Method for producing biphenanthrene-skeleton-containing dihydroxy compound

Abstract

The present invention addresses the problem of providing a method for more efficiently and stably producing a biphenanthrene-skeleton-containing dihydroxy compound. As a solution, provided is a method for producing a biphenanthrene-skeleton-containing dihydroxy compound represented by general formula (1a), the method comprising a reaction step in which a biphenanthrol represented by general formula (2a) and a hydroxy alkyleneoxylating agent are reacted in the presence of a basic compound and a C5-9 aliphatic ketone solvent to obtain a reaction solution that contains a biphenanthrene-skeleton-containing dihydroxy compound represented by general formula (1a). (In the formula, each R1 independently represents a C2-4 alkylene group, each R2 independently represents a C1-6 alkyl group, a C6-18 aryl group, or a halogen atom, and each n independently represents an integer of 0 or 1-4.) (In the formula, R2 and n are defined in the same manner as in general formula (1a).)

Description

Method for producing dihydroxy compounds containing a biphenanthrene skeleton

[0001] The present invention relates to a method for producing a biphenanthrene skeleton-containing dihydroxy compound, and more specifically, to a method relating to a reaction step for synthesizing a biphenanthrene skeleton-containing dihydroxy compound.

[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 this way, there is concern that a manufacturing method for compound (1a-1) containing large amounts of bases and metals will cause similar problems as the metals contained in the raw material remain in compound (1a-1). 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 perform 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 became clear that the manufacturing method described in Patent Document 3 for producing compound (1a-1) has significant 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 of the present invention diligently investigated methods for producing biphenanthrene skeleton-containing dihydroxy compounds such as compound (1a-1). As a result, they discovered a method that allows for the production of the target compound with high reaction selectivity and production efficiency by carrying out the synthesis reaction under specific reaction conditions in the reaction step, thereby completing the present invention.

[0007] The present invention is as follows: 1. A method for producing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), comprising a reaction step of reacting biphenantrols represented by general formula (2a) and a hydroxyalkylene oxidizing agent in the presence of a basic compound to obtain a reaction solution containing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), wherein the reaction step is further carried out in the presence of an aliphatic ketone solvent 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. (In the formula, R ２, n is the same as the definition of general formula (1a). 2. The method for producing a product 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 product according to 1, wherein the hydroxyalkylene oxidizing agent is a carbonate represented by general formula (3). (In the formula, R １ (This is the same as the definition of general formula (1a).) 4. The method for producing the basic compound according to 1, wherein the basic compound is at least one selected from alkali metal carbonates, alkali metal hydroxides, and alkali metal bicarbonates. 5. The method for producing 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), and the biphenantrols represented by general formula (2a) are any of the biphenantrols represented by chemical formulas (2a-1) to (2a-3). 6. The manufacturing method according to 1, wherein the aliphatic ketone solvent having 5 to 9 carbon atoms is cyclohexanone, and the manufacturing method further comprises a post-treatment step including at least one of the following steps: a hydrolysis step of mixing water with the reaction solution obtained in the reaction step, a neutralization step of adding an acid to the reaction solution, and an alkali treatment step of mixing a basic compound with the reaction solution, and further comprises a crystallization step of precipitating crystals of a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) from the reaction solution after the post-treatment step. 7. The manufacturing method according to 1 or 6, wherein the reaction step further includes the use of a phase transfer catalyst. 8. The manufacturing method according to 6, wherein the post-treatment step further includes a washing step after at least one of the hydrolysis step, the neutralization step, and the alkali treatment step. [1] A method for producing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), comprising a reaction step of reacting biphenantrols represented by general formula (2a) with a hydroxyalkylene oxidizing agent in the presence of a basic compound to obtain a reaction solution containing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), wherein the reaction step is carried out in the presence of an aprotic organic solvent and a phase transfer catalyst. (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. (In the formula, R ２ (where n is the same as the definition of general formula (1a).) [2] The method for producing an organic solvent according to [1], wherein the aprotic organic solvent is at least one selected from aromatic hydrocarbon organic solvents having 6 to 9 carbon atoms, amide organic solvents, and aliphatic ketone solvents. [3] The method for producing an organic solvent according to [1], wherein the hydroxyalkylene oxidizing agent is a carbonate represented by general formula (3). (In the formula, R １(This is the same as the definition of general formula (1a).) [4] The method for producing the product according to [1], wherein the basic compound is an alkali metal hydroxide and the phase transfer catalyst is a quaternary ammonium salt. [5] The method for producing the product 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), and the biphenantrols represented by general formula (2a) are any of the biphenantrols represented by chemical formulas (2a-1) to (2a-3).

[0008] According to the manufacturing method of the present invention, the reactivity in the synthesis of biphenanthrene skeleton-containing dihydroxy compounds is improved, making it possible to efficiently produce biphenanthrene skeleton-containing dihydroxy compounds of higher purity.

[0009] The present invention provides a method for producing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) (hereinafter sometimes referred to as "dihydroxy compound (1a)"), comprising a reaction step of reacting a biphenantrol (represented by general formula (2a)) (hereinafter sometimes referred to as "biphenantrol (2a)") with a hydroxyalkylene oxidizing agent in the presence of a basic compound to obtain a reaction solution containing the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), wherein the reaction step is further carried out in the presence of an aliphatic ketone solvent having 5 to 9 carbon atoms (production method 1). According to the production method of the present invention, the reactivity in the synthesis of the biphenanthrene skeleton-containing dihydroxy compound is improved, and a biphenanthrene skeleton-containing dihydroxy compound of higher purity can be efficiently produced.

