of 2.0 to 3.0 moles, per mole of biphenantrols (2a).

[0015] The present invention provides an example of a reaction equation for a method of producing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) of the present invention, in which carbonates (3) are used as the hydroxyalkylene oxidizing agent. The following is an example of a reaction equation when compound (2a-1) is used as a biphenantrol (2a) and compound (1a-1) is synthesized as a dihydroxy compound (1a) by performing a hydroxyalkylene oxidization reaction using ethylene carbonate as a hydroxyalkylene oxidizing agent.

[0016] (Basic Compounds) The reaction step to obtain the dihydroxy compound (1a) is carried out in the presence of a basic compound. As the basic compound, basic compounds commonly used in hydroxyalkoxylation reactions can be used, specifically, for example, triorganophosphine compounds, nitrogen-containing heterocyclic basic compounds, alkali metal compounds, and alkaline earth metal compounds. Examples of triorganophosphine compounds include triphenylphosphine and tributylphosphine. Examples of nitrogen-containing heterocyclic basic compounds include 1-methylimidazole. Examples of alkali metal compounds include alkali metal carbonates such as potassium carbonate, calcium carbonate, and magnesium carbonate; alkali metal hydroxides such as magnesium hydroxide, calcium hydroxide, and sodium hydroxide; alkali metal bicarbonates such as sodium bicarbonate; and alkali metal salts of hydrocarbon hydroxy compounds such as sodium methoxy and sodium phenoxy. Examples of alkaline earth metal compounds include calcium hydroxide and barium hydroxide. Among these basic compounds, alkali metal compounds are preferred, alkali metal carbonates, alkali metal hydroxides, or alkali metal bicarbonates are more preferred, alkali metal carbonates or alkali metal hydroxides are even more preferred, and alkali metal carbonates are particularly preferred. The alkali metal in these alkali metal compounds is preferably sodium or potassium, and more preferably potassium. That is, at least one selected from sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, and potassium bicarbonate is preferred, at least one selected from sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide is more preferred, potassium carbonate or potassium hydroxide is even more preferred, and potassium carbonate is particularly preferred. These basic compounds may be used alone or in combination of two or more. The amount of this basic compound used is preferably in the range of 0.001 to 10% by weight of biphenantrols (2a), more preferably in the range of 0.01 to 5% by weight, and even more preferably in the range of 0.1 to 5% by weight.

[0017] (Reaction Solvent) The reaction step to obtain the dihydroxy compound (1a) is preferably carried out in the presence of an organic solvent. A non-protic organic solvent is preferred. Specifically, examples of such non-protic organic solvents include aprotic nonpolar organic solvents such as aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms, aliphatic hydrocarbon organic solvents, and ether organic solvents, as well as aprotic polar organic solvents such as amide organic solvents, ester organic solvents, carbonate organic solvents, and aliphatic ketone organic solvents. Specific examples of aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms include benzene, toluene, orthoxylene, metaxylene, paraxylene, mixed xylene, and mesitylene, with at least one of these being preferred, at least one of toluene, orthoxylene, metaxylene, and paraxylene being more preferred, and toluene being particularly preferred. Specific examples of aliphatic hydrocarbon organic solvents include hexane, heptane, and octane. Specific examples of ether organic solvents include diethyl ether, tetrahydrofuran, and dioxane. Specific examples of amide organic solvents include N,N-dimethylformamide, N,N-dimethylacetamide, and N-methyl-2-pyrrolidone. Specific examples of ester organic solvents include γ-butyrolactone, γ-valerolactone, δ-valerolactone, γ-caprolactone, ε-caprolactone, α-methyl-γ-butyrolactone, butyl acetate, ethyl acetate, and isobutyl acetate. Specific examples of carbonate organic solvents include ethylene carbonate and propylene carbonate. Specific examples of aliphatic ketone organic solvents include acetone (3 carbon atoms), methyl ethyl ketone (4 carbon atoms), diethyl ketone, cyclopentanone (5 carbon atoms), methyl isobutyl ketone, cyclohexanone (6 carbon atoms), methyl amyl ketone, cycloheptanone (7 carbon atoms), methylhexyl ketone, and cyclooctanone (8 carbon atoms).Among aprotic organic solvents, at least one aprotic organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms, amide organic solvents, and aliphatic ketone solvents is preferred, at least one aprotic organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms, amide organic solvents, and aliphatic ketone solvents having 5 to 9 carbon atoms is more preferred, aliphatic ketone organic solvents having 6 to 8 carbon atoms are even more preferred, aliphatic ketone organic solvents having 6 or 7 carbon atoms are even more preferred, and aliphatic ketone organic solvents having 6 carbon atoms are particularly preferred. Specific examples of preferred aliphatic ketone solvents include diethyl ketone, cyclopentanone, methyl isobutyl ketone, cyclohexanone, methyl amyl ketone, cycloheptanone, methylhexyl ketone, and cyclooctanone, with at least one of these being preferred, and methyl isobutyl ketone or cyclohexanone being particularly preferred. There are no particular restrictions on the amount of organic solvent used, but it is preferably in the range of 1 to 20 times the weight of biphenantrols (2a), more preferably in the range of 2 to 15 times, even more preferably in the range of 2 to 10 times, and particularly preferably in the range of 2 to 8 times.

[0018] (Phase Transfer Catalyst) In the reaction step to obtain the dihydroxy compound (1a), it is preferable to use a phase transfer catalyst. Specific examples of the phase transfer catalyst include quaternary ammonium salts or quaternary phosphonium salts, which are preferred, with quaternary ammonium salts being more preferred. Specific examples of quaternary ammonium salts include tetraalkylammonium halides, specifically tetrabutylammonium chloride, tetrabutylammonium bromide, tetraethylammonium chloride, tetraethylammonium bromide, tetramethylammonium chloride, and tetramethylammonium bromide, which are tetraalkylammonium halides in which the alkyl group has 1 to 4 carbon atoms. Among quaternary ammonium salts, tetraalkylammonium halides are preferred, tetraalkylammonium halides in which the alkyl group has 1 to 4 carbon atoms are more preferred, and it is even more preferable that at least one is selected from the compounds of the specific examples above, with tetrabutylammonium bromide being particularly preferred. Specific examples of quaternary phosphonium salts include tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, and tetraphenylphosphonium bromide, and it is preferable that at least one is selected from these compounds. These phase transfer catalysts may be used individually or in combination of two or more types. The amount of the phase transfer catalyst used is preferably in the range of 0.001 to 10% by weight of biphenantrols (2a), more preferably in the range of 0.01 to 5% by weight, and even more preferably in the range of 0.1 to 5% by weight.

