Polycyclic aromatic compound having hydroxyl group and production method for said compound

Abstract

It was found that a compound represented by formula (1) can be produced via a production method in which a boron-containing polycyclic aromatic compound represented by general formula (2) and hydrogen peroxide are reacted in the presence of a base. (In the formula, each of R1a to R1d independently represents a 1-8C alkyl group which may have a substituent, a 3-8C cycloalkyl group which may have a substituent, a phenyl group, or a 7-15C aralkyl group which may have a substituent. Additionally, R1a and R1b may be integrated forming a ring, and R1c and R1d may be integrated forming a ring.)

Description

Polycyclic aromatic compound having a hydroxyl group and method for producing the compound

[0001] The present invention relates to a polycyclic aromatic compound having a hydroxyl group and a method for producing the same.

[0002] The following formula (3):

[0003] Polycyclic aromatic compounds represented by the formula (3) (hereinafter, compounds represented by (general) formula (○) may be referred to as "formula (○) compounds", where "○" represents the formula number) have a highly extended π-conjugated structure but possess a band gap not found in graphene, and are therefore expected to be applicable to organic semiconductor devices and are also known to be useful as organic electroluminescent devices. Patent Document 1, for example, has proposed a method for producing such compounds of formula (3).

[0004] Japanese Patent Application Laid-Open No. 2018-184393

[0005] However, the production method described in Patent Document 1 is a method for producing the compound of formula (3) by an intramolecular cyclization reaction using a large amount of iron chloride, and when an attempt is made to produce a polycyclic aromatic compound having a structure in which a substituent has been introduced into the compound of formula (3) by this method, the substituent that can be introduced may be limited.

[0006] An object of the present invention is to provide a polycyclic aromatic compound having a structure in which a hydroxyl group is introduced into the compound of formula (3), in order to further develop polycyclic aromatic compounds.

[0007] As a result of extensive research conducted by the present inventors to solve the above-mentioned problems, they have found that the above-mentioned problems can be solved by reacting a boron-containing polycyclic aromatic compound represented by the general formula (2) described below with hydrogen peroxide in the presence of a base. Specifically, the present invention includes the following inventions.

[0008] [1] The following formula (1):

[0009] A compound represented by the formula:

[0010] [2] In the presence of a base, a compound represented by the following general formula (2):

[0011] (In the formula, R１ａ ~R １ｄ each independently represents an alkyl group having 1 to 8 carbon atoms which may have a substituent, a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, a phenyl group, or an aralkyl group having 7 to 15 carbon atoms which may have a substituent. １ａ and R １ｂ may be joined together to form a ring, and R １ｃ and R １ｄ may be joined together to form a ring) with hydrogen peroxide.

[0012] According to the present invention, it is possible to provide a polycyclic aromatic compound having a hydroxyl group represented by the above formula (1). In addition, since the compound of formula (1) has a hydroxyl group, it has improved affinity with water and alcohol and may be more easily introduced into a living body, and therefore, it is expected to be applied to, for example, a biomarker.

[0013] Furthermore, the following formula (4):

[0014] is known to be useful as an organic scintillator (WO 2022 / 250087), and if the compound of formula (1) is used, the compound of formula (4) can be produced in one step by methylation using, for example, dimethyl sulfate.

[0015] 1 is a mass spectrometry chart of the compound of formula (1).

[0016] In the present invention, when a range is expressed as "A to B", it means A or more and B or less, unless otherwise specified.

[0017] The compound of formula (1) of the present invention can be produced by reacting a compound of formula (2) with hydrogen peroxide in the presence of a base. First, the compound of formula (2) and a method for producing the compound will be described in detail.