[0010] In the production method 1, among aliphatic ketone solvents having 5 to 9 carbon atoms, a reaction step is included in which the reaction is carried out in the presence of cyclohexane. Further, a post-treatment step including at least one of a hydrolysis step of mixing water with the reaction solution obtained in the reaction step, a neutralization step of adding an acid to the reaction solution, and an alkali treatment step of mixing a basic compound with the reaction solution is included. Then, a crystallization step of precipitating crystals of a dihydroxy compound containing a biphenanthrene skeleton represented by the general formula (1a) from the reaction solution after the post-treatment step is included. There is a production method characterized by this (Production method 2). According to the production method 2 of the present invention, the dihydroxy compound containing a biphenanthrene skeleton (dihydroxy compound (1a)) represented by the general formula (1a) has high reaction efficiency in the reaction step, and from the reaction step, subsequent post-treatment steps, purification steps, and crystallization steps can be carried out without changing the solvent. Therefore, industrial production can be carried out efficiently and stably.

[0011] In another aspect of the production method of the dihydroxy compound containing a biphenanthrene skeleton represented by the general formula (1a) of the present invention, biphenanthrols represented by the general formula (2a) and a hydroxyalkylene oxidizing agent are reacted in the presence of a basic compound to obtain a reaction solution containing a dihydroxy compound containing a biphenanthrene skeleton represented by the general formula (1a). There is a production method characterized in that in the reaction step, the reaction is further carried out in the presence of an aprotic organic solvent and a phase transfer catalyst (Production method 3). According to the production method 3 of the present invention, in the reaction step of synthesizing a dihydroxy compound containing a biphenanthrene skeleton, by using a basic compound and a phase transfer catalyst in the presence of an aprotic organic solvent, even if a reaction solvent of a type from which the target compound could not be obtained conventionally is used, the reactivity is improved. Therefore, the synthesis reaction of the dihydroxy compound containing a biphenanthrene skeleton can be carried out promptly and with a high reaction selectivity, and a high-purity dihydroxy compound containing a biphenanthrene skeleton can be produced. Hereinafter, Production methods 1 to 3 will be described in detail.

[0012] <Dihydroxy compound containing a biphenanthrene skeleton represented by the general formula (1a)> R in the general formula (1a) １Each independently represents an alkylene group having 2 to 4 carbon atoms. In particular, each is preferably independently a 1,2-ethylene group, a 1-methyl-1,2-ethylene group, or a 2-methyl-1,2-ethylene group, with 1,2-ethylene groups being especially preferred for both. R in general formula (1a) １ Two R's １ It is preferable that both substituents are the same. R in general formula (1a) 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. ２ If it 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. ２ If it 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. ２ Examples of halogen atoms in include chlorine, bromine, and iodine atoms, with bromine being preferred. ２ Each of these is preferably an alkyl group having 1 to 4 carbon atoms, a naphthyl group, a phenyl group, or a bromine atom, more preferably a methyl group, an ethyl group, a naphthyl group, a phenyl group, or a bromine atom, even more preferably a phenyl group, a naphthyl group, or a bromine atom, and particularly preferably a phenyl group or a bromine atom. In general formula (1a), n is each independently 0 or an integer from 1 to 4. Among these, each is preferably 0, 1, or 2, more preferably 0 or 1, and particularly preferably 0. Among the dihydroxy compounds (1a), the compounds represented by chemical formulas (1a-1) to (1a-3), which are preferred compounds, are shown below. Among these, compounds represented by chemical formula (1a-1) or chemical formula (1a-2) are more preferred, and 10,10'-bis(2-hydroxyethoxy)-9,9'-biphenanthryl (compound (1a-1)), which is the compound represented by chemical formula (1a-1), is particularly preferred.

[0013] <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 embodiments are also the same. Biphenantrols (2a) can be produced, for example, by the manufacturing method described in Japanese Patent Application 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 Application Publication No. 60-181043 and Journal of American Chemical Society, 2008, 130, 6840, etc. 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).

[0014] <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).

[0015] 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).

[0016] The reaction equation for the production method of the present invention, when carbonates (3) are used as the hydroxyalkylene oxidizing agent, is illustrated below. 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.

[0017] (Basic Compounds) Basic compounds used in production methods 1 to 3 of the present invention can be basic compounds commonly used in hydroxyalkoxylation reactions. Specifically, examples include 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 methoxysodium and sodium phenoxysodium. Examples of alkaline earth metal compounds include calcium hydroxide and barium hydroxide. Among these basic compounds, alkali metal compounds are preferred, at least one selected from alkali metal carbonates, alkali metal hydroxides, and alkali metal bicarbonates is 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. Specifically, 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.

