JP4983009B2 - Method for producing difluorobenzene derivative - Google Patents

Description

The present invention relates to a method for producing a difluorobenzene derivative.

  Liquid crystal display elements are currently widely used because of their excellent features such as low voltage operation and thin display. Conventional liquid crystal display element display methods include TN (twisted nematic), STN (super twisted nematic), or active matrix (TFT: thin film transistor) based on TN, and these have positive dielectric anisotropy values. The liquid crystal composition is used. However, one of the disadvantages of these display methods is a narrow viewing angle, and with the increasing demand for larger liquid crystal panels in recent years, the improvement has become a major issue.

  In recent years, display methods such as vertical alignment and IPS (in-plane switching) have been newly put to practical use as a solution. The vertical alignment method is a method in which the viewing angle is improved by utilizing the vertical alignment of liquid crystal molecules, and a liquid crystal composition having a negative dielectric anisotropy value is used. IPS is a method of improving viewing angle by switching liquid crystal molecules using a horizontal electric field in the horizontal direction with respect to a glass substrate, and a liquid crystal composition having a positive or negative dielectric anisotropy value is used. Is done. As described above, the vertical alignment method and the IPS, which are effective display methods for improving the viewing angle, require a liquid crystal compound and a liquid crystal composition having a negative dielectric anisotropy value. It has become.

  Examples of the liquid crystal compound used in the liquid crystal composition having a negative dielectric anisotropy include 2,3-difluorobenzene derivatives (see Patent Document 1). However, Patent Document 1 discloses only a compound having an alkyl group in the side chain, and does not disclose any compound having an alkenyl group in the side chain, and the production method has not been known. In addition, the development of a method for producing the compound has progressed due to the knowledge that a compound having a cyclohexylmethoxy group at the 1-position and 4-position of the benzene ring is chemically unstable and cannot be used as a liquid crystal material (see Non-Patent Document 1). I did not.

Special Publication No. 2-503568 Numata, “Trends in Liquid Crystal Materials,” Monthly Display, March 1998, Volume 4, Issue 3 (5 pages)

  It is to provide a method for producing a difluorobenzene derivative having an alkenyl group in the side chain. Another object of the present invention is to provide an intermediate compound useful for the production of a difluorobenzene derivative having an alkenyl group in the side chain.

As a result of intensive studies in order to solve the above problems, the present inventors have completed the present invention.
The present invention relates to general formula (1)

（式中、R¹およびR²はそれぞれ独立的にメチル基、エチル基またはプロピル基を表すか、R¹およびR²は-CH₂CH₂-、-CH₂CH₂CH₂-または-CH₂C(CH₃)₂CH₂-を表し、X¹は塩素、臭素、よう素、ベンゼンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基又はトリフルオロメタンスルホニルオキシ基を表す。）で表される化合物に2,3-ジフルオロフェノールより調製されるフェノラートを反応させることにより一般式(2)

(Wherein R ¹ and R ² each independently represent a methyl group, an ethyl group or a propyl group, or R ¹ and R ² are —CH ₂ CH ₂ —, —CH ₂ CH ₂ CH ₂ — or —CH ₂ C (CH ₃ ) ₂ CH ₂ —, and X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group. By reacting a phenolate prepared from 2,3-difluorophenol with the compound represented by the general formula (2)

（式中、R¹およびR²は一般式(1)と同じ意味を表す。）で表される化合物とし、この化合物を脱保護して式(3)

(Wherein R ¹ and R ² represent the same meaning as in the general formula (1)), and this compound is deprotected to give the formula (3)

で表される化合物とし、この化合物をメトキシメチルリンイリドと反応させた後加水分解することにより式(4)

By reacting this compound with methoxymethyl phosphorylide and then hydrolyzing it, the compound represented by formula (4)

で表される化合物とし、この化合物にアルキルリンイリドを反応させることにより一般式(5)

By reacting this compound with an alkyl phosphorus ylide, the compound represented by the general formula (5)

（式中、R³は水素原子または炭素原子数１から５のアルキル基を表す。）
で表される化合物とし、この化合物を酸化して一般式(6)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
The compound represented by general formula (6)