[0019] (Reaction Conditions) The reaction temperature in the reaction step to obtain the dihydroxy compound (1a) is not particularly limited as long as the reaction proceeds at a temperature, but it is usually carried out under heating. Depending on the type of solvent used, it is in the range of 50 to 250°C, preferably in the range of 70 to 200°C, and more preferably in the range of 100 to 180°C. It is even more preferable that the reaction be carried out at a temperature under reflux of the solvent. The reaction time depends on the reaction temperature, the amount and type of biphenantrols (2a), hydroxyalkylene oxidizing agent, basic compound, organic solvent and phase transfer catalyst used, etc., but it is usually carried out for about 3 to 48 hours. When carbonates (3) are used as the hydroxyalkylene oxidizing agent, the point at which carbon dioxide generation is no longer observed can be used as an indicator of the end of the reaction.

[0020] <Neutralization Step> It is preferable to perform a neutralization step in which the dihydroxy compound (1a) obtained in the reaction step is neutralized by adding an acid (for example, hydrochloric acid, sulfuric acid, acetic acid, propionic acid, etc.) or an aqueous solution of an acid to neutralize the basic compound contained in the reaction solution. This neutralization step may also be performed after the hydrolysis step described later.

[0021] <Hydrolysis Step> In the reaction step described above, the dihydroxy compound (1a) obtained using carbonates (3) as a hydroxyalkylene oxidizing agent has an excess amount of carbonates (3) added, so carbonates (3) remain in the reaction solution even after the reaction is complete. If heating or other treatment is performed in this state, side reactions may proceed, potentially reducing the purity and yield of the target compound, dihydroxy compound (1a). Therefore, it is preferable to add water to the obtained reaction solution to perform a hydrolysis step of carbonates (3). The amount of water used is in the range of 1 to 10 molar times the amount of carbonates (3) used in the above reaction. The temperature should be below the boiling point of the reaction solution, but is usually in the range from room temperature to below the boiling point of the reaction solution. Specifically, the lower limit of the temperature is 10°C or higher, preferably 20°C or higher, more preferably 40°C or higher, and even more preferably 60°C or higher. The upper limit of the temperature depends on the boiling point of the solvent used, but is preferably 150°C or lower.

[0022] <Alkali Treatment Step> In the reaction step described above, when carbonates (3) are used as the hydroxyalkylene oxidizing agent, a by-product is produced in which carbonates (3) are added in excess to the dihydroxy compound (1a). To reduce this by-product, it is preferable to mix a basic compound with the reaction solution obtained in the reaction step and perform an alkaline treatment. In the alkaline treatment step, a basic compound of the same type as the basic compound used in the reaction step, and water (which may be an aqueous solution of the basic compound) are mixed as needed. Among the basic compounds used in the alkaline treatment step, sodium hydroxide or potassium hydroxide is preferred. In order to efficiently reduce excess reaction products, the amount of basic compound used is usually 0.4 moles or more, preferably in the range of 0.4 to 20 moles, and more preferably in the range of 0.5 to 10 moles, per mole of biphenanthrene skeleton-containing dihydroxy compound (1a).

[0023] <Crystallization step of the manufacturing method of the present invention> A crystallization solution containing the dihydroxy compound (1a) used in the crystallization step of the present invention and at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms can be obtained by using the dihydroxy compound (1a) obtained in the reaction step described above, or, if necessary, by using the dihydroxy compound (1a) isolated through the neutralization step, hydrolysis step, alkali treatment step described above, followed by separation steps such as crystallization, filtration, distillation, or column chromatography, and dissolving it in at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms. A crystallization step to obtain crystals can be carried out from such a crystallization solution as a recrystallization operation. Furthermore, when at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms, according to the manufacturing method of the present invention, is used in the reaction step, if the dihydroxy compound (1a) obtained in the reaction step is uniformly dissolved in the reaction solution, depending on the solubility of the solvent used, the reaction solution can be used as is, or, if necessary, the solution can be used after undergoing the neutralization step, hydrolysis step, and alkali treatment step described above. From such a solution, a crystallization step can be performed as a recrystallization operation to obtain crystals. On the other hand, depending on the solubility of the solvent used, the obtained dihydroxy compound (1a) may precipitate as crystals as it is generated in the reaction step, resulting in a reaction solution containing crystals. In this case, the reaction step and the crystallization step according to the manufacturing method of the present invention can be performed simultaneously to obtain crystals of the dihydroxy compound (1a). In this way, a crystallization step to obtain crystals can be performed as a reaction crystallization operation, in which the reaction and crystallization operations are performed simultaneously. The various reaction conditions in the reaction crystallization operation, including the reaction solvent and its type, are as described later, and other conditions are the same as those for the raw materials and various conditions described in the reaction step above.

[0024] Among the aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms used in the crystallization process, those having 7 to 9 carbon atoms are preferred, more preferably 7 or 8, and particularly preferred to have 7 carbon atoms. Specific examples of aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms include benzene, toluene, orthoxylene, metaxylene, paraxylene, mixed xylene, and mesitylene. At least one of these is preferred, at least one of toluene, orthoxylene, metaxylene, and paraxylene is more preferred, and toluene is particularly preferred. The amount of aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms used relative to the dihydroxy compound (1a) can be adjusted as appropriate in light of the solubility of the aromatic hydrocarbon organic solvent used, but is preferably in the range of 20 to 100 times by weight, more preferably in the range of 25 to 80 times by weight, even more preferably in the range of 30 to 75 times by weight, and particularly preferably in the range of 40 to 75 times by weight. Since the solubility of aromatic hydrocarbon organic solvents relative to the dihydroxy compound (1a) is not very high, it is preferable to perform a crystallization step to obtain crystals as a reaction crystallization operation.

[0025] Among the aliphatic ketone solvents having 5 to 9 carbon atoms used in the crystallization process, those having 6 to 9 carbon atoms are preferred, more preferably 6 to 8, even more preferably 6 or 7, and particularly preferred to be 6. Specific examples of aliphatic ketone solvents to be used include diethyl ketone, cyclopentanone, methyl isobutyl ketone, cyclohexanone, methyl amyl ketone, cycloheptanone, methylhexyl ketone, and cyclooctanone, of which at least one is preferred, and methyl isobutyl ketone or cyclohexanone is particularly preferred. The amount of aliphatic ketone solvent having 5 to 9 carbon atoms used relative to the dihydroxy compound (1a) can be adjusted as appropriate in light of the solubility of the aliphatic ketone solvent used, but is preferably in the range of 3 to 30 times by weight, more preferably in the range of 4 to 25 times by weight, and even more preferably in the range of 4 to 20 times by weight. If the solubility of the aliphatic ketone solvent in the dihydroxy compound (1a) is not very high, the crystallization method can be a reaction crystallization operation to obtain crystals, and if the solubility is relatively high, the crystallization operation can be a recrystallization operation, which is preferable. Specifically, among the dihydroxy compounds (1a), compound (1a-1) has high solubility in methyl isobutyl ketone and cyclohexanone among the aliphatic ketone solvents, and cyclohexanone has even greater solubility than methyl isobutyl ketone.