[0018] (Reaction Solvent) In the reaction step of the manufacturing method 1 of the present invention, an aliphatic ketone solvent having 5 to 9 carbon atoms is used as the reaction solvent, and the reaction is carried out in its presence. The aliphatic ketone solvent used preferably has 6 to 9 carbon atoms, more preferably 6 to 8, even more preferably 6 or 7, and particularly preferably 6. Specific examples of aliphatic ketone solvents having 5 to 9 carbon atoms include 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). It is preferable to use at least one of these, more preferably at least one of methyl isobutyl ketone and cyclohexanone, even more preferably methyl isobutyl ketone or cyclohexanone, and particularly preferably cyclohexanone. There are no particular restrictions on the amount of aliphatic ketone solvent having 5 to 9 carbon atoms 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.

[0019] In the reaction step of the manufacturing method 2 of the present invention, cyclohexanone is used as the reaction solvent, and the reaction is carried out in its presence. There are no particular restrictions on the amount 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. Other solvents besides cyclohexanone solvent may be included as long as they do not hinder the effects of the present invention. Examples include aliphatic ketone solvents other than cyclohexanone such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, and acetonitrile, and aromatic hydrocarbon solvents such as toluene and xylene. In such cases, it is preferable to use cyclohexanone solvent in an amount of 50% by weight or more, more preferably 80% by weight or more, and even more preferably 90% by weight or more, based on the total amount of reaction solvent used. It is particularly preferable to use substantially only cyclohexanone as the reaction solvent.

[0020] In the reaction step of the manufacturing method 3 of the present invention, an aprotic organic solvent is used as the reaction solvent, and the reaction is carried out in its presence. Specifically, examples of such aprotic 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, and 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 at least one of diethyl ketone, cyclopentanone, methyl isobutyl ketone, cyclohexanone, methyl amyl ketone, cycloheptanone, methylhexyl ketone, and cyclooctanone, with 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.

[0021] (Phase Transfer Catalyst) In the reaction steps of production methods 1 and 2 of the present invention, it is preferable to further use a phase transfer catalyst and carry out the reaction in its presence. 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 above specific examples, with tetrabutylammonium bromide being particularly preferred. Specific examples of quaternary phosphonium salts include tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, and tetraphenylphosphonium bromide, and it is preferable to use at least one of these compounds. These phase transfer catalysts may be used individually or in combination of two or more types. The amount of this 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.

[0022] The manufacturing method 3 of the present invention uses a phase transfer catalyst in the reaction step. Specific examples and preferred embodiments of the phase transfer catalyst, as well as the amount of the phase transfer catalyst used and its preferred embodiments, are the same as those described in manufacturing methods 1 and 2 above. According to manufacturing method 3 of the present invention, by using a basic compound and a phase transfer catalyst in the reaction step for synthesizing a biphenanthrene skeleton-containing dihydroxy compound, reactivity is improved even when using a type of reaction solvent that conventionally could not yield the target compound. Therefore, the synthesis reaction of a biphenanthrene skeleton-containing dihydroxy compound can be carried out quickly and with high reaction selectivity, and a high-purity biphenanthrene skeleton-containing dihydroxy compound can be produced.

[0023] (Reaction Conditions) The reaction temperature in the reaction step of the production method 1 of the present invention 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 is 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, reaction 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 the generation of carbon dioxide gas stops can be used as an indicator of the end of the reaction.

[0024] In the case of the production method 2 of the present invention, where cyclohexanone is used as the reaction solvent, the temperature is in the range of 50 to 155°C, preferably 70 to 155°C, and more preferably 100 to 155°C. The reaction may also be carried out at a temperature at which the cyclohexanone solvent refluxes. The reaction time depends on the reaction temperature, the amount and type of biphenantrols (2a), hydroxyalkylene oxidizing agent, basic compound, reaction solvent, and phase transfer catalyst used, but is usually carried out for about 3 to 48 hours. When carbonates (3) are used as the hydroxyalkylene oxidizing agent, the point at which the generation of carbon dioxide gas stops can be used as an indicator of the end of the reaction.

[0025] In the reaction step of Production Method 3 of the present invention, the reaction temperature and reaction time are the same as those of Production Method 1 described above, and the preferred embodiments are also the same.

[0026] <Post-treatment step after the reaction step> The reaction solution obtained in the reaction step of the production method of the present invention can be subjected to a post-treatment step for isolating a biphenanthrene skeleton-containing dihydroxy compound represented by the general formula (1a). In Production Methods 1 and 3 of the present invention, as the post-treatment step described below, a neutralization step, a hydrolysis step, an alkali treatment step, and a washing step can be performed. A crystallization step can be performed using the reaction solution obtained in the reaction step or the reaction solution that has undergone the post-treatment step. In Production Method 2 of the present invention, a post-treatment step including at least one of the hydrolysis step, the neutralization step, and the alkali treatment step is performed on the reaction solution obtained in the above-described reaction step. The post-treatment step may include at least one of the hydrolysis step, the neutralization step, and the alkali treatment step. However, when carbonates (3) are used as the hydroxyalkylene oxidizing agent, it is preferable to include at least the hydrolysis step among these steps, and it is particularly preferable to include the hydrolysis step, the neutralization step, and the alkali treatment step. There is no limitation on the order of performing the hydrolysis step, the neutralization step, and the alkali treatment step, but it is preferable to perform them in the order of the hydrolysis step, the neutralization step, and the alkali treatment step. A washing step can further be performed in the post-treatment step. Production Method 2 of the present invention then includes a crystallization step of precipitating crystals of the biphenanthrene skeleton-containing dihydroxy compound represented by the general formula (1a) from the reaction solution that has undergone the post-treatment step.

