JP2019014675A - Phenyl phenol derivative and method for producing dibenzofuran derivative using the same - Google Patents

Abstract

To provide a dibenzofuran production intermediate that makes it possible to obtain a dibenzofuran derivative conveniently and in high yields, and a method for producing dibenzofuran using the dibenzofuran production intermediate.SOLUTION: The present invention provides a dibenzofuran production intermediate compound represented by formula (i). The present invention provides a method for producing dibenzofuran that obtains a dibenzofuran derivative conveniently and in high yields by heating the compound represented by formula (i) for a reaction in the presence of a base.SELECTED DRAWING: None

Description

  The present invention relates to a novel compound useful for producing a liquid crystal composition and the like.

  A compound that exhibits a liquid crystal phase when used alone or as a mixture is particularly useful as a liquid crystal composition used in a liquid crystal display device or the like. As one kind of such a liquid crystal compound, a dibenzofuran derivative is known.

  Dibenzofuran derivatives are expected to be applied to a wide range of fields including liquid crystal composition applications due to their excellent properties. However, the present condition is that the method for manufacturing this compound simply and with a high yield is not yet established.

JP2015-174864 US9096795B2

  In the method described in Document 1, an expensive reagent such as CsF is required, so that the production cost is difficult, and a large number of reaction steps are required to obtain a desired compound. In the method described in Document 2, the yield is low, and no specific reaction conditions are described.

  On the other hand, this invention can implement | achieve obtaining a dibenzofuran derivative simply and with a high yield. That is, the present invention provides a phenylphenol derivative useful as a production intermediate of a dibenzofuran derivative and a production method for deriving a dibenzofuran derivative from the intermediate.

  The present inventors have found that a compound having a novel structural characteristic is useful as an intermediate for producing a dibenzofuran derivative, and has completed the present invention. That is, the present invention relates to the general formula (i)

(In the formula, X ⁱ¹ represents a halogen atom, X ⁱ² represents a hydrogen atom or an electron-withdrawing group, and R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , R ⁱ⁵ , R ⁱ⁶ and R ⁱ⁷ are independent of each other. Represents H or a substituent.
It is a compound represented by these.

  The compound of the present invention is useful for obtaining a dibenzofuran derivative simply and in high yield. In addition, according to the present invention, a highly polar dibenzofuran derivative particularly suitable for a liquid crystal composition for a liquid crystal display element can be easily produced.

<Compound represented by formula (i)>
In general formula (i), X ⁱ¹ is a fluorine atom from the viewpoint of easy elimination of the X ⁱ¹ group and the OH group, and lowering the electron density of the carbon atom substituted by the X ⁱ¹ group and improving the reactivity. Is preferred.

In the general formula (i), X ⁱ² represents a halogen atom, a nitro group, a cyano group, an aldehyde, a ketone, an ester, an amide, an imine, a sulfoxide, or a sulfone from the viewpoint of reducing the electron density of the substituted carbon atom of the X ⁱ¹ group. Of these, a halogen atom, a nitro group, and a cyano group are more preferable, and a halogen atom and a nitro group are more preferable.

In general formula (i), R ⁱ¹ preferably represents a halogen atom, more preferably a fluorine atom, from the viewpoint of lowering the electron density of the biphenyl moiety.

In the general formula (i), R ⁱ² and R ⁱ⁵ are a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 20 carbon atoms (one or non-adjacent two or more —CH in the alkyl group). _2- may be each independently substituted by —CH═CH—, —C≡C—, —O—, —CO—, —COO—, or —OCO—, or a hydrogen atom in an alkyl group May be substituted with a fluorine atom.), A hydroxyl group, and —B (OH) ₂ .

In at least one of R ⁱ² and R ⁱ⁵ , one or two or more non-adjacent —CH ₂ — in the group are each independently —CH═CH—, —C≡C—, —O—, —CO. It preferably represents an alkyl group having 1 to 8 carbon atoms which may be substituted by —, —COO— or —OCO—, and one or non-adjacent two or more —CH ₂ — in the group represents More preferably, each independently represents an alkyl group having 1 to 8 carbon atoms which may be substituted by -O-, -CO-, -COO- or -OCO-, more preferably an alkoxyl group, Particularly preferred is a group, an ethoxy group, an n-propoxy group, an n-butoxy group or an n-pentoxy group.