[0026] In the crystallization step, the amount of organic solvent relative to the amount of dihydroxy compound (1a) may be adjusted by pre-distilling or adding the organic solvent as needed, in light of the solubility of the dihydroxy compound (1a) in the organic solvent used. Also, if a solvent other than aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms was used in the reaction step or post-treatment step, part or all of it may be pre-distilled as needed. Then, as a method for precipitating the crystals, methods such as cooling crystallization, poor solvent addition crystallization, and solvent distillation crystallization may be used. In the case of cooling crystallization, the crystallization solution is heated to a temperature where the upper limit is the boiling point temperature and the lower limit is 80°C, preferably 90°C, more preferably 100°C, and even more preferably 110°C, and then cooled to a range of 0 to 40°C, preferably 10 to 40°C, more preferably 15 to 40°C, and even more preferably 15 to 35°C. In poor solvent-added crystallization, a poor solvent refers to a solvent in which the solubility of the dihydroxy compound (1a) is lower than that of the aromatic hydrocarbon organic solvent with 6 to 9 carbon atoms or the aliphatic ketone solvent with 5 to 9 carbon atoms used. By mixing in a poor solvent, the solubility is reduced, thereby causing crystal precipitation. Examples of poor solvents include lower alcohol solvents such as methanol, ethanol, isopropanol, and 1-butanol, as well as aliphatic hydrocarbon solvents such as pentane, hexane, heptane, and octane. In addition, other aromatic hydrocarbon organic solvents with 6 to 9 carbon atoms and aliphatic ketone solvents with 5 to 9 carbon atoms that are poor solvents compared to the aromatic hydrocarbon organic solvents with 6 to 9 carbon atoms and the aliphatic ketone solvent with 5 to 9 carbon atoms already used to dissolve the dihydroxy compound (1a) can be listed. Solvent distillation crystallization is a method of precipitating crystals by distilling off the organic solvent contained in the crystallization solution. These crystallization methods may be carried out not by using only one method, but by combining multiple methods. Examples of crystallization methods include crystallization by cooling crystallization and poor solvent addition crystallization, crystallization by solvent distillation crystallization and cooling crystallization, and methods combining cooling crystallization, poor solvent addition crystallization, and solvent distillation crystallization. Among these, the crystallization method by cooling crystallization or the crystallization method by cooling crystallization and poor solvent addition crystallization are preferred as methods for precipitating crystals.The crystallization solution used in the crystallization step by the method of precipitating these crystals may contain water, which may be included by washing with water as described later, or organic solvents such as the reaction solvent used in the process of obtaining the dihydroxy compound (1a), as long as it does not interfere with the effects of the present invention. However, the total amount of dihydroxy compound (1a) and the aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms or the aliphatic ketone solvent having 5 to 9 carbon atoms in the crystallization solution is preferably 80% by weight or more, more preferably 90% by weight or more, and even more preferably 95% by weight or more, based on the total weight of the crystallization solution. It is particularly preferable to prepare the crystallization solution of dihydroxy compound (1a) and the aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms or the aliphatic ketone solvent having 5 to 9 carbon atoms by using the aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms alone.

[0027] In the crystallization step according to the present invention, when crystals are precipitated by a recrystallization operation, it is preferable to use a crystallization solution that has undergone a washing step with water. This washing step is preferable because it removes water-soluble impurities such as basic compounds used in the reaction step and alkali treatment step, salts produced in the neutralization step, and glycols produced in the hydrolysis step, thereby enabling the production of a higher purity dihydroxy compound (1a). In the washing step with water, the crystallization solution can be washed by mixing water with a crystallization solution containing the dihydroxy compound (1a) and at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms, mixing the water and the crystallization solution to distribute water-soluble impurities into the aqueous layer, and then removing the water. The amount of water used in the washing step is not particularly limited, but is preferably in the range of 0.05 to 5.0 times the weight of the solution, more preferably in the range of 0.1 to 3.0 times the weight, and even more preferably in the range of 0.1 to 1.5 times the weight. The temperature of the solution during the washing step is not particularly limited as long as the dihydroxy compound (1a) dissolves and separates well from water. However, the upper limit of the temperature that can be heated is limited by the boiling point of the solvent used and the temperature at which it forms an azeotrope with water. The range is preferably 30 to 150°C, more preferably 40 to 140°C, even more preferably 60 to 130°C, and particularly preferably 70 to 120°C. The number of times the solution is washed with water in the washing step is not particularly limited as long as water-soluble impurities can be sufficiently removed, and an appropriate number of times can be set, whether once or multiple times. Finally, it is preferable to perform the washing step such that when the metal content of the resulting dihydroxy compound (1a) crystals is analyzed, the total content of each metal, sodium, potassium, iron, and copper, is 40 ppm or less. It is more preferable that the content of each metal be as described later. The manufacturing method of the present invention preferably includes a crystallization step in which crystals of dihydroxy compound (1a) are precipitated from the crystallization solution that has undergone the washing step.

[0028] The crystals of dihydroxy compound (1a) obtained by the crystallization process can be filtered, washed with a solvent if necessary, and dried in a drying process to evaporate the adhering solvent and dry the crystals, thereby obtaining crystals of dihydroxy compound (1a). The resulting crystals may partially or completely possess the characteristics of the composition or powder described later. One of the effects of the present invention is that such crystals are easy to handle, such as being easy to filter, dry, and transport, and can be efficiently manufactured industrially. To further increase the purity, further purification by distillation, recrystallization, or column chromatography may be performed in accordance with conventional methods.

[0029] The crystals of dihydroxy compound (1a) obtained by the production method of the present invention are very useful because they have excellent handling properties and a reduced solvent content. Specifically, the crystals of dihydroxy compound (1a) obtained by the production method of the present invention are in the form of a composition in which the content of an organic solvent, an aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms and an aliphatic ketone solvent having 5 to 9 carbon atoms, is 3.0% by weight or less, and the water content is 1.0% by weight or less. The content of the organic solvent, an aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms and an aliphatic ketone solvent having 5 to 9 carbon atoms, is preferably 2.0% by weight or less, more preferably 1.0% by weight or less, even more preferably 0.8% by weight or less, and particularly preferably 0.5% by weight or less. The water content is preferably 0.8% by weight or less, more preferably 0.6% by weight or less, even more preferably 0.5% by weight or less, and particularly preferably 0.3% by weight or less. The values ​​for the organic solvent content and water content can be treated as the values ​​obtained by rounding the quantitative analysis results of the content to two decimal places, and it is preferable that these values ​​fall within the above range.

