JP2007261956A - Method for producing 2-naphthol derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for inexpensively producing a 2-naphthol derivative containing one or more halogen atoms bonded to a naphthalene ring useful as a raw material for an electronic material, etc. by a simple operation. <P>SOLUTION: The method for producing a 2-naphthol derivative containing one or more halogen atoms bonded to a naphthalene ring comprises reacting a phenylacetic acid halide containing one or more halogen atoms bonded to a benzene ring with a vinyl halide in the presence of a Lewis acid catalyst such as aluminum chloride. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method for producing a 2-naphthol derivative useful as a raw material for pharmaceuticals, agricultural chemicals, electronic materials and the like.

  A 2-naphthol derivative in which one or more chlorine atoms or fluorine atoms are bonded to a naphthalene ring is particularly useful as an intermediate material for liquid crystal compounds. In order to produce such an intermediate raw material using 2-naphthol as a raw material by chlorinating or fluorinating the desired position of the naphthalene ring, one or more chlorine atoms are added to the benzene ring. Several production methods using phenylacetic acid halide derivatives bonded with atoms or fluorine atoms as raw materials have been proposed. For example, after a phenylacetic acid halide derivative having one or more chlorine atoms or fluorine atoms bonded to a benzene ring is reacted with ethylene in the presence of a Lewis acid such as aluminum chloride to form a 2-tetralone derivative, bromine or the like Oxidative dehydrogenation with a brominating agent to give a 1-bromo-2-naphthol derivative and further reduced by catalytic reduction or sulfite to give a 2-naphthol derivative (Patent Document 1), A method (Patent Document 2) is known in which the obtained 2-tetralone derivative is subjected to oxidative dehydrogenation using an oxidizing agent such as copper (II) bromide to obtain a 2-naphthol derivative. Also known is a method for directly producing a 2-naphthol derivative by reacting a phenylacetic acid halide derivative having one or more chlorine atoms or fluorine atoms bonded to a benzene ring with acetylene in the presence of a Lewis acid. (Patent Document 3).

  Among these methods, the method described in Patent Document 1 has a drawback in that when oxidative dehydrogenation is performed with a brominating agent, a nuclear bromide is generated, so that a reduction treatment is required, which requires a long process and a long operation. In addition, the method described in Patent Document 2 does not have such a drawback, but it is necessary to use copper (II) bromide at least 2 mol times the intermediate 2-tetralone derivative, and in terms of waste treatment. There is a drawback that the load is large. Furthermore, the method described in Patent Document 3 has the disadvantage that acetylene is difficult to handle and the yield is very low.

JP 2004-91361 A JP 2004-91362 A JP-A-2005-97198

  Therefore, an object of the present invention is to use a phenylacetic acid halide derivative in which one or more halogen atoms are bonded to a benzene ring as a raw material, and to bond one or more halogen atoms to a naphthalene ring in a simpler operation and at a lower cost. -To provide a method for producing a naphthol derivative.

で示されるフェニル酢酸ハロゲン化物誘導体（式中、Ｘ^１、Ｘ^２、Ｘ^３及びＸ^４は、それぞれ独立して水素原子、ハロゲン原子又は炭化水素基を表すが、Ｘ^１、Ｘ^２、Ｘ^３及びＸ^４の少なくとも一つはハロゲン原子である。またＸ^５は塩素原子又は臭素原子を表す）を、ルイス酸触媒の存在下、ハロゲン化ビニルと反応させることを特徴とする、下記一般式（２）

で示される２−ナフトール誘導体（式中、Ｘ^１、Ｘ^２、Ｘ^３及びＸ^４は、上記と同じ）の製造方法が提供される。 That is, according to the present invention, the following general formula (1)

(Wherein, X ¹ , X ² , X ³ and X ⁴ each independently represents a hydrogen atom, a halogen atom or a hydrocarbon group, but X ¹ , X ² , X ³⁾ And at least one of X ⁴ is a halogen atom, and X ⁵ represents a chlorine atom or a bromine atom), and is reacted with vinyl halide in the presence of a Lewis acid catalyst. 2)

A method for producing a 2-naphthol derivative represented by the formula (wherein X ¹ , X ² , X ³ and X ⁴ are the same as described above) is provided.