[0018] <Regarding the compound of formula (2)> R １ａ ~R １ｄ may be all the same, some may be the same, or all may be different. １ａ ~R１ｄ In the formula (I), the alkyl group having 1 to 8 carbon atoms, which may have a substituent, may be branched, and specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isoamyl group, a neopentyl group, a 1-ethylpropyl group, a 1-methylbutyl group, a 2-methylbutyl group, an n-hexyl group, an isohexyl group, an n-heptyl group, a 1-methylhexyl group, an n-octyl group, and the like. These alkyl groups may be substituted with one or more halogen atoms, alkylthio groups, alkoxy groups, and the like. Examples of cycloalkyl groups having 3 to 8 carbon atoms, which may have a substituent, include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclooctyl group. Furthermore, these cycloalkyl groups may be substituted with one or more alkyl groups having 1 to 4 carbon atoms. Examples of the aralkyl group having 7 to 15 carbon atoms, which may have a substituent, include a benzyl group, a 1-phenylethyl group, and a 1-phenylpropyl group. These aralkyl groups may be substituted on the aromatic ring with one or more alkyl groups having 1 to 8 carbon atoms, alkoxy groups having 1 to 6 carbon atoms, etc. １ａ and R １ｂ may be joined together to form a ring, and R １ｃ and R １ｄ may be joined together to form a ring, and may be represented by the following general formula (2-1):

[0019] (In the formula, R ２ａ ~R ２ｈ each independently represents an alkyl group having 1 to 6 carbon atoms.

[0020] R in the above general formula (2-1) ２ａ ~R ２ｈ may be all the same, some may be the same, or all may be different, but it is preferable that all are the same. ２ａ ~R ２ｈThe alkyl group having 1 to 6 carbon atoms in the formula (I) may be branched, and specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isoamyl group, a neopentyl group, a 1-ethylpropyl group, a 1-methylbutyl group, a 2-methylbutyl group, an n-hexyl group, an isohexyl group, etc. Among these alkyl groups having 1 to 6 carbon atoms, an alkyl group having 1 to 4 carbon atoms which may be branched is preferred.

[0021] <Method for producing compound of formula (2)> The compound of formula (2) can be produced by reacting a compound of the following general formula (5):

[0022] (In the formula, R ３ａ and R ３ｂ and are the same or different and represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group.

[0023] (In the formula, R １ａ ~R １ｄ The compound can be produced by a method including a step of reacting a pyrene compound represented by the formula (I) with a pyrene compound represented by the formula (I)

[0024] R in the above general formula (5) ３ａ and R ３ｂ The alkyl group having 1 to 4 carbon atoms in R may be branched, and specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group. Among these substituents, a methyl group, an ethyl group, or a phenyl group is preferred from the viewpoint of ease of production of the compound of formula (5). ３ａ and R ３ｂ These silole compounds may be used alone or in combination of two or more kinds, if necessary.

[0025] The substituent R in the above general formula (6) １ａ ~R １ｄ Specific embodiments of R are as described above. １ａ and R １ｂ , R１ｃ and R １ｄ are bonded together to form a ring, and have the following general formula (6-1):

[0026] (In the formula, R ２ａ ~R ２ｈ These pyrene compounds may be used alone or in combination of two or more, if necessary.

[0027] The compound of formula (6) is usually used in an amount of 0.1 to 0.6 moles, preferably 0.3 to 0.5 moles, per mole of the compound of formula (5).

[0028] As the palladium compound used in the production of the compound of formula (2), various palladium compounds known as catalysts for organic synthesis can be used. Examples of the palladium compound that can be used include Pd(OH) ２ , Pd(OCOCH ３ ) ２ , Pd ２ (dba) ３ , Pd(OCOCF ３ ) ２ , Pd(acac) ２ , PdCl ２ , PdBr ２ , PdI ２ , Pd(NO ３ ) ２ , Pd(CH ３ CN) ４ (SbF ６ ) ２ In addition, acac means acetylacetonate, and dba means dibenzylideneacetone. Among these palladium compounds, Pd(OCOCH ３ ) ２ , Pd(OCOCF ３ ) ２ and Pd(acac) ２ These palladium compounds may be used alone or in combination of two or more, if necessary.

[0029] The amount of the palladium compound used is usually 0.01 to 0.5 moles, preferably 0.01 to 0.2 moles, per mole of the compound of formula (5).

[0030] The amount of o-chloranil used in the production of the compound of formula (2) is usually 1 to 5 moles, preferably 1.5 to 3 moles, per mole of the compound of formula (5).

