JP2009079024A - Method for producing 2-naphthol derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for production by which a 2-naphthol derivative using a 2-tetralone derivative as a raw material can more inexpensively be produced by simpler operation. <P>SOLUTION: The method for producing the 2-naphthol derivative represented by general formula (II) (wherein, X<SP>1</SP>to X<SP>4</SP>are each a hydrogen or a halogen selected from among fluorine, chlorine and bromine, and at least one thereof is the halogen) comprises dehydrogenating the 2-tetralone derivative represented by general formula (I) with sulfuric acid in the presence of an acid anhydride using a water-immiscible organic solvent and then hydrolyzing the resultant product. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

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

The present invention relates to a process for producing a 2-naphthol derivative by dehydrogenating a 2-tetralone derivative with sulfuric acid in the presence of an acid anhydride.
As a method for producing a 2-naphthol derivative from a 2-tetralone derivative, the 2-tetralone derivative is oxidatively dehydrogenated with a brominating agent such as bromine to obtain a 1-bromo-2-naphthol derivative, and catalytic reduction or sulfite. Or the like (Patent Document 1) or oxidative dehydrogenation using an oxidizing agent such as copper (II) bromide to form a 2-naphthol derivative (Patent Document 1) Document 2), a method of reacting a mixture of 2-tetralone and 1,2-dialine oxide in the presence of a noble metal catalyst (Patent Document 3), or dehydrogenating a 2-tetralone derivative in the presence of a dehydrogenation catalyst. -As a method of synthesizing a naphthol derivative, there is a method of reacting under reflux in the presence of a palladium carbon catalyst using mesitylene as a solvent (Non-patent Document 1).

  However, in Patent Document 1, bromine which is highly toxic and difficult to handle is used in a large amount of 2 mole times or more, which is not preferable. Moreover, since the 1st-position brominated thing produces | generates, a reduction process is needed and operation becomes complicated. Patent Document 2 also has a drawback that copper (II) bromide, which is highly toxic, is used in a large amount of 2 mole times, and the load on the waste treatment surface is large.

  In Patent Document 3, it is difficult to obtain 1,2-dialine oxide, and there are also disadvantages that the yield of 2-tetralol is large and the yield is low. In patent document 4, it is necessary to make it react under mesitylene reflux, and there exists a fault that reaction temperature is high. Moreover, there is no problem when using a 2-tetralone derivative having an alkyl group or an alkoxy group as a raw material as in Non-Patent Document 1, but when using a halogenated 2-tetralone derivative as a raw material, When a dehydrogenation reaction is carried out by the method, halogens undergo hydrogenolysis and are desorbed, resulting in a decrease in purity and yield of the target product and corrosion problems due to the desorbed hydrogen halide. In particular, in the case of industrial production, hydrogen tends to accumulate, and the side reaction tends to proceed, which is not preferable.

On the other hand, there is a method in which a cyclohexanone derivative is used as a raw material, dehydrogenated with sulfuric acid in the presence of an acetic acid solvent and acetic anhydride, and then hydrolyzed under basic conditions to synthesize a phenol derivative (Non-patent Document 2).
However, although it is a technology that attracts attention as a dehydrogenation method, when dehydrogenation is performed with sulfuric acid in the presence of acetic acid medium and acetic anhydride using 2-tetralone derivative as a raw material, it is sufficiently satisfactory as shown in Reference Example 1. The yield which can be obtained is not obtained.

JP 2004-91361 A JP 2004-91362 A U.S. Pat. No. 3,890,397 J. Org. Chem., 63, 4140 (1998) J. Org. Chem., 39, 2126 (1974)

  The objective of this invention is providing the manufacturing method which can manufacture 2-naphthol derivative which used 2-tetralone derivative as a raw material by simpler operation and cheaply.