In the general formula (i), R ⁱ³ , R ⁱ⁴ , R ⁱ⁶ and R ⁱ⁷ preferably represent hydrogen.

  Among the compounds represented by the general formula (i), preferable specific compounds include compounds represented by the following formulas (i-1) to (i-135).

  Although the manufacturing method of the compound of this invention is not specifically limited, For example, it can manufacture by the following procedures.

  Compound (a) (100 mmol), imidazole (8.2 g, 120 mmol) and dichloromethane (100 mL) are mixed, and triethylsilyl chloride (18.1 g, 120 mmol) is added dropwise under ice cooling. The resulting reaction solution was stirred at room temperature for 1 hour, and water and dichloromethane were added for liquid separation, the aqueous layer was extracted with dichloromethane, and the combined organic layer was washed with water and saturated brine, and anhydrous sodium sulfate was added. In addition, dry. The solvent in the crude product is distilled off under reduced pressure, and then purified by silica gel column chromatography (silica gel 25 g, mobile phase: hexane) to quantitatively obtain the compound (b) as a liquid.

Under a nitrogen atmosphere, the compound (b) (38 mmol), dichlorobis [di-t-butyl (p-dimethylaminophenyl) phosphino] palladium (II) (1.3 g, 1.9 mmol), 2 mol / L aqueous potassium carbonate solution ( 42 mL, 84 mmol) and THF (50 mL) are mixed and heated to 60 ° C. Under heating, a solution of compound (c) (42 mmol) in THF (25 mL) is added dropwise and stirred at 60 ° C. for 1.5 hours. Next, the ice-cooled reaction mixture was added to a mixture of concentrated hydrochloric acid and ice and stirred for 1 hour. The aqueous layer is separated and extracted twice with toluene. The organic layers are combined, washed with saturated brine, and dried over anhydrous sodium sulfate. After the solvent in the crude product was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (silica gel 15 g, mobile phase: toluene), and then recrystallized from a toluene / hexane mixed solvent. Is obtained as a solid.
<Method for Producing Compound Represented by General Formula (ii)>
One embodiment of the present invention uses a compound represented by general formula (i) as a production intermediate.

(Wherein X ⁱ² , R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , R ⁱ⁵ , R ⁱ⁶ and R ⁱ⁷ are X ⁱ² , R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , It represents the same meaning as R ⁱ⁵ , R ^i6, and R ⁱ⁷ ).

  By using the compound of the present invention as a production intermediate, an ether bond can be generated in the compound by a simple method and derived into a dibenzofuran derivative. That is, an intramolecular cyclization reaction may be performed.

  According to the said manufacturing method, since a dibenzofuran derivative can be obtained with a high yield and a short process rather than the conventional manufacturing method, it is preferable.

  In the above elimination reaction, for example, the following conditions can be employed.

  It is preferable to react the compound represented by the general formula (i) by heating in the presence of a base.

  The yield can be confirmed by a conventional GC analysis.

  The compound represented by the general formula (i) may be used as a purified single compound, or may be used in a mixed state with a raw material for production such as phenols. In the latter case, a dibenzofuran derivative may be produced as a consistent continuous process from production raw materials such as phenols without undergoing an isolation process for the compound represented by formula (i).

  The base is low in nucleophilicity and needs to be basic enough to deprotonate a phenolic hydroxyl group, and is preferably an inorganic base, more preferably sodium hydride, cesium carbonate, or potassium carbonate.

  Heating is preferably performed under the following conditions. The temperature is preferably 60 ° C. or higher, more preferably 80 ° C. or higher, more preferably 100 ° C. or higher, and 200 ° C. or lower in terms of process simplicity. Preferably, it is 150 degrees C or less. However, it is not always necessary to keep the temperature constant during the reaction, and the temperature may be varied according to the progress of the reaction as long as it is within the above range. The heating time is preferably 1 hour or longer from the viewpoint of the yield of the product.

  Heating is preferably performed in the presence of a solvent from the viewpoint of reaction control. For example, it is preferable to dissolve or disperse the compound represented by the general formula (i) and the base in a solvent and to heat in a solution or dispersion state.