[0031] Examples of silver compounds used in the production of the compound of formula (2) include organic silver compounds such as silver acetate, silver pivalate (AgOPiv), silver trifluoromethanesulfonate (AgOTf), and silver benzoate (AgOCOPh); silver nitrate, silver fluoride, silver chloride, silver bromide, silver iodide, silver sulfate, silver oxide, silver sulfide, and silver tetrafluoroborate (AgBF ４ ), silver hexafluorophosphate (AgPF ６ ), silver hexafluoroantimonate (AgSbF ６ Among these silver compounds, inorganic silver compounds are preferred, and silver tetrafluoroborate (AgBF ４ ), silver hexafluorophosphate (AgPF ６ ) and silver hexafluoroantimonate (AgSbF ６ ) is more preferred. These silver compounds may be used alone or in combination of two or more, if necessary. If a silver compound is not used, the reaction will not proceed, or even if it does proceed, the reaction rate will be very slow.

[0032] The amount of the silver compound used is usually 0.1 to 3.0 moles, preferably 0.2 to 1.5 moles, more preferably 0.5 to 1.2 moles per mole of the palladium compound.

[0033] The production of the compound of Formula (2) can be carried out in a solvent, if necessary. Usable solvents include, for example, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and halogenated aromatic hydrocarbons. Examples of aliphatic hydrocarbons include pentane, hexane, heptane, and cyclohexane. Examples of halogenated aliphatic hydrocarbons include dichloromethane, dichloroethane, chloroform, carbon tetrachloride, and trichloroethylene. Examples of halogenated aromatic hydrocarbons include monochlorobenzene, dichlorobenzene, bromobenzene, and 1,3,5-tribromobenzene. These solvents may be used alone or in combination with two or more types, if necessary. Among these solvents, halogenated aliphatic hydrocarbons or halogenated aromatic hydrocarbons are preferred. When a solvent is used, the amount used is, for example, 1 to 20 parts by mass, preferably 5 to 15 parts by mass, per 1 part by mass of the compound of Formula (5).

[0034] The reaction of the compound of formula (5) with the compound of formula (6) can be carried out, for example, at 10 to 150° C., preferably 20 to 100° C. This reaction may be carried out under at least one of anhydrous conditions and an inert gas (nitrogen gas, argon gas, etc.) atmosphere.

[0035] After completion of the reaction, the compound of formula (2) can be isolated by a conventional method such as concentration, crystallization, filtration, drying, etc. If necessary, the compound of formula (2) obtained may be purified by a conventional purification procedure such as adsorption, steam distillation, or recrystallization.

[0036] <Method for producing compound of formula (1)> Examples of the base used in producing the compound of formula (1) include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and lithium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and barium hydroxide; and alkali metal carbonates such as sodium carbonate and potassium carbonate. Among these bases, alkali metal hydroxides are preferred, and sodium hydroxide is particularly preferred. The amount of the base used is, for example, 1 to 10 mol, preferably 4 to 7 mol, per 1 mol of the compound of formula (2).

[0037] The hydrogen peroxide used in producing the compound of formula (1) is usually used as aqueous hydrogen peroxide. The concentration of hydrogen peroxide contained in the aqueous hydrogen peroxide is, for example, 27 to 50 wt %, preferably 27 to 35 wt %. The amount of hydrogen peroxide used is, for example, 1 to 10 mol, preferably 4 to 7 mol, per mol of the compound of formula (2).

[0038] The production of the compound of formula (1) can be carried out in a solvent, if necessary. Usable solvents include, for example, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, halogenated aromatic hydrocarbons, and ethers. Examples of aliphatic hydrocarbons include pentane, hexane, heptane, and cyclohexane. Examples of halogenated aliphatic hydrocarbons include dichloromethane, dichloroethane, chloroform, carbon tetrachloride, and trichloroethylene. Examples of halogenated aromatic hydrocarbons include monochlorobenzene, dichlorobenzene, bromobenzene, and 1,3,5-tribromobenzene. Examples of aromatic hydrocarbons include benzene, toluene, and xylene. Examples of ethers include cyclic ethers such as tetrahydrofuran and 4-methyltetrahydropyran, and cycloalkyl alkyl ethers such as cyclopentyl methyl ether. These solvents may be used alone or in combination, if necessary. Among these solvents, ethers are preferred, and cyclic ethers and cycloalkyl alkyl ethers are more preferred. When a solvent is used, the amount used is, for example, 1 to 300 parts by mass, preferably 10 to 100 parts by mass, per part by mass of the compound of formula (2).