[0030] When the metal content of the crystals of dihydroxy compound (1a) obtained by the manufacturing method of the present invention is analyzed, the total content of each metal, sodium, potassium, iron, and copper, is preferably 40 ppm or less, more preferably 20 ppm or less, even more preferably 12 ppm or less, even more preferably 5 ppm or less, even more preferably 3 ppm or less, and particularly preferably 1 ppm or less. Since the lower the content of these metals, the better, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more. When the metal content of the crystals of dihydroxy compound (1a) obtained by the manufacturing method of the present invention is analyzed, the sodium content is preferably 10 ppm or less, more preferably 5 ppm or less, even more preferably 3 ppm or less, even more preferably 1 ppm or less, and particularly preferably 0.5 ppm or less. Since the lower the content of this metals, the better, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more. When the metal content of the crystals of dihydroxy compound (1a) obtained by the manufacturing method of the present invention is analyzed, the potassium content is preferably 10 ppm or less, more preferably 5 ppm or less, even more preferably 3 ppm or less, even more preferably 1 ppm or less, and particularly preferably 0.5 ppm or less. Since a lower content is preferable, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more. When the metal content of the crystals of dihydroxy compound (1a) obtained by the manufacturing method of the present invention is analyzed, the iron content is preferably 10 ppm or less, more preferably 5 ppm or less, even more preferably 3 ppm or less, even more preferably 1 ppm or less, and particularly preferably 0.5 ppm or less. Since a lower content is preferable, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more.When analyzing the metal content of the crystal of the dihydroxy compound (1a) obtained by the production method of the present invention, the copper content is preferably 10 ppm or less, more preferably 5 ppm or less, still more preferably 3 ppm or less, even more preferably 1 ppm or less, and particularly preferably 0.5 ppm or less. Since it is more preferable that this content is less, there is no limitation on the lower limit value, but it may be 0.001 ppm or more, or may be 0.01 ppm or more. As a method for analyzing the metal content of the crystal of the dihydroxy compound (1a), the method described in the examples below can be mentioned.

[0031] The factors for the inclusion of sodium and potassium as impurities in the crystal of the dihydroxy compound (1a) are due to the use of basic compounds containing sodium or potassium, such as potassium carbonate, during the reaction, or the use of basic compounds containing sodium or potassium, such as sodium hydroxide, added during the alkali treatment after the reaction. The factors for the inclusion of iron and copper as impurities in the crystal of the dihydroxy compound (1a) are that biphenanthrols (2a), such as the compound (2a-1) used as a raw material, have been conventionally used in the production of compounds containing metals such as copper and iron, and this is contained in the biphenanthrols (2a) and may not be removed and remain even after the production of the dihydroxy compound (1a). In the conventionally known synthesis method of the dihydroxy compound (1a), it has now been clarified that there is a problem that the product contains a large amount of metal. However, the embodiment in which the metal content analyzed for the crystal of the dihydroxy compound (1a) of the present invention is within the above range is very useful because it can solve such a problem.

[0032] The crystals of the dihydroxy compound (1a) obtained by the production method of the present invention are further in the form of a powder, and preferably have an average particle diameter in the range of 20 to 150 μm in the volume-based cumulative particle size distribution measured using a wet laser diffraction particle size distribution measuring device. The lower limit value of such an average particle diameter is more preferably 30 μm or more, and even more preferably 80 μm or more. The upper limit value of such an average particle diameter is more preferably 130 μm or less, and even more preferably 110 μm or less.

[0033] The purity of the crystals of the dihydroxy compound (1a) obtained by the method of the present invention is preferably in the form of a composition in which the ratio of the peak area of the dihydroxy compound (1a) to the peak areas of all components detected at a wavelength of 280 nm in high performance liquid chromatography (HPLC) analysis is 90.0% or more. The purity of the crystals is more preferably 93.0% or more, even more preferably 95.0% or more, still more preferably 98.0% or more, and particularly preferably 99.0% or more. The HPLC analysis method for the purity of the crystals of the dihydroxy compound (1a) obtained by the method of the present invention is in accordance with the HPLC analysis for purity analysis in the analysis method of the examples described below.

[0034] The crystals of the dihydroxy compound (1a) or the crystals of the composition obtained by the production method of the present invention preferably have a hue of 400 APHA or less when made into a 10% by weight cyclohexanone solution. The APHA value of such a hue is more preferably 300 or less, even more preferably 200 or less, and particularly preferably 100 or less. The numerical value indicating the hue of the cyclohexanone solution can be treated as the numerical value obtained by rounding off the units digit of the hue analysis result value, and it is preferable that the numerical value is within the above range.

[0035] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. The analytical method is as follows: <Analytical Method> 1. Reaction Selectivity Analysis, Purity Analysis The area % of the target compound when the target compound and reaction solution obtained under the following apparatus and conditions were analyzed was defined as the purity and reaction selectivity. Apparatus: ProminenceUFLC (liquid chromatography) manufactured by Shimadzu Corporation Pump: LC-20AD Column oven: CTO-20A Detector: SPD-20A Column: HALO C18 (inner diameter 3 mm, length 75 mm) Oven temperature: 50℃ Flow rate: 0.7 mL / min. Mobile phase: (A) 0.2 volume % aqueous acetic acid solution, (B) methanol gradient Conditions: (B) volume % 0-7 min., 50% → 70% 7-13 min., 70% 13-20 min., 70% → 100% 20-23 min. 100% Sample injection volume: 5 μL Detection wavelength: 280 nm

[0036] 2. Melting Point Measurement: Differential Scanning Calorimetry (DSC) The crystals were precisely weighed into an aluminum pan and measured using a differential scanning calorimetry system (Hitachi High-Tech Science Co., Ltd.: DSC-7020) with aluminum oxide as a control under the following operating conditions. (Operating conditions) Heating rate: 10°C / min. Measurement temperature range: 30 to 400°C Measurement atmosphere: Open, 50 mL / min. nitrogen Sample volume: 2 to 3 mg

[0037] 3. A 10% by weight solution was prepared by dissolving the hue evaluation sample in cyclohexanone. After calibrating the measuring instrument described below with cyclohexanone, the dissolved color of the prepared 10% by weight solution was measured. Measuring instrument: TZ 6000, manufactured by Nippon Denshoku Industries Co., Ltd.

[0038] 4. NMR analysis using Fourier transform nuclear magnetic resonance (NMR) with AVANCE III HD 400 (BRUKER) and deuterated chloroform (CDCl). ３ ) Sample １ The 1H-NMR spectrum was measured.

[0039] 5. Refractive Index The compound to be measured was dissolved in N,N-dimethylformamide to prepare solutions with concentrations of 30% by weight, 20% by weight, and 10% by weight. The refractive index was measured using the refractometer described below. From the obtained results, the relationship between concentration and refractive index was derived, and the value at a concentration of 100% by weight was calculated by extrapolation. This value was defined as the refractive index of the compound. Equipment: Refractometer (Kyoto Electronics Manufacturing Co., Ltd.: RA-500)

[0040] 6. Powder X-ray Diffraction (XRD) 0.1 g of the obtained solid was filled into the material-filled section of a glass test plate and measured using the following equipment and conditions. Equipment: Rigaku Corporation: SmartLab (powder X-ray diffractometer) X-ray source: CuKα Scan axis: 2θ / θ Mode: Continuous measurement range 2θ = 5° to 90° Step: 0.01° Speed ​​measurement time: 2θ = 33.9° / min. IS: 2 / 3 RS: 20.00 mm Output: 40 kV, 30 mA

[0041] 7. Analysis of Metal Content: After dry ashing of 1 g of the sample, acid dissolution was performed. The amounts of sodium and potassium were analyzed by atomic absorption spectrometry, and the amounts of iron and copper were analyzed by inductively coupled plasma mass spectrometry. In this analysis, if the measurement result for sodium and potassium was less than 0.1 ppm (not undetectable), it was indicated as "less than 0.1 ppm." Similarly, if the measurement result for iron and copper was less than 0.01 ppm (not undetectable), it was indicated as "less than 0.01 ppm." These values ​​were not added together when summing the contents of each metal.