  As a result of intensive studies to solve the above-described problems of the prior art, the present inventors have found that a halogenated 2-tetralone derivative is sulfuric acid in the presence of an acid anhydride using an organic medium that is not miscible with water. After dehydrogenation, it was investigated that a 2-naphthol derivative halogenated in a high yield was produced by hydrolysis, and the present invention was completed.

(式中、Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４は、おのおの独立して水素原子、またはフッ素原子、塩素原子および臭素原子から選ばれるハロゲン原子を表す。Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４のうち少なくとも一つは前記ハロゲン原子である。)
水と混和しない有機容媒を用いて、酸無水物の存在下、硫酸により脱水素した後に、加水分解することを特徴とする一般式(II)で表される２−ナフトール誘導体の製造方法を提供する。 The present invention provides a 2-tetralone derivative represented by the following general formula (I):

(Wherein X ¹ , X ² , X ³ and X ⁴ each independently represents a hydrogen atom or a halogen atom selected from a fluorine atom, a chlorine atom and a bromine atom. X ¹ , X ² , X ³ and At least one of X ⁴ is the halogen atom.)
A method for producing a 2-naphthol derivative represented by the general formula (II), characterized by dehydrating with sulfuric acid in the presence of an acid anhydride using an organic solvent immiscible with water, followed by hydrolysis. provide.

(式中、Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４は、前記と同様)

(Wherein X ¹ , X ² , X ³ and X ⁴ are the same as above)

The production method of the present invention will be described in detail below.
The raw material used in the present invention is a 2-tetralone derivative represented by the following general formula (I).

式中、Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４は、おのおの独立して水素原子、またはフッ素原子、塩素原子および臭素原子から選ばれるハロゲン原子を表す。Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４のうち少な<とも一つは前記ハロゲン原子である。

In the formula, X ¹ , X ² , X ³ and X ⁴ each independently represent a hydrogen atom or a halogen atom selected from a fluorine atom, a chlorine atom and a bromine atom. At least ^{one of} X ¹ , X ² , X ³ and X ⁴ is the halogen atom.

(式中、Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４は、おのおの独立して水素原子、またはフッ素原子、塩素原子および臭素原子から選ばれるハロゲン原子を表す。Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４のうち少なくとも一つは前記ハロゲン原子である。)
塩化チオニル等の塩素化剤を用いることによって下記一般式（ＩＶ）で表されるフェニル酢酸ハロゲン化物誘導体へと導き、 If the example of manufacture of the 2-tetralone derivative represented by general formula (I) is given, for example, the phenylacetic acid derivative represented by general formula (III),

(Wherein X ¹ , X ² , X ³ and X ⁴ each independently represents a hydrogen atom or a halogen atom selected from a fluorine atom, a chlorine atom and a bromine atom. X ¹ , X ² , X ³ and At least one of X ⁴ is the halogen atom.)
By using a chlorinating agent such as thionyl chloride, it leads to a phenylacetic acid halide derivative represented by the following general formula (IV):

(式中、Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４は、前記と同様。Ｘ^５は塩素原子または臭素原子を表す。)
次いで塩化アルミニウム等のルイス酸触媒存在下でエチレンと反応させることにより容易に製造できる。

(In the formula, X ¹ , X ² , X ³ and X ⁴ are the same as described above. X ⁵ represents a chlorine atom or a bromine atom.)
Subsequently, it can be easily produced by reacting with ethylene in the presence of a Lewis acid catalyst such as aluminum chloride.

  However, the raw material used by this invention should just be a 2-tetralone derivative represented by the said general formula (I), and there is no restriction | limiting in particular in the manufacturing method.

(式中、Ｘ^１、Ｘ^２、Ｘ^３およびＸ^４は、前記と同様。) The first step in the present invention is a step of dehydrogenating the 2-tetralone derivative represented by the general formula (I) to obtain a 2-acetoxynaphthalene derivative represented by the following general formula (V).

(Wherein X ¹ , X ² , X ³ and X ⁴ are the same as described above.)