[0039] The compound of formula (1) can be produced, for example, by adding aqueous hydrogen peroxide to a reaction mixture containing the compound of formula (2), a base, and, if necessary, a solvent, and reacting the compound of formula (2) with hydrogen peroxide. The temperature during the addition of the aqueous hydrogen peroxide and the reaction is usually 0 to 50°C, preferably 10 to 30°C. The aqueous hydrogen peroxide may be added all at once, continuously, or intermittently (so-called dropwise).

[0040] After completion of the reaction, the compound of formula (1) can be isolated by a conventional method such as concentration, crystallization, filtration, drying, etc. If necessary, the compound of formula (1) obtained may be purified by a conventional purification procedure such as adsorption, steam distillation, or recrystallization.

[0041] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. The purity in the following examples is an area percentage value measured by HPLC under the following conditions.

[0042] [1] UPLC Measurement Apparatus: Waters Acquity UPLC H-Class Column: ACQUITY UPLC® BEH C18 1.7 μm (2.1 × 100 mm Column) Column temperature: 45° C. Detection wavelength: UV 254 nm Mobile phase: Solution A = 0.1% formic acid aqueous solution, Solution B = 0.1% formic acid acetonitrile (Note: Analysis was performed by changing the concentration of Solution B as follows.) Solution B concentration: 50% → 10 min → 100% (10 min hold) Mobile phase flow rate: 0.3 ml / min Sample injection volume: 1.0 μL

[0043] [2] NMR measurement １ H-NMR and １３ C-NMR was performed using deuterated chloroform (CDCl ３ ) or deuterated tetrahydrofuran (THF-d ８ ) using JEOL-ESC400 ( １ H 400MHz, １３ The data was recorded using a C 100 MHz spectrometer. Each data item was described as follows:

[0044] Chemical shift, multiplicity (s=singlet, m=multiplet) and integration.

[0045] [3] LC-MS Measurement LC-MS was used to separate and analyze the mass under the following measurement conditions, and the target substance was identified.

[0046] Apparatus: Acquity UPLC H-Class PLUS + PDA / SQD2 system manufactured by Waters Column: ACQUITY UPLC® BEH C18 1.7 μm (2.1 × 100 mm Column) Column temperature: 45°C Detection wavelength: UV 254 nm Mobile phase: Solution A = 10 mM ammonium acetate aqueous solution, Solution B = acetonitrile, Solution C = 2-isopropanol (Note: Analysis was performed by changing the concentration of Solution B as follows.) Solution B concentration: 40% → 10 min → 90% (10 min hold) Solution C concentration: 10% Mobile phase flow rate: 0.4 ml / min Detection method: Q-MS Ionization method: ESI method Ion Source: Voltage (+) 30 V, temperature 150°C Capillary: 3.50 kV APCI probe Temp: 500°C Corona: 0.3 μA Desolvation Gas: Temperature 500°C, gas flow 350 L / h

[0047] <Production Example 1> The following formula (2-A):

[0048] An example of the production of a compound represented by the formula:

[0049] In a nitrogen-purged four-neck flask equipped with a stirrer and a condenser, a solution of the following formula (5-A):

[0050] 12.5 g (57.2 mmol) of a silole compound represented by the following formula (6-A):

[0051] 10 g (22.0 mmol) of a pyrene compound represented by the formula (I) ３ )) 1.09 g (4.84 mmol), silver hexafluoroantimonate (AgSbF ６1.66 g (4.84 mmol) of o-chloranil, 28.2 g (114.5 mmol), and 1,2-dichloroethane (234 g) were added, and the mixture was heated to 30°C while stirring under a nitrogen stream, and stirred at 30°C for 1 hour. After stirring was completed, the reaction mixture was filtered to remove insoluble matter and then concentrated under reduced pressure to remove 1,2-dichloroethane. 100 g of heptane was added to the flask, and the mixture was heated to 80°C and stirred at the same temperature for 0.5 hours. The mixture was then cooled to 25°C and the crystals were filtered off. The crystals were then dried under reduced pressure and isolated, yielding 8.3 g of compound of formula (2-A) (50% apparent yield, 87% purity). The spectral values ​​of the resulting compound of formula (2-A) are shown below.