The solvent is not particularly limited, preferably has a boiling point of a compound of the above _{60 ℃, DMF, DMSO, CH} 3 CN, one or two or more selected from the group consisting of THF and NMP More preferably, it is used.

  The atmosphere in which the above reaction is performed is not particularly limited. However, when a reagent having high reactivity with oxygen and water is used, the reaction is preferably performed in an inert atmosphere such as nitrogen or argon.

The compound represented by the general formula (ii) obtained by the above production method or a mixture containing the compound can be purified by a conventional method.
<Compound represented by formula (ii)>
General formula (ii) which is the target compound of the production method of the present invention

(Wherein X ⁱ² , R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , R ⁱ⁵ , R ⁱ⁶ and R ⁱ⁷ are X ⁱ² , R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , The compound represented by R ⁱ⁵ , R ^i6, and R ⁱ⁷ has the same meaning), and the structure thereof is not limited at all. However, depending on the combination of groups represented by R ^{i1 to} R ⁱ⁷ in the general formula (ii), the effect of the production method of the present invention may be reduced. That is, depending on the combination of each group represented by R ^{i1 to} R ⁱ⁷ , there is a possibility that the reaction efficiency of the compound represented by the general formula (i) used as the production intermediate is inhibited.

In such a case, among the compounds represented by the general formula (i), after producing the compound represented by the general formula (ii) using any one of the above-mentioned preferred compound groups as a production intermediate, the compound is again produced. What is necessary is just to introduce | transduce 1 or 2 or more of each group represented by desired R ^<i1 > -R ^{< i7} > in it.

  The method for producing the compound of the general formula (ii) through these series of steps is naturally included in the scope of the production method of the present invention.

  Among the compounds represented by the general formula (ii), preferred specific compounds include compounds represented by the following formulas (ii-1) to (ii-125).

EXAMPLES The present invention will be described in further detail with reference to examples below, but the present invention is not limited to these examples. Further, “%” in the compositions of the following Examples and Comparative Examples means “% by mass”.
The following abbreviations are used below.
Me: methyl group Et: ethyl group iPr: isopropyl group Bu: butyl group Pent: pentyl group DMF: N, N-dimethylformamide DMSO: dimethyl sulfoxide NMP: N-methylpyrrolidone THF: tetrahydrofuran amphos: di-t-butyl (p -Dimethylaminophenyl) phosphine NFSI: N-fluorobenzenesulfonimide DMAP: N, N-dimethyl-4-aminopyridine Cr: crystal
Sm: Smectic phase Iso: Isotropic liquid (Example 1)

(1-1) 2-Chloro-6-fluorophenol (14.7 g, 100 mmol), imidazole (8.2 g, 120 mmol) and dichloromethane (100 mL) were mixed, and triethylsilyl chloride (18.1 g, 120 mmol) was added dropwise. The reaction solution is stirred at room temperature for 1 hour, and water and dichloromethane are added for liquid separation, the aqueous layer is extracted with dichloromethane, and the combined organic layer is washed with water and saturated brine, and dried over anhydrous sodium sulfate. did. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (silica gel 25 g, mobile phase: hexane) to quantitatively obtain 2-chloro-6-fluorophenoxytriethylsilane (27.1 g) as a colorless liquid. .

(1-2) Under a nitrogen atmosphere, 2-chloro-6-fluorophenoxytriethylsilane (10.0 g, 38 mmol), dichlorobis [di-t-butyl (p-dimethylaminophenyl) phosphino] palladium (II) (1. 3 g, 1.9 mmol), 2 mol / L aqueous potassium carbonate solution (42 mL, 84 mmol) and THF (50 mL) were mixed and heated to 60 ° C. Under heating, a solution of (4-ethoxy2,3-difluorophenyl) boronic acid (8.4 g, 42 mmol) in THF (25 mL) was added dropwise and stirred at 60 ° C. for 1.5 hours. The ice-cooled reaction mixture was added to a mixture of concentrated hydrochloric acid and ice and stirred for 1 hour. The aqueous layer was separated and extracted twice with toluene. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. After the solvent was distilled off under reduced pressure, purification was performed by silica gel column chromatography (silica gel 15 g, mobile phase: toluene), followed by recrystallization from a toluene / hexane mixed solvent to obtain 4′-ethoxy-2 ′, 3,3 ′. -Trifluoro- [1,1'-biphenyl] -2-ol (5.7 g, 56% yield) was obtained as an orange solid.
(Example 2)