  In the first stage, the 2-tetralone derivative represented by the above general formula (I) is dehydrogenated with sulfuric acid in the presence of an acid anhydride using an organic solvent immiscible with water.

  As the acid water in the present invention, acetic anhydride, propionic anhydride and the like can be used, but acetic anhydride is preferable. The used amount of the acid anhydride is 2 to 30 times, preferably 2.5 to 20 times in terms of molar ratio with respect to the 2-tetralone derivative.

  The oxidizing agent used in the present invention is sulfuric acid. The sulfuric acid concentration is not particularly limited, but is usually 90 to 98% concentrated sulfuric acid. If the sulfuric acid concentration is low, an excessive amount of acetic anhydride is required, which is not preferable. The amount of sulfuric acid used is about 0.8 to 5 times, preferably about 0.9 to 3 times in molar ratio to the 2-tetralone derivative.

The present invention uses an organic medium that is immiscible with water. The organic solvent used is not particularly limited as long as it is stable under the reaction conditions, but is not limited to aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, and aliphatic carbons such as hexane, heptane, octane, nonane and decane. Examples thereof include hydrogen, halogenated hydrocarbons such as methylene chloride, chloroform, and the like, tetrabutyl methyl ether, cyclopentyl methyl ether, and the like. These organic solvents may be used alone or in combination.
The usage-amount of a solvent is 0.5-30 weight times normally with respect to 2-tetralone derivative, Preferably it is about 1-15 weight times.

  The reaction temperature is usually 20 to 160 ° C., preferably 40 to 140 ° C., and the reaction time may be continued until the raw materials are almost disappeared, but is usually about 0.1 to 24 hours.

  After completion of the dehydrogenation reaction, when using an organic solvent that is not miscible with water, by adding water, the organic layer and the aqueous layer are separated, so that the organic layer is separated, and if necessary, washed with water. The organic solvent is concentrated as it is or until the organic layer reaches a predetermined amount, and then the second stage reaction is performed.

In the second step of the present invention, the 2-acetoxynaphthalene derivative represented by the above general formula (V) produced by the dehydrogenation reaction is hydrolyzed to give a 2-naphthol derivative represented by the following general formula (II) ( Wherein X ¹ , X ² , X ³ and X ⁴ are the same as described above.

  Examples of the hydrolysis catalyst used in the present invention include acids such as sulfuric acid and hydrochloric acid, and bases such as sodium hydroxide, potassium hydroxide and ammonia. The amount of these catalysts used is about 1 to 50 times, preferably about 2 to 20 times in terms of molar ratio with respect to the 2-tetralone derivative. These catalysts are used as an aqueous solution of about several percent to 60%.

  The reaction temperature is usually about 0 to 50 ° C. in the case of a base catalyst, and usually 80 to 130 ° C. in the case of an acid catalyst. The reaction time may be continued until the raw materials almost disappear, but is usually about 0.1 to 24 hours.

  After completion of the reaction, after acidification in the case of using a base catalyst, if the acid catalyst is used, it is extracted as it is, extracted with an organic solvent, washed with water if necessary, and the obtained organic layer is cooled as it is. Crystals are precipitated by cooling or crystallization by removing the solvent or by adding a solvent, and by cooling with a poor solvent, crystals of the 2-naphthol derivative can be obtained by separating the crystals.

EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited to the following Example.
The analysis was performed using gas chromatography, and 2-acetoxy-7,8-difluoronaphthalene and 7,8-difluoro-2-naphthol were quantified by an internal standard method using naphthalene as an internal standard substance.