（式中、R³は一般式(5)と同じ意味を表す。）
で表される化合物とし、この化合物から調製されるフェノラートを一般式(7)

(In the formula, R ³ represents the same meaning as in general formula (5).)
And a phenolate prepared from this compound is represented by the general formula (7)

（式中、X²は塩素、臭素、よう素、ベンゼンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基又はトリフルオロメタンスルホニルオキシ基を表し、R⁴は炭素原子数1から12のアルキル基、炭素原子数2から12のアルケニル基、炭素原子数1から12のアルコキシ基、炭素原子数3から12のアルケニルオキシ基を表し、nは1または2を表す。）で表される化合物と反応させることによる一般式(8)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

（式中、R³は一般式(5)と同じ意味を表し、R⁴およびnは一般式(7)と同じ意味を表す。）で表される化合物の製造方法を提供する。また、各製造中間体化合物もあわせて提供する。

(Wherein R ³ represents the same meaning as in general formula (5), and R ⁴ and n represent the same meaning as in general formula (7)). Each production intermediate compound is also provided.

  The production method of the present invention is useful as a production method of a difluorobenzene derivative. In addition, the compound of the present invention is useful as an intermediate for producing a difluorobenzene derivative.

  A compound represented by the general formula (2) is obtained by reacting a base with 2,3-difluorophenol to form a phenolate and then reacting with the compound represented by the general formula (1). Metal hydrides, metal carbonates, metal phosphates, metal hydroxides, metal carboxylates, metal amides, metals, etc. can be mentioned, among others alkali metal hydrides, alkali metal phosphates, alkali metal phosphoric acids Salts, alkali metal carbonates, alkali metal hydroxides, alkali metal amides and alkali metals are preferred, and alkali metal phosphates, alkali metal hydrides and alkali metal carbonates are more preferred. Lithium hydride, sodium hydride and potassium hydride as alkali metal hydrides, tripotassium phosphate as alkali metal phosphates, sodium carbonate, sodium hydrogen carbonate, cesium carbonate, potassium carbonate as alkali metal carbonates And potassium hydrogen carbonate can be preferably mentioned.

  Any reaction solvent may be used as long as it allows the reaction to proceed suitably. Ether solvents, chlorine solvents, hydrocarbon solvents, aromatic solvents, polar solvents, and the like can be preferably used. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether and t-butyl methyl ether. Examples of chlorine solvents include dichloromethane, 1,2-dichloroethane and carbon tetrachloride. Examples of hydrocarbon solvents include pentane, hexane, cyclohexane, heptane and octane, aromatic solvents such as benzene, toluene, xylene, mesitylene, chlorobenzene and dichlorobenzene, and polar solvents such as N, N-dimethylformamide, Preferable examples include N-methylpyrrolidone, dimethyl sulfoxide, and sulfolane. Among these, ether solvents such as tetrahydrofuran and diethyl ether and polar solvents such as N, N-dimethylformamide are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.

  The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably from 0 ° C to 150 ° C, more preferably from 30 ° C to 120 ° C. The phenolate produced may be isolated once and then reacted with the compound represented by the general formula (1), or may be reacted without isolation, but it is allowed to react without isolation for ease of work. Better.

R ¹ and R ² each independently represent a methyl group, an ethyl group or a propyl group, or R ¹ and R ² are —CH ₂ CH ₂ —, —CH ₂ CH ₂ CH ₂ — or —CH ₂ C (CH ₃ ) ₂ CH ₂ — represents that R ¹ and R ² are both methyl groups, or R ¹ and R ² are —CH ₂ CH ₂ — or —CH ₂ CH ₂ CH ₂ —. Is preferred. X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, preferably bromine or methanesulfonyloxy group.

  The deprotection of the compound represented by the general formula (2) is preferably performed under acidic conditions. Examples of the acid used include protonic acids such as formic acid, acetic acid, trifluoroacetic acid, oxalic acid, and p-toluenesulfonic acid, and Lewis acids such as boron trifluoride. Formic acid is preferably used.