[0052] １ H-NMR (CDCl ３ , 400MHz): δ = 1.41ppm (24H, s), 7.74-7.77ppm (8H, m), 8.77-8.80ppm (4H, m), 8.92-8.94ppm (4H, m), 9.41ppm (4H, s)

[0053] １３ C-NMR (CDCl ３ , 100MHz): δ = 24.99ppm (C8), 84.13ppm (C4), 123.59ppm (C4), 126.28ppm (C2), 126.69ppm (C4), 126.77ppm (C4), 127.21 ppm (C2), 128.03ppm (C4), 128.95ppm (C4), 129.00ppm (C4), 129.69ppm (C4), 131.16ppm (C4), 132.19ppm (C4)

[0054] Mass spectrometry value ([M+H] ＋ ): 755.41 (calculated molecular weight of the compound of formula (2-A) ([C ５２ H ４４ B ２ O ４ + H] ＋ : 755.34)

[0055] Example 1 To a nitrogen-purged four-neck flask equipped with a stirrer and a condenser, 10 g (13.3 mmol) of the compound of formula (2-A), 3.2 g (79.5 mmol) of sodium hydroxide, and 663 g of 4-methyltetrahydropyran were added, and then 7.72 g (79.5 mmol) of 35% aqueous hydrogen peroxide was added dropwise at 20 to 30° C. with stirring under a nitrogen stream. After completion of the dropwise addition, the mixture was stirred for an additional 3 hours at 20 to 30° C. to obtain a reaction mixture. The resulting reaction mixture was neutralized with 30.6 g (85.0 mmol) of a 10% aqueous hydrochloric acid solution, and 132 g (1.32 mmol) of 4-methyltetrahydropyran was added and stirred for a while, after which the aqueous layer was removed by a separation operation. After removing insoluble matter from the remaining organic layer by filtration, 4-methyltetrahydropyran was removed under reduced pressure to obtain a concentrate. 100 g of heptane was added to the obtained concentrate, and the mixture was stirred at 80°C for 0.5 hours and then cooled to 25°C to precipitate crystals. After stirring at the same temperature for 1 hour, the crystals were separated by filtration. The separated crystals were then dried under reduced pressure to obtain 4.3 g of the compound of formula (1) (as-obtained yield 60%, purity 90%). The spectral values ​​of the obtained compound of formula (1) are shown below.

[0056] １ H-NMR (THF-d ８ , 400MHz): δ = 7.641-7.73ppm (8H, m), 8.46ppm (4H, s), 8.82-8.86ppm (4H, m), 8.96-8.98ppm (4H, m)

[0057] １３ C-NMR (THF-d ８ , 100MHz): δ=114.06ppm (C4), 120.37ppm (C2), 124.47ppm (C4), 127.20ppm (C4), 127.44ppm (C4), 128.8 7ppm (C4), 129.07ppm (C4), 129.76ppm (C4), 130.64ppm (C4), 131.90ppm (C4), 155.77ppm (C2)

[0058] Mass spectrometry value ([M+H] ＋ ): 535.21 (calculated molecular weight of the compound of formula (1) ([C ４０ H ２２ O ２ + H]＋ ：５３５．１７）

Claims

1. The following formula (1): A compound represented by the formula:

2. In the presence of a base, a compound represented by the following general formula (2): (In the formula, R １ａ ~R １ｄ each independently represents an alkyl group having 1 to 8 carbon atoms which may have a substituent, a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, a phenyl group, or an aralkyl group having 7 to 15 carbon atoms which may have a substituent. １ａ and R １ｂ may be joined together to form a ring, R １ｃ and R １ｄ may be joined together to form a ring) with hydrogen peroxide.

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