[0042] <Comparative Example 1> Compound (1a-1) was synthesized based on the description in Example 1 of Patent Document 3. 10.03 g of 10,10'-dihydroxy-9,9'-biphenanthrene:compound (2a-1) (metal content: iron 2.4 ppm, copper 3.8 ppm, sodium 1.3 ppm, potassium 0.1 ppm), 5.24 g of ethylene carbonate, 0.37 g of potassium carbonate, and 20 mL of dimethylformamide (DMF) were added to a 100 mL four-necked flask. Nitrogen was blown into the flask to replace the air with nitrogen, and the mixture was heated to 120°C and stirred for 5 hours while maintaining the temperature. After the reaction, the reaction solution was cooled to room temperature, and then 14.16 g of DMF and 2.18 g of 10% NaOH aqueous solution were added. The solution was then heated to 110°C and stirred for 2 hours while maintaining the temperature to perform alkali treatment. The reaction solution was then cooled to 40°C. 102.97 g of water was placed in a 200 mL Erlenmeyer flask, and while stirring the water with a magnetic stirrer, the alkali-treated reaction solution was added dropwise to the water using a pipette. The water immediately became cloudy upon addition of the reaction solution, and after the entire volume of the reaction solution had been added, a pale yellow slurry was obtained. This slurry was filtered by suction using a Kiriyama funnel (filter paper No. 5C) to obtain 40.78 g of a pale yellow paste. 40.78 g of the filtered paste and 89.97 g of water were added to a 200 mL Erlenmeyer flask and stirred with a magnetic stirrer at room temperature for 1 hour. The slurry in the Erlenmeyer flask was filtered to separate the solids using a Kiriyama funnel (filter paper No. 5C) to obtain a pale yellow paste containing 35.19 g of solvent. Next, the obtained paste was transferred to a 100 mL round-bottom flask, and the solvent was removed by evaporation for 7.5 hours using an evaporator (internal pressure 0.9–1 MPa, bath temperature 100°C). 11.93 g of a milky white, lumpy solid of compound (1a-1) was obtained. The purity of the obtained compound (1a-1) was low at 92.9%, and a large amount of by-products resulting from the excess reaction of ethylene carbonate (1.6%) were present (area percentage determined by high-performance liquid chromatography). In addition, residual 10,10'-dihydroxy-9,9'-biphenanthrene from the starting material and many other unidentifiable impurities were observed.The color evaluation result of the solid containing the obtained compound (1a-1) was APHA 500 or higher. The solid containing the obtained compound (1a-1) contained 3.1 ppm of iron, 4.9 ppm of copper, 44.4 ppm of sodium, and 44.0 ppm of potassium, with a total content of 96.4 ppm for each metal.

[0043] The composition containing compound (1a-1) obtained in Comparative Example 1 had low purity due to residual raw materials, by-products from the excessive reaction of ethylene carbonate, and other impurities. Furthermore, the hue value of the composition containing the obtained compound (1a-1) was very high, indicating strong coloration. It was revealed that the obtained compound (1a-1) contained a large amount of sodium and potassium resulting from the potassium carbonate used during the reaction and the sodium hydroxide added after the reaction, as well as iron and copper contained in the raw material compound (2a-1).

[0044] <Comparative Example 2> Using a solid containing the compound (1a-1) obtained in Comparative Example 1, an experiment to recrystallize compound (1a-1) was conducted based on the description in Example 2 of Patent Document 3. 6.04 g of the solid containing compound (1a-1) obtained in Comparative Example 1 and 8.44 g (5.9 mL) of chloroform were added to a 100 mL round-bottom flask, but no change was observed, and the dissolution of the solid could not be observed. In other words, it was confirmed that the recrystallization operation based on the description in Example 2 of Patent Document 3 could not be performed. Furthermore, an additional 75.85 g of chloroform was added (total 84.29 g), but the solid still did not dissolve. In an attempt to further increase the solubility, the solid-liquid mixture was heated and stirred in a water bath at 50-60°C for more than 2 hours, but the solid of compound (1a-1) still did not dissolve. Therefore, the solubility of compound (1a-1) in chloroform was measured, and the results were 0.6% by weight at 25°C, 1.2% by weight at 45°C, and 2.3% by weight at 60°C.

[0045] In light of the experimental procedure for recrystallization and the solubility measurement results of Comparative Example 2, it was concluded that the method described in Example 2 of Patent Document 3 cannot purify a solid containing compound (1a-1) by recrystallization. Although Patent Document 3 describes an example of a purification method for compound (1a-1) by recrystallization, it was concluded that there is still no practical purification method.

[0046] <Example 1> In a 500 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 29.5 g (76 mmol) of compound (2a-1), 20.2 g (229 mmol) of ethylene carbonate, 1.7 g (31 mmol) of potassium hydroxide, 1.3 g (4 mmol) of tetrabutylammonium bromide, and 150 g of toluene were charged. The mixture was heated to 110°C under a nitrogen atmosphere and stirred for 21 hours. The reaction solution after this reaction was measured by high-performance liquid chromatography, and the selectivity for compound (1a-1) was 87.3%. The reaction solution after the reaction was a slurry containing crystals of compound (1a-1). After the reaction was complete, in order to remove the remaining ethylene carbonate, 4.4 g (0.243 mol) of water was added to the reaction solution. Furthermore, a Dean-Stark tube was attached to the flask, and the internal temperature was heated to 110°C to hydrolyze the remaining ethylene carbonate. After cooling the reaction solution to room temperature, pure water (61.0 g) was added, and the crystals were recovered by filtration. The purity of the obtained compound (1a-1) crystals by liquid chromatography analysis was 91.3%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 62 mol%. Example 1 is a specific example in which a crystallization step is performed to obtain crystals as a reaction crystallization operation, in which the reaction and crystallization operations are carried out simultaneously.