[0027] <Neutralization step> In the reaction step of Production Methods 1 to 3 of the present invention, in order to neutralize the basic compound used, it is preferable to perform a neutralization step of adding acid-containing water (for example, hydrochloric acid, sulfuric acid), acetic acid, propionic acid, etc. to the obtained reaction solution. This neutralization step may be performed after the hydrolysis step described below.

[0028] <Hydrolysis Step> In the reaction steps of Production Methods 1 to 3 of the present invention, when carbonates (3) are used as the hydroxyalkylene oxidizing agent, an excessive amount of carbonates (3) is added, so carbonates (3) remain in the reaction solution even after the reaction ends. If a treatment such as heating is performed in this state, side reactions may proceed, and the purity and yield of the dihydroxy compound (1a) may decrease. Therefore, it is preferable to perform a hydrolysis step of mixing water with the obtained reaction solution to hydrolyze 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 may be below the boiling point of the reaction solution, but usually, it is 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 still 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.

[0029] <Alkali Treatment Step> In the reaction steps of Production Methods 1 to 3 of the present invention, when carbonates (3) are used as the hydroxyalkylene oxidizing agent, a by-product in which carbonates (3) are further added excessively is generated with respect to the dihydroxy compound (1a) produced in the reaction. In order to reduce this by-product, it is preferable to perform an alkali treatment by mixing a basic compound with the obtained reaction solution. In the alkali treatment step, the same type of basic compound as the basic compound used in the reaction step and, if necessary, water (which may be an aqueous solution of the basic compound) are mixed and used. In the alkali treatment step, sodium hydroxide or potassium hydroxide is preferable among the basic compounds. The amount of the basic compound used is usually 0.4 mol or more, preferably in the range of 0.4 to 20 mol, and more preferably in the range of 0.5 to 10 mol, per 1 mol of the dihydroxy compound (1a) in order to efficiently reduce the excess reactant.

[0030] <Washing Step> In manufacturing methods 1 to 3 of the present invention, if necessary, a washing step may be performed in which a solvent that dissolves the dihydroxy compound (1a) and separates it from water (for example, an aliphatic ketone solvent having 5 to 9 carbon atoms) is added or the solvent is replaced to obtain a solution of the dihydroxy compound (1a), and the solution is washed with water. In manufacturing methods 1 and 3, it is preferable to use an aliphatic ketone solvent having 5 to 9 carbon atoms as the solvent that dissolves the dihydroxy compound (1a) and separates it from water. In manufacturing method 2, cyclohexanone is used as the solvent. It is preferable to perform such a washing step, and it is even more preferable to perform the washing step after the neutralization step, hydrolysis step and alkali treatment step. The amount of water used in the washing process is not particularly limited, but is preferably in the range of 0.05 to 5.0 times the weight of the solution containing the dihydroxy compound (1a) and the solvent, 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 process is not particularly limited, as long as the dihydroxy compound (1a) dissolves and separates well from water, but is preferably in the range of 30 to 150°C, more preferably in the range of 40 to 140°C, even more preferably in the range of 60 to 130°C, and particularly preferably in the range of 70 to 120°C. The number of times the solution is washed with water in the washing process is not particularly limited, as long as water-soluble impurities can be sufficiently removed, and an appropriate number of times can be set, which may be once or multiple times. It is preferable to carry out the washing process so that the final composition containing the dihydroxy compound (1a) has a total content of 40 ppm or less of the metals sodium, potassium, iron, and copper, as described later. It is more preferable that the content of each metal be as described later. Since the manufacturing methods 1 and 2 of the present invention use aliphatic ketone solvents having 5 to 9 carbon atoms and cyclohexanone among them as reaction solvents, the reaction catalyst and excess reaction substrate can be decomposed, and water-soluble impurities and metals can be reduced by washing with water without changing the solvent from the reaction step.In particular, the second manufacturing method of the present invention uses cyclohexanone as the solvent, which has high solubility for the dihydroxy compound (1a) synthesized in the reaction step and separates from water. Therefore, this post-treatment step can be carried out without changing the type of solvent from that used in the reaction step. In these post-treatment steps, a portion of the cyclohexanone used during the reaction may be distilled off to reduce the amount, or cyclohexanone may be added to increase the amount. Alternatively, a solvent that dissolves the dihydroxy compound (1a) and separates from water may be mixed in to prevent precipitation of the dihydroxy compound (1a) produced in the reaction step. Thus, the ability to efficiently produce the dihydroxy compound (1a) in a higher quality and industrially feasible manner is another extremely useful aspect of the present invention.

[0031] <Separation Process> The reaction solution that has undergone the above post-treatment process can be separated by crystallization, filtration, distillation, column chromatography, etc., and then dried to obtain dihydroxy compound (1a). To further increase the purity, distillation, recrystallization, and purification by column chromatography may be performed according to conventional methods. Although there are no restrictions on the means applied in the separation process in manufacturing methods 1 and 3 of the present invention, it is preferable to perform a crystallization process. Although there are no restrictions on the means of the crystallization process, when performing the crystallization process, if an aliphatic ketone solvent having 5 to 9 carbon atoms is used as the crystallization solvent, the resulting crystals are easy to handle, such as being easy to filter, dry, and transport, and industrial production can be carried out efficiently. Since manufacturing method 1 of the present invention uses an aliphatic ketone solvent having 5 to 9 carbon atoms as the reaction solvent, it is possible to perform a separation process by crystallization to precipitate crystals of dihydroxy compound (1a) without changing the solvent from the reaction process, which is one of the effects of the present invention.