Any reaction solvent may be used as long as it allows the reaction to proceed suitably, but ether solvents, chlorine solvents, ketone solvents, hydrocarbon solvents, aromatic solvents, polar solvents, and the like are preferably used. And may be reacted without solvent. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of chlorine solvents include dichloromethane, 1,2-dichloroethane, chloroform, and carbon tetrachloride. Acetone, 2-butanone and the like as ketone solvents, pentane, hexane, cyclohexane, heptane and octane as hydrocarbon solvents, and benzene, toluene, xylene, mesitylene, chlorobenzene and dibenzene as aromatic solvents. Preferable examples include chlorobenzene and acetonitrile, dimethyl sulfoxide and the like as polar solvents. Of these, hydrocarbon solvents such as pentane, hexane, cyclohexane, heptane and octane, and aromatic solvents such as benzene, toluene and xylene are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably 0 ° C to 100 ° C, more preferably 30 ° C to 60 ° C.

  The compound represented by the formula (3) can be obtained by reacting the compound represented by the formula (3) with methoxymethyl phosphorylide and then hydrolyzing it. The phosphorus ylide can be prepared from a phosphonium salt, a phosphonic acid ester, or the like, but is preferably prepared from a methoxymethyltriphenylphosphonium salt.

When adjusting ylide using methoxymethyltriphenylphosphonium salt, it is carried out by allowing a base to act. As the base to be used, potassium tert-butoxide, n-butyllithium, phenyllithium, sodium hydride and the like are preferable. t-Butoxide is more preferred. As the reaction solvent, ether solvents, aromatic solvents, polar solvents and the like can be preferably used. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of aromatic solvents include benzene, toluene, xylene, mesitylene, and the like as polar solvents. A good example is N, N-dimethylformamide. Of these, tetrahydrofuran and toluene are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably -40 ° C to 30 ° C, more preferably -20 ° C to 20 ° C. The obtained ylide is preferably reacted with the compound represented by the formula (3) without isolation. Further, a base may be added to the mixture of the methoxymethyltriphenylphosphonium salt and the compound represented by the formula (3).

Hydrolysis can be carried out under an acid catalyst. Examples of the acid to be used include dilute hydrochloric acid and sulfuric acid aqueous solution. Any reaction solvent may be used as long as it allows the reaction to proceed suitably, but ether solvents, hydrocarbon solvents, aromatic solvents and the like can be preferably used, and the reaction may be performed without solvent. . Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of hydrocarbon solvents include pentane, hexane, cyclohexane, heptane, and octane. Examples of the group solvent include benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene and the like. Of these, tetrahydrofuran is more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably from 0 ° C to 80 ° C.

  The compound represented by the formula (4) thus obtained is obtained as a mixture of a cis isomer and a trans isomer relating to a cyclohexane ring, but is preferably a trans isomer for use as an intermediate of a liquid crystal compound. With respect to the cyclohexane ring of the compound represented by the formula (4), cis-trans isomerization can be performed by acting a base, and an excess of trans isomer can be obtained. The base used at this time is preferably sodium hydroxide, potassium hydroxide or the like, the reaction solvent is preferably methanol, ethanol or tetrahydrofuran, the reaction temperature is preferably -40 ° C to 20 ° C, more preferably -20 ° C to 10 ° C. preferable.

  A compound represented by the general formula (5) can be obtained by reacting the compound represented by the formula (4) with an alkyl phosphorus ylide. The phosphorus ylide can be adjusted from a phosphonium salt, a phosphonic acid ester or the like, but is preferably adjusted from an alkyltriphenylphosphonium salt.

  When adjusting an ylide using an alkyltriphenylphosphonium salt, a base is allowed to act. As the base to be used, potassium-t-butoxide, n-butyllithium, phenyllithium, sodium hydride and the like are preferable, and potassium-t -Butoxide is more preferred. As the reaction solvent, ether solvents, aromatic solvents, polar solvents and the like can be preferably used. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of aromatic solvents include benzene, toluene, xylene, mesitylene, and the like as polar solvents. A good example is N, N-dimethylformamide. Tetrahydrofuran and toluene are more preferred. Each of the above solvents may be used alone, or two or more solvents may be mixed and used. The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably -40 ° C to 30 ° C, more preferably -20 ° C to 20 ° C. The obtained ylide is preferably reacted with the compound represented by the formula (4) without isolation. Further, a base may be added to the mixture of the alkyltriphenylphosphonium salt and the compound represented by the formula (4). As the alkyltriphenylphosphonium salt, methyltriphenylphosphonium salt is preferable.