  According to the present invention, unlike the reactions disclosed in Patent Documents 1 and 2, an independent reaction step for producing an intermediate 2-tetralone derivative is not required, and the intended 2 step reaction step is performed. -Naphthol derivatives can be produced. That is, according to the reaction of the present invention, it is considered that the production of a halogenated 2-tetralone derivative and the subsequent dehydrohalogenation can proceed under the same conditions. Furthermore, when compared with the reaction disclosed in Patent Document 3, a 2-naphthol derivative can be produced in a high yield by using a raw material that is easy to handle.

The phenylacetic acid halide derivative used as a raw material in the present invention is represented by the above formula (1). In formula (1), X ¹ , X ² , X ³ and X ⁴ each independently represent a hydrogen atom, a halogen atom or a hydrocarbon group, but at least one of X ¹ , X ² , X ³ and X ⁴ One is a halogen atom. The halogen atom is fluorine, chlorine, bromine or iodine, but fluorine or chlorine is particularly preferable. Examples of the hydrocarbon group include alkyl groups such as methyl, ethyl, n-propyl, isopropyl and t-butyl. In Formula (1), X ⁵ is a chlorine atom or a bromine atom. Specific examples of such phenylacetic acid halide derivatives include 2-fluorophenylacetic acid chloride, 3-fluorophenylacetic acid chloride, 4-fluorophenylacetic acid chloride, 2-chlorophenylacetic acid chloride, 3-chlorophenylacetic acid chloride. 4-chlorophenylacetic acid chloride, 2-bromophenylacetic acid chloride, 3-iodophenylacetic acid chloride, 2-fluorophenylacetic acid bromide, 3-fluorophenylacetic acid bromide, 4-fluorophenylacetic acid bromide, 2-chlorophenylacetic acid bromide, 3-chlorophenylacetic acid bromide, 4-chlorophenylacetic acid bromide, 2,3-difluorophenylacetic acid chloride, 2,4-difluorophenylacetic acid chloride, 2,5-difluorophenylacetic acid chloride, 2,3-dichlorophenylacetic acid chloride Product, 2,4-dichlorophenylacetic acid chloride 2,5-dichlorophenylacetic acid chloride, 2,3-difluorophenylacetic acid bromide, 2,4-difluorophenylacetic acid bromide, 2,5-difluorophenylacetic acid bromide, 2,3-dichlorophenylacetic acid bromide, 2,4- Dichlorophenylacetic acid bromide, 2,5-dichlorophenylacetic acid bromide, 3,5-difluorophenylacetic acid chloride, 3,5-difluorophenylacetic acid bromide, 2,3,4-trifluorophenylacetic acid chloride, 2-fluoro-4- Methylphenylacetic acid chloride, 3-fluoro-4-methylphenylacetic acid chloride, 4-fluoro-2-methylphenylacetic acid chloride, 4-fluoro-3-methylphenylacetic acid chloride, 2-chloro-4-methylphenyl Acetic acid chloride, 3-chloro-4-methylphenylacetic acid chloride, 4-chloro-2-methylphenol Le acetate chloride, and the like can be exemplified 4-chloro-3-methyl-phenylacetic acid chloride. A mixture of two or more of these can also be used as a raw material. These may be manufactured by any manufacturing method. For example, the corresponding phenylacetic acid halide derivative can be easily prepared by reacting a nucleus-substituted phenylacetic acid having one or more halogen atoms in the benzene ring with a halogenating agent such as thionyl chloride. This can be used as a raw material.

  In the present invention, the vinyl halide to be reacted with the phenylacetic acid halide derivative is vinyl fluoride, vinyl chloride, vinyl bromide or vinyl iodide, and it is particularly preferable to use vinyl chloride or vinyl bromide.

  In the present invention, the phenylacetic acid halide derivative and the vinyl halide are reacted in the presence of a Lewis acid catalyst. Examples of the Lewis acid that can be used in the present invention include aluminum chloride (III), aluminum fluoride (III), aluminum bromide (III), zinc chloride (IV), tin chloride (IV), iron chloride ( III), titanium (IV) chloride, gallium chloride (IV) and the like can be exemplified, but aluminum chloride (III) is particularly preferable in view of the yield.