[0047] <Example 2> In a 2 L four-necked flask equipped with a refluxer, stirrer, and thermometer, crystals of compound (1a-1) obtained in Example 1, methyl isobutyl ketone (641.9 g), water (117.5 g), and acetic acid (1.88 g, 0.031 mol) were added. The mixture was heated to 88°C and stirred under reflux to completely dissolve the crystals. After stirring for 1 hour, the potassium hydroxide remaining in the obtained crystals was neutralized, and the aqueous layer was separated. Water was added to the obtained oil layer and stirred, and the washing operation to separate the aqueous layer was repeated four times to remove the potassium acetate generated by neutralization. The oil layer was then filtered while hot at a temperature of 80°C. After filtration, the oil layer was heated to 90°C, then cooled, and when the liquid temperature was 70°C, heptane (214.0 g) was added and cooled to room temperature. By filtering off the precipitated crystals, pale yellow crystals of compound (1a-1) were obtained. １ ¹H-NMR analysis confirmed that the obtained crystals contained compound (1a-1). １¹H-NMR: 1.86 (t, 2H), 3.36–3.44 (m, 2H), 3.47–3.52 (m, 2H), 3.65–3.70 (m, 2H), 3.98–4.04 (m, 2H), 7.35–7.36 (m, 2H), 7.59–7.63 (m, 2H), 7.71–7.75 (m, 2H), 7.79–7.83 (m, 2H), 8.41–8.43 (dd, 2H), 8.80 (d, 2H), 8.86 (d, 2H). The yield of compound (1a-1) relative to the starting compound (2a-1) was 57 mol%. The purity of the obtained compound (1a-1) crystals measured by high-performance liquid chromatography was 96.6%. Differential scanning calorimetry analysis of the obtained compound (1a-1) crystals revealed that the crystals had an endothermic peak top temperature (melting point) of 249°C. Weight loss measured by a differential thermogravimetric analyzer was 0.1% at 249°C and 0.2% at 280°C, confirming that there was almost no weight loss near the melting point. The boiling points of both methyl isobutyl ketone (boiling point 116°C) and heptane (boiling point 98°C) used in crystallization are lower than the melting point of the obtained compound (1a-1) (249°C). Furthermore, as mentioned above, the obtained compound (1a-1) crystals showed almost no weight loss after melting, suggesting that they are not adduct crystals. The refractive index (nD2O) of compound (1a-1) measured by the above analytical method was 1.686. The resulting compound (1a-1) crystals contained 0.7 ppm of sodium, less than 0.1 ppm of potassium, 3.6 ppm of iron, and 0.11 ppm of copper, with a total content of 4.4 ppm for all metals. Table 1 shows the main diffraction peaks (those with a relative intensity greater than 5%) obtained by powder X-ray diffraction (PXRD) of the resulting compound (1a-1) crystals.

[0048]

[0049] <Example 3> In a 1 L four-necked flask equipped with a refluxer, stirrer, and thermometer, 123.7 g (0.32 mol) of compound (2a-1) (metal content: iron 2.4 ppm, copper 4.4 ppm, sodium 0.2 ppm, potassium 0.1 ppm), 84.5 g (0.96 mol) of ethylene carbonate, 7.2 g (0.13 mol) of potassium hydroxide, 5.2 g (0.009 mol) of tetrabutylammonium bromide, and 375.1 g of methyl isobutyl ketone were charged and dissolved. The flask was heated to 120°C under a nitrogen atmosphere and stirred for 6.5 hours. When the reaction solution after this reaction was measured by high-performance liquid chromatography, all of the starting compound (2a-1) was consumed, and the selectivity of compound (1a-1) was 86.0%. The reaction solution after the reaction was a slurry containing crystals. After the reaction was complete, 84.6 g (4.7 mol) of water and 13.0 g of 36% hydrochloric acid were added to the reaction mixture to remove the remaining ethylene carbonate and neutralize the remaining potassium hydroxide. The mixture was then heated under reflux for 1 hour to hydrolyze the remaining ethylene carbonate. After the reaction mixture was cooled to room temperature, it was filtered and the crystals were recovered. The purity of the obtained compound (1a-1) crystals, as determined by liquid chromatography, was 94.4%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 84 mol%.

[0050] <Example 4> In a 5 L four-necked flask equipped with a refluxer, stirrer, and thermometer, crystals of compound (1a-1) obtained in Example 3, methyl isobutyl ketone (2742.3 g), pure water (318.9 g), and 36% hydrochloric acid (6.4 g) were added. The mixture was heated to 88°C and stirred under reflux to completely dissolve the crystals. After stirring for 1 hour, the potassium hydroxide remaining in the obtained crystals was neutralized and the aqueous layer was separated. Pure water was added to the obtained oil layer and stirred, and the washing operation to separate the aqueous layer was repeated four times to remove the potassium chloride generated by neutralization. Then, hot filtration was performed at an oil layer temperature of 80°C. The filtered liquid was heated to 119°C, and the solvent (1850.6 g) was removed by distillation, with crystals precipitating during the process, and then cooled to room temperature. The precipitated crystals were filtered off to obtain pale yellow crystals of compound (1a-1). The yield of compound (1a-1) relative to the starting compound (2a-1) was 74 mol%. The purity of the obtained compound (1a-1) crystals measured by high-performance liquid chromatography was 98.1%. The endothermic peak top temperature (melting point) of the obtained compound (1a-1) crystals measured by differential scanning calorimetry was 248°C. The obtained compound (1a-1) crystals contained 0.3 ppm of sodium, less than 0.1 ppm of potassium, 0.02 ppm of iron, and 0.34 ppm of copper, with a total content of 0.66 ppm for each metal.

[0051] <Example 5> In a 100 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 15.0 g (0.039 mol) of compound (2a-1), 8.5 g (0.097 mol) of ethylene carbonate, 0.87 g (0.016 mol) of potassium hydroxide, 0.63 g (0.002 mol) of tetrabutylammonium bromide, and 47.5 g of methyl isobutyl ketone were charged and dissolved. The flask was heated to 118°C under a nitrogen atmosphere and stirred for 13 hours. The reaction solution after this reaction was measured by high-performance liquid chromatography, and the selectivity of compound (1a-1) was 86.1%. The reaction solution after the reaction was a slurry containing crystals. After the reaction was complete, in order to remove the remaining ethylene carbonate, 7.9 g (0.438 mol) of water and 1.6 g (0.016 mol) of concentrated hydrochloric acid were added to the reaction solution to neutralize the remaining potassium hydroxide. The liquid was then heated to 92°C to hydrolyze the remaining ethylene carbonate. After cooling the reaction solution to room temperature, it was filtered to recover the crystals of compound (1a-1). The purity of the obtained compound (1a-1) crystals, as determined by liquid chromatography, was 95.2%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 70.1 mol%. The average particle size of the obtained compound (1a-1) crystals, measured using a wet laser diffraction particle size distribution analyzer, was 103 μm.

[0052] <Example 6> In a 100 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 12.5 g of crystals of compound (1a-1) obtained in Example 5 (including the solvent used for filtration), 43.9 g of cyclohexanone, 25.1 g of pure water, and 0.6 g (0.0078 mol) of concentrated hydrochloric acid were added. The solution was heated to 84°C and stirred to completely dissolve the crystals. After stirring for 1 hour, the potassium hydroxide remaining in the obtained compound (1a-1) crystals was neutralized and the aqueous layer was separated. Water was added to the obtained oil layer and stirred, and the washing operation to separate the aqueous layer was repeated four times to remove the potassium chloride generated by neutralization. The solution was then cooled, and methyl isobutyl ketone (43.9 g) was added when the solution temperature was 60°C and cooled to room temperature. By filtering off the precipitated crystals, pale yellow crystals of compound (1a-1) were obtained. The purity of the obtained compound (1a-1) crystals, as measured by high-performance liquid chromatography, was 98.4%. The yield of compound (1a-1) relative to the starting compound (2a-1) used in Example 5 was 62.6 mol%. The average particle size in the volume-based cumulative particle size distribution of the obtained compound (1a-1) crystals, as measured using a wet laser diffraction particle size distribution analyzer, was 39 μm.