  The oxidation of the compound represented by the general formula (5) can be carried out by deprotonation with an organometallic reagent and then reacting with a trialkyl borate to form a boron compound, followed by the action of an oxidizing agent. Any reaction solvent may be used as long as it allows the reaction to proceed suitably, and examples thereof include ether solvents and hydrocarbon solvents. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of hydrocarbon solvents include pentane, hexane, cyclohexane, heptane, and octane. Of these, tetrahydrofuran is preferred. Examples of the organometallic reagent include n-butyllithium, sec-butyllithium, tert-butyllithium, methyllithium and lithium diisopropylamide, and n-butyllithium and sec-butyllithium are Preferably, sec-butyllithium that can be efficiently deprotonated is more preferable. In the deprotonation, a base such as potassium tert-butoxide or tetramethylethylenediamine may be used as an additive together with the organometallic reagent. The reaction temperature at the time of deprotonation is preferably -100 ° C to -20 ° C, more preferably -78 ° C to -40 ° C.

  Trimethyl borate is preferably used as the trialkyl borate. The reaction temperature during boriding is preferably from -100 ° C to -20 ° C, more preferably from -78 ° C to -40 ° C. The obtained boron compound may be isolated once or may be reacted with an oxidizing agent without isolation. Further, the obtained boron compound may be hydrolyzed and converted into a boric acid compound and then reacted with an oxidizing agent.

  As the oxidizing agent, it is preferable to use hydrogen peroxide, peracetic acid or performic acid. The reaction temperature is preferably -78 ° C to 70 ° C, more preferably 0 ° C to 50 ° C. Moreover, water may be contained in the solvent at the time of reaction with an oxidizing agent.

The reaction for converting the compound represented by the general formula (6) into the compound represented by the general formula (8) is a reaction for converting the compound represented by the general formula (1) into the general formula (2) (described above). Can be done as well. X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, preferably bromine or methanesulfonyloxy group.

In General Formula (7) and General Formula (8), R ⁴ is an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, or 3 carbon atoms. To an alkenyloxy group having 1 to 12 carbon atoms, preferably an alkyl group having 1 to 12 carbon atoms or an alkenyl group having 2 to 12 carbon atoms, and particularly preferred is the production of a compound representing an alkyl group having 1 to 7 carbon atoms.

EXAMPLES Hereinafter, although an Example is given and this invention is further explained in full detail, this invention is not limited to these Examples. The structure of the compound was confirmed by nuclear magnetic resonance spectrum (NMR), mass spectrum (MS) and the like.
The following abbreviations are used in compound descriptions.
THF: tetrahydrofuran
DMF: N, N-dimethylformamide
Me: methyl group
Et: ethyl group
Bu: Butyl group
Ph: phenyl group
Ms: Methanesulfonyl group (Example 1) Synthesis of 1-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluorobenzene (Ia)

Methanesulfonic acid ((4 ′, 4′-ethylenedioxy) cyclohexyl) methyl (721 g), 2,3-difluorophenol (393 g), sodium carbonate (320 g) and DMF (2.1 L) were mixed and stirred at 130 ° C. for 2 hours. After adding 4.2 L of water and extracting with hexane / toluene = 1/1, the organic layer was washed with water and saturated brine and then subjected to column chromatography, and the solvent was distilled off under reduced pressure. The residue was purified by recrystallization to obtain 493 g of 1-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluorobenzene (Ia). Compound (Ia) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 284 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 1.3 2.0 (m, 9 H), 3.8 4.0 (m, 6 H), 6.4 6.6 (m, 2 H), 6.8 7.0 (m, 1 H)
Example 2 Synthesis of 2,3-difluoro-1- (4-oxocyclohexyl) methoxybenzene (Ib)

