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

Abstract

To provide a polycyclic aromatic compound having a hydroxyl group and a production method for the compound.SOLUTION: It was found that a compound represented by formula (1) can be produced by 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, R1a to R1d each independently represent 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).SELECTED DRAWING: None

Description

[Technical field]

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

[0002] Formula (3) below:

[0003] [ka] Polycyclic aromatic compounds represented by the formula (hereinafter, compounds represented by (general) formula (○) may be referred to as "compounds of formula (○)". Note that "○" represents the formula number.) have a highly extended π-conjugated structure, but have a band gap that graphene does not have, and are therefore expected to be applied to organic semiconductor devices and are also known to be useful as organic electroluminescent elements. As a method for producing such a compound of formula (3), for example, the method described in Patent Document 1 has been proposed. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2018-184393 A Summary of the Invention [Problem to be solved by the invention]

[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 attempting 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 the polycyclic aromatic compound. [Means for solving the problem]

[0007] As a result of intensive research by the present inventors to solve the above problems, it was found that the above 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] Formula (1) below:

[0009] [ka] A compound represented by the formula:

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

[0011] [ka] (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.) The method for producing the compound according to [1], comprising reacting a compound represented by the formula: Effect of the Invention

[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 an 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] In addition, the following formula (4):

[0014] [ka] Compounds represented by the formula (1) are known to be useful as organic scintillators (International Publication No. 2022 / 250087), and by using the compound of formula (1), it is possible to produce the compound of formula (4) in one step, for example, by methylation using dimethyl sulfate. [Brief description of the drawings]

[0015] [Figure 1] 1 is a mass spectrometry chart of the compound of formula (1). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[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 the 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 in the above general formula (2) 1a ~R 1d may be all the same, some may be the same, or all may be different. 1a ~R 1dIn the above, the alkyl group having 1 to 8 carbon atoms, which may have a substituent, may have a branched chain, and specific examples thereof include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isoamyl group, neopentyl group, 1-ethylpropyl group, 1-methylbutyl group, 2-methylbutyl group, n-hexyl group, isohexyl group, n-heptyl group, 1-methylhexyl group, and n-octyl group. These alkyl groups may be substituted with one or more halogen atoms, alkylthio groups, alkoxy groups, and the like. Examples of the cycloalkyl group having 3 to 8 carbon atoms, which may have a substituent, include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, and cyclooctyl group. 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] [ka] (In the formula, R 2a ~R 2h each independently represents an alkyl group having 1 to 6 carbon atoms.) The compound may be represented by the following formula:

[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 2hIn the formula, the alkyl group having 1 to 6 carbon atoms may have a branch, 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 have a branch is preferred.

[0021] <Method of producing compound of formula (2)> The compound of formula (2) can be reacted with a compound of the following general formula (5): in the presence of a palladium compound, o-chloranil and a silver compound.

[0022] [ka] (In the formula, R 3a and R 3b are the same or different and represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group. and a silole compound represented by the following general formula (6):

[0023] [ka] (In the formula, R 1a ~R 1d is as above) The compound can be produced by a method including a step of reacting a pyrene compound represented by the following formula:

[0024] R in the above general formula (5) 3a and R 3b The alkyl group having 1 to 4 carbon atoms in 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, from the viewpoint of ease of production of the compound of formula (5), a methyl group, an ethyl group, or a phenyl group is preferred, and R 3a and R 3bThese 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 are as described above. 1a and R 1b , R 1c and R 1d are linked together to form a ring, and have the following general formula (6-1):

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

[0027] The compound of formula (6) is usually used in an amount of 0.1 to 0.6 mol, preferably 0.3 to 0.5 mol, per 1 mol 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 palladium compounds that can be used include Pd(OH)2, Pd(OCOCH3)2, Pd2(dba)3, Pd(OCOCF3)2, Pd(acac)2, PdCl2, PdBr2, PdI2, Pd(NO3)2, and Pd(CH3CN)4(SbF6)2. Note that acac means acetylacetonate, and dba means dibenzylideneacetone. Among these palladium compounds, Pd(OCOCH3)2, Pd(OCOCF3)2, and Pd(acac)2 are preferred. These palladium compounds may be used alone or in combination of two or more kinds as necessary.

[0029] The amount of the palladium compound used is usually 0.01 to 0.5 mol, preferably 0.01 to 0.2 mol, per 1 mol of the compound of the 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); and inorganic silver compounds such as silver nitrate, silver fluoride, silver chloride, silver bromide, silver iodide, silver sulfate, silver oxide, silver sulfide, silver tetrafluoroborate (AgBF4), silver hexafluorophosphate (AgPF6), and silver hexafluoroantimonate (AgSbF6). Among these silver compounds, inorganic silver compounds are preferred, and silver tetrafluoroborate (AgBF4), silver hexafluorophosphate (AgPF6), and silver hexafluoroantimonate (AgSbF6) are more preferred. These silver compounds may be used alone or in combination of two or more as necessary. If no silver compound is used, the reaction does not proceed, or if it does proceed, the reaction rate is very slow.