[0053] <Example 7> In a reaction vessel equipped with a refluxer, stirrer, and thermometer, 12 parts by weight of compound (2a-1) (metal content: iron 2.4 ppm, copper 3.8 ppm, sodium 1.3 ppm, potassium less than 0.1 ppm), 6.8 parts by weight of ethylene carbonate, 0.7 parts by weight of potassium hydroxide, 0.5 parts by weight of tetrabutylammonium bromide, and 33.8 parts by weight of methyl isobutyl ketone were charged and dissolved. The reaction vessel was heated to 118°C under a nitrogen atmosphere and stirred for 10 hours. When the reaction solution after this reaction was measured by high-performance liquid chromatography, the selectivity of compound (1a-1) was 92.3%. The reaction solution after the reaction was a slurry containing crystals. After the reaction was complete, 16.7 parts by weight of methyl isobutyl ketone were mixed in while maintaining the liquid temperature at 80°C. Then, 1.2 parts by weight of water was added to the reaction solution to remove the remaining ethylene carbonate, and 6.2 parts by weight of water and 0.8 parts by weight of acetic acid were mixed in to neutralize the remaining potassium hydroxide. After the reaction solution was cooled from 80°C to room temperature, the crystallized slurry was filtered. The filtered crystals were washed with methyl isobutyl ketone and water to recover the crystals of compound (1a-1). The solvent content of the recovered crystals was 7% by weight of water and 3% by weight of methyl isobutyl ketone. The purity of the obtained crystals of compound (1a-1) by liquid chromatography analysis was 96.1%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 91.8 mol%. The average particle size of the obtained compound (1a-1) crystals, measured using a wet laser diffraction particle size distribution analyzer, was 82 μm in the volume-based cumulative particle size distribution.

[0054] <Example 8> In a reactor equipped with a refluxer, stirrer, and thermometer, 5 parts by weight of the crystals of compound (1a-1) obtained in Example 7 (including the solvent used for filtration), 103.1 parts by weight of methyl isobutyl ketone, and 11.8 parts by weight of pure water were added. The mixture was heated to 85°C and stirred to completely dissolve the crystals. After stirring for 0.5 hours, the aqueous layer was separated. Water was added to the obtained oil layer and stirred, and the washing operation to separate the aqueous layer was repeated. Then, the mixture was heated to 115°C under atmospheric pressure and distilled at atmospheric pressure, distilling off the solvent containing 66.8 parts by weight of water. The mixture was then cooled to 25°C. Crystals were obtained by filtering off the precipitated crystals. The filtered crystals were heated to 75°C under reduced pressure and dried. The purity of the obtained crystals of compound (1a-1) measured by high-performance liquid chromatography was 98.4%. The yield of compound (1a-1) relative to the raw material compound (2a-1) used in Example 11 was 75.8 mol%. The hue of the obtained compound (1a-1) crystals when prepared as a 10 wt% cyclohexanone solution was APHA 30. The average particle size in the volume-based cumulative particle size distribution of the obtained compound (1a-1) crystals, measured using a wet laser diffraction particle size distribution analyzer, was 73 μm. The obtained compound (1a-1) crystals contained 0.04 wt% methyl isobutyl ketone and 0.05 wt% water. The obtained compound (1a-1) crystals contained less than 0.1 ppm of sodium, 1.5 ppm of potassium, 0.46 ppm of iron, and 0.24 ppm of copper, with a total content of 2.2 ppm for each metal.

[0055] <Example 9> 5.0 g (0.013 mol) of compound (2a-1), 2.9 g (0.032 mol) of ethylene carbonate, 0.29 g (0.0052 mol) of potassium hydroxide, 0.21 g (0.00065 mol) of tetrabutylammonium bromide, and 20.0 g of cyclohexanone were charged into a 100 mL test tube. The mixture was heated to 120°C under a nitrogen atmosphere and stirred for 6 hours. The reaction solution after this reaction was measured by high-performance liquid chromatography, and the selectivity of compound (1a-1) was 92.8%. The reaction solution after the reaction was a slurry containing crystals. After the reaction was complete, 7.5 g of cyclohexanone and, in order to remove the remaining ethylene carbonate, 2.9 g (0.15 mol) of water and 0.52 g (0.0052 mol) of concentrated hydrochloric acid were added to the reaction solution. The solution was then heated to 85°C to hydrolyze the remaining ethylene carbonate, and the aqueous layer was separated. Next, 6.5 g (0.013 mol) of 8% sodium hydroxide aqueous solution was added, and the solution was heated to 85°C for alkaline treatment. After that, the solution was allowed to stand at 85°C to separate the aqueous layer, neutralized with acid, and the washing operation was repeated by adding pure water to separate the aqueous layer. The solution was then cooled, and methyl isobutyl ketone was added when the solution temperature was 60°C, and the solution was cooled to room temperature. The precipitated crystals were recovered by filtration. The purity of the obtained compound (1a-1) crystals by liquid chromatography analysis was 98.7%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 53.0 mol%.

[0056] <Example 10> In a 300 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 25.0 g (0.065 mol) of compound (2a-1), 14.2 g (0.162 mol) of ethylene carbonate, 1.45 g (0.026 mol) of potassium hydroxide, 1.0 g (0.0032 mol) of tetrabutylammonium bromide, and 100.0 g of cyclohexanone were charged. The mixture was heated to 120°C under a nitrogen atmosphere and stirred for 5.5 hours. High-performance liquid chromatography analysis of the reaction solution after the reaction showed a selectivity of 93.4% for compound (1a-1). The reaction solution after the reaction was a slurry containing crystals. After the reaction was complete, 32.4 g of 8% sodium hydroxide aqueous solution was added, the liquid temperature was heated to 85°C, and the mixture was stirred for 1 hour for alkali treatment. 25.0 g of cyclohexanone and 25.0 g of water were mixed, stirring was stopped, and the mixture was allowed to stand at a temperature of 85°C. The mixture then separated into three layers from top to bottom: an oil layer, a slurry layer, and an aqueous layer. The lower aqueous layer was removed. After neutralization with acetic acid, 67.5 g of pure water was added, and the crystals in the intermediate slurry layer dissolved. The mixture was allowed to stand at 85°C to remove the aqueous layer, and the washing of the oil layer was repeated. The filtrate was then obtained by hot filtration using a Kiriyama funnel (filter paper No. 5C). To remove some of the cyclohexanone from the filtrate, the mixture was heated to 80°C and 9 kPa under reduced pressure and subjected to vacuum distillation. Afterward, 70.0 g of methyl isobutyl ketone was mixed in, and the mixture was cooled to room temperature, causing crystals to precipitate. The precipitated crystals were filtered off, and the crystals were washed with 25.0 g of methyl isobutyl ketone to recover the crystals of compound (1a-1). The purity of the obtained compound (1a-1) crystals, as measured by high-performance liquid chromatography, was 99.1%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 94.6 mol%. The color of the obtained compound (1a-1) crystals when prepared as a 10 wt% cyclohexanone solution was APHA290.