  In the reaction of the phenylacetic acid halide derivative and the vinyl halide, a solvent is preferably used. Usable solvents include, for example, chlorinated aliphatics such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, etc. Examples include hydrocarbons, saturated hydrocarbons such as hexane, heptane, octane, cyclohexane and decahydronaphthalene, aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, and mixtures of two or more of these. Of these, chlorinated aliphatic hydrocarbons are preferred.

  The reaction of the present invention can be carried out by mixing a phenylacetic acid halide derivative, a Lewis acid catalyst and a vinyl halide, preferably a solvent, by any method. For example, it can be carried out by a method in which gaseous vinyl halide is blown into a mixture comprising the phenylacetic acid halide derivative, Lewis acid catalyst and solvent. Alternatively, it can also be carried out by dissolving vinyl halide in a solvent and dropping it into a mixture comprising the phenylacetic acid halide derivative, Lewis acid catalyst and solvent. Furthermore, it can also carry out by dripping the solution which melt | dissolved the phenyl acetic acid halide derivative or the phenyl acetic acid halide derivative in the solvent in the mixture which consists of a vinyl halide, a Lewis' acid catalyst, and a solvent.

  In the above reaction, the solvent is preferably used in an amount of usually 1 to 50 parts by weight, particularly 2 to 20 parts by weight per 1 part by weight of the phenylacetic acid halide derivative. Further, the preferred amount of vinyl halide used is 1 mol or more per 1 mol of phenylacetic acid halide derivative, and may be an amount sufficient for the disappearance of the phenylacetic acid halide derivative in the reaction system. , 10 mol or less is sufficient for 1 mol of phenylacetic acid halide derivative. The amount of Lewis acid used is preferably 0.9 to 10 moles, particularly 1.0 to 5.0 moles per mole of phenylacetic acid halide derivative in consideration of yield and economy. .

  Suitable reaction temperatures are in the range of -40 to + 10 ° C. If the reaction temperature is too low, the reaction is difficult to proceed, while if the reaction temperature is too high, the selectivity of the reaction tends to decrease. The reaction time may be usually the time until the starting phenylacetic acid halide derivative disappears, and it varies depending on the type of raw material and the amount of the raw material used, as well as the reaction conditions such as the reaction temperature. It is about 1 to 24 hours.

  After completion of the reaction, the reaction solution is added to water or an aqueous hydrochloric acid solution to deactivate the catalyst, followed by liquid separation. The solvent is distilled off from the obtained organic layer to obtain a crude 2-naphthol derivative. You can get a product. When a high-purity 2-naphthol derivative is required, the crude product is dissolved in an aqueous solution such as caustic soda, and then an acid is added to precipitate crystals, or an appropriate organic solvent such as methanol, ethanol, Purification operations such as recrystallization using isopropanol, ethyl acetate, heptane and the like can be added.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to the following Example. In addition, the analysis in an Example was quantified by the absolute calibration curve method by the high performance liquid chromatography of the following conditions.
Measurement conditions Column: Inertsil-gel ODS-80A Length 250 mm, inner diameter 4.6 mm
Eluent: Methanol: 0.1 wt% phosphoric acid water = 70: 30
Flow rate: 1 ml / min Oven temperature: 40 ° C
Detector: UV (254 nm)

[Reference Example] Synthesis of 2,3-difluorophenylacetic acid chloride In a 200 ml glass flask equipped with a stirrer, thermometer, reflux condenser and calcium chloride drying tube, 30.0 g of 2,3-difluorophenylacetic acid (0.174 Mol), 0.02 g (0.0003 mol) of pyridine and 120 g of methylene chloride were charged, and 41.5 g (0.349 mol) of thionyl chloride was added dropwise to the mixed solution. Thereafter, the temperature was raised to the reflux temperature and held for 5 hours under reflux. After completion of the reaction, the reaction solution was cooled and filtered to remove pyridine hydrochloride, and further methylene chloride was distilled off from the filtrate to obtain 2,3-difluorophenylacetic acid chloride. This was used as a raw material in the following examples.

Example 1 Synthesis of 7,8-difluoro-2-naphthol Into a 100 ml glass flask equipped with a stirrer, thermometer, reflux condenser and calcium chloride drying tube, 4.2 g (0.032 mol) of aluminum (III) chloride was added. ) And 17.5 g of dichloromethane, and cooled to -15 ° C. Thereto, 5.0 g (0.026 mol) of the above 2,3-difluorophenylacetic acid chloride dissolved in 17.5 g of dichloromethane was added dropwise while maintaining at −10 ° C., and then at −10 to −15 ° C. Hold for 5 hours. A vinyl chloride gas was blown into the mixture over 1 hour until 2,3-difluorophenylacetic acid chloride disappeared while maintaining the temperature at −10 to −15 ° C., and then maintained at the same temperature for 1 hour.