(Reference Example 1)
In a 200 ml glass flask equipped with a stirrer, a thermometer, and a reflux condenser, 7,98-difluoro-2-tetralone 7.98 g (purity 91.3%; 40 mmol), acetic anhydride 54.2 g (530.4). Mmol) and 52.5 g of acetic acid were added, and 9.0 g (88.1 mmol) of 96% sulfuric acid was added dropwise over 36 minutes, and then the temperature was raised to 117 ° C. and kept at the same temperature for 1 hour.
After completion of the reaction, the reaction solution was cooled to room temperature, deactivated by adding the reaction solution in 150 g of water, extracted with 50 g of toluene three times, and then the solvent was distilled off to give 2-acetoxy-7,8-difluoronaphthalene. A concentrate containing was obtained.
To this concentrate, 25 g of methanol and 25 g of 30% aqueous sodium hydroxide solution were added, reacted at room temperature for 1 hour, acidified with hydrochloric acid, extracted three times with 50 g of toluene, and the organic layer was washed with 50 g of saturated brine. The solvent was distilled off to obtain 13.37 g of a concentrate.
When this concentrate was analyzed using gas chromatography, the content of 7,8-difluoro-2-naphthol was 38.4% by weight and the yield was 71.2% by mole.

Example 1
In a 100 ml glass flask equipped with a stirrer, thermometer and reflux condenser, 7,8-difluoro-2-tetralone 5.0 g (purity 80.1%; 21.7 mmol), acetic anhydride 32.5 g (318) 0.2 mmol) and 24.4 g of toluene were added, and 4.44 g (43.5 mmol) of 96% sulfuric acid was added dropwise over 30 minutes, then the temperature was raised to 110 ° C. and kept at the same temperature for 2 hours.
After completion of the reaction, the reaction solution was cooled to room temperature, and the reaction solution was added to 20 g of water to deactivate it. Toluene was distilled off from the separated organic layer to obtain 6.52 g of a concentrate.
When this concentrate was analyzed using gas chromatography, the content of 2-acetoxy-7,8-difluoronaphthalene was 67.4% by weight and the yield was 90.0% by mole.
Next, toluene was distilled off until the organic layer became 15 g, 5 g of isopropanol and 15 g of 50% sulfuric acid aqueous solution were added, the temperature was raised to 100 ° C., and the temperature was maintained for 3 hours.
After completion of the reaction, the reaction mixture was cooled to room temperature, and the aqueous layer was separated. Then, the organic layer was washed with 5 g of water to obtain 13.9 g of an organic layer. When the organic layer was analyzed by gas chromatography, the content of 7,8-difluoro-2-naphthol was 25.0% by weight, and the yield based on 7,8-difluoro-2-tetralone was 87.8. Mol%.

(Example 2)
A 100 ml glass flask equipped with a stirrer, thermometer and reflux condenser was charged with 2.0 g of 7,8-difluoro-2-tetralone (purity 80.1%; 8.8 mmol) and 13 g of acetic anhydride (127.3). Mmol) and 14.2 g of methylene chloride were added, and 1.78 g (17.4 mmol) of 96% sulfuric acid was added dropwise over 10 minutes, then the temperature was raised to 44 ° C. and kept at the same temperature for 4 hours.
After completion of the reaction, the reaction solution was cooled to room temperature, and the reaction solution was added to 15 g of water to deactivate it, and methylene chloride was distilled off from the separated organic layer to obtain 4.52 g of a concentrate.
When this concentrate was analyzed using gas chromatography, the content of 2-acetoxy-7,8-difluoronaphthalene was 33.1% by weight and the yield was 76.6% by mole.
Next, methylene chloride was distilled off from this organic layer, 4 g of toluene, 2 g of isopropanol, and 4 g of 50% sulfuric acid aqueous solution were added, and the temperature was raised to 100 ° C. and kept at the same temperature for 3 hours.
After completion of the reaction, the reaction mixture was cooled to room temperature, and the aqueous layer was separated. Then, the organic layer was washed with 4 g of water to obtain 5.3 g of an organic layer. The organic layer was analyzed by gas chromatography. As a result, the content of 7,8-difluoro-2-naphthol was 22.6% by weight, and the yield based on 7,8-difluoro-2-tetralone was 75.7. Mol%.