[0032] The second manufacturing method of the present invention includes a crystallization step as a separation step, in which crystals of the dihydroxy compound (1a) are precipitated from the reaction solution that has undergone the post-treatment step. The reaction solution that has undergone the post-treatment step and contains the dihydroxy compound (1a) handled in the crystallization step is a solution containing cyclohexanone as a solvent. When precipitating crystals from such a solution, the amount of cyclohexanone relative to the amount of dihydroxy compound (1a) may be adjusted by pre-distilling or adding cyclohexanone as necessary, in light of the solubility of the dihydroxy compound (1a). Furthermore, if a solvent other than cyclohexanone was used in the reaction step or post-treatment step, part or all of it may be pre-distilled as necessary. As for methods of precipitating the crystals, cooling crystallization, poor solvent addition crystallization, and solvent distillation crystallization methods 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 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, the poor solvent refers to a solvent in which the solubility of the dihydroxy compound (1a) is lower than that of cyclohexanone, and crystals are precipitated by reducing the solubility through mixing with the poor solvent. Examples of poor solvents include solvents other than cyclohexanone, such as aliphatic ketone solvents other than cyclohexanone, such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; lower alcohol solvents such as methanol, ethanol, isopropanol, and 1-butanol; aromatic hydrocarbon solvents such as toluene and xylene; and aliphatic hydrocarbon solvents such as pentane, hexane, heptane, and octane. Solvent distillation crystallization is a method of precipitating crystals by distilling off cyclohexanone and other solvents contained in the crystallization solution. These crystallization methods may be carried out not by using only one method, but by combining multiple methods. For example, there are methods of crystallization by cooling crystallization and poor solvent addition crystallization, methods of crystallization by solvent distillation crystallization and cooling crystallization, and methods that combine cooling crystallization, poor solvent addition crystallization, and solvent distillation crystallization.As for the method of precipitating the crystals, a crystallization method by cooling crystallization or a crystallization method by cooling crystallization and crystallization with the addition of a poor solvent is preferred among these. The crystals of dihydroxy compound (1a) obtained by the above crystallization step are filtered off, washed with a solvent if necessary, and dried in a drying step in which the adhering solvent is evaporated to dry the crystals, thereby obtaining dihydroxy compound (1a). The crystals of dihydroxy compound (1a) obtained by the production method 2 of the present invention are easy to handle, such as being easy to filter, dry, and transport, and one of the effects of the present invention is that it 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.

[0033] <Dihydroxy compound (1a) obtained by the production method 2 of the present invention> The dihydroxy compound (1a) obtained by the production method 2 of the present invention is a composition containing the dihydroxy compound (1a), and can be obtained in crystalline form, which is very useful because it has excellent handling properties and a reduced solvent content. Specifically, the production method 2 of the present invention can be used to obtain a composition containing the dihydroxy compound (1a) having a cyclohexanone content of 3.0% by weight or less and a water content of 1.0% by weight or less. The cyclohexanone content 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 numerical values ​​for the cyclohexanone content and water content can be treated as the values ​​obtained by rounding the quantitative analysis result of the content to the second decimal place, and it is preferable that the values ​​fall within the above range. Furthermore, these numerical ranges can be arbitrarily combined. The composition containing the dihydroxy compound (1a) obtained by the production method 2 of the present invention is further preferably such that the hue of a cyclohexanone solution with a concentration of 10% by weight is APHA 400 or less. The APHA value of such 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 solution can be treated as the value obtained by rounding the hue analysis result to the ones place, and it is preferable that the values ​​fall within the above range.

[0034] The dihydroxy compound (1a) obtained by the production method 2 of the present invention is preferable because, in addition to the post-treatment step, a further washing step with water can be included to remove water-soluble impurities contained in the dihydroxy compound (1a) or its solution. This washing step can reduce metals such as basic compounds used in the reaction step and post-treatment step, salts produced in the neutralization step, and metal impurities originating from the raw materials used, and this reduction is one of the useful effects of the present invention. The dihydroxy compound (1a) obtained thereby can be obtained as a composition containing dihydroxy compound (1a) with a low metal content. The composition containing dihydroxy compound (1a) obtained by the production method 2 of the present invention preferably has a total content of 40 ppm or less of each metal: sodium, potassium, iron, and copper; 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 content of these substances is preferably as low as possible, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more. The sodium content of the composition 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 content of this substance is preferably as low as possible, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more. The potassium content of the composition 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 content of this substance is preferably as low as possible, there is no lower limit, but it may be 0.001 ppm or more, or 0.01 ppm or more.The iron content of the composition 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. The copper content of the composition 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. An example of an analytical method for the metal content contained in a composition containing a dihydroxy compound (1a) is the method described in the examples below. In manufacturing methods 1 and 3, it is preferable that the total content of sodium, potassium, iron, and copper, and the individual content of each of these metals, of the composition containing the dihydroxy compound (1a) obtained by performing a post-treatment step using the reaction solution obtained in the reaction step, and then performing a crystallization step using the reaction solution that has undergone the post-treatment step, are similarly within the above range.