  After completion of the reaction, the reaction solution was added little by little in 38.5 g of an ice-cooled 4.5% hydrochloric acid aqueous solution to deactivate the catalyst, and the mixture was separated, and the resulting organic layer was washed with water and then with saturated brine. Then, after dehydrating with anhydrous sodium sulfate, the solvent was distilled off to obtain 6.3 g of liquid. When this liquid was analyzed using high performance liquid chromatography, it contained 23.6% by weight of 7,8-difluoro-2-naphthol. The yield was 31.4 mol%.

Example 2 Synthesis of 7,8-difluoro-2-naphthol Into a 100 ml glass flask equipped with a stirrer, thermometer, reflux condenser and calcium chloride drying tube, 4.2 g (0.032 mol) of aluminum (III) chloride was added. ) And 17.5 g of 1,2-dichloroethane were charged and cooled to -15 ° C. Thereto, 5.0 g (0.026 mol) of the 2,3-difluorophenylacetic acid chloride dissolved in 17.5 g of 1,2-dichloroethane was added dropwise while maintaining at −10 ° C., and then −10 to −15 Hold at 0.5 ° C. for 0.5 hour. A vinyl chloride gas was blown into the mixture over 1 hour until 2,3-difluorophenylacetic acid chloride disappeared while maintaining the temperature at −10 to −15 ° C., and then maintained at the same temperature for 1 hour.

  After completion of the reaction, the reaction solution was added little by little in 38.5 g of an ice-cooled 4.5% hydrochloric acid aqueous solution to deactivate the catalyst, and the mixture was separated, and the resulting organic layer was washed with water and then with saturated brine. And dehydrated with anhydrous sodium sulfate, and then the solvent was distilled off to obtain 5.9 g of a liquid. When this liquid was analyzed using high performance liquid chromatography, it contained 23.7% by weight of 7,8-difluoro-2-naphthol. The yield was 29.6 mol%.

Example 3 Synthesis of 7,8-difluoro-2-naphthol 4.2 g (0.032 mol) of aluminum (III) chloride was placed in a 100 ml glass flask equipped with a stirrer, thermometer, reflux condenser and calcium chloride drying tube. ) And 17.5 g of dichloromethane, and cooled to -15 ° C. Thereto, 5.0 g (0.026 mol) of the above 2,3-difluorophenylacetic acid chloride dissolved in 17.5 g of dichloromethane was added dropwise while maintaining at −10 ° C., and then at −10 to −15 ° C. Hold for 5 hours. A solution prepared by dissolving 6.1 g (0.057 mol) of vinyl bromide in 17.5 g of dichloromethane was added dropwise to the mixture over 0.5 hours while maintaining the temperature at −10 to −15 ° C. Held for hours.

After completion of the reaction, the reaction solution was added little by little in 38.5 g of an ice-cooled 4.5% hydrochloric acid aqueous solution to deactivate the catalyst, and the mixture was separated, and the resulting organic layer was washed with water and then with saturated brine. Then, after dehydrating with anhydrous sodium sulfate, the solvent was distilled off to obtain 6.1 g of liquid. When this liquid was analyzed using high performance liquid chromatography, it contained 31.8% by weight of 7,8-difluoro-2-naphthol. The yield was 41.0 mol%.

Claims (2)

The following general formula (1)

(Wherein, X ¹ , X ² , X ³ and X ⁴ each independently represents a hydrogen atom, a halogen atom or a hydrocarbon group, but X ¹ , X ² , X ³⁾ And at least one of X ⁴ is a halogen atom, and X ⁵ represents a chlorine atom or a bromine atom), and is reacted with vinyl halide in the presence of a Lewis acid catalyst. 2)

A method for producing a 2-naphthol derivative represented by the formula (wherein X ¹ , X ² , X ³ and X ⁴ are the same as above).   The method for producing a 2-naphthol derivative according to claim 1, wherein the vinyl halide is vinyl chloride or vinyl bromide.