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

[0033] The production of the compound of formula (2) can be carried out in a solvent as necessary. Examples of the solvent that can be used include aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and halogenated aromatic hydrocarbons. Examples of the aliphatic hydrocarbons include pentane, hexane, heptane, and cyclohexane. Examples of the halogenated aliphatic hydrocarbons include dichloromethane, dichloroethane, chloroform, carbon tetrachloride, and trichloroethylene. Examples of the halogenated aromatic hydrocarbons include monochlorobenzene, dichlorobenzene, bromobenzene, and 1,3,5-tribromobenzene. These solvents may be used alone or in combination of two or more as necessary. Among these solvents, halogenated aliphatic hydrocarbons or halogenated aromatic hydrocarbons are preferred. When a solvent is used, the amount of the solvent is, for example, 1 to 20 parts by mass, preferably 5 to 15 parts by mass, per 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 at 20 to 100° C. This reaction may be carried out under at least either anhydrous conditions or 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, recrystallization, etc.

[0036] <Method of producing compound of formula (1)> Examples of the base used in the production of 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 moles, preferably 4 to 7 moles, per mole of the compound of formula (2).

[0037] Hydrogen peroxide used in the production of 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% by weight, preferably 27 to 35% by weight. 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 as necessary. Examples of solvents that can be used include 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 of two or more as 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, and preferably 10 to 100 parts by mass, per part by mass of the compound of the formula (2).

[0039] The compound of formula (1) can be produced, for example, by adding hydrogen peroxide to a reaction mixture containing the compound of formula (2), a base, and a solvent as necessary, and reacting the compound of formula (2) with hydrogen peroxide. The temperature during the addition of the hydrogen peroxide and the reaction is usually 0 to 50° C., preferably 10 to 30° C. The 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, recrystallization, etc. EXAMPLES

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

[0042] [1] UPLC measurement Equipment: Waters Acquity UPLC H-Class Column: ACQUITY UPLC(R) BEH C18 1.7μm (2.1×100mm Column) Column temperature: 45 °C Detection wavelength: UV 254nm Mobile phase: Solution A = 0.1% formic acid aqueous solution, Solution B = 0.1% formic acid acetonitrile (The concentration of Solution B was changed as follows for analysis.) B liquid concentration: 50%→10min→100%(10min hold) ·Mobile phase flow rate: 0.3ml / min Sample injection volume: 1.0μL

[0043] [2] NMR measurement 1 H-NMR and 13 C-NMR was performed using a JEOL-ESC400 ( 1 H 400MHz, 13 The data was recorded using a C 100 MHz spectrometer. Each data item was recorded as follows:

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

[0045] [3] LC-MS measurement The target substance was identified by separation and mass spectrometry using LC-MS under the following measurement conditions.

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

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

[0048] [ka] A production example of a compound represented by the following formula:

[0049] Into a nitrogen-purged four-neck flask equipped with a stirrer and a condenser, was added the following compound (5-A):

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

[0051] [ka] A mixture of 10 g (22.0 mmol) of a pyrene compound represented by the following formula (I), 1.09 g (4.84 mmol) of palladium acetate (Pd(OCOCH3)), 1.66 g (4.84 mmol) of silver hexafluoroantimonate (AgSbF6), 28.2 g (114.5 mmol) of o-chloranil, and 234 g of 1,2-dichloroethane was added and heated to 30°C with stirring under a nitrogen stream, and then stirred at 30°C for 1 hour. After stirring, the reaction solution was filtered to remove insoluble matter, then concentrated under reduced pressure to remove 1,2-dichloroethane, and 100 g of heptane was added to the flask, heated to 80°C and stirred at the same temperature for 0.5 hours, then cooled to 25°C and filtered to separate the crystals. The crystals were then dried under reduced pressure and extracted to obtain 8.3 g of compound of formula (2-A) (50% apparent yield, 87% purity). The spectral values ​​of the compound of formula (2-A) obtained are shown below.

[0052] 1 H-NMR (CDCl3, 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 (CDCl3, 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 compound of formula (2-A) ([C 52 H 44 B2O4+H] + :755.34)

[0055] <Example 1> In a four-neck flask equipped with a nitrogen-substituted stirring device and a cooling tube, 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% hydrogen peroxide solution was added dropwise at 20 to 30 ° C. while stirring under a nitrogen stream, and after the completion of the dropwise addition, the mixture was stirred for 3 hours at 20 to 30 ° C. to obtain a reaction mixture. The reaction mixture obtained 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, and the aqueous layer was removed by a liquid 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, then cooled to 25°C to precipitate crystals, and stirred at the same temperature for 1 hour, after which the crystals were filtered off. The filtered crystals were then dried under reduced pressure to obtain 4.3 g of the compound of formula (1) (as-reduced yield 60%, purity 90%). The spectral values ​​of the obtained compound of formula (1) are shown below.

[0056] 1 H-NMR (THF-d8, 400MHz): δ = 7.641 - 7.73 ppm (8H, m), 8.46 ppm (4H, s), 8.82 - 8.86 ppm (4H, m), 8.96 - 8.98 ppm (4H, m)

[0057] 13 C-NMR (THF-d8, 100 MHz): δ = 114.06 ppm (C4), 120.37 ppm (C2), 124.47 ppm (C4), 127.20 ppm (C4), 127.44 ppm (C4), 128.87 ppm (C4), 129.07 ppm (C4), 129.76 ppm (C4), 130.64 ppm (C4), 131.90 ppm (C4), 155.77 ppm (C2)

[0058] Mass spectrometry value ([M + H] + ): 535.21 (Calculated molecular weight of the compound of formula (1) ([C 40 H 22 O2 + H] + : 535.17)

Claims

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

2. In the presence of a base, a compound represented by the following general formula (2): 【Chemistry 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.) A method for producing the compound according to claim 1, comprising reacting a compound represented by the following formula: with hydrogen peroxide.

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