(Example 3)
In a 100 ml glass flask equipped with a stirrer, thermometer and reflux condenser, 7,8-difluoro-2-tetralone 5.0 g (purity 84.7%; 23.2 mmol), acetic anhydride 16.3 g (159) 0.1 mmol) and 48.8 g of toluene were added, and 3.56 g (34.8 mmol) of 96% sulfuric acid was added dropwise over 30 minutes, then the temperature was raised to 110 ° C. and kept at the same temperature for 2 hours.
After completion of the reaction, the reaction mixture was cooled to room temperature, the reaction solution was added to 20 g of water to deactivate it, and toluene was distilled off from the separated organic layer to obtain 5.7 g of a concentrate.
When this concentrate was analyzed using gas chromatography, the content of 2-acetoxy-7,8-difluoronaphthalene was 85.2% by weight and the yield was 94.0% by mole.
Next, toluene was distilled off until the organic layer became 15 g, 5 g of isopropanol and 15 g of 50% sulfuric acid aqueous solution were added, the temperature was raised to 100 ° C., and the temperature was maintained for 3 hours.
After completion of the reaction, the reaction mixture was cooled to room temperature, and the aqueous layer was separated. Then, the organic layer was washed with 5 g of water to obtain 14.2 g of an organic layer. When the organic layer was analyzed by gas chromatography, the content of 7,8-difluoro-2-naphthol was 27.2% by weight, and the yield based on 7,8-difluoro-2-tetralone was 92.1. Mol%.

Example 4
In a 5 L glass flask equipped with a stirrer, a thermometer, and a reflux condenser, 272.8 g of 7,8-difluoro-2-tetralone (purity 87.5%; 1.31 mol), 802.7 g of acetic anhydride (7 .86 mol) and 2455 g of xylene were added, 154.2 g (1.51 mol) of 96% sulfuric acid was added dropwise over 2 hours, the temperature was raised to 110 ° C., and the temperature was maintained for 2 hours.
After completion of the reaction, the mixture was cooled to room temperature, the reaction solution was added to 1091 g of water to deactivate it, and liquid separation was performed to obtain 2657.9 g of an organic layer. When this organic layer was analyzed using gas chromatography, the content of 2-acetoxy-7,8-difluoronaphthalene was 10.1 wt% and the yield was 92.1 mol%.
Next, 238.7 g of isopropanol and 540.5 g of hydrochloric acid were added to the organic layer, the temperature was raised to 95 ° C., and the mixture was held at the same temperature for 10 hours.
After completion of the reaction, the mixture was cooled to room temperature, and the aqueous layer was separated. The organic layer was washed with 724.7 g of water, and xylene was partially distilled off to obtain 801.3 g of an organic layer. When the organic layer was analyzed by gas chromatography, the content of 7,8-difluoro-2-naphthol was 27.0% by weight, and the yield based on 7,8-difluoro-2-tetralone was 91.6. Mol%.

(Example 5)
In a 100 ml glass flask equipped with a stirrer, thermometer and reflux condenser, 7,72-difluoro-2-tetralone (5.72 g; purity: 27.5 mmol), acetic anhydride (11.2 g) (109 g) 0.7 mmol) and 44.2 g of xylene were added, and 2.8 g (27.4 mmol) of 96% sulfuric acid was added dropwise over 30 minutes, and then the temperature was raised to 110 ° C. and kept at the same temperature for 2 hours.
After completion of the reaction, the mixture was cooled to room temperature, the reaction solution was added to 11.4 g of water to deactivate it, and liquid separation was performed to obtain 55.2 g of an organic layer. When this organic layer was analyzed using gas chromatography, the content of 2-acetoxy-7,8-difluoronaphthalene was 10.6 wt% and the yield was 96.0 mol%.
Next, xylene was distilled off until the organic layer became 17.2 g, 5 g of isopropanol and 15 g of a 50% sulfuric acid aqueous solution were added, the temperature was raised to 100 ° C., and the temperature was maintained for 3 hours.
After completion of the reaction, the mixture was cooled to room temperature, and the aqueous layer was separated, and then the organic layer was washed with 5 g of water to obtain 15.6 g of an organic layer. When this organic layer was analyzed by gas chromatography, the content of 7,8-difluoro-2-naphthol was 29.5% by weight, and the yield based on 7,8-difluoro-2-tetralone was 93.1. Mol%.