(2-1) Under a nitrogen atmosphere, sodium hydride (60%, 2.6 g, 65 mmol) and DMF (50 mL) were mixed at room temperature, and 4′-ethoxy-2 ′, 3,3′-trifluoro was mixed there. A solution of [1,1′-biphenyl] -2-ol (14.5 g, 54 mmol) in DMF (100 mL) was added. After stopping the foaming, the inside of the reaction vessel was again purged with nitrogen by flow, gradually heated to 100 ° C. and stirred with heating for 5 hours. After allowing to cool, water and toluene were added for liquid separation, the aqueous layer was extracted with toluene, and the combined organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (silica gel 15 g, mobile phase: toluene), and then recrystallized from a mixed solvent of acetone / ethanol to give 3-ethoxy-4,6-difluorodibenzofuran (9 0.8 g, 73% yield) was obtained as a white solid.

(2-2) Under a nitrogen atmosphere, a 1.6 mol / L normal butyl lithium hexane solution (14 mL, 23 mmol) was added to a THF (50 mL) solution of 3-ethoxy-4,6-difluorodibenzofuran (4.7 g, 19 mmol). After dropping at −60 ° C. and stirring for 1 hour, trimethyl borate (2.6 g, 25 mmol) was added dropwise at −60 ° C. and stirred for 0.5 hour. The temperature was raised to room temperature, water and a saturated aqueous ammonium chloride solution were added, the aqueous layer was extracted with a toluene / THF mixed solvent, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained solid was suspended and washed three times with toluene to give (7-ethoxy-4,6-difluorodibenzofuran-3-yl) boronic acid (4.2 g, yield 76%). ) Was obtained as a white solid.

(2-3) Hydrogen peroxide solution (30% aqueous solution) at room temperature in a mixture of (7-ethoxy-4,6-difluorodibenzofuran-3-yl) boronic acid (4.2 g, 14 mmol) and THF (20 mL) 2.1 g, 18 mmol) was added dropwise, sodium hydrogen carbonate (36 mg, 0.4 mmol) was added, and the mixture was heated and stirred at 40 ° C. for 5 hours. Under ice-cooling, a 10% aqueous sodium sulfite solution and saturated brine were added, and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (silica gel 4 g, mobile phase: toluene / ethyl acetate = 1/1), and then suspended and washed with a toluene / hexane mixed solvent to obtain 7-ethoxy- 4,6-difluorodibenzofuran-3-ol (3.5 g, yield 98%) was obtained.

(2-4) 7-Ethoxy-4,6-difluorodibenzofuran-3-ol (3.0 g, 11 mmol), 1-iodopentane (2.5 g, 12.5 mmol), potassium carbonate (2. 4 g, 17 mmol), DMF (12 mL) was stirred at 40 ° C. for 5 h.
Water was added to the reaction solution cooled to room temperature, and the aqueous layer was extracted three times with toluene. The combined organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (silica gel 3.5 g, mobile phase: toluene / hexane = 1/1), and then recrystallized twice from acetone / ethanol to give 3-ethoxy- 4,6-Difluoro-7- (pentyloxy) dibenzo [b, d] furan (3.0 g, 81% yield) was obtained.
The phase transition temperature is Cr 56 Sm 61 Iso.
¹ H NMR: (CDCl ₃ , TMS internal standard) δ (ppm) = 0.94 (t, 3H, J = 7.2 Hz), 1.49 (m, 7H), 1.86 (m, 2H), 4.12 (t, 2H, J = 6.6 Hz), 4.22 (q, 2H, J = 7.2 Hz), 6.98 (dd, 2H, J = 8.4 Hz, 6.8 Hz), 7 .47 (d, 2H, J = 8.4 Hz)
[M]: 316
(Example 3)