[0035] The reason why dihydroxy compound (1a) compositions contain sodium and potassium is due to the use of basic compounds containing sodium and potassium, such as potassium carbonate, during the reaction, and the use of basic compounds containing sodium and potassium, such as sodium hydroxide, added during the alkali treatment after the reaction. The reason why dihydroxy compound (1a) compositions contain iron and copper is that biphenantrols (2a), such as compound (2a-1) used as a raw material, have conventionally used compounds containing metals such as copper and iron during their manufacture, and these are contained in biphenantrols (2a), and may remain present even after the production of dihydroxy compound (1a) without being removed. It has become clear that conventionally known methods for synthesizing dihydroxy compound (1a) have the problem of the product containing a large amount of metal. However, the composition containing dihydroxy compound (1a) obtained by the production method 2 of the present invention can solve this problem and is therefore very useful.

[0036] The composition containing the dihydroxy compound (1a) obtained by the manufacturing method 2 of the present invention preferably has an average particle size in the volume-based cumulative particle size distribution measured using a wet laser diffraction particle size distribution analyzer in the range of 20 to 150 μm. The lower limit of such average particle size is more preferably 30 μm or more, and even more preferably 80 μm or more. The upper limit of such average particle size is more preferably 130 μm or less, and even more preferably 110 μm or less. Similarly, the average particle size of the composition containing the dihydroxy compound (1a) obtained by performing a post-treatment step using the reaction solution obtained in the reaction step, and then performing a crystallization step using the reaction solution that has undergone the post-treatment step, is also preferably within the above range.

[0037] The purity of the composition containing the dihydroxy compound (1a) obtained by the production method 2 of the present invention is preferably such that the ratio of the peak area of ​​the dihydroxy compound (1a) to the peak area of ​​all components detected at a wavelength of 280 nm in high-performance liquid chromatography (HPLC) analysis is 90.0% or more, more preferably 93.0% or more, even more preferably 95.0% or more, even more preferably 98.0% or more, and particularly preferably 99.0% or more. The method for HPLC analysis of the purity of the composition containing the dihydroxy compound (1a) is the same as the HPLC analysis method in the examples described later. Similarly, the purity of the composition containing the dihydroxy compound (1a) obtained by performing a post-treatment step using the reaction solution obtained in the reaction step, and then performing a crystallization step using the reaction solution that has undergone the post-treatment step, is also preferably within the above range.

[0038] 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

[0039] 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

[0040] 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.

[0041] 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.

[0042] 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)

[0043] 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

[0044] 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.

[0045] <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.

[0046] The compound (1a-1) obtained in Comparative Example 1 above had low purity due to residual raw materials, by-products resulting from the excessive reaction of ethylene carbonate, and other impurities. Furthermore, the hue value of 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).

[0047] <Comparative Example 2> Using the solid of 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 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 (the ratio of the amount of solid used to the amount of chloroform used was 7.2% by weight). 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.

[0048] 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 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.

[0049] <Comparative Example 3> 6.9 g (18 mmol) of compound (2a-1), 4.8 g (54 mmol) of ethylene carbonate, 0.06 g (0.9 mmol) of potassium hydroxide, and 22.6 g of toluene were charged into a test tube and heated to 117°C under a nitrogen atmosphere. Four hours after the start of the reaction, 0.14 g (2.1 mmol) of potassium hydroxide was added. The mixture was stirred for a further 44 hours while maintaining the temperature of 117°C (total 48 hours). When the reaction solution after this reaction was measured by high-performance liquid chromatography, the selectivity of compound (1a-1) was 35.5%.

[0050] <Comparative Example 4> 1.5 g (4 mmol) of compound (2a-1), 1.0 g (12 mmol) of ethylene carbonate, 0.08 g (1.6 mmol) of potassium hydroxide, and 6.8 g of dimethylformamide were charged into a test tube and heated to 153°C under a nitrogen atmosphere, and stirred for 3.5 hours. The reaction solution was measured by high-performance liquid chromatography after 1 hour and 3.5 hours of stirring, and the selectivity for compound (1a-1) was 82.0% and 65.5%, respectively.

[0051] Comparative Example 3 is an experimental example of a hydroxyethoxylation reaction to synthesize compound (1a-1) using toluene as the reaction solvent. The reaction was carried out for a total of 48 hours, but the reaction selectivity for compound (1a-1) was 35.5%, which was remarkably low, similar to the description in Patent Document 1. Comparative Example 4 is an experimental example using dimethylformamide, which is described in Patent Document 1 as a preferred solvent to use during the reaction. Dimethylformamide is a solvent with a high boiling point, so the temperature can be raised to increase the reaction rate, and the reaction selectivity for compound (1a-1) when used as a solvent is high. However, dimethylformamide is known to decompose slowly at high temperatures of 100°C or higher, releasing dimethylamine. At even higher temperatures, decomposition is accelerated, and in industrial production, there is a risk of a rapid increase in pressure inside the apparatus due to the release of dimethylamine, and it is necessary to take more stringent measures against odor caused by the strong pungent odor of dimethylamine, which presents significant difficulties.