493 g of 1-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluorobenzene (Ia) was dissolved in 1 L of toluene, 1 L of formic acid was added, and the mixture was stirred at room temperature for 2 hours. Stir at 50 ° C. for 1.5 hours. After cooling to room temperature, water and saturated brine were added, and the organic layer was separated, washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, subjected to column chromatography, and then the solvent was distilled off under reduced pressure. Thus, 412.4 g of 3-difluoro-1- (4-oxocyclohexyl) methoxybenzene (Ib) was obtained. Compound (Ib) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 240 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 1.6 1.9 (m, 4 H), 2.0 2.4 (m, 5 H), 3.8 4.0 (m, 2 H), 6.4 6.6 (m, 2 H), 6.8 7.0 (m, 1 H)
Example 3 Synthesis of 2,3-difluoro-1- (trans-4-formylcyclohexyl) methoxybenzene (Ic)

Disperse 412.4 g of 2,3-difluoro-1- (4-oxocyclohexyl) methoxybenzene (Ib) and 706 g of methoxymethyltriphenylphosphonium chloride in 1200 mL of THF, and add 231 g of potassium-t-butoxide in THF (450 mL). ) The solution was added at an internal temperature of -10 to 5 ° C and stirred for 30 minutes. After adding 50 mL of water, the solvent was distilled off under reduced pressure, 50% aqueous methanol and hexane were added to the residue, and the organic layer was separated. The organic layer was washed with 50% aqueous methanol solution and saturated brine, subjected to column chromatography, and then the solvent was distilled off under reduced pressure. 800 mL of THF and 400 mL of 10% hydrochloric acid were added to the residue, and the mixture was heated to reflux for 1.5 hours. After cooling to room temperature, the mixture was extracted with a THF / hexane mixed solvent, and the organic layer was washed with saturated brine and saturated aqueous sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. A solution of 20 g of sodium hydroxide in methanol (1 L) was added to the residue, and the mixture was stirred at an internal temperature of −20 to −5 ° C. for 1 hour. 1 L of water, 500 mL of saturated brine, 200 mL of THF and 500 mL of ethyl acetate were added to separate the organic layer, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give 363 g of 2,3-difluoro-1- (trans-4-formylcyclohexyl) methoxybenzene (Ic). Obtained. Compound (Ic) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 254 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 1.3 2.0 (m, 9 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 2 H), 6.4 6.6 (m, 2 H), 6.8 7.0 (m, 1 H), 9.6 9.8 ( m, 1 H)
Example 4 Synthesis of 2,3-difluoro-1- (trans-4-vinylcyclohexyl) methoxybenzene (Id)

612 g of methyltriphenylphosphonium chloride and 363 g of 2,3-difluoro-1- (trans-4-formylcyclohexyl) methoxybenzene (Ic) were dispersed in 1 L of THF, and 192 g of potassium-t-butoxide (200 g) mL) The solution was added dropwise at an internal temperature of −10 ° C. and stirred for 30 minutes. After adding 50 mL of water, the solvent was distilled off under reduced pressure, 50% aqueous methanol and hexane were added to the residue, and the organic layer was separated. The organic layer was washed with 50% aqueous methanol solution and saturated brine, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography, distillation under reduced pressure and recrystallization to obtain 146.8 g of 2,3-difluoro-1- (trans-4-vinylcyclohexyl) methoxybenzene (Id) as colorless crystals. The compound (Id) is useful as an intermediate for producing a liquid crystal compound.
Boiling point 125 ° C / 0.4 mmHg
MS m / z: 252 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 1.3 1.5 (m, 8 H), 1.8 2.2 (m, 2 H), 3.8 4.0 (m, 2 H), 4.8 5.0 (m, 2 H), 5.7 5.9 (m, 1 H), 6.4 6.6 ( m, 2 H), 6.8 7.0 (m, 1 H)
Example 5 Synthesis of 2,3-difluoro-4- (trans-4-vinylcyclohexyl) methoxyphenol (Ie)