[0057] <Example 11> In a 300 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 25.0 g of crystals of compound (1a-1) obtained in Example 10 and 75.0 g of methyl isobutyl ketone were charged. The mixture was heated to 85°C under a nitrogen atmosphere and stirred in a slurry state for 1 hour. After that, it was cooled to 25°C, the crystals were filtered off, and the crystals were washed with 25.0 g of methyl isobutyl ketone to recover the crystals containing the solvent. The recovered crystals were dried under reduced pressure at 80°C to obtain powder of compound (1a-1). The purity of the obtained crystals of compound (1a-1) measured by high-performance liquid chromatography was 99.3%. The endothermic peak top temperature (melting point) of the obtained crystals of compound (1a-1) measured by differential scanning calorimetry was 248.6°C. The color of the obtained compound (1a-1) when its crystals were prepared as a 10% by weight cyclohexanone solution was APHA230. The obtained compound (1a-1) crystals contained 1.8 ppm of sodium, 0.4 ppm of potassium, 0.2 ppm of iron, and less than 0.01 ppm of copper, with a total content of 2.2 ppm for each metal.

[0058] <Example 12> In a 300 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 10.0 g (0.026 mol) of compound (2a-1), 5.7 g (0.065 mol) of ethylene carbonate, 0.58 g (0.01 mol) of potassium hydroxide, 0.42 g (0.001 mol) of tetrabutylammonium bromide, and 40.0 g of cyclohexanone were charged. The mixture was heated to 120°C under a nitrogen atmosphere and stirred for 5 hours. High-performance liquid chromatography analysis of the reaction solution after the reaction showed a selectivity of 93.1% for compound (1a-1). The reaction solution after the reaction was a slurry containing crystals. After the reaction was complete, 20.0 g of water was added to the reaction solution to remove the remaining ethylene carbonate. Then, 2.2 g of 48% sodium hydroxide aqueous solution was added, the solution was heated to 85°C, and stirred for 1 hour to perform alkali treatment. 5.0 g of methyl isobutyl ketone was mixed, stirring was stopped, and the mixture was allowed to stand at a temperature of 85°C. After separating the aqueous layer, the mixture was neutralized with acetic acid, and the washing operation was repeated by adding pure water and separating the aqueous layer. Then, the mixture was filtered hot using a Kiriyama funnel (filter paper No. 5C), and the filtrate was heated to 90°C to redissolve all the precipitated crystals. The solution was then cooled, and 68.5 g of methyl isobutyl ketone was mixed in the middle of the cooling process. When the mixture cooled to room temperature, crystals precipitated. The precipitated crystals were filtered off, washed with 20.0 g of methyl isobutyl ketone, and the crystals were recovered. The purity of the obtained compound (1a-1) crystals measured by high-performance liquid chromatography was 98.9%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 69.1 mol%. The color of the obtained compound (1a-1) when it was dissolved in a 10% by weight cyclohexanone solution was APHA270.

[0059] Examples of the present invention involve synthesizing compound (1a-1) through a reaction process using toluene as the reaction solvent in Example 1, and using methyl isobutyl ketone as the reaction solvent in Examples 3, 5, and 7, and performing a crystallization step to obtain crystals as a reaction crystallization operation, thereby precipitating crystals as the reaction progresses. The liquid containing the obtained crystals could be easily filtered even after neutralization and hydrolysis steps, and the filtered crystals could be easily broken down and obtained in an easy-to-handle powder form. Compared with the results of Comparative Example 1, in which compound (1a-1) was synthesized based on the description of Example 1 in Patent Document 3, it became clear that the crystals obtained by the method of the present invention are easy to implement in industrial production and are an efficient and stable method of production.

[0060] Examples 9, 10, and 12 are specific examples of the present invention in which compound (1a-1) was synthesized by carrying out a reaction step using cyclohexanone as the reaction solvent, and the obtained reaction solution was subjected to a water washing step and other post-treatment steps (hydrolysis step, neutralization step, and alkali treatment), followed by a crystallization step. Similar to Examples 1, 3, 5, and 7 described above, the liquid containing the obtained crystals could be easily filtered, and the filtered crystals were in an easily handled powder form that could be easily broken apart. Furthermore, based on the results of Example 11, in which the obtained crystals were re-slurry purified using methyl isobutyl ketone, it was possible to obtain crystals of compound (1a-1) with a significantly low metal content because a washing step was performed with water to remove water-soluble impurities before the crystallization step in Example 10.

[0061] Examples 2, 4, 6, and 8 are specific examples of the present invention, in which crystals of compound (1a-1) obtained in Examples 1, 3, 5, and 7 were used, and the crystallization process was carried out by recrystallization using cyclohexanone or methyl isobutyl ketone as the solvent for the crystallization process. Similar to Examples 1, 3, 5, and 7 described above, the liquid containing the obtained crystals could be easily filtered, and the filtered crystals were in an easily handled powder form that could be easily broken apart. Furthermore, because a washing step was performed with water to remove water-soluble impurities before the crystallization process, it was possible to obtain crystals of compound (1a-1) with a remarkably low metal content. Based on the results of Examples 2 and 8, it is clear that the crystals obtained by the method of the present invention are easy to handle crystals with low organic solvent and water content.

[0062] From the above, it has become clear that, according to the crystal production method of the present invention, dihydroxy compounds containing a biphenanthrene skeleton, such as compound (1a-1), can be obtained as crystals with excellent handling properties and reduced solvent content, and that purification by recrystallization is possible.

Claims

1. A method for producing crystals of a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), comprising a crystallization step of precipitating crystals of the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) from a crystallization solution containing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) and at least one organic solvent selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms and aliphatic ketone solvents having 5 to 9 carbon atoms. (In the formula, R １ Each independently represents an alkylene group with 2 to 4 carbon atoms, R ２ Each of these independently represents an alkyl group having 1 to 6 carbon atoms, an aryl group having 6 to 18 carbon atoms, or a halogen atom, and each of these independently represents 0 or an integer from 1 to 4.

2. The manufacturing method according to claim 1, wherein the aliphatic ketone solvent having 5 to 9 carbon atoms is at least one selected from methyl isobutyl ketone and cyclohexanone.

3. The manufacturing method according to claim 1, wherein the aromatic hydrocarbon organic solvent having 6 to 9 carbon atoms is at least one selected from benzene, toluene, orthoxylene, metaxylene, paraxylene, mixed xylene, and mesitylene.

4. The manufacturing method according to claim 1, wherein the crystallization solution is a crystallization solution that has undergone a washing step with water.

5. The manufacturing method according to claim 1, wherein the biphenanthrene skeleton-containing dihydroxy compound represented by the general formula (1a) is any of the biphenanthrene skeleton-containing dihydroxy compounds represented by chemical formulas (1a-1) to (1a-3).

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