[0052] <Experimental Example 1, Manufacturing Method 3> 1.6 g (4 mmol) of compound (2a-1), 1.0 g (12 mmol) of ethylene carbonate, 0.08 g (1.6 mmol) of potassium hydroxide, 0.03 g (0.08 mmol) of tetrabutylammonium bromide, and 6.8 g of toluene were charged into a test tube. The mixture was heated to 117°C under a nitrogen atmosphere and stirred for 27 hours. The reaction solution was then analyzed by high-performance liquid chromatography, and the selectivity for compound (1a-1) was 87%. After the reaction was complete, 0.17 g of pure water was added to the reaction solution to remove the remaining ethylene carbonate, and 0.11 g of acetic acid was added to neutralize the remaining potassium hydroxide. After the solution was cooled from 117°C to room temperature, the solution containing the solid was filtered, and the solid was recovered. The purity of the obtained solid compound (1a-1) by liquid chromatography analysis was 95.7%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 74.8 mol%.

[0053] <Experimental Example 2, Manufacturing Method 3> In a 500 mL four-necked flask equipped with a reflux condenser, 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 using 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 mixture to room temperature, water (61.0 g) was added, and the mixture was filtered to recover the crystals. The purity of the obtained compound (1a-1) crystals, as determined by liquid chromatography, was 91.3%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 62 mol%.

[0054] <Experimental Example 3, Manufacturing Method 3> 1.5 g (4 mmol) of compound (2a-1), 1.1 g (12 mmol) of ethylene carbonate, 0.07 g (1.6 mmol) of potassium hydroxide, 0.03 g (0.08 mmol) of tetrabutylammonium bromide, and 6.9 g of dimethylformamide (DMF) were charged into a test tube and dissolved. The solution was heated to 117°C and stirred for 3 hours. The reaction solution after this reaction was analyzed by high-performance liquid chromatography, and the selectivity of compound (1a-1) was 85%. After the reaction was complete, 0.14 g of water was added to the reaction solution to remove the remaining ethylene carbonate, and 0.15 g of acetic acid was added to neutralize the remaining potassium hydroxide. After the solution was cooled to room temperature, the solution containing the solid was filtered, and the solid precipitated and was recovered. The purity of the obtained compound (1a-1) solid by liquid chromatography analysis was 82.9%. The yield of compound (1a-1) relative to the starting compound (2a-1) was 67.9 mol%.

[0055] <Example 1, Manufacturing Method 1> 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, and 47.5 g of methyl isobutyl ketone were charged into a 100 mL four-necked flask equipped with a refluxer, stirrer, and thermometer. The mixture was heated to 118°C under a nitrogen atmosphere and stirred for 4 hours. The reaction solution after this reaction was analyzed by high-performance liquid chromatography, and the selectivity for compound (1a-1) was 35%.

[0056] <Example 2, Manufacturing Method 1, Manufacturing Method 3> 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 into a 1 L four-necked flask equipped with a refluxer, stirrer, and thermometer, and dissolved. The flask was heated to 120°C under a nitrogen atmosphere and stirred for 6.5 hours. The reaction solution after this reaction was measured by high-performance liquid chromatography, and it was found that 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%.

[0057] <Reference Example 1> In a 5 L four-necked flask equipped with a refluxer, stirrer, and thermometer, crystals of compound (1a-1) obtained in Example 2, methyl isobutyl ketone (2742.3 g), 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. Water was added to the obtained aqueous 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 a 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 solid was filtered off to obtain pale yellow crystals of compound (1a-1). The yield of the raw material compound (2a-1) used in Example 2 was 74 mol%. The purity of the obtained compound (1a-1) crystals by liquid chromatography analysis was 98.1%. The endothermic peak top temperature (melting point) of the obtained compound (1a-1) crystals by differential scanning calorimetry analysis 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.

[0058] <Example 3, Manufacturing Method 1, Manufacturing Method 3> 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 into a 100 mL four-necked flask equipped with a refluxer, stirrer, and thermometer, 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.

[0059] <Reference Example 2> 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 3 (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. 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. 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 3 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.

[0060] <Example 4, Manufacturing Method 1, Manufacturing Method 3> 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.

[0061] <Reference Example 3> In a reactor equipped with a refluxer, stirrer, and thermometer, 5 parts by weight of the crystals of compound (1a-1) obtained in Example 4 (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 compound (1a-1) crystals 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 4 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.

[0062] <Example 5, Manufacturing Method 2, Manufacturing Method 3> 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%.

[0063] <Example 6, Manufacturing Method 2, Manufacturing Method 3> 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. The reaction solution was analyzed by high-performance liquid chromatography, and the selectivity for compound (1a-1) was 93.4%. 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 to perform 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. This resulted in the separation of the mixture into three layers: 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 solid 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.

[0064] <Reference Example 4> 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 6 and 75.0 g of methyl isobutyl ketone were charged and 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 hue of the obtained crystals of compound (1a-1) when prepared as a 10 wt% cyclohexanone solution was APHA230. The resulting 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.

[0065] <Example 7, Manufacturing Method 2, Manufacturing Method 3> 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 of the precipitated solid. 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.

[0066] Example 1 is an experimental example using methyl isobutyl ketone, an aliphatic ketone, as the reaction solvent. In Example 1, the reaction time was 4 hours and the reaction selectivity was 35%. Compared to Comparative Example 3, it was clear that the same level of reaction selectivity was achieved significantly faster despite the shorter reaction time. By selecting a specific reaction solvent, industrial manufacturing can be carried out more efficiently, stably, and with greater consideration for safety.