Dissolve 146.8 g of 2,3-difluoro-1- (trans-4-vinylcyclohexyl) methoxybenzene (Id) in 500 mL of THF, and add 611 mL of sec-butyllithium (1.0 M in hexane, cyclohexane) to an internal temperature of -40. The solution was added dropwise at ˜−55 ° C. and stirred for 20 minutes while maintaining the internal temperature. 66.5 g of trimethyl borate was added dropwise at an internal temperature of -40 to -55 ° C, and the temperature was raised to 0 ° C. 99 mL of 30% hydrogen peroxide solution was added dropwise over 5 minutes, and the mixture was stirred at 40 ° C. for 2 hours. Dilute hydrochloric acid was added, and the mixture was stirred for a while and extracted with a hexane / THF mixed solvent. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 2,3-difluoro-4- (trans-4-vinylcyclohexyl) methoxyphenol as almost colorless crystals ( Ie) 165 g was obtained. Compound (Ie) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 268 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 1.3 1.5 (m, 8 H), 1.8 2.2 (m, 2 H), 3.8 4.0 (m, 2 H), 4.8 5.0 (m, 2 H), 5.7 5.9 (m, 1 H), 6.3 6.5 ( m, 2 H), 4.0 6.0 (s, 1 H)
Example 6 Synthesis of 2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (If)

2,3-difluoro-4- (trans-4-vinylcyclohexyl) methoxyphenol (Ie) 80 g, (trans-4-butylcyclohexyl) bromomethane 83.4 g, tripotassium phosphate 76 g and DMF 240 mL were mixed, The mixture was stirred at 110 ° C. for 4.5 hours. After cooling to room temperature, water, toluene and hexane were added to separate the organic layer. The aqueous layer was extracted with a toluene / hexane mixed solvent, the organic layers were combined and washed with water and saturated brine, and the solvent was distilled off under reduced pressure. The residue was purified by recrystallization and column chromatography to give 2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (If) as colorless crystals. It was.
Phase transition temperature: C 55.2 N 95.8 I
MS m / z: 420 (M ⁺ ), 146 (100)
¹ H-NMR (400 MHz, CDCl ₃ )
δ: 0.80 1.35 (m, 15 H), 0.889 (t, J = 6.8 Hz, 3 H), 1.65 2.00 (m, 11 H), 3.76 (d, J = 6.4 Hz, 2 H), 3.78 (d, J = 6.4 Hz, 2 H), 4.85 5.05 (m, 2 H), 5.79 (ddd, J = 6.8 Hz, J = 10.4 Hz, J = 17.2 Hz, 1 H), 6.59 (d, J = 5.6 Hz, 2 H)
Example 7 Synthesis of 2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (IIf)

In Example 6, the same operation was carried out by using methanesulfonic acid (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methyl in place of (trans-4-butylcyclohexyl) bromomethane, and performing the same procedure. -Difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (IIf) was obtained.
Phase transition temperature: C 75.6 N 195.2 I
MS m / z: 474 (M ⁺ ), 146 (100)
¹ H-NMR (400 MHz, CDCl ₃ )
δ: 0.75 1.25 (m, 17 H), 0.86 (t, J = 7.2 Hz, 3 H), 1.65 2.00 (m, 15 H), 3.75 (d, J = 6.8 Hz, 2 H), 3.78 (d, J = 6.4 Hz, 2 H), 4.87 5.03 (m, 2 H), 5.79 (ddd, J = 6.8 Hz, J = 10.4 Hz, J = 17.2 Hz, 1 H), 6.59 (d, J = 5.2 Hz, 2 H)

The production method of the present invention is useful as a production method of a liquid crystal compound. Moreover, the compound of this invention is useful as a manufacturing intermediate of a liquid crystal compound.

Claims (19)

General formula (1)

(In the formula, R ¹ and R ² each independently represent a methyl group, an ethyl group or a propyl group, or R ¹ and R ² together represent —CH ₂ CH ₂ —, —CH ₂ CH ₂ CH ₂ -Or -CH ₂ C (CH ₃ ) ₂ CH _2- , wherein X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group. By reacting a phenolate prepared from 2,3-difluorophenol with the compound represented by formula (2)

(Wherein R ¹ and R ² represent the same meaning as in the general formula (1)), and this compound is deprotected to give the formula (3)

By reacting this compound with methoxymethyl phosphorylide and then hydrolyzing it, the compound represented by formula (4)

By reacting this compound with an alkyl phosphorus ylide, the compound represented by the general formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
The compound represented by general formula (6)

(In the formula, R ³ represents the same meaning as in general formula (5).)
And a phenolate prepared from this compound is represented by the general formula (7)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