(Example 6)
In a 100 ml glass flask equipped with a stirrer, a thermometer and a reflux condenser, 7,8-difluoro-2-tetralone 2.0 g (purity 94.4%; 10.4 mmol), acetic anhydride 13.5 g (132) 1.6 mmol), 13.1 g of acetic acid and 21.7 g of toluene were added, and 2.12 g (20.8 mmol) of 96% sulfuric acid was added dropwise over 5 minutes, then the temperature was raised to 109 ° C. and kept at the same temperature for 2 hours. did.
After completion of the reaction, the reaction solution was cooled to room temperature, deactivated by adding the reaction solution in 50 g of water, extracted three times with 30 g of toluene, and then the solvent was distilled off to give 2-acetoxy-7,8-difluoronaphthalene. A concentrate containing was obtained.
To this concentrate was added 5 g of methanol and 15 g of a 10% aqueous sodium hydroxide solution, reacted at room temperature for 1 hour, acidified with hydrochloric acid, extracted three times with 50 g of toluene, and the organic layer was washed with 50 g of saturated brine. The solvent was distilled off to obtain 4.05 g of a concentrate.
When this concentrate was analyzed using gas chromatography, the content of 7,8-difluoro-2-naphthol was 40.7% by weight and the yield was 88.1 mol%.

(Example 7)
In a 100 ml glass flask equipped with a stirrer, a thermometer and a reflux condenser, 7,8-difluoro-2-tetralone 2.0 g (purity 94.4%; 10.4 mmol), acetic anhydride 13.5 g (132) 1.6 mmol), 13.1 g of acetic acid and 27.6 g of chlorobenzene were added, and 2.12 g (20.8 mmol) of 96% sulfuric acid was added dropwise over 5 minutes, then the temperature was raised to 110 ° C. and kept at the same temperature for 1 hour. did.
After completion of the reaction, the reaction solution was cooled to room temperature, deactivated by adding the reaction solution into 30 g of water, extracted with 30 g of toluene three times, and then the solvent was distilled off to give 2-acetoxy-7,8-difluoronaphthalene. A concentrate containing was obtained.
To this concentrate was added 5 g of methanol and 15 g of a 10% aqueous sodium hydroxide solution, reacted at room temperature for 1 hour, acidified with hydrochloric acid, extracted three times with 50 g of toluene, and the organic layer was washed with 50 g of saturated brine. The solvent was distilled off to obtain 3.78 g of a concentrate.
When this concentrate was analyzed using gas chromatography, the content of 7,8-difluoro-2-naphthol was 39.6% by weight and the yield was 80.1 mol%.
The results of Reference Example 1 and Examples 1 to 7 are summarized in Table 1.

Claims (1)

A 2-tetralone derivative represented by the following general formula (I):

(Wherein X ¹ , X ² , X ³ and X ⁴ each independently represents a hydrogen atom or a halogen atom selected from a fluorine atom, a chlorine atom and a bromine atom. X ¹ , X ² , X ³ And at least one of X ⁴ is the halogen atom.)
A method for producing a 2-naphthol derivative represented by the general formula (II), wherein an organic solvent immiscible with water is used for dehydrogenation with sulfuric acid in the presence of an acid anhydride, followed by hydrolysis.

(Wherein X ¹ , X ² , X ³ and X ⁴ are the same as above)