[0067] Examples 1-3 and 2-7 are experimental examples concerning the synthesis of compound (1a-1) in the hydroxyalkylene oxidization reaction using tetrabutylammonium bromide (TBAB) and varying the type of reaction solvent. Examples 2-7, which used aliphatic ketone solvents with 5-9 carbon atoms, showed that compound (1a-1) could be synthesized with a shorter reaction time and higher reaction selectivity compared to Examples 1 and 2, which used toluene. It was also revealed that the purity and yield of the isolated compound (1a-1) were higher, indicating a more efficient production method. Furthermore, although the reaction time of Examples 2-4, which used methyl isobutyl ketone, was slightly longer than that of Example 3, which used dimethylformamide, Examples 2 and 3 had comparable reaction selectivity, while Example 4 showed higher reaction selectivity. In addition, although the reaction time of Examples 5-7, which used cyclohexanone, was slightly longer than that of Example 3, which used dimethylformamide, it showed higher reaction selectivity. Furthermore, while the purity of the isolated compound (1a-1) was only 82.9% in Experimental Example 3, which used dimethylformamide, the purity was high in all of Examples 2 to 7, demonstrating that high-purity compound (1a-1) can be produced more efficiently.

[0068] In Experimental Example 3, dimethylformamide is a solvent that does not separate from water, so it was necessary to perform the crystallization step without separation, and it became clear that even if the solid was separated by crystallization, the purity of the solid would be low. Furthermore, in Experimental Example 2, which used toluene as the reaction solvent, and Examples 2 and 3, which used MIBK as the reaction solvent, solid precipitated in the reaction solution after the synthesis of compound (1a-1) in the reaction step, so it was clear that post-treatment had to be performed without being able to obtain a homogeneous solution, and the crystallization step had to be performed without being able to separate and remove the unnecessary aqueous phase from the oil phase. On the other hand, in Examples 5 to 7, which used cyclohexanone as the reaction solvent, it was clear that the selectivity of compound (1a-1) improved in the post-reaction step. Furthermore, it became clear that after the synthesis reaction of compound (1a-1) was completed, compound (1a-1) was dissolved in cyclohexanone, and since it is a solvent that can separate from water, it was possible to perform hydrolysis, neutralization, alkali treatment, washing, and crystallization steps directly. Furthermore, it was found that the crystals obtained in the crystallization process exhibit favorable handling and liquid extraction properties when filtered from the crystallization solution, and the filtered crystals become a powder, yielding a highly pure compound (1a-1) that is easy to handle. The fact that the various steps in the manufacturing method of the present invention can be carried out using cyclohexanone solvent is due to the inventors' various studies, which revealed that cyclohexanone readily dissolves the biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), has significantly higher solubility compared to other aliphatic ketone solvents such as toluene, acetone, and methyl isobutyl ketone, and solvents such as 1-butanol, is separable from water, and exhibits a large change in solubility with temperature, which is an extremely remarkable effect. From the above, it has become clear that using cyclohexanone as a reaction solvent streamlines the manufacturing process of the target compound.

[0069] In the production of hydroxy compounds (1a), when reacting biphenantrols (2a) with a hydroxyalkylene oxidizing agent, compared to Comparative Examples 1-4 and Example 1, which used only basic compounds, Experimental Examples 1-3 and Examples 2-7, which used basic compounds and a phase-transfer catalyst, showed improved reactivity even in organic solvents such as toluene, where the target compound could not be obtained conventionally. As a result, the synthesis reaction of dihydroxy compounds (1a) could be carried out rapidly and with high selectivity, and it became clear that high-purity dihydroxy compounds (1a) could be produced.

Claims

1. A method for producing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), comprising a reaction step of reacting biphenantrols represented by general formula (2a) with a hydroxyalkylene oxidizing agent in the presence of a basic compound to obtain a reaction solution containing a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a), wherein the reaction step is further carried out in the presence of an aliphatic ketone solvent 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. (In the formula, R ２ (where n is the same as the definition in general formula (1a).) 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 hydroxyalkylene oxidizing agent is a carbonate represented by general formula (3). (In the formula, R １ This is the same as the definition in general formula (1a).

4. The manufacturing method according to claim 1, wherein the basic compound is at least one selected from alkali metal carbonates, alkali metal hydroxides, and alkali metal bicarbonates.

5. The manufacturing method according to claim 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), and the biphenantrols represented by general formula (2a) are any of the biphenantrols represented by chemical formulas (2a-1) to (2a-3).

6. The manufacturing method according to claim 1, wherein the aliphatic ketone solvent having 5 to 9 carbon atoms is cyclohexanone, and the method includes a post-treatment step comprising at least one of the following steps: a hydrolysis step of mixing water with the reaction solution obtained in the reaction step, a neutralization step of adding an acid to the reaction solution, and an alkali treatment step of mixing a basic compound with the reaction solution, and further includes a crystallization step of precipitating crystals of a biphenanthrene skeleton-containing dihydroxy compound represented by general formula (1a) from the reaction solution after the post-treatment step.

7. The manufacturing method according to claim 1 or 6, wherein a phase transfer catalyst is further used in the reaction step.

8. The manufacturing method according to claim 6, wherein the post-treatment step further includes a washing step after at least one of the hydrolysis step, neutralization step and alkali treatment step.

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