JP4872121B2 - 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-を表す。）で表される化合物を酸化して一般式(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 — represents a compound represented by 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、この化合物から調製されるフェノラートを一般式(3)

(Wherein R ¹ and R ² represent the same meaning as in general formula (1)), and a phenolate prepared from this compound is represented by general formula (3)

（式中、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し、R³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て一般式(4)

(Wherein X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ³ 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. Reaction to general formula (4)

（式中、R¹およびR²は一般式(1)と同じ意味を表し、R³およびnは一般式(3)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一般式(5)

(Wherein R ¹ and R ² represent the same meaning as in general formula (1), and R ³ and n represent the same meaning as in general formula (3)). General formula (5)

（式中、R³およびnは一般式(3)と同じ意味を表す。）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る一般式(6)

(Wherein R ³ and n represent the same meaning as in the general formula (3)), and the compound represented by the general formula (6) obtained by reacting this compound with an alkyl phosphorus ylide.

（式中、R⁴は水素原子または炭素原子数１から５のアルキル基を表し、R³およびnは一般式(3)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、本願発明の製造中間体である一般式(2)及び一般式(4)で表される化合物もあわせて提供する。

(Wherein R ⁴ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ³ and n have the same meaning as in general formula (3)). . In addition, the compounds represented by the general formula (2) and the general formula (4) which are production intermediates of the present invention are 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.

  The oxidation of the compound represented by the general formula (1) 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.

  A compound represented by the general formula (4) is obtained by reacting a compound represented by the general formula (2) with a base to react with a compound represented by the general formula (3). Examples of bases that can be used include metal hydrides, metal carbonates, metal phosphates, metal hydroxides, metal carboxylates, metal amides and metals, among which alkali metal hydrides, alkali metal phosphates, Alkali metal phosphates, 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 generated phenolate may be isolated once and then reacted with the compound represented by the general formula (3), or may be reacted without isolation, but it is allowed to react without isolation for ease of work. Better.

  The deprotection of the compound represented by the general formula (4) 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 (5) thus obtained may be 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. . Regarding the cyclohexane ring of the compound represented by the formula (5), cis-trans isomerization can be carried out by allowing a base to act as necessary, and an excess of the 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.

  The compound represented by the general formula (6) can be obtained by reacting the compound represented by the formula (5) 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 (5) without isolation. Further, a base may be added to the mixture of the alkyltriphenylphosphonium salt and the compound represented by the formula (5). As the alkyltriphenylphosphonium salt, methyltriphenylphosphonium salt is preferable.

In the general formula (1) and the general formula (2), 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- , wherein 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.

In the general formula (3), X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, but bromine or methanesulfonyloxy group is preferable.

In General Formula (3) to General Formula (6), R ³ 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, an alkyl group having 1 to 12 carbon atoms or an alkenyl group having 2 to 12 carbon atoms is preferable, and the production of a compound representing an alkyl group having 1 to 7 carbon atoms is particularly preferable.

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 4- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-2,3-difluorophenol (Ib)

1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-2,3-difluorobenzene (Ia) is dissolved in THF, and sec-butyllithium (1.0 M in hexane, cyclohexane) is added to the internal temperature. The solution was added dropwise at -40 to -55 ° C and stirred for 20 minutes while maintaining the internal temperature. Trimethyl borate was added dropwise at an internal temperature of -40 to -55 ° C, and the temperature was raised to 0 ° C. 30% aqueous hydrogen peroxide was slowly added, and the mixture was stirred at 40 ° C. for 2 hours. Water 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 evaporated under reduced pressure to give 4- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-2,3 -Difluorophenol (Ib) was obtained. Compound (Ib) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 314 (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, 6 H), 4.0 6.0 (s, 1 H), 4.7 5.0 (m, 1 H), 6.3 6.4 ( m, 2 H)
Example 2 1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-2,3-difluorobenzene Synthesis of (Ic)

Methanesulfonic acid (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methyl, 4- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-2,3-difluorophenol (Ib), Tripotassium phosphate and DMF were mixed and stirred at 120 ° C. for 2 hours. Water was added and the mixture was extracted with a mixed solvent of hexane / toluene. 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 give 1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-2,3 -Difluorobenzene (Ic) was obtained. Compound (Ic) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 520 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 0.9 1.0 (m, 3 H), 1.2 1.6 (m, 29 H), 1.8 2.2 (m, 3 H), 3.8 4.0 (m, 8 H), 4.7 5.0 (m, 1 H), 6.4 6.5 ( m, 2 H)
Example 3 Synthesis of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Id)

1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-2,3-difluorobenzene (Ic) in toluene The formic acid was added and stirred at 50 ° C. for 3 hours. After cooling to room temperature, water and saturated brine were added, 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. -(Trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Id) was obtained. The compound (Id) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 476 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 0.9 2.0 (m, 34 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H), 9.6 9.8 (m, 1 H)
Example 4 Synthesis of 2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (Ie)