(2-2) Sodium hydride (60%, 24 mg, 0.5 mmol), DMSO (1 mL), and 4′-ethoxy-2 ′, 3,3′-trifluoro- [1,1 ′ under a nitrogen atmosphere -Biphenyl] -2-ol (134 mg, 0.5 mmol) was mixed at room temperature, heated to 100 ° C., and heated and stirred for 9 hours. An organic layer diluted with toluene and washed with water was used as a sample and analyzed by GC. In the GC area ratio, the yield of 3-ethoxy-4,6-difluorodibenzofuran was 90%.
(Example 4)

(2-3) In a nitrogen atmosphere, potassium carbonate (138 mg, 1 mmol), NMP (1 mL), and 4′-ethoxy-2 ′, 3,3′-trifluoro- [1,1′-biphenyl] -2- All (134 mg, 0.5 mmol) was mixed at room temperature, heated to 100 ° C., and heated and stirred for 9 hours. An organic layer diluted with toluene and washed with water was used as a sample and analyzed by GC. In the GC area ratio, the yield of 3-ethoxy-4,6-difluorodibenzofuran was 90%.
(Comparative Example 1)
Following the method described in JP-A-2015-174864, difluorodibenzofuran was obtained by the following production method.
(Step 1 to Step 8)

  According to the method of Comparative Example 1, for example, 4 steps are required to obtain a difluorobenzofuran skeleton (step 4), and 8 steps are required to obtain a difluorobenzofuran compound having an alkoxy group at both ends (step 4). Up to 8).

  On the other hand, according to the method of the present invention, a desired compound, for example, a compound having a difluorobenzofuran skeleton can be obtained in one step ((2-1) of Example 2). Moreover, the difluoro benzofuran compound which has an alkoxy group in both terminal is obtained in 4 processes ((2-1)-(2-4) of Example 2). Even if the production method of the intermediate is added to the number of steps, for example, a difluorobenzofuran skeleton compound can be obtained in 3 steps, and a difluorobenzofuran compound having an alkoxy group at both ends can be obtained in 7 steps. Furthermore, in the method of Comparative Example 1, there are processes (Step 1 and Step 4) including a fluorination reaction, and the process involves toxicity and corrosion due to decomposition of a fluorinating agent such as NFSI (N-fluorobenzenesulfonimide). Highly dangerous hydrogen fluoride may be generated, and the danger is high. On the other hand, in the present invention, since there is no process (Step 1, Step 4) including a dangerous fluorination reaction, a desired dibenzofuran compound can be obtained more easily and safely.

Claims (7)

Formula (i)

(In the formula, X ⁱ¹ represents a halogen atom, X ⁱ² represents a hydrogen atom or an electron-withdrawing group, and R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , R ⁱ⁵ , R ⁱ⁶ and R ⁱ⁷ are independent of each other. Represents H or a substituent.
A compound represented by The compound according to claim 1, wherein in the general formula (i), X ⁱ² represents a halogen atom, a nitro group, a cyano group, an aldehyde, a ketone, an ester, an amide, an imine, a sulfoxide, or a sulfone. The compound according to claim 1 or 2, wherein in general formula (i), R ⁱ¹ represents a halogen atom or a hydrogen atom. In General Formula (i), at least one of R ⁱ² and R ⁱ⁵ represents an alkyl group having 1 to 8 carbon atoms, and one or non-adjacent two or more —CH ₂ — in the alkyl group are each independent. The compound according to any one of claims 1 to 3, which may be substituted by -CH = CH-, -C≡C-, -O-, -CO-, -COO- or -OCO-. . The compound according to any one of claims 1 to 4, wherein, in the general formula (i), R ⁱ³ , R ⁱ⁴ , R ⁱ⁶ and R ⁱ⁷ represent hydrogen. A compound represented by the general formula (i) according to any one of claims 1 to 5, wherein the compound represented by the general formula (ii) is used as a production intermediate.

(Wherein X ⁱ² , R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , R ⁱ⁵ , R ⁱ⁶ and R ⁱ⁷ are X ⁱ² , R ⁱ¹ , R ⁱ² , R ⁱ³ , R ⁱ⁴ , (It represents the same meaning as R ⁱ⁵ , R ⁱ⁶ and R ⁱ⁷ .)
The manufacturing method of the dibenzofuran derivative represented by these.   The production method according to claim 6, wherein the compound represented by the general formula (i) is reacted by heating in the presence of a base.