(Wherein R ³ represents the same meaning as in general formula (5), and R ⁴ and n represent the same meaning as in general formula (7)). General formula (2)

(In the formula, R ¹ and R ² each independently represent a methyl group, an ethyl group or a propyl group, or R ¹ and R ² together represent —CH ₂ CH ₂ —, —CH ₂ CH ₂ CH ₂ -Or -CH ₂ C (CH ₃ ) ₂ CH _2- represents a compound represented by the formula (3)

By reacting this compound with methoxymethyl phosphorylide and then hydrolyzing it, the compound represented by formula (4)

By reacting this compound with an alkyl phosphorus ylide, the compound represented by the general formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
The compound represented by general formula (6)

(In the formula, R ³ represents the same meaning as in general formula (5).)
And a phenolate prepared from this compound is represented by the general formula (7)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

(Wherein R ³ represents the same meaning as in general formula (5), and R ⁴ and n represent the same meaning as in general formula (7)). Formula (3)

The compound represented by formula (4) is reacted with methoxymethyl phosphorylide and then hydrolyzed.

By reacting this compound with an alkyl phosphorus ylide, the compound represented by the general formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
The compound represented by general formula (6)

(In the formula, R ³ represents the same meaning as in general formula (5).)
And a phenolate prepared from this compound is represented by the general formula (7)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

(Wherein R ³ represents the same meaning as in general formula (5), and R ⁴ and n represent the same meaning as in general formula (7)). Formula (4)

By reacting an alkyl phosphorus ylide with a compound represented by general formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
The compound represented by general formula (6)

(In the formula, R ³ represents the same meaning as in general formula (5).)
And a phenolate prepared from this compound is represented by the general formula (7)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

(Wherein R ³ represents the same meaning as in general formula (5), and R ⁴ and n represent the same meaning as in general formula (7)). General formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
Oxidizing the compound represented by general formula (6)

(In the formula, R ³ represents the same meaning as in general formula (5).)
And a phenolate prepared from this compound is represented by the general formula (7)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

(Wherein R ³ represents the same meaning as in general formula (5), and R ⁴ and n represent the same meaning as in general formula (7)). General formula (6)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
A phenolate prepared from the compound represented by the general formula (7)

(Wherein X ² represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ⁴ represents alkyl having 1 to 12 carbon atoms. A alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkenyloxy group having 3 to 12 carbon atoms, and n represents 1 or 2. General formula (8) by reacting

(Wherein R ³ represents the same meaning as in general formula (6), and R ⁴ and n represent the same meaning as in general formula (7)). General formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
General formula (6) by oxidizing a compound represented by

(In the formula, R ³ represents the same meaning as in general formula (5).)
The manufacturing method of the compound represented by these. The process according to claim 1, 2, 3 or 4, wherein the methoxymethyl phosphorus ylide is an ylide prepared from a methoxymethyl triphenylphosphonium salt. 4. The process according to claim 1, 2, or 3, wherein the alkyl phosphorus ylide is an ylide prepared from an alkyl triphenylphosphonium salt. In the method of oxidizing the compound represented by the general formula (5), the 4-position of the compound represented by the general formula (5) is deprotonated with an organometallic reagent, reacted with a trialkyl borate, and then peroxide. The manufacturing method in any one of Claim 1, 2, 3, 4, 5 or 7 by making this react. The production method according to claim 10 , wherein n-butyl lithium or sec-butyl lithium is used as the organometallic reagent, and trimethyl borate is used as the trialkyl borate. The production method according to claim 8 or 9, wherein hydrogen peroxide, performic acid or peracetic acid is used as the oxidizing agent. The production method according to claim 1, wherein X ¹ represents bromine or a methanesulfonyloxy group. The production method according to any one of claims 1 to 6, wherein X ² represents bromine or a methanesulfonyloxy group. The production according to claim 1 or 2, wherein R ¹ and R ² both represent a methyl group, or R ¹ and R ² together represent -CH ₂ CH ₂ -or -CH ₂ CH ₂ CH _2-. Method. Formula (3)

A compound represented by Formula (4)

A compound represented by General formula (5)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
A compound represented by General formula (6)

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.)
A compound represented by