36 g of methyltriphenylphosphonium bromide and 40 g of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Id) Was dispersed in 200 mL of THF, and a solution of 11.3 g of potassium-t-butoxide in THF (100 mL) was added dropwise under ice cooling, followed by stirring for 30 minutes. After adding 10 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 recrystallization and column chromatography, and 2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) as colorless crystals 23.9 g of methoxybenzene (Ie) 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)
Example 5 Synthesis of 1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4-butylcyclohexyl) methoxy-2,3-difluorobenzene (IIc)

In Example 2, the same procedure was performed by using (trans-4-butylcyclohexyl) bromomethane in place of (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methyl methanesulfonate, and performing the same procedure. -4- (2,5-Dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4-butylcyclohexyl) methoxy-2,3-difluorobenzene (IIc) was obtained. Compound (IIc) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 466 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 0.9 1.0 (m, 3 H), 1.2 1.6 (m, 23 H), 1.8 2.2 (m, 3 H), 3.8 4.0 (m, 8 H), 4.7 5.0 (m, 1 H), 6.4 6.5 ( m, 2 H)
Example 6 Synthesis of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IId)

In Example 3, 1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-2,3-difluorobenzene 1- (trans-4- (2,5-dioxacyclopentyl) cyclohexyl) methoxy-4- (trans-4-butylcyclohexyl) methoxy-2,3-difluorobenzene (IIc) is used instead of (Ic) By performing the same operation, 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IId) was obtained. Compound (IId) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 422 (M ⁺ )
¹ H-NMR (60 MHz, CDCl ₃ )
δ: 0.9 2.0 (m, 28 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H), 9.6 9.8 (m, 1 H)
Example 7 Synthesis of 2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (IIe)

In Example 4, instead of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Id) By performing the same operation using (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IId), 2,3-difluoro-1- (Trans-4-butylcyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (IIe) was obtained.
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)

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 (12)

General formula (1)

(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 — represents a compound represented by general formula (2)

(Wherein R ¹ and R ² represent the same meaning as in general formula (1)), and a phenolate prepared from this compound is represented by general formula (3)

(Wherein X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ³ 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. Reaction to general formula (4)

(Wherein R ¹ and R ² represent the same meaning as in general formula (1), and R ³ and n represent the same meaning as in general formula (3)). General formula (5)

(Wherein R ³ and n represent the same meaning as in the general formula (3)), and the compound represented by the general formula (6) obtained by reacting this compound with an alkyl phosphorus ylide.

(Wherein R ⁴ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ³ and n have the same meaning as in formula (3)). General formula (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 A phenolate prepared from a compound represented by ₂ C (CH ₃ ) ₂ CH _2- ) is represented by the general formula (3)

(Wherein X ¹ represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, and R ³ 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. Reaction to general formula (4)

(Wherein R ¹ and R ² have the same meaning as in general formula (2), and R ³ and n have the same meaning as in general formula (3)). General formula (5)

(Wherein R ³ and n represent the same meaning as in the general formula (3)), and the compound represented by the general formula (6) obtained by reacting this compound with an alkyl phosphorus ylide.

(Wherein R ⁴ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ³ and n have the same meaning as in formula (3)). General formula (4)

(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 - represents, R ³ is an alkyl group having 1 to 12 carbon atoms, an alkenyl group having from 2 to 12 carbon atoms, an alkoxy group having from 12 1 carbon atom, carbon atoms 3 To 12 represents an alkenyloxy group, and n represents 1 or 2.) The compound represented by formula (5)

(Wherein R ³ and n represent the same meaning as in the general formula (4)), and the compound represented by the general formula (6) is obtained by reacting this compound with an alkyl phosphorus ylide.

(Wherein R ⁴ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ³ and n have the same meaning as in formula (4)). 4. The process according to claim 1, 2, or 3, wherein the alkyl phosphorus ylide is an ylide prepared from an alkyl triphenylphosphonium salt. General formula (1)

(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 — represents the general formula (2) by oxidizing the compound represented by

(Wherein R ¹ and R ² represent the same meaning as in general formula (1)). In the method of oxidizing the compound represented by the general formula (1), the 4-position of the compound represented by the general formula (1) is deprotonated with an organometallic reagent and reacted with a trialkyl borate. The manufacturing method of Claim 1 or 5 by making it react. 7. The process according to claim 6, wherein n-butyllithium or sec-butyllithium is used as the organometallic reagent, and trimethyl borate is used as the trialkyl borate. The production method according to claim 6 or 7, wherein hydrogen peroxide, performic acid or peracetic acid is used as the oxidizing agent. The production method according to claim 1 or 2, wherein X ¹ represents bromine or a methanesulfonyloxy group. The production according to claim 1, 2, 3 or 5, wherein R ¹ and R ² both represent a methyl group, or R ¹ and R ² represent -CH ₂ CH ₂ -or -CH ₂ CH ₂ CH _2-. Method. General formula (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 — represents a compound. General formula (4)

(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 - represents, R ³ is an alkyl group having 1 to 12 carbon atoms, an alkenyl group having from 2 to 12 carbon atoms, an alkoxy group having from 12 1 carbon atom, carbon atoms 3 To 12 alkenyloxy groups, and n represents 